1
Ni(II)-Catalyzed Enantioselective Mukaiyama-Mannich Reaction Between Silyl Enol Ethers and Cyclic N-Sulfonyl α-Ketiminoesters
Lei Xie, Hongli Ma, Jiaqi Li, Yuan Yu, Zhaohai Qin, Bin Fu*
Department of Applied Chemistry, China Agricultural University, Beijing 100193, China
Contents
1. General information……………………………………………………………………….…2
2. Preparation of N-sulfonyl cyclic ketimines ……………………………………………....….2
3. Preparation of enol silyl ethers……………………………………………………………….3
4. General procedure for the catalytic asymmetric Mukaiyama-Mannich reaction…………….3
5. Characterization data for the products 3………………………………………………….….4
6. Transformations of product 3 to 4, 5 and 6………………………………………………….17
7. HPLC chromatograms for products 3~6………………………..……….……….…….……20
8. 1H and 13C NMR spectra for products 3~6………………………………..…..…………….59
9. The structure of 3ka and 3aw’ by X-ray diffraction analysis………………………….……98
Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers.This journal is © the Partner Organisations 2017
2
1. General Information:
All solvents were purified and dried according to standard methods prior to use. Organic solutions
were concentrated under reduced pressure on a rotary evaporator. Flash column chromatography
was performed using Qingdao Haiyang flash silica gel (100–200 mesh). NMR spectra were
recorded with a Bruker Avance DPX300 spectrometer with tetramethylsilane as the internal
standard. Mass spectra were obtained on Bruker APEX II FT-ICRMS mass spectrometer. Optical
rotations were measured on a Perkine-Elmer 341 LC polarimeter. The enantiomeric excesses were
determined by HPLC analysis over a chiral column (Daicel Chiralcel OD-H or Chiralpak AD-H,
eluted with hexane-isopropyl alcohol; monitored by UV detector).1
2. Preparation of N-sulfonyl cyclic ketimines 12
NS
OO
EtOOC OH
NS
OO
COOEt
NHS
O
O
n-BuLi
(COOEt)2
HCOOH
Under nitrogen atmosphere, a solution of aryl sulfonamide (10 mmol) in THF (40 mL) was cooled
to –78 °C in an acetone-ice bath. The solution of n-Butyllithium in hexanes (25 mmol) was added
dropwise over a 20 minute period. After stirred at -20 °C for 1 h, the yellow mixture was cooled
further to -78 °C and diethyl oxalate (30 mmol) was added. The solution was allowed to stir for 1
h then warm slowly to room temperature, and stirred at ambient temperature for another 2 h. The
reaction was quenched with 5% HCl (20 mL), water (100 mL) was added, and extracted with ethyl
acetate (60 mL×3). The organic phase was washed with brine (100 ml), dried over sodium sulfate.
The solvent was removed and the obtained crude product was further purified by flash
chromatography (PE/EA = 10/1 – 5/1).
Under nitrogen atmosphere, the above product was dissolved in formic acid (10 mL), and
subsequently stirred at room temperature. After 24 h the solution was concentrated and the residue
was dissolved in CH2Cl2 (50 mL) and washed with NaHCO3 saturated solution (50 mL×2) to
remove traces of formic acid. Then the organic phase was washed with brine, dried over sodium
sulfate, and concentrated under reduced pressure. Purification by flash column chromatography
(PE/EA = 5/1, v/v) gave the title products 1a-k in high yield.
3. Preparation of enol silyl ethers
3
General procedure I 3a (for 2a-2r, 2t, 2v, 2x):
To a stirred solution of aromatic ketone (5 mmol) in THF (20 mL), LiHMDS (6 mmol, 1M in
THF) was added dropwise over a period of 5 min at room temperature. After 20 min, the mixture
was quenched with chlorotrimethylsilane (5.5 mmol). and was stirred for another 2h. The solvent
was removed and the mixture was diluted with hexane. The resulting precipitate was filtered
through the Celite (washing with pentane), and the filtrate was concentrated in vacuo to afford the
crude enol silyl ether, which was stored at -20 oC, and the obtained product was distilled prior to
use.
Other enol silyl ethers such as 2s, 2w, 2u, 2y and 2z were prepared according to the
corresponding literatures3b, 3c, 3d
4. General procedure for the catalytic asymmetric Mukaiyama-Mannich reaction.
Under nitrogen atmosphere, ligand (L2) (0.0022mmol) and Ni(ClO4)2·6H2O (0.002mmol) were
dissolved in CHCl3 (1.0 mL), and stirred for 1 h at room temperature. Subsequently N-sulfonyl
cyclic ketimines 1 (0.1 mmol) was added, and the resulting mixture was cooled to 0°C and stirred
for 10 min before the silyl enol ether 2 (0.20 mmol) was added. The reaction mixture was stirred
at 0 °C until the completion of the reaction (monitored by TLC). Then the mixture was directly
subjected to flash column chromatography (Petroleum / Ethyl acetate, 10/1~3/1, V/V) to afford
the corresponding product 3.
Table ST1. Screening of Lewis acidsa
NS
O O
COOEt
OTMSNH
SO O
EtOOC
OMetal / L2
temperature, CHCl3
1b 2a 3ba
Entry Metal T (oC) Time (h) Yield (%)b ee (%)c
1 Co(ClO4)2·6H2O 0 12 96 97
2 Zn(ClO4)2·6H2O 0 12 89 94
3 Cu(ClO4)2·6H2O 0 48 54 57
4 Mg(ClO4)2·6H2O 0 36 90 93
5 Mg(OTf)2 0 96 36 8
6 Cu(OTf)2 0 48 40 20
4
7 Ni(OTf)2 0 48 43 80
8 Ni(acac)2 0 96 trace -
9 Ni(OAc)2·4H2O 0 72 75 93
10 Ni(ClO4)2·6H2O 25 12 98 86
a Reaction conditions: 1b (0.1 mmol) and 2a (0.2 mmol), 10 mol % metal salts and 11 mol % L2 in 2.0 mL CHCl3
at 0 oC b Isolated yields. c Determined by chiral HPLC analysis. d Not determined.
Table ST2 Optimization of reaction conditions for 1-tetralone derived enol silyl ether as
the substratea
NS
O O
COOEt
OTMSNH
SO O
EtOOC
OMetal / L2
0oC, CHCl3
1a 2x 3ax
Entry Metal Time (h) Yield (%)b d.r.c ee (%)c
1 Ni(ClO4)2·6H2O 48 94 1.1:1 64, 662 Cu(ClO4)2·6H2O 96 trace -d -3 Co(ClO4)2·6H2O 96 33 3.5:1 96, 984 Mg(ClO4)2·6H2O 96 trace - -5 Zn(ClO4)2·6H2O 48 95 11.5:1 986 Ni(OTf)2 96 trace - -7 Fe(OTf)2 96 trace - -8 Cu(OTf)2 96 35 - -9 Zn(OTf)2 48 95 25:1 99
a Reaction conditions: 1a (0.1 mmol) and 2x (0.2 mmol), 10 mol % metal salts and 11 mol % L2 in 2.0 mL CHCl3
at 0 oC; b Isolated yields; c Determined by chiral HPLC analysis; d Not determined.
5. Characterization data for the Mukaiyama-Mannich products 3
White solid, m.p. 59−60 oC, 99% yield. [α]20 D = –167.9 (c, 1.20, CH2Cl2); 99%
ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-hexane/i-
PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 17.85 min, t (minor) = 24.75
min]; 1H NMR (300 MHz, CDCl3) δ 7.95–7.87 (m, 2H), 7.85–7.78 (m, 1H),
7.75 –7.53 (m, 4H), 7.50 –7.41 (m, 2H), 6.09 (s, 1H), 4.31 (qq, J = 10.8, 7.2 Hz, 2H), 4.08 (d, J =
17.8 Hz, 1H), 3.72 (d, J = 17.8 Hz, 1H), 1.29 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
195.65, 169.27, 136.60, 135.28, 133.67, 133.33, 130.49, 128.47, 127.86, 123.92, 121.54, 65.16,
63.17, 48.81, 13.61. ESI-HRMS: Calcd for C18H17NNaO5S+ ([M+Na+]): 382.0720; Found:
NHS
O O
CO2Et Ph
O
3aa
5
382.0723.
White solid, m.p. 60 – 62 oC, 99% yield; [α]20 D = –117.4 (c, 1.02,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 13.44
min, t (minor) = 21.91 min]; 1H NMR (300 MHz, CDCl3) δ 7.96 – 7.88 (m,
2H), 7.73 – 7.67 (m, 1H), 7.65 – 7.56 (m, 1H), 7.52 – 7.40 (m, 4H), 6.04 (s, 1H), 4.42 – 4.22 (m,
2H), 4.09 (d, J = 17.8 Hz, 1H), 3.70 (d, J = 17.8 Hz, 1H), 2.50 (s, 3H), 1.31 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 195.73, 169.39, 144.51, 136.90, 135.34, 133.61, 132.57, 131.40,
128.44, 127.85, 124.05, 121.26, 76.28, 65.00, 63.07, 48.95, 21.53, 13.61. ESI-HRMS: Calcd for
C19H20NO5S+ ([M+H+]): 374.1057; Found: 374.1060.
White solid, m.p. 152–153.5 oC, 99% yield; [α]20 D = –170.9 (c, 0.67,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-
H column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) =
14.83 min, t (minor) = 22.17 min]; 1H NMR (300 MHz, CDCl3) δ
7.95–7.86 (m, 2H), 7.74 –7.66 (m, 1H), 7.63 –7.54 (m, 1H), 7.50–7.40 (m, 2H), 7.15 – 7.08 (m,
2H), 6.09 (s, 1H), 4.44–4.20 (m, 2H), 4.08 (d, J = 17.8 Hz, 1H), 3.91 (s, 3H), 3.72 (d, J = 17.8 Hz,
1H), 1.30 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 195.65, 169.27, 163.62, 139.18,
135.29, 133.63, 128.44, 127.84, 127.19, 122.88, 116.94, 108.30, 64.85, 63.11, 55.73, 48.94, 13.65.
ESI-HRMS: Calcd for C19H20NO6S+ ([M+H+]): 390.1006; Found: 390.1007.
White solid, m.p. 150–151 oC, 98% yield. [α]20 D = –163.4 (c, 0.76,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 7.20
min, t (minor) = 12.30 min]; 1H NMR (300 MHz, CDCl3) δ 7.96 – 7.89 (m, 2H), 7.77 – 7.71 (m,
1H), 7.70 – 7.63 (m, 2H), 7.63 – 7.55 (m, 1H), 7.51 – 7.41 (m, 2H), 6.08 (s, 1H), 4.47 – 4.18 (m,
2H), 4.08 (d, J = 17.8 Hz, 1H), 3.75 (d, J = 17.8 Hz, 1H), 1.38 (s, 9H), 1.31 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 195.72, 169.40, 157.82, 136.77, 135.35, 133.62, 132.52, 128.43,
128.14, 127.89, 121.04, 120.31, 65.19, 62.96, 48.89, 35.29, 30.86, 13.70. ESI-HRMS: Calcd for
NHS
O O
EtO2C
O
3ba
NHS
OO
EtOOC
O
3da
NHS
O O
EtO2C
OMeO
3ca
6
C22H25NNaO5S+ ([M+Na+]): 438.1346; Found: 438.1350.
White solid, m.p. 63 –64 oC, 99% yield. [α]20 D = –124.1 (c, 0.80,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) =
10.85 min, t (minor) = 17.42 min]; 1H NMR (300 MHz, CDCl3) δ 7.96 –
7.87 (m, 2H), 7.85 – 7.77 (m, 1H), 7.64 – 7.56 (m, 1H), 7.52 – 7.28 (m, 4H), 6.20 (s, 1H), 4.43 –
4.25 (m, 2H), 4.05 (d, J = 17.7 Hz, 1H), 3.75 (d, J = 17.7 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H). 13C
NMR (75 MHz, CDCl3) δ 195.30, 168.80, 165.28 (d, J = 256.0 Hz), 139.82 (d, J = 9.1 Hz),
135.15, 133.77, 131.40 (d, J = 2.7 Hz), 128.50, 127.87, 123.81 (d, J = 9.9 Hz), 118.48 (d, J = 24.0
Hz), 111.33 (d, J = 25.0 Hz), 64.74 (d, J = 2.1 Hz), 63.44, 48.69, 13.60. ESI-HRMS: Calcd for
C18H16FNNaO5S+ ([M+Na+]): 400.0625; Found: 400.0625.
White solid, m.p. 65–66.5 oC,; [α]20 D = –161.4 (c, 0.66, CH2Cl2); 99%
ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 10.82 min, t
(minor) = 19.38 min]; 1H NMR (300 MHz, CDCl3) δ 7.97 – 7.86 (m,
2H), 7.79 – 7.72 (m, 1H), 7.71 – 7.67 (m, 1H), 7.65 –7.55 (m, 2H), 7.51 – 7.42 (m, 2H), 6.19 (s,
1H), 4.34 (qq, J = 10.7, 7.1 Hz, 2H), 4.07 (d, J = 17.7 Hz, 1H), 3.73 (d, J = 17.7 Hz, 1H), 1.32 (t, J
= 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 195.32, 168.77, 139.76, 138.66, 135.14, 133.87,
133.77, 130.98, 128.50, 127.88, 124.28, 122.74, 64.78, 63.46, 48.69, 13.61. ESI-HRMS: Calcd for
C18H17ClNO5S+ ([M+H+]): 394.0510; Found: 394.0514.
White solid, m.p. 58–59 oC, 97% yield. [α]20 D = –138.3 (c, 0.83,
CH2Cl2); 97% ee, determined by HPLC analysis [Daicel Chiralcel
OD-H column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major)
= 8.26 min, t (minor) = 18.11 min]; 1H NMR (300 MHz, CDCl3) δ 8.02
– 7.87 (m, 5H), 7.65 – 7.56 (m, 1H), 7.51 – 7.43 (m, 2H), 6.29 (s, 1H), 4.48 – 4.24 (m, 2H), 4.13
(d, J = 17.7 Hz, 1H), 3.76 (d, J = 17.7 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 195.23, 168.63, 138.69, 137.73, 135.36 (q, J = 33.3 Hz), 135.07, 133.84, 128.51, 127.90,
NHS
O O
EtO2C
OF
3ea
NHS
O O
EtO2C
OCl
3fa
NHS
O O
EtO2C
OF3C
3ga
7
127.79 (dd, J = 7.3, 3.8 Hz), 122.58 (d, J = 273.4 Hz), 122.48, 121.43 (q, J = 3.9 Hz), 65.07, 63.54,
48.59, 13.56. ESI- HRMS: Calcd for C19H16F3NNaO5S+ ([M+Na+]): 450.0593; Found: 450.0597.
White solid, m.p. 92– 94 oC, 99% yield. [α]20 D = –161.1 (c, 1.24,
CH2Cl2); 94% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) =
16.34 min, t (minor) = 21.53 min]; 1H NMR (300 MHz, CDCl3) δ 8.00 –
7.89 (m, 2H), 7.73 – 7.57 (m, 3H), 7.54 – 7.34 (m, 3H), 6.33 (s, 1H), 4.50 (d, J = 17.8 Hz, 1H),
4.37 – 4.19 (m, 2H), 3.61 (d, J = 17.8 Hz, 1H), 1.25 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 195.94, 168.32, 157.66 (d, J = 257.7 Hz), 137.79 (d, J = 2.6 Hz), 135.33, 133.73, 133.07
(d, J = 7.2 Hz), 128.49, 127.87, 122.68 (d, J = 16.8 Hz), 120.71 (d, J = 21.3 Hz), 117.72 (d, J =
4.3 Hz), 64.30, 64.25, 63.19, 45.36, 45.33, 13.43. ESI-HRMS: Calcd for C18H16FNNaO5S+
([M+H+]): 400.0625; Found: 400.0629.
White solid, m.p. 66–68 oC, 97% yield. [α]20 D = –128 (c, 1.23, CH2Cl2);
97% ee, determined by HPLC analysis [Chiralpak AD-H column, n-
hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; t (minor) = 22.10 min, t
(major) = 26.94 min]; 1H NMR (300 MHz, CDCl3) δ 7.95 – 7.86 (m, 2H),
7.68 – 7.52 (m, 4H), 7.49 – 7.42 (m, 2H), 6.20 (s, 1H), 4.33 (qq, J = 10.7, 7.1 Hz, 2H), 4.05 (d, J =
17.7 Hz, 1H), 3.73 (d, J = 17.7 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
195.28, 168.83, 139.36, 135.17, 134.48, 133.75, 133.36, 131.25, 129.19, 128.50, 127.85, 122.25,
64.20, 63.43, 48.61, 13.61. ESI-HRMS: Calcd for C18H16ClNNaO5S+ ([M+H+]): 416.0330; Found:
416.0334.
White solid, m.p. 50–52 oC, 98% yield. [α]20 D = –133.6 (c, 1.33,
CH2Cl2); 96% ee, determined by HPLC analysis [Daicel Chiralcel
OD-H column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t
(major) = 8.04 min, t (minor) = 18.02 min]; 1H NMR (300 MHz,
CDCl3) δ 7.96 – 7.82 (m, 3H), 7.65 – 7.41 (m, 5H), 6.25 (s, 1H), 4.47 – 4.22 (m, 2H), 4.05 (d, J =
17.7 Hz, 1H), 3.78 (d, J = 17.7 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
NHS
O O
EtO2C
O
F
3ha
NHS
O O
EtO2C
O
Cl
3ia
NHS
O O
EtO2C
OF3CO
3ja
8
195.19, 168.64, 152.47 (q, J = 1.7 Hz), 139.42, 135.12, 133.79, 133.70, 128.50, 127.89, 123.47,
122.98, 119.83 (q, J = 260.2 Hz), 116.15, 64.81, 63.49, 48.56, 13.52. ESI-HRMS: Calcd for
C19H17F3NO6S+ ([M+H+]): 444.0723; Found: 444.0725.
White solid, m.p. 92–95 oC, 99% yield. [α]20 D = –163.3 (c, 0.73,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 15.86
min, t (minor) = 24.68 min]; 1H NMR (300 MHz, CDCl3) δ 8.45 – 8.38 (m,
1H), 8.17 – 8.10 (m, 1H), 8.02 – 7.95 (m, 1H), 7.94 – 7,86 (m, 2H), 7.77 – 7.62 (m, 3H), 7.61 –
7.53 (m, 1H), 7.48 – 7.39 (m, 2H), 6.28 (s, 1H), 4.43 – 4.25 (m, 2H), 4.21 (d, J = 17.7 Hz, 1H),
3.75 (d, J = 17.8 Hz, 1H), 1.30 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 195.58, 169.26,
135.43, 135.29, 134.60, 133.67, 130.76, 129.12, 128.46, 128.36, 128.12, 127.85, 125.14, 122.86,
119.42, 65.21, 63.24, 48.57, 13.66. ESI-HRMS: Calcd for C22H19NNaO5S+ ([M+H+]): 432.0876;
Found: 432.0879.
White solid, m.p. 58–61 oC, 99% yield. [α]20 D = (c, 1.26, CH2Cl2); 97%
ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 16.90 min, t
(minor) = 19.91 min]; 1H NMR (300 MHz, CDCl3) δ 7.86 – 7.77 (m, 3H),
7.73 – 7.59 (m, 3H), 7.29 – 7.23 (m, 2H), 6.09 (s, 1H), 4.39 – 4.22 (m, 2H), 4.07 (d, J = 17.7 Hz,
1H), 3.70 (d, J = 17.7 Hz, 1H), 2.41 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3)
δ 195.22, 169.33, 144.67, 136.65, 135.26, 133.29, 132.86, 130.43, 129.13, 127.98, 123.95, 121.50,
65.21, 63.10, 48.70, 21.37, 13.60. ESI-HRMS: Calcd for C19H19NNaO5S+ ([M+Na+]): 396.0876;
Found: 396.0874.
White solid, m.p. 68–70 oC, 98% yield. [α]20 D = –142.8 (c, 0.86,
CH2Cl2); 95% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; t (minor) =
28.09 min, t (major) = 86.78 min]; 1H NMR (300 MHz, CDCl3) δ 7.91 –
7.84 (m, 2H), 7.83 – 7.78 (m, 1H), 7.73 – 7.58 (m, 3H), 7.47 – 7.29 (m, 5H), 7.03 – 6.96 (m, 2H),
NHS
O O
CO2Et
O
3ab
NHS
O O
EtO2C
O
OBn3ac
NHS
O O
EtO2C
O
3ka
9
6.10 (s, 1H), 5.12 (s, 2H), 4.30 (qq, J = 10.7, 7.1 Hz, 2H), 4.04 (d, J = 17.6 Hz, 1H), 3.66 (d, J =
17.6 Hz, 1H), 1.29 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 194.02, 169.39, 162.99,
136.68, 135.65, 135.26, 133.27, 130.42, 130.24, 128.58, 128.38, 127.96, 127.13, 123.95, 121.50,
114.50, 69.89, 65.27, 63.08, 48.50, 29.35, 13.62. ESI-HRMS: Calcd for C25H23NNaO6S+
([M+Na+]): 488.1138; Found: 488.1144.
White solid, m.p. 62–64 oC, 96% yield. [α]20 D = –153.1 (c, 0.70,
CH2Cl2); 98% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (minor) = 19.04
min, t (major) = 25.08 min]; 1H NMR (300 MHz, CDCl3) δ 7.99 – 7.90 (m,
2H), 7.85 – 7.79 (m, 1H), 7.74 – 7.60 (m, 3H), 7.18 – 7.07 (m, 2H), 6.12 (s, 1H), 4.32 (qq, J =
10.7, 7.1 Hz, 2H), 4.07 (d, J = 17.7 Hz, 1H), 3.69 (d, J = 17.7 Hz, 1H), 1.30 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 194.09, 169.19, 165.87 (d, J = 256.4 Hz), 136.52, 135.23, 133.39,
131.79 (d, J = 3.1 Hz), 130.61 (d, J = 11.0 Hz), 130.55, 123.96, 121.48, 115.63 (d, J = 22.1 Hz),
65.13, 63.20, 48.61, 13.59. ESI-HRMS: Calcd for C18H17FNO5S+ ([M+H+]): 378.0806; Found:
378.0809.
White solid, m.p. 65–68 oC, 94% yield. [α]20 D= –135.2 (c, 1.0, CH2Cl2);
98% ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (minor) = 21.77 min, t
(major) = 31.21 min]; 1H NMR (300 MHz, CDCl3) δ 7.86 – 7.54 (m, 8H),
6.12 (s, 1H), 4.32 (qq, J = 10.8, 7.1 Hz, 2H), 4.06 (d, J = 17.8 Hz, 1H), 3.68 (d, J = 17.8 Hz, 1H),
1.30 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 194.74, 169.15, 136.44, 135.18, 133.98,
133.44, 131.80, 130.58, 129.36, 128.99, 123.95, 121.51, 65.06, 63.27, 48.64, 13.63. ESI-HRMS:
Calcd for C18H16BrNNaO5S+ ([M+Na+]): 459.9825; Found: 459.9830.
White solid, m.p. 66–68 oC, 95% yield. [α]20 D = –133.7 (c, 1.10,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel
OD-H column, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; t
(minor) = 16.73 min, t (major) = 38.84 min]; 1H NMR (300 MHz,
NHS
O O
EtO2C
O
F3ad
NHS
O O
EtO2C
O
Br3ae
NHS
O O
EtO2C
O
CO2Me3af
10
CDCl3) δ 8.20 – 8.05 (m, 2H), 8.03 – 7.92 (m, 2H), 7.86 – 7.81 (m, 1H), 7.77 – 7.59 (m, 3H), 6.10
(s, 1H), 4.33 (qq, J = 10.7, 7.1 Hz, 2H), 4.10 (d, J = 17.8 Hz, 1H), 3.95 (s, 3H), 3.75 (d, J = 17.9
Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 195.22, 169.08, 165.62, 138.38,
136.47, 135.31, 134.33, 133.38, 130.57, 129.63, 127.79, 123.88, 121.57, 65.03, 63.28, 52.19,
49.02, 13.61. ESI-HRMS: Calcd for C20H19NNaO7S+ ([M+Na+]): 440.0774; Found: 440.0779.
White solid, m.p. 60 –62 oC, 97% yield. [α]20 D = –126.7 (c, 1.34,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (minor) =
17.22 min, t (major) = 26.03 min]; 1H NMR (300 MHz, CDCl3) δ 8.06 –
7.99 (m, 2H), 7.86 – 7.81 (m, 1H), 7.78 – 7.60 (m, 5H), 6.10 (s, 1H), 4.34 (qq, J = 10.7, 7.1 Hz,
2H), 4.09 (d, J = 17.8 Hz, 1H), 3.75 (d, J = 17.8 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (75
MHz, CDCl3) δ 194.81, 169.00, 137.93, 136.46, 135.34, 134.84 (q, J = 32.7 Hz), 133.42, 130.61,
128.25, 125.54 (q, J = 3.6 Hz), 123.88, 123.07 (q, J = 272.9 Hz), 121.57, 65.01, 63.34, 48.86,
13.60. ESI-HRMS: Calcd for C19H16F3NNaO5S+ ([M+Na+]): 450.0593; Found: 450.0588.
White solid, m.p. 73 –74 oC, 96% yield. [α]20 D = –133.2 (c, 0.88,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; t (minor) =
30.95 min, t (major) = 60.06 min]; 1H NMR (300 MHz, CDCl3) δ 8.36 –
8.27 (m, 2H), 8.13 – 8.05 (m, 2H), 7.87 – 7.81 (m, 1H), 7.77 – 7.62 (m, 3H), 6.09 (s, 1H), 4.35 (qq,
J = 10.7, 7.1 Hz, 2H), 4.10 (d, J = 17.8 Hz, 1H), 3.78 (d, J = 17.8 Hz, 1H), 1.33 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 194.33, 168.85, 150.45, 139.65, 136.37, 135.36, 133.48, 130.70,
128.99, 123.84, 123.67, 121.61, 64.95, 63.45, 48.98, 13.62. ESI-HRMS: Calcd for
C18H16N2NaO7S+ ([M+Na+]): 427.0570; Found: 427.0572.
White solid, m.p. 50 – 52 oC, 98% yield. [α]20 D = –140.8 (c, 1.18 CH2Cl2);
99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 13.98 min, t (minor)
= 26.64 min]; 1H NMR (300 MHz, CDCl3) δ 7.86 – 7.79 (m, 1H), 7.72 – 7.59
NHS
O O
EtO2C
O
CF33ag
NHS
O O
EtO2C
O
NO23ah
NHS
O O
EtO2C
O
3ai
11
(m, 4H), 7.45 – 7.36 (m, 1H), 7.29 – 7.21 (m, 2H), 6.11 (s, 1H), 4.42 – 4.25 (m, 2H), 4.05 (d, J =
17.7 Hz, 1H), 3.65 (d, J = 17.7 Hz, 1H), 2.53 (s, 3H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 198.88, 169.36, 138.78, 136.68, 135.45, 135.32, 133.28, 131.97, 131.94, 130.42, 128.68,
125.52, 123.89, 121.52, 65.36, 63.13, 51.07, 21.18, 13.64. ESI-HRMS: Calcd for C19H19NNaO5S+
([M+Na+]): 396.0876; Found: 396.0879.
White solid, m.p. 132–133 oC, 96% yield. [α]20 D = –147.7 (c, 0.97,
CH2Cl2); 96% ee, determined by HPLC analysis [Chiralpak AD-H column,
n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; t (major) = 31.50 min, t
(minor) = 40.03 min]; 1H NMR (300 MHz, CDCl3) δ 7.89 – 7.76 (m, 2H),
7.74 – 7.58 (m, 3H), 7.55 – 7.47 (m, 1H), 7.05 – 6.93 (m, 2H), 6.09 (s, 1H), 4.29 (qt, J = 14.2, 5.3
Hz, 2H), 4.12 (t, J = 11.4 Hz, 1H), 3.86 (d, J = 6.6 Hz, 3H), 3.74 (d, J = 18.6 Hz, 1H), 1.29 (t, J =
7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 196.50, 169.63, 159.15, 136.86, 135.16, 134.69,
133.30, 130.50, 130.30, 125.42, 124.09, 121.38, 120.48, 111.42, 65.60, 62.91, 55.25, 54.12, 13.63.
ESI-HRMS: Calcd for C19H19NNaO6S+ ([M+Na+]): 412.0825; Found: 412.0830.
White solid, m.p. 92–93 oC, 97% yield. [α]20 D = –147.5 (c, 1.11, CH2Cl2);
99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 12.69 min, t (minor)
= 15.30 min]; 1H NMR (300 MHz, CDCl3) δ 7.99 – 7.89 (m, 1H), 7.86 – 7.80
(m, 1H), 7.76 – 7.50 (m, 4H), 7.31 – 7.23 (m, 1H), 7.19 – 7.09 (m, 1H), 6.06 (s, 1H), 4.32 (qq, J =
10.7, 7.1 Hz, 2H), 4.14 (dd, J = 18.6, 3.7 Hz, 1H), 3.67 (dd, J = 18.6, 3.6 Hz, 1H), 1.31 (t, J = 7.1
Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 193.54 (d, J = 3.9 Hz), 169.29, 162.06 (d, J = 255.7 Hz),
136.41, 135.45 (d, J = 9.3 Hz), 135.18, 133.34, 130.46, 130.37 (d, J = 2.1 Hz), 124.41 (d, J = 3.3
Hz), 123.97, 123.64 (d, J = 12.4 Hz), 121.52, 116.46 (d, J = 23.6 Hz), 65.16 (d, J = 3.2 Hz), 63.14,
53.41 (d, J = 9.0 Hz), 13.60. ESI-HRMS: Calcd for C18H16FNNaO5S+ ([M+Na+]): 400.0625;
Found: 400.0629.
White solid, m.p. 50 – 53 oC,, 96% yield. [α]20 D = –125.1 (c, 1.09, CH2Cl2);
99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
NHS
O O
EtO2C
O OMe
3aj
NHS
O O
EtO2C
O F
3ak
NHS
O O
EtO2C
O Cl
3al
12
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 15.80 min, t (minor) = 24.28 min]; 1H
NMR (300 MHz, CDCl3) δ 7.85 – 7.79 (m, 1H), 7.72 – 7.58 (m, 4H), 7.47 – 7.29 (m, 3H), 6.09 (s,
1H), 4.44 – 4.28 (m, 2H), 4.14 (d, J = 18.0 Hz, 1H), 3.69 (d, J = 18.0 Hz, 1H), 1.35 (t, J = 7.1 Hz,
3H). 13C NMR (75 MHz, CDCl3) δ 197.80, 169.03, 136.68, 136.50, 135.29, 133.36, 132.51,
131.28, 130.56, 130.51, 129.51, 126.81, 123.91, 121.51, 65.29, 63.33, 52.44, 13.65. ESI-HRMS:
Calcd for C18H16ClNNaO5S+ ([M+Na+]): 416.0330; Found: 416.0334.
White solid, m.p. 45−46 oC, 96% yield. [α]20 D = –71.2 (c, 0.83, CH2Cl2);
99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 12.91 min, t (minor)
= 20.69 min]; 1H NMR (300 MHz, CDCl3) δ 7.83 – 7.76 (m, 1H), 7.70 – 7.57
(m, 4H), 7.53 – 7.47 (m, 1H), 7.41 – 7.27 (m, 2H), 6.08 (s, 1H), 4.45 – 4.26 (m, 2H), 4.08 (d, J =
18.0 Hz, 1H), 3.65 (d, J = 18.0 Hz, 1H), 1.34 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
198.75, 168.95, 139.01, 136.50, 135.31, 133.76, 133.36, 132.22, 130.52, 128.97, 127.29, 123.88,
121.51, 118.77, 77.15, 76.73, 76.31, 65.21, 63.39, 51.93, 13.70. ESI-HRMS: Calcd for
C18H17BrNO5S + ([M+H+]): 438.0005; Found: 438.0009.
White solid, m.p. 57–58 oC, 98% yield. [α]20 D = –156.3 (c, 1.13,
CH2Cl2); 98% ee, determined by HPLC analysis [Daicel Chiralcel
OD-H column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major)
= 14.96 min, t (minor) = 26.69 min]; 1H NMR (300 MHz, CDCl3) δ 7.84
– 7.78 (m, 1H), 7.77 – 7.58 (m, 5H), 7.44 – 7.30 (m, 2H), 6.11 (s, 1H), 4.31 (qq, J = 10.7, 7.1 Hz,
2H), 4.09 (d, J = 17.8 Hz, 1H), 3.72 (d, J = 17.8 Hz, 1H), 2.38 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 195.82, 169.30, 138.33, 136.65, 135.31, 135.27, 134.43, 133.35,
130.47, 128.37, 128.34, 125.09, 123.99, 121.48, 65.19, 63.13, 48.86, 20.94, 13.62. ESI-HRMS:
Calcd for C19H20NO5S+ ([M+H+]): 374.1057; Found: 374.1058.
White solid, m.p. 53–54 oC, 96% yield. [α]20 D = –146.7 (c, 1.09,
CH2Cl2); 98% ee, determined by HPLC analysis [Daicel Chiralcel OD-
H column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) =
22.95 min, t (minor) = 69.05 min]; 1H NMR (300 MHz, CDCl3) δ 7.86
NHS
O O
EtO2C
O
3an
NHS
O O
EtO2C
O
OMe3ao
NHS
O O
O BrEtO2C
3am
13
– 7.80 (m, 1H), 7.75 – 7.58 (m, 3H), 7.51 – 7.42 (m, 2H), 7.40 – 7.32 (m, 1H), 7.17 – 7.11 (m,
1H), 6.08 (s, 1H), 4.32 (qq, J = 10.7, 7.1 Hz, 2H), 4.07 (d, J = 17.8 Hz, 1H), 3.84 (s, 3H), 3.71 (d,
J = 17.8 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 195.50, 169.24, 159.63,
136.62, 135.31, 133.31, 130.48, 129.44, 123.92, 121.53, 120.52, 120.29, 111.94, 65.18, 63.17,
55.16, 48.89, 13.62. ESI-HRMS: Calcd for C19H20NO6S+ ([M+H+]): 390.1006; Found: 390.1005.
White solid, m.p. 58 – 60 oC, 98% yield. [α]20 D = –137.2 (c, 1.13,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H
column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) =
17.99 min, t (minor) = 30.46 min]; 1H NMR (300 MHz, CDCl3) δ 8.06 –
8.01 (m, 1H), 7.89 – 7.79 (m, 2H), 7.76 – 7.60 (m, 4H), 7.39 – 7.31 (m, 1H), 6.07 (s, 1H), 4.33 (qq,
J = 10.7, 7.1 Hz, 2H), 4.05 (d, J = 17.8 Hz, 1H), 3.69 (d, J = 17.8 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 194.36, 169.06, 136.97, 136.48, 135.32, 133.38, 130.90, 130.57,
130.07, 126.39, 123.89, 122.80, 121.57, 65.00, 63.29, 48.77, 13.62. ESI-HRMS: Calcd for
C18H16BrNNaO5S+ ([M+Na+]): 459.9825; Found: 459.9828.
White solid, m.p. 73 –74 oC, 98% yield. [α]20 D = –134.4 (c, 1.17,
CH2Cl2); 99% ee, determined by HPLC analysis [Daicel Chiralcel OD-
H column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (minor) =
23.68 min, t (major) = 26.01 min]; 1H NMR (300 MHz, CDCl3) δ 8.41 (s,
1H), 8.03 – 7.49 (m, 10H), 6.15 (s, 1H), 4.44 – 4.25 (m, 2H), 4.22 (d, J = 17.7 Hz, 1H), 3.88 (d, J
= 17.7 Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 195.55, 169.32, 136.71,
135.60, 135.37, 133.33, 132.64, 132.04, 130.49, 130.00, 129.28, 128.64, 128.41, 127.51, 126.72,
124.00, 123.08, 121.56, 65.27, 63.19, 48.87, 13.64. ESI-HRMS: Calcd for C22H19NNaO5S+
([M+Na+]): 432.0876; Found: 432.0880.
White solid, m.p. 56–58 oC, 98% yield. [α]20 D = –133.6 (c, 1.09, CH2Cl2);
98% ee, determined by HPLC analysis [Daicel Chiralpak AD-H column, n-
hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; t (major) = 24.23 min, t (minor)
= 36.80 min]; 1H NMR (300 MHz, CDCl3) δ 7.86 –7.79 (m, 1H), 7.74–7.58 (m, 4H), 7.27 – 7.23
NHS
O O
EtO2C
O
Br
3ap
NHS
O O
EtO2C
O
3aq
NHS
O O
EtO2C
O
O3ar
14
(m, 1H), 6.59 – 6.55 (m, 1H), 6.07 (s, 1H), 4.44–4.21 (m, 2H), 3.95 (d, J = 17.7 Hz, 1H), 3.60 (d,
J = 17.7 Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 184.31, 169.05, 151.37,
146.77, 136.53, 135.21, 133.32, 130.47, 123.94, 121.48, 117.93, 112.35, 64.87, 63.26, 48.15,
13.59. ESI-HRMS: Calcd for C16H15NNaO6S+ ([M+Na+]): 372.0512; Found: 372.0516.
White solid, m.p. 64–66 oC, 97% yield. [α]20 D = –154 (c, 1.14, CH2Cl2); 97%
ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (minor) = 20.85 min, t (major)
= 23.03 min]; 1H NMR (300 MHz, CDCl3) δ 7.83 – 7.78 (m, 1H), 7.76 – 7.57
(m, 5H), 7.15 – 7.10 (m, 1H), 6.09 (s, 1H), 4.42 – 4.22 (m, 2H), 4.04 (d, J = 17.4 Hz, 1H), 3.65 (d,
J = 17.4 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 188.27, 169.04, 142.17,
136.47, 135.21, 134.57, 133.41, 132.76, 130.54, 128.10, 124.01, 121.45, 65.16, 63.27, 48.86,
13.61. ESI-HRMS: Calcd for C16H16NO5S2+ ([M+H+]): 366.0464; Found: 366.0466.
White solid, m.p. 64–65 oC, 93% yield. [α]20 D = –157 (c, 0.73, CH2Cl2);
98% ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (minor) = 25.49 min, t
(major) = 34.44 min]; 1H NMR (300 MHz, CDCl3) δ 7.85–7.78 (m, 1H), 7.72–7.49 (m, 6H), 7.45
– 7.35 (m, 3H), 6.71 (d, J = 16.3 Hz, 1H), 6.08 (s, 1H), 4.31 (qq, J = 10.7, 7.1 Hz, 2H), 3.83 (d, J
= 17.6 Hz, 1H), 3.42 (d, J = 17.5 Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
195.37, 169.20, 144.34, 136.64, 135.23, 133.61, 133.29, 130.72, 130.42, 128.72, 128.16, 124.72,
123.92, 121.48, 65.13, 63.15, 50.09, 13.62. ESI-HRMS: Calcd for C20H20NO5S+ ([M+H+]):
386.1057; Found: 386.1058.
White solid, m.p. 49 – 51 oC, 96% yield. [α]20 D = –111.2 (c, 0.91, CH2Cl2);
99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (minor) = 14.45 min, t (major)
= 30.54 min]; 1H NMR (300 MHz, CDCl3) δ 7.84 – 7.77 (m, 1H), 7.72 –
7.58 (m, 3H), 7.58 – 7.51 (m, 2H), 7.51 – 7.42 (m, 1H), 7.42 – 7.33 (m, 2H), 5.99 (s, 1H), 4.43 –
4.20 (m, 2H), 3.84 (d, J = 18.2 Hz, 1H), 3.40 (d, J = 18.2 Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H). 13C
NHS
O O
EtO2C
O
S3as
NHS
O O
EtO2C
O
Ph3at
NHS
O O
EtO2C
O
Ph3au
15
NMR (75 MHz, CDCl3) δ 182.20, 168.68, 136.10, 135.21, 133.37, 132.84, 130.91, 130.57, 128.40,
123.83, 121.54, 118.92, 93.14, 86.60, 64.66, 63.42, 54.39, 13.61. ESI-HRMS: Calcd for
C20H18NO5S+ ([M+H+]): 384.0900; Found: 384.0900.
White solid, m.p. 47–49 oC, 98% yield. [α]20 D = –50.1 (c, 1.22, CH2Cl2);
99% ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 10.29 min, t (minor)
= 13.34 min]; 1H NMR (300 MHz, CDCl3) δ 7.97–7.88 (m, 2H), 7.84–7.75
(m, 2H), 7.68–7.52 (m, 3H), 7.49 –7.40 (m, 2H), 6.15 (s, 1H), 4.43 (q, J = 7.1 Hz, 2H), 4.27 (q, J
= 7.5 Hz, 1H), 1.48 (d, J = 7.5 Hz, 3H), 1.41 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
200.78, 168.81, 136.93, 135.43, 133.33, 132.35, 130.24, 128.49, 128.27, 126.08, 121.31, 68.62,
63.18, 49.94, 14.38, 13.72. ESI-HRMS: Calcd for C19H19NNaO5S+ ([M+Na+]): 396.0876; Found:
396.0877.
White solid, m.p. 52–53 oC, 97% yield. [α]20 D=–142.1 (c, 1.15,
CH2Cl2); >20:1 dr, 99% ee, determined by HPLC analysis [Daicel
Chiralcel OD-H column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm;
t (major) = 13.18 min, t (minor) = 21.00 min]; 1H NMR (300 MHz,
CDCl3) δ 8.02 – 7.94 (m, 2H), 7.93 – 7.86 (m, 1H), 7.86 – 7.80 (m, 1H), 7.75 – 7.64 (m, 2H), 7.00
– 6.90 (m, 2H), 5.99 (s, 1H), 5.65 (d, J = 46.1 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 1.33
(t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ190.00 (d, J = 20.0 Hz), 167.45, 164.37, 135.71,
133.26, 133.01, 131.86, 131.81, 130.91, 126.91, 126.84, 121.25, 113.75, 92.08 (d, J = 201.3 Hz),
66.19 (d, J = 22.6 Hz), 63.48, 55.27, 13.62. ESI-HRMS: Calcd for C19H18FNNaO6S+ ([M+Na+]):
430.0731; Found: 430.0735.
White solid, m.p. 85–86 oC, 95% yield. [α]20 D = –141.0 (c, 1.07, CH2Cl2);
98:2 dr, 99% ee, determined by HPLC analysis [Daicel Chiralpak AD-H
column, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; t (minor) = 32.82
min, t (major) = 35.45 min]; 1H NMR (300 MHz, CDCl3) δ 8.04 – 7.95 (m, 1H), 7.84–7.77 (m,
1H), 7.76–7.59 (m, 3H), 7.52 –7.44 (m, 1H), 7.35 – 7.27 (m, 1H), 7.24 – 7.17 (m, 1H), 5.85 (s,
NHS
O O
O
EtO2C
3awMe
NHS
O O
O
FEtO2C
OMe3ax
NHS
O O
O
EtO2C
3ay
16
1H), 4.44 –4.22 (m, 2H), 3.81 (dd, J = 13.9, 4.2 Hz, 1H), 3.07 – 2.84 (m, 2H), 2.29 – 2.08 (m, 1H),
1.56 – 1.42 (m, 1H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 196.25, 169.90,
143.61, 135.45, 135.22, 133.84, 133.54, 131.54, 130.52, 128.45, 127.23, 126.55, 123.87, 121.65,
69.16, 63.16, 55.95, 28.48, 23.08, 13.59. ESI-HRMS: Calcd for C20H19NNaO5S+ ([M+Na+]):
408.0876; Found: 408.0881.
White solid, m.p. 40–41 oC, 96% yield. [α]20 D = –65 (c, 1.08, CH2Cl2); 96%
ee, determined by HPLC analysis [Daicel Chiralcel OD-H column, n-
hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; t (major) = 20.35 min, t
(minor) = 23.37 min]; 1H NMR (300 MHz, CDCl3) δ 7.91–7.84 (m, 2H), 7.83–7.74 (m, 2H), 7.74
– 7.53 (m, 3H), 7.51–7.42 (m, 2H), 6.99 (d, J = 15.5 Hz, 1H), 6.92–6.79 (m, 1H), 5.86 (s, 1H),
4.36 (q, J = 7.1 Hz, 2H), 3.23 (dd, J = 14.1, 7.2 Hz, 1H), 2.98 (dd, J = 14.1, 6.9 Hz, 1H), 1.35 (t, J
= 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 189.98, 168.64, 139.74, 137.15, 136.89, 135.31,
133.38, 132.72, 130.83, 130.51, 128.36, 128.31, 124.42, 121.35, 67.85, 63.72, 42.89, 13.82. ESI-
HRMS: Calcd for C20H19NNaO5S+ ([M+Na+]): 408.0876; Found: 408.0881.
Viscous oil, 21% yield. [α]20 D = –46 (c, 0.43, CHCl3); 30% ee, determined by
HPLC analysis [Daicel Chiralcel AD-H column, n-hexane/i-PrOH = 60:40, 1.0
mL/min, 230 nm; t (major) = 14.95 min, t (minor) = 25.56 min]; 1H NMR (300
MHz, CDCl3) δ 8.14 – 8.07 (m, 2H), 8.00 – 7.94 (m, 1H), 7.91 – 7.85 (m, 1H),
7.81 – 7.65 (m, 3H), 7.56 – 7.48 (m, 2H), 6.01 (s, 1H), 4.47 – 4.36 (m, 2H), 1.36 (t, J = 7.1 Hz,
3H). 13C NMR (75 MHz, CDCl3) δ 187.48 (dd, J = 32.0, 28.9 Hz), 165.26 (dd, J = 7.2, 2.0 Hz),
136.32, 134.89, 133.26, 131.48, 130.88, 130.11 (d, J = 2.2 Hz), 130.06 (d, J = 2.5 Hz), 128.52,
126.72 (d, J = 5.6 Hz), 121.62, δ 115.10 (t, J = 269.8 Hz), 68.23 (dd, J = 26.0, 23.9 Hz), 64.08,
13.52. ESI-HRMS: Calcd for C18H14F2NO5S- ([M-H-]): 394.0566; Found: 394.0569.
6. Transformations of product 3 to 4, 5 and 6
6.1 The preparation of 4
NHS
O O
EtO2CPh
O
3az
SNH
O O
EtO2C
O
PhFF
3ax'
17
Pd/C, H2
MeOH/EtOAc, 10:1(v/v)NH
SO O
EtO2C Ph4
NHS
O O
Ph
O
EtO2C
3ba
A solution of 3ba (0.2 mmol) in MeOH (8.5 mL) and EtOAc(0.8 mL) was added to a mixture of
Pd/C(10% on carbon, 35 mg) in MeOH (0.5 mL).The mixture was stirred under H2 (1atm) for 24
hours. The reaction mixture was then filtered through Celite and the filtrate was concentrated
under reduced pressure. The remained oil was purified through flash column chromatography
(PE/EA = 5/1) to give product 4ba as a viscous liquid. 78% yield. [α]20 D= –32.1 (c, 1.33,
CH2Cl2); 97% ee, determined by HPLC analysis [Daicel Chiralpak AD-H column, n-hexane/i-
PrOH = 80:20, 1.0 mL/min, 220 nm; t (minor) = 15.73 min, t (major) = 24.16 min]; 1H NMR (300
MHz, CDCl3) δ 7.66 – 7.60 (m, 1H), 7.49 – 7.44 (m, 1H), 7.40 – 7.33 (m, 1H), 7.30 – 7.11 (m,
5H), 5.84 (s, 1H), 4.34 – 4.18 (m, 2H), 2.81 – 2.59 (m, 2H), 2.57 – 2.47 (m, 1H), 2.45 (s, 3H),
2.37–2.22 (m, 1H), 1.34 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 169.68, 144.33, 139.93,
138.13, 132.35, 131.11, 128.14, 128.11, 125.90, 124.70, 120.88, 68.48, 63.24, 41.67, 30.61, 21.53,
13.79. ESI-HRMS: Calcd for C18H19NNaO4S+ ([M+Na+]): 368.0927; Found: 368.0926.
6.2 The preparation of 5 8
NHS
O O
Ph
O TBHP, KI
THF
3aa
NS
O O
EtO2CPh
O
5
EtO2C
95%yield,98%ee
To a suspension of product 3aa (0.3mmol), KI (0.6 mmol) and THF (3 mL) was added TBHP
(0.60 mmol, 5.5 mol/L in n-decane) in portions during 2 h. After completion of the reaction
(monitored by TLC), the solvent was evaporated in vacuo. Purification of the residue by column
chromatography (PE/EA = 10/1 − 5/1, V/V) afforded the desired aziridine product 5.
95% yield. [α]20 D = +78.8 (c, 0.92, EtOAc); 98% ee, determined by HPLC analysis [Daicel
Chiralcel OD-H column, n-hexane/i-PrOH = 70:30, 0.8 mL/min, 215 nm; t (major) = 11.39 min, t
(minor) = 12.86 min]; 1H NMR (300 MHz, CDCl3) δ 8.27 – 8.21 (m, 1H), 8.16 – 8.08 (m, 2H),
7.85 – 7.74 (m, 2H), 7.73 – 7.63 (m, 2H), 7.59 – 7.49 (m, 2H), 4.46 – 4.20 (m, 2H), 3.94 (s, 1H),
1.27 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 187.36, 163.08, 134.34, 134.31, 133.73,
18
133.23, 132.87, 130.90, 128.82, 128.68, 126.90, 123.02, 77.12, 76.70, 76.28, 62.75, 59.60, 53.32,
13.43. ESI-HRMS: Calcd for C18H16NO5S + ([M+H+]): 358.0743; Found: 358.0744.
The preparation of 6
6 95%yield, 98 % ee3am
Toluene, 50oC
K2CO3, CuI, DMEDANHS
O O
EtO2C
O Br NS
O O
OEtO2C
Under nitrogen atmosphere, to a solution of 3am (88mg, 0.2mmol) in anhydrous toluene (3 mL)
was added CuI (0.5 equiv), DMEDA (1.0 equiv), K2CO3 (2.5 equiv). After heating for 1 h at 50
°C, the heterogeneous mixture was cooled to room temperature and AcOEt (6 mL) was added, the
mixture was then passed through a pad of Celite. The filtrate was concentrated under reduced
pressure and the residue was purified by silica gel column chromatography (PE/EA = 3/1m V’V)
to afford the product 6 in 95% yield.
White solid, m.p. 55 −56 oC, 95% yield. [α]20 D = –143.5 (c, 0.35, CH2Cl2); 98% ee, determined
by HPLC analysis [Daicel Chiralcel OD-H column, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220
nm; t (mnior) = 24.53 min, t (major) = 26.23 min]; 1H NMR (300 MHz, CDCl3) δ 8.06 – 7.97 (m,
1H), 7.97 – 7.89 (m, 1H), 7.89 – 7.82 (m, 1H), 7.80 – 7.59 (m, 4H), 7.25 – 7.18 (m, 1H), 4.21 –
3.97 (m, 2H), 3.76 (d, J = 16.4 Hz, 1H), 2.97 (d, J = 13.3 Hz, 1H), 1.02 (t, J = 7.1 Hz, 3H). 13C
NMR (75 MHz, CDCl3) δ 188.33, 167.91, 138.31, 135.76, 133.95, 133.64, 133.54, 130.82, 127.99,
123.99, 123.19, 121.74, 121.67, 118.01, 77.19, 76.76, 76.34, 68.62, 63.12, 45.86, 13.37. ESI-
HRMS: Calcd for C18H15NNaO5S+ ([M+Na+]): 380.0563; Found: 380.0566.
References.
1 Liu, R.-R.; Wang, D.-J.; Wu, L.; Xiang, B.; Zhang, G.-Q.; Gao, J.-R.; Jia, Y.-X. ACS Catal.
2015 , 5 , 6524.
2 (a) Wang, H.; Jiang T.; Xu, M.-H. J. Am. Chem. Soc. 2013, 135, 971; (b) Yan, Z., Wu, B., Gao,
X., Chen, M. W., Zhou, Y. G. Org. Lett. 2016, 18, 692.
3 (a) Wiles, C., Watts, P., Haswell, S. J., Pombo-Villar, E. Tetrahedron. 2005, 61, 10757; (b)
Tanis, S. P., Evans, B. R., Nieman, J. A., Parker, T. T., Taylor, W. D., Heasley, S. E., Hester, M.
19
R. Tetrahedron: Asymmetry. 2006 17, 2154. (c) Ferrié, L., Boulard, L., Pradaux, F., Bouzbouz, S.,
Reymond, S., Capdevielle, P., Cossy, J. J. Org. Chem. 2008, 73, 1864. (d) Hoffmann, R.V.; Kim,
O. J. Org. Chem. 1991, 36, 1014.
4. He, Y., Zhang, X., Shen, N., Fan, X. J. Fluorine Chem. 2013, 156, 9.
5 Schuler, M., Silva, F., Bobbio, C., Tessier, A., Gouverneur, V. Angew. Chem. Int. Ed. 2008, 47,
7927-7930.
6. Qiao, B., Huang, Y. J., Nie, J., Ma, J. A. Org. Lett. 2015, 17, 4608.
7 Fu, J.P.;; Karur, S.; Madera, A. M.; Pecchi, S.; Sweeney, Z. K.; Tjandra, M.; Yifru, A. Patent
Appl. WO 2014160649A1, 2014.
8. Lai, B. N., Qiu, J. F., Zhang, H. X., Nie, J., Ma, J. A. Org. Lett. 2016, 18, 520.
7. HPLC Chromatograms for All Products
20
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 17.85
min, tR (minor) = 24.75 min; 99% ee.
min0 5 10 15 20 25 30
mAU
0
50
100
150
200
250
300
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000012.D)
17.
854
Area
: 76.7
615
24.
754
# Time Area Height Width Area% Symmetry1 17.854 20333.3 307.1 0.9559 99.624 0.3312 24.754 76.8 9.5E-1 1.3508 0.376 0.847
min0 5 10 15 20 25 30
mAU
0
25
50
75
100
125
150
175
200
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000011.D)
18.
169
24.
055
# Time Area Height Width Area% Symmetry1 18.169 14190.9 211.6 0.9528 49.744 0.3512 24.055 14337.2 167.1 1.2454 50.256 0.481
NHS
OO
EtO2C
O
3aa
NHS
OO
O
rac-3aa
EtO2C
21
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 13.44 min, tR (minor) = 21.91 min; 99% ee.
min5 10 15 20 25
mAU
0
50
100
150
200
250
VWD1 A, Wavelength=220 nm (H:\2016-10-24001285%-E-PH-CHCL3-5ME5+SI.D)
13.
440
Area
: 68.1
405
21.
910
# Time Area Height Width Area% Symmetry1 13.44 19219.6 257.7 1.0363 99.647 0.3152 21.91 68.1 6.8E-1 1.6601 0.353 0.506
min5 10 15 20 25
mAU
0
20
40
60
80
100
120
VWD1 A, Wavelength=220 nm (H:\2016-10-2400127R-5ME5+SI.D)
13.
898
21.
530
# Time Area Height Width Area% Symmetry1 13.898 8208.2 120.3 0.98 50.768 0.312 21.53 7959.8 101.2 1.1943 49.232 0.6
NHS
OO
EtO2CPh
O
3ba
rac-3ba
22
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 14.83 min, tR (minor) = 22.17 min; 99% ee.
min0 5 10 15 20 25
mAU
0
100
200
300
400
500
600
700
800
900
VWD1 A, Wavelength=220 nm (XL2016\20160515000009.D)
14.
826
Area
: 160
.407
22.
165
# Time Area Height Width Area% Symmetry1 14.826 73485.6 905.1 1.1176 99.782 0.2182 22.165 160.4 1.9 1.4436 0.218 0.5
min0 5 10 15 20 25
mAU
0
50
100
150
200
250
300
350
400
VWD1 A, Wavelength=220 nm (XL2016\20160515000008.D)
15.
548
21.
702
# Time Area Height Width Area% Symmetry1 15.548 32253 371.8 1.2379 51.771 0.362 21.702 30046.8 400.9 1.1424 48.229 0.575
NHS
OO
EtO2CPh
O
3ca
MeO
rac-3ca
23
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 7.20 min, tR (minor) = 12.30 min; 99% ee.
min0 2 4 6 8 10 12 14 16
mAU
0
250
500
750
1000
1250
1500
1750
VWD1 A, Wavelength=220 nm (XL2016\20160519000002.D)
Area
: 527
80
7.2
01
Area
: 210
.456
12.
301
# Time Area Height Width Area% Symmetry1 7.201 52780 1933.7 0.4549 99.603 0.2952 12.301 210.5 6.3 0.5557 0.397 0.829
min0 2 4 6 8 10 12 14 16
mAU
0
100
200
300
400
500
600
700
VWD1 A, Wavelength=220 nm (XL2016\20160516000003.D)
Area
: 204
75
7.6
59
Area
: 194
45.8
13.
183
# Time Area Height Width Area% Symmetry1 7.659 20475 743 0.4593 51.289 0.3672 13.183 19445.8 478.8 0.6769 48.711 0.726
NHS
OO
EtO2C
O
3da
t-Bu
rac-3da
24
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 10.85 min, tR (minor) = 17.42 min; 99% ee.
min0 2.5 5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
200
400
600
800
1000
VWD1 A, Wavelength=220 nm (XL2016\20160518000001.D)
Are
a: 48
852
10.
847
Are
a: 21
1.72
17.
423
# Time Area Height Width Area% Symmetry1 10.847 48852 1124.2 0.7242 99.568 0.3072 17.423 211.7 4.8 0.7385 0.432 0.73
min0 2.5 5 7.5 10 12.5 15 17.5 20
mAU
0
50
100
150
200
250
300
350
400
VWD1 A, Wavelength=220 nm (XL2016\20160516000006.D)
11.
481
17.
535
# Time Area Height Width Area% Symmetry1 11.481 18344.4 408 0.6454 50.863 0.3082 17.535 17722 321.2 0.8433 49.137 0.584
NHS
OO
EtO2C
O
3ea
F
rac-3ea
25
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 10.82 min, tR (minor) = 19.38 min; 99% ee.
min0 2.5 5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
200
400
600
800
VWD1 A, Wavelength=220 nm (XL2016\20160515000002.D)
Are
a: 46
298.5
10.
818
Are
a: 28
9.469
19.
382
# Time Area Height Width Area% Symmetry1 10.818 46298.5 919.2 0.8394 99.379 0.2612 19.382 289.5 5.1 0.9453 0.621 0.871
min0 5 10 15 20 25
mAU
0
200
400
600
800
1000
VWD1 A, Wavelength=220 nm (XL2016\20160515000001.D)
Are
a: 60
112.7
10.
833
Are
a: 56
558.6
19.
127
# Time Area Height Width Area% Symmetry1 10.833 60112.7 1099.6 0.9111 51.523 0.292 19.127 56558.6 881.5 1.0693 48.477 0.649
NHS
OO
EtO2C
O
3fa
Cl
rac-3fa
26
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 8.26 min, tR (minor) = 18.11 min; 97% ee.
min0 5 10 15 20 25
mAU
0
200
400
600
800
VWD1 A, Wavelength=220 nm (XL2016\20160515000007.D)
Area
: 317
91.5
8.2
85
Area
: 483
.844
18.
113
# Time Area Height Width Area% Symmetry1 8.285 31791.5 983.4 0.5388 98.501 0.3692 18.113 483.8 8.8 0.9178 1.499 1.016
min0 5 10 15 20
mAU
0
100
200
300
400
500
600
700
VWD1 A, Wavelength=220 nm (XL2016\20160515000006.D)
8.3
12
17.
712
# Time Area Height Width Area% Symmetry1 8.312 23086.3 722.1 0.4676 50.138 0.3742 17.712 22958.9 403.5 0.8735 49.862 0.655
NHS
OO
EtO2C
O
3ga
F3C
rac-3ga
27
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 16.34 min, tR (minor) = 21.53 min; 94% ee.
min0 5 10 15 20 25
mAU
0
50
100
150
200
250
300
350
VWD1 A, Wavelength=254 nm (XL2016\20160524000017.D)
Are
a: 33
725.2
16.
336
Are
a: 10
13.71
21.
529
# Time Area Height Width Area% Symmetry1 16.336 33725.2 384.3 1.4626 97.082 0.2612 21.529 1013.7 16.4 1.0331 2.918 0.612
min0 5 10 15 20 25 30
mAU
0
25
50
75
100
125
150
175
VWD1 A, Wavelength=220 nm (XL2016\20160516000013.D)
18.
027
22.
251
# Time Area Height Width Area% Symmetry1 18.027 14665.4 159.7 1.2707 50.891 0.2852 22.251 14151.9 195.9 1.089 49.109 0.54
NHS
OO
EtO2C
O
3ha
F
rac-3ha
28
Daicel Chiralpak AD-H, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; tR (minor) = 18.95 min, tR (major) = 23.01 min; 97% ee.
min0 5 10 15 20 25 30 35
mAU
0
100
200
300
400
500
600
700
800
VWD1 A, Wavelength=220 nm (G:\XL\2%图图\2016-10-21001242%-E-PH-CHCL3-7CL5+SI.D)
22.
097
26.
944
# Time Area Height Width Area% Symmetry1 22.097 1058.9 15.4 1.0323 1.432 0.5872 26.944 72874.1 851.9 1.285 98.568 0.712
min0 5 10 15 20 25 30 35
mAU
0
50
100
150
200
250
300
350
VWD1 A, Wavelength=220 nm (G:\XL\2%图图\2016-10-2100123R-7CL5+SI.D)
21.
980
26.
593
# Time Area Height Width Area% Symmetry1 21.98 25093.1 369.8 1.0077 49.860 0.5572 26.593 25233.6 314.6 1.2167 50.140 0.599
NHS
OO
EtO2C
O
3ia
Cl
rac-3ia
29
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 7.62 min, tR (minor) = 15.36 min; 96% ee.
min0 2.5 5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
100
200
300
400
500
600
VWD1 A, Wavelength=220 nm (G:\XL\2%图图\2016-10-19001152%-E-PH-CHCL3-5CF3O5+SI.D)
Area
: 191
34.5
8.0
43
Area
: 356
.25
18.
015
# Time Area Height Width Area% Symmetry1 8.043 19134.5 657.6 0.485 98.172 0.3762 18.015 356.3 6.6 0.8978 1.828 0.842
min0 2.5 5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
50
100
150
200
250
VWD1 A, Wavelength=220 nm (G:\XL\2%图图\2016-10-1900116R-CHCL3-5CF3O5+SI.D)
Area
: 861
6.8
8.1
72
Area
: 834
4.88
17.
932
# Time Area Height Width Area% Symmetry1 8.172 8616.8 283.8 0.506 50.802 0.4722 17.932 8344.9 150.9 0.9215 49.198 0.754
NHS
OO
EtO2C
O
3ja
F3CO
rac-3ja
30
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 15.86 min, tR (minor) = 24.68 min; 99% ee.
min0 5 10 15 20 25 30
mAU
0
500
1000
1500
2000
2500
3000
VWD1 A, Wavelength=220 nm (XL2016\20160515000005.D)
Area
: 192
901
15.
895
Area
: 870
.564
24.
682
# Time Area Height Width Area% Symmetry1 15.895 192901.2 3248.4 0.9897 99.551 0.4442 24.682 870.6 10.9 1.3344 0.449 0.759
min0 5 10 15 20 25 30
mAU
0
100
200
300
400
500
600
700
VWD1 A, Wavelength=220 nm (XL2016\20160515000004.D)
Area
: 461
58.6
16.
307
Area
: 438
60.6
24.
444
# Time Area Height Width Area% Symmetry1 16.307 46158.6 774.8 0.9929 51.276 0.5022 24.444 43860.6 491.4 1.4875 48.724 0.632
NHS
OO
EtO2C
O
3ka
rac-3ka
31
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 19.62 min, tR (major) = 20.80 min; 99% ee.
min0 2.5 5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
50
100
150
200
250
VWD1 A, Wavelength=220 nm (G:\XL\2%图图\2016-10-19001062%-E-PH-CHCL3-5+4MESI.D)
Area
: 165
73.5
16.
898
Area
: 65.7
891
19.
909
# Time Area Height Width Area% Symmetry1 16.898 16573.5 278.5 0.992 99.605 0.3962 19.909 65.8 1.5 0.7291 0.395 0
min0 2.5 5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
50
100
150
200
250
VWD1 A, Wavelength=220 nm (G:\XL\2%图图\2016-10-1900107R-CHCL3-5+4MESI.D)
Area
: 148
10.4
16.
803
Area
: 149
61.2
19.
062
# Time Area Height Width Area% Symmetry1 16.803 14810.4 263.4 0.9372 49.747 02 19.062 14961.2 238.7 1.0447 50.253 0.555
NHS
OO
EtO2C
O
3ab
rac-3ab
32
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; tR (minor) = 28.09 min, tR (major) = 86.78 min; 95% ee.
min0 20 40 60 80 100
mAU
0
50
100
150
200
250
300
350
400
VWD1 A, Wavelength=220 nm (G:\2016-07-25000520-CHCL3-E-PH-5+4BNOSI.D)
28.
092
Area
: 137
443
86.
778
# Time Area Height Width Area% Symmetry1 28.092 3548.7 34.8 1.5428 2.517 0.6062 86.778 137443.2 446.5 5.1309 97.483 0.439
min0 20 40 60 80 100
mAU
0
100
200
300
400
500
600
700
VWD1 A, Wavelength=220 nm (G:\2016-07-2500051R-5+4BNOSI.D)
Area
: 793
59.6
27.
233
Area
: 811
56.2
89.
073
# Time Area Height Width Area% Symmetry1 27.233 79359.6 720.6 1.8355 49.440 0.4422 89.073 81156.2 268.7 5.0336 50.560 0.498
NHS
OO
EtO2C
O
3ac OBn
rac-3ac
33
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 19.04 min, tR (major) = 25.08 min; 98% ee.
min0 5 10 15 20 25 30 35
mAU
0
50
100
150
200
250
300
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000008.D)
19.
043
25.
085
# Time Area Height Width Area% Symmetry1 19.043 314.8 3.5 1.0687 0.818 0.822 25.085 38145.9 312 1.6188 99.182 0.25
min0 5 10 15 20 25 30 35
mAU
0
25
50
75
100
125
150
175
200
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000007.D)
Area
: 156
31.8
17.
638
Area
: 143
58.5
25.
812
# Time Area Height Width Area% Symmetry1 17.638 15631.8 199.6 1.3054 52.123 0.3772 25.812 14358.5 118.9 2.012 47.877 0.26
NHS
OO
EtO2C
O
3ad F
rac-3ad
34
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 21.77 min, tR (major) = 31.21 min; 98%.
min0 5 10 15 20 25 30 35 40 45
mAU
0
20
40
60
80
100
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000004.D)
Area
: 130
.288
21.
772
Area
: 173
37.1
31.
212
# Time Area Height Width Area% Symmetry1 21.772 130.3 1.7 1.2896 0.746 0.7772 31.212 17337.1 109 2.6502 99.254 0.262
min0 5 10 15 20 25 30 35 40 45
mAU
0
20
40
60
80
100
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000003.D)
Area
: 101
69.8
20.
817
Area
: 978
5.73
32.
203
# Time Area Height Width Area% Symmetry1 20.817 10169.8 99 1.7126 50.962 0.4132 32.203 9785.7 62.5 2.6102 49.038 0.299
NHS
OO
EtO2C
O
3ae Br
rac-3ae
35
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; tR (minor) = 16.73 min, tR (major) = 38.84 min; 99% ee.
min5 10 15 20 25 30 35 40 45 50
mAU
0
10
20
30
40
50
60
70
VWD1 A, Wavelength=220 nm (G:\XL\2016-09-28000910-E-PH-CHCL3-5+4COOMESI.D)
Area
: 54.3
005
16.
725
Area
: 112
03.3
38.
842
# Time Area Height Width Area% Symmetry1 16.725 54.3 8.8E-1 1.031 0.482 0.7362 38.842 11203.3 73.2 2.5503 99.518 0.423
min5 10 15 20 25 30 35 40 45 50
mAU
0
50
100
150
200
VWD1 A, Wavelength=220 nm (G:\XL\2016-09-2800090R-5+4COOMESI.D)
Area
: 135
39.4
16.
217
Area
: 143
86.2
38.
256
# Time Area Height Width Area% Symmetry1 16.217 13539.4 241.4 0.9349 48.484 0.572 38.256 14386.2 92.9 2.5812 51.516 0.411
NHS
OO
EtO2C
O
3af CO2Me
rac-3af
36
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 17.22 min, tR (major) = 26.03 min; 99% ee.
min0 5 10 15 20 25 30 35 40
mAU
0
50
100
150
200
250
300
350
400
VWD1 A, Wavelength=220 nm (G:\5+SI\20160330\20160330000002.D)
Area
: 225
.333
17.
224
26.
034
#
Time Area Height Width Area% Symmetry1 17.224 225.3 3 1.2328 0.313 0.8672 26.034 71848.7 447.6 2.1057 99.687 0.19
min0 5 10 15 20 25 30 35 40
mAU
0
25
50
75
100
125
150
175
VWD1 A, Wavelength=220 nm (G:\5+SI\20160330\20160330000001.D)
Area
: 129
25.1
16.
058
Area
: 137
43.5
27.
829
# Time Area Height Width Area% Symmetry1 16.058 12925.1 181.4 1.1875 48.466 0.4282 27.829 13743.5 96.8 2.3662 51.534 0.256
NHS
OO
EtO2C
O
3ag CF3
rac-3ag
37
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; tR (minor) = 30.95 min, tR (major) = 60.06 min; 99% ee.
min20 30 40 50 60 70
mAU
0
50
100
150
200
VWD1 A, Wavelength=220 nm (XL2016\20160518000005.D)
Area
: 212
.086
30.
952
Area
: 634
65.6
60.
062
# Time Area Height Width Area% Symmetry1 30.952 212.1 1.9 1.8912 0.333 1.0272 60.062 63465.6 242.8 4.357 99.667 0.405
min20 30 40 50 60 70
mAU
0
20
40
60
80
100
120
140
160
VWD1 A, Wavelength=220 nm (XL2016\20160518000004.D)
Area
: 208
29.6
29.
374
Area
: 213
69.9
62.
098
# Time Area Height Width Area% Symmetry1 29.374 20829.6 173.7 1.9984 49.360 0.4662 62.098 21369.9 85.1 4.1875 50.640 0.444
rac-3ah
NHS
OO
EtO2C
O
NO2
38
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 13.98 min, tR (minor) = 26.44 min; 99% ee.
min0 5 10 15 20 25 30
mAU
0
100
200
300
400
500
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160325000004.D)
13.
979
Area
: 89.8
061
26.
441
# Time Area Height Width Area% Symmetry1 13.979 27900.8 511.9 0.7757 99.679 0.2922 26.441 89.8 1.1 1.3116 0.321 1.129
min0 5 10 15 20 25 30
mAU
0
100
200
300
400
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160325000003.D)
13.
962
25.
108
# Time Area Height Width Area% Symmetry1 13.962 24622.2 454.7 0.7789 49.980 0.2982 25.108 24642.4 282.9 1.2943 50.020 0.611
NHS
OO
EtO2C
O
3ai
rac-3ai
39
Daicel Chiralpak AD-H, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; tR (major) = 31.50 min, tR (minor) = 40.03 min; 96% ee.
min10 15 20 25 30 35 40 45
mAU
0
100
200
300
400
500
VWD1 A, Wavelength=220 nm (XL2016\20160524000011.D)
Area
: 356
91
31.
495
Area
: 692
.76
40.
033
# Time Area Height Width Area% Symmetry1 31.495 35691 529 1.1246 98.096 0.7762 40.033 692.8 8.6 1.3488 1.904 0.726
min10 15 20 25 30 35 40 45
mAU
0
100
200
300
400
500
600
700
VWD1 A, Wavelength=220 nm (XL2016\20160524000001.D)
Area
: 576
87.1
31.
150
Area
: 543
87.2
40.
158
# Time Area Height Width Area% Symmetry1 31.15 57687.1 793.4 1.2118 51.472 0.7792 40.158 54387.2 557.8 1.6249 48.528 1.058
NHS
OO
EtO2C
O
3aj
OMe
rac-3aj
40
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 12.69 min, tR (minor) = 15.30 min; 99% ee.
min0 2.5 5 7.5 10 12.5 15 17.5 20
mAU
0
100
200
300
400
500
600
VWD1 A, Wavelength=220 nm (G:\5+SI\20160324\20160324000012.D)
Area
: 282
09.8
12.
693
Area
: 169
.993
15.
304
# Time Area Height Width Area% Symmetry1 12.693 28209.8 624.8 0.7525 99.401 0.3762 15.304 170 3.1 0.9207 0.599 0
min0 2.5 5 7.5 10 12.5 15 17.5 20
mAU
0
100
200
300
400
VWD1 A, Wavelength=220 nm (G:\5+SI\20160324\20160324000011.D)
Area
: 196
81.5
12.
744
Area
: 182
43.7
14.
948
# Time Area Height Width Area% Symmetry1 12.744 19681.5 450.2 0.7287 51.896 0.3972 14.948 18243.7 321.1 0.9471 48.104 0.42
NHS
OO
EtO2C
O
3ak
F
rac-3ak
41
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 15.80 min, tR (minor) = 24.28 min; 99% ee.
min0 5 10 15 20 25 30
mAU
0
100
200
300
400
500
600
700
800
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160325000002.D)
15.
798
24.
280
# Time Area Height Width Area% Symmetry1 15.798 50280.4 819.4 0.8906 99.680 0.3082 24.28 161.3 2.3 0.8352 0.320 1.104
min0 5 10 15 20 25 30
mAU
0
100
200
300
400
500
600
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160325000001.D)
Area
: 389
58.9
15.
983
Area
: 371
08.4
23.
342
# Time Area Height Width Area% Symmetry1 15.983 38958.9 652.1 0.9958 51.216 0.3462 23.342 37108.4 448 1.3806 48.784 0.482
NHS
OO
EtO2C
O
3al
Cl
rac-3al
42
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 12.91 min, tR (major) = 20.69 min; 99% ee.
min5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
200
400
600
800
1000
VWD1 A, Wavelength=220 nm (I:\170121\2017-01-07-2%-5+2BRSI.D)
12.
905
20.
690
# Time Area Height Width Area% Symmetry1 12.905 44398.8 1075.7 0.6165 99.662 0.4312 20.69 150.4 2.3 0.8493 0.338 0.742
min5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
50
100
150
200
250
300
VWD1 A, Wavelength=220 nm (I:\170121\2017-01-07-R-(RAC-E-BN)-5+2BRSI.D)
13.
347
20.
741
# Time Area Height Width Area% Symmetry1 13.347 12482 303.7 0.5874 49.755 0.5032 20.741 12604.9 193.8 0.9919 50.245 0.594
NHS
OO
EtO2C
O
3am
Br
rac-3am
43
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 14.96 min, tR (minor) = 26.69 min; 98% ee.
min0 5 10 15 20 25 30
mAU
0
100
200
300
400
500
600
700
800
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000006.D)
14.
960
26.
688
# Time Area Height Width Area% Symmetry1 14.96 52905.9 837.2 0.9062 98.964 0.2912 26.688 553.8 4.8 1.3484 1.036 0.628
min0 5 10 15 20 25 30
mAU
0
50
100
150
200
250
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000005.D)
15.
365
25.
079
# Time Area Height Width Area% Symmetry1 15.365 15185.5 257.7 0.8477 51.433 0.3632 25.079 14339.3 138.6 1.4345 48.567 0.431
NHS
OO
EtO2C
O
3an
rac-3an
44
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 22.95 min, tR (minor) = 69.05 min; 98% ee.
min0 10 20 30 40 50 60 70 80
mAU
0
200
400
600
800
1000
VWD1 A, Wavelength=220 nm (G:\5+SI\20160324\20160324000010.D)
Area
: 102
078
22.
953
Area
: 108
9.46
69.
053
# Time Area Height Width Area% Symmetry1 22.953 102077.6 1039.7 1.6363 98.944 0.3482 69.053 1089.5 3.2 5.7164 1.056 0.827
min0 10 20 30 40 50 60 70 80
mAU
0
200
400
600
800
VWD1 A, Wavelength=220 nm (G:\5+SI\20160324\20160324000009.D)
Area
: 884
74
22.
915
Area
: 680
18.7
61.
003
# Time Area Height Width Area% Symmetry1 22.915 88474 935.4 1.5764 56.536 0.3592 61.003 68018.7 247 4.5891 43.464 0.314
NHS
OO
EtO2C
O
3ao
OMe
rac-3ao
45
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 17.99 min, tR (minor) = 30.46 min; 99% ee.
min0 5 10 15 20 25 30 35
mAU
0
200
400
600
800
1000
VWD1 A, Wavelength=220 nm (G:\XL\2016-09-28000890-E-PH-CHCL3-5+3BRSI.D)
17.
988
30.
456
# Time Area Height Width Area% Symmetry1 17.988 57941 1056.3 0.8169 99.596 0.4392 30.456 235.3 2.7 1.1501 0.404 0.794
min0 5 10 15 20 25 30 35
mAU
-50
0
50
100
150
200
250
VWD1 A, Wavelength=220 nm (G:\XL\2016-09-2800088R-5+3BRSI.D)
Area
: 168
90.3
18.
245
Area
: 162
11.5
29.
887
# Time Area Height Width Area% Symmetry1 18.245 16890.3 323.2 0.871 51.025 0.5532 29.887 16211.5 172.4 1.5673 48.975 0.615
NHS
OO
EtO2C
O
3ap
Br
rac-3ap
46
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 23.68min, tR (major) = 26.01 min; 99% ee.
min10 15 20 25 30 35
mAU
0
50
100
150
200
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000014.D)
Area
: 100
.797
23.
683
26.
007
# Time Area Height Width Area% Symmetry1 23.683 100.8 1.8 0.9157 0.382 8.8892 26.007 26288.4 245.3 1.5432 99.618 0.408
min10 15 20 25 30 35
mAU
0
20
40
60
80
100
VWD1 A, Wavelength=220 nm (G:\5+SI\20160325-0328\20160326000013.D)
22.
496
26.
625
# Time Area Height Width Area% Symmetry1 22.496 11355.3 101 1.5955 49.928 0.472 26.625 11387.9 106.2 1.4722 50.072 0.497
NHS
OO
EtO2C
O
3aq
rac-3aq
47
Daicel Chiralpak AD-H, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; tR (major) = 24.23 min, tR (minor) = 36.80 min; 98% ee.
min0 5 10 15 20 25 30 35 40
mAU
0
100
200
300
400
500
600
700
800
VWD1 A, Wavelength=220 nm (XL2016\20160524000013.D)
Area
: 538
47.9
24.
227
Area
: 697
.427
36.
801
# Time Area Height Width Area% Symmetry1 24.227 53847.9 878.2 1.0219 98.721 1.0082 36.801 697.4 8.9 1.3074 1.279 0.9
min0 5 10 15 20 25 30 35 40
mAU
0
100
200
300
400
VWD1 A, Wavelength=220 nm (XL2016\20160524000012.D)
Area
: 265
97.8
24.
133
Area
: 240
99.4
36.
964
# Time Area Height Width Area% Symmetry1 24.133 26597.8 488.4 0.9076 52.464 0.8372 36.964 24099.4 290.1 1.3846 47.536 0.677
NHS
OO
EtO2C
O
3ar O
rac-3ar
48
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 20.85min, tR (major) = 23.03 min; 97% ee.
min5 10 15 20 25 30
mAU
0
50
100
150
200
250
300
350
400
VWD1 A, Wavelength=220 nm (G:\5+SI\20160405-0409\20160407000005.D)
20.
848
23.
025
# Time Area Height Width Area% Symmetry1 20.848 529.2 7.8 0.8119 1.508 0.7942 23.025 34570.1 413.1 1.1788 98.492 0.348
min5 10 15 20 25 30
mAU
0
25
50
75
100
125
150
175
200
VWD1 A, Wavelength=220 nm (G:\5+SI\20160405-0409\20160407000004.D)
19.
441
23.
033
# Time Area Height Width Area% Symmetry1 19.441 14454.4 199.5 1.0476 47.216 0.4142 23.033 16159 189.3 1.2144 52.784 0.44
NHS
OO
EtO2C
O
3as S
rac-3as
49
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 25.49 min, tR (major) = 34.44 min; 98% ee.
min0 5 10 15 20 25 30 35 40
mAU
0
100
200
300
400
500
600
700
VWD1 A, Wavelength=220 nm (G:\5+SI\20160405-0409\20160407000002.D)
25.
485
34.
435
# Time Area Height Width Area% Symmetry1 25.485 1089.5 10.1 1.275 0.946 0.6972 34.435 114050.5 765.5 1.9771 99.054 0.282
min0 5 10 15 20 25 30 35 40
mAU
0
100
200
300
400
500
600
700
VWD1 A, Wavelength=220 nm (G:\5+SI\20160405-0409\20160407000001.D)
Area
: 757
94.2
23.
814
Area
: 769
65.8
35.
105
# Time Area Height Width Area% Symmetry1 23.814 75794.2 781.6 1.6161 49.617 0.3942 35.105 76965.8 521.5 2.4599 50.383 0.335
NHS
OO
EtO2CPh
O
3at
rac-3at
50
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 14.45 min, tR (major) = 30.54min; 99% ee.
min0 5 10 15 20 25 30 35
mAU
0
200
400
600
800
VWD1 A, Wavelength=220 nm (G:\2016-08-29000710-NI-E-PH-5+QUETONGSI.D)
Area
: 636
.351
14.
446
Area
: 953
98.9
30.
541
# Time Area Height Width Area% Symmetry1 14.446 636.4 16.4 0.6482 0.663 0.7792 30.541 95398.9 988.2 1.6089 99.337 0.344
min0 5 10 15 20 25 30 35
mAU
0
100
200
300
400
500
600
700
800
VWD1 A, Wavelength=220 nm (G:\2016-08-2900070R-5+QUETONGSI.D)
13.
847
30.
726
# Time Area Height Width Area% Symmetry1 13.847 34450.8 887.9 0.5837 49.522 0.4922 30.726 35115.5 379.4 1.3527 50.478 0.404
NHS
O O
EtO2CPh
O
3au
rac-3au
51
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 10.29 min, tR (minor) = 13.43 min; 99% ee.
min0 2 4 6 8 10 12 14 16 18
mAU
0
200
400
600
800
1000
1200
1400
VWD1 A, Wavelength=220 nm (G:\5+SI\20160421\20160421000004.D)
10.
294
13.
432
# Time Area Height Width Area% Symmetry1 10.294 53298.6 1578.2 0.5192 99.228 0.4342 13.432 414.6 7.9 0.6681 0.772 0.64
min0 2 4 6 8 10 12 14 16 18
mAU
0
100
200
300
400
VWD1 A, Wavelength=220 nm (G:\5+SI\20160421\20160421000003.D)
Area
: 142
73.5
10.
453
Area
: 138
90.8
13.
145
# Time Area Height Width Area% Symmetry1 10.453 14273.5 459.5 0.5177 50.679 0.5122 13.145 13890.8 337.5 0.686 49.321 0.486
NHS
OO
EtO2C
O
3aw
rac-3aw
52
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 70:30, 0.9 mL/min, 220 nm; tR (major) = 13.18 min, tR (minor) = 21.00 min; 99% ee.
min0 5 10 15 20 25
mAU
0
250
500
750
1000
1250
1500
1750
2000
VWD1 A, Wavelength=220 nm (G:\0-NI-E-PH-CHCL3-5+F-4MEOSI.D)
Area
: 994
32.6
13.
177
Area
: 641
.143
21.
003
# Time Area Height Width Area% Symmetry1 13.177 99432.6 2011.1 0.824 99.359 0.3322 21.003 641.1 7.8 1.368 0.641 0.638
min0 5 10 15 20 25
mAU
0
200
400
600
800
1000
VWD1 A, Wavelength=210 nm (G:\2016-07-1700029R-5+F-4MEOSI.D)
13.
446
20.
002
# Time Area Height Width Area% Symmetry1 13.446 53427.5 1078.3 0.7261 50.287 0.3592 20.002 52817 703.2 1.1052 49.713 0.382
NHS
OO
EtO2C
O
3ax
F
OMe
rac-3ax
53
Daicel Chiralpak AD-H, n-hexane/i-PrOH = 70:30, 1.0 mL/min, 220 nm; tR (minor) = 32.82 min, tR (major) = 35.45 min; 99% ee. Zn(ClO4)2–L2 as catalyst: 92:8, 97%ee
min0 5 10 15 20 25 30 35 40
mAU
0
50
100
150
200
250
300
350
VWD1 A, Wavelength=220 nm (XL2016\20160524000006.D)
Area: 399.022
31.93
6
Area: 31658.9
34.46
6
# Time Area Height Width Area% Symmetry1 31.936 399 5.4 1.2394 1.245 0.9582 34.466 31658.9 360.2 1.4647 98.755 0.454
Zn(OTf)2–L2 as catalyst: dr 98:2; 99% ee
min0 5 10 15 20 25 30 35 40
mAU
0
50
100
150
200
250
300
VWD1 A, Wavelength=220 nm (XL2016\20160524000010.D)
Area: 112.415
32.81
7
Area: 27992.7
35.44
5
# Time Area Height Width Area% Symmetry1 32.817 112.4 1.5 1.2558 0.400 1.1212 35.445 27992.7 315.7 1.4778 99.600 0.466
min0 5 10 15 20 25 30 35 40
mAU
0
50
100
150
200
250
VWD1 A, Wavelength=220 nm (XL2016\20160524000005.D)
32.22
6
34.81
4
# Time Area Height Width Area% Symmetry1 32.226 19376.5 270.3 1.0707 49.189 0.7232 34.814 20015.6 240.6 1.2369 50.811 0.519
NHS
OO
EtO2C
O
3ay
rac-3ay
NHS
OO
EtO2C
O
3ay
54
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (major) = 20.35 min, tR (minor) = 23.37 min; 96% ee.
min0 5 10 15 20 25
mAU
0
100
200
300
400
500
600
VWD1 A, Wavelength=220 nm (G:\2016-07-19000370-E-PH-CHCL3-5+==PHOTBS.D)
Area
: 377
16.6
20.
349
Area
: 674
.246
23.
367
# Time Area Height Width Area% Symmetry1 20.349 37716.6 621.6 1.0113 98.244 02 23.367 674.2 9.4 1.1992 1.756 0.324
min0 5 10 15 20 25
mAU
0
50
100
150
200
250
300
VWD1 A, Wavelength=220 nm (G:\2016-07-1900036R-5+==PHOTBS.D)
20.
598
22.
642
# Time Area Height Width Area% Symmetry1 20.598 18863.8 27 0.8791 48.783 0.5422 22.642 19805.1 259.7 1.1248 51.217 0.445
NHS
O O
EtO2CO
3az
rac-3az
55
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 60:40, 1.0 mL/min, 230 nm; tR (major) = 14.95 min, tR (minor) = 25.56 min; 30% ee.
min10 12.5 15 17.5 20 22.5 25 27.5 30
mAU
0
2
4
6
8
10
12
VWD1 A, Wavelength=230 nm (H:\2017-06-14+746+A-5+TWOSI.D)
Area
: 498
.512
14.
949
Area
: 270
.681
25.
562
# Time Area Height Width Area% Symmetry1 14.949 498.5 12.4 0.67 64.810 0.5992 25.562 270.7 3.9 1.1591 35.190 0.617
min10 12.5 15 17.5 20 22.5 25 27.5 30
mAU
0
20
40
60
80
100
120
140
160
VWD1 A, Wavelength=230 nm (H:\2017-06-14+745+R-5+TWOSI.D)
14.
911
25.
458
# Time Area Height Width Area% Symmetry1 14.911 6861.5 172.8 0.5923 50.308 0.5292 25.458 6777.4 96.1 1.0471 49.692 0.488
SNH
O O
EtO2C
O
PhFF
3ax'
56
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 15.73 min, tR (major) = 24.16 min; 97% ee.
min0 5 10 15 20 25
mAU
0
200
400
600
800
1000
1200
VWD1 A, Wavelength=220 nm (G:\2016-07-0800016A-4ME5+SI-PD_C.D)
Area
: 122
4.4
15.
730
Area
: 902
63.1
24.
164
# Time Area Height Width Area% Symmetry1 15.73 1224.4 37.1 0.5506 1.338 0.7412 24.164 90263.1 1388.3 1.0836 98.662 0.44
min0 5 10 15 20 25
mAU
0
500
1000
1500
2000
2500
VWD1 A, Wavelength=220 nm (G:\2016-07-0800015R-4ME5+SI-PD_C.D)
Area
: 129
316
15.
782
Area
: 127
908
24.
254
# Time Area Height Width Area% Symmetry1 15.782 129316.5 2980.1 0.7232 50.274 0.482 24.254 127907.7 1929.2 1.105 49.726 0.405
NHS
O O
4
EtO2C
rac-4
57
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 70:30, 0.8 mL/min, 215 nm; tR (major) = 11.39 min, tR (minor) = 12.86 min; 98% ee.
min0 2 4 6 8 10 12 14
mAU
0
500
1000
1500
2000
2500
VWD1 A, Wavelength=215 nm (H:\170413\2017-04-13+633+A-5+SI+TBHP+KI+O.D)
Area
: 793
18.9
11.
386
Area
: 849
.034
12.
861
# Time Area Height Width Area% Symmetry1 11.386 79318.9 2790.7 0.4737 98.941 0.5272 12.861 849 26.9 0.5251 1.059 0.7
min0 2 4 6 8 10 12 14
mAU
0
50
100
150
200
250
300
VWD1 A, Wavelength=215 nm (H:\170413\2017-04-13+631+R-5+SI+TBHP+KI+CUBR2.D)
Area
: 789
3.13
11.
508
Area
: 778
6.52
12.
730
# Time Area Height Width Area% Symmetry1 11.508 7893.1 322.9 0.4074 50.340 0.6252 12.73 7786.5 277.4 0.4678 49.660 0.646
NS
OO
O
PhEtO2C
5
rac-5
58
Daicel Chiralcel OD-H, n-hexane/i-PrOH = 80:20, 1.0 mL/min, 220 nm; tR (minor) = 24.53 min, tR (major) = 26.23 min; 98% ee.
min5 10 15 20 25 30
mAU
0
200
400
600
800
1000
1200
VWD1 A, Wavelength=220 nm (I:\170121\2017-01-07+324+99%-50%CUI-5+2BRSI+CUI.D)
图图 图 : 663.43
24.52
8
图图 图 : 76108.6
26.23
3
# Time Area Height Width Area% Symmetry1 24.528 663.4 12.8 0.8664 0.864 0.8922 26.233 76108.6 1211.4 1.0471 99.136 0.486
min5 10 15 20 25 30
mAU
0
100
200
300
400
500
VWD1 A, Wavelength=220 nm (I:\170121\2017-01-07+323+R-5+2BRSI+CUI.D)
23.62
4
26.62
4
# Time Area Height Width Area% Symmetry1 23.624 33157.2 489.4 0.9944 49.619 0.3572 26.624 33666.7 534.7 0.9535 50.381 0.537
6
NS
O O
OEtO2C
rac-6
59
8. 1H and 13C NMR Spectra for Products 3~6.
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.02
1.00
1.00
2.00
0.95
2.02
3.97
1.00
2.00
-0.0
1
1.27
1.29
1.32
3.69
3.75
4.05
4.11
4.24
4.26
4.27
4.28
4.29
4.30
4.31
4.33
4.34
4.35
4.36
4.37
6.09
7.25
7.43
7.45
7.48
7.56
7.59
7.60
7.61
7.63
7.64
7.65
7.67
7.69
7.70
7.81
7.83
7.86
7.88
7.89
7.91
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
1
48.8
1
63.1
765
.16
76.2
976
.71
77.1
3
121.
5412
3.92
127.
8612
8.47
130.
4913
3.33
133.
6713
5.28
136.
60
169.
27
195.
65
NHS
O O
EtO2CO
NHS
O O
EtO2CO
60
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.03
3.00
1.00
1.00
2.05
0.95
4.01
1.06
1.01
2.00
0.00
1.29
1.31
1.33
2.50
3.67
3.73
4.06
4.12
4.25
4.26
4.28
4.29
4.31
4.33
4.34
4.35
4.37
4.38
4.39
6.04
7.42
7.44
7.44
7.46
7.47
7.49
7.57
7.57
7.58
7.60
7.60
7.62
7.66
7.69
7.71
7.90
7.90
7.92
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
1
21.5
3
48.9
5
63.0
765
.00
76.2
876
.71
76.9
177
.13
121.
2612
4.05
127.
8512
8.44
131.
4013
2.57
133.
6113
5.34
136.
9014
4.51
169.
39
195.
73
NHS
O O
EtO2C
O
NHS
O O
EtO2C
O
61
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.06
1.00
3.01
1.00
2.02
0.95
2.00
2.01
1.01
1.00
2.00
0.00
1.28
1.30
1.33
3.69
3.75
3.91
4.05
4.10
4.22
4.24
4.26
4.27
4.28
4.29
4.30
4.31
4.33
4.34
4.35
4.36
4.37
4.38
4.40
4.42
6.09
7.10
7.10
7.12
7.13
7.42
7.45
7.47
7.56
7.59
7.61
7.68
7.71
7.71
7.89
7.89
7.91
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
5
48.9
4
55.7
3
63.1
164
.85
76.3
576
.77
77.2
0
108.
30
116.
9412
2.88
127.
1912
7.84
128.
4413
3.63
135.
2913
9.18
163.
62
169.
27
195.
65
NHS
O O
EtO2C
OMeO
NHS
O O
EtO2C
OMeO
62
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.10
9.00
1.00
1.00
2.05
0.99
2.02
1.02
2.03
1.04
2.00
-0.0
0
1.28
1.31
1.33
1.38
3.72
3.78
4.05
4.11
4.20
4.22
4.23
4.25
4.26
4.27
4.28
4.31
4.36
4.38
4.39
4.41
4.42
4.43
4.44
4.47
6.08
7.43
7.46
7.48
7.57
7.59
7.62
7.65
7.65
7.67
7.68
7.72
7.74
7.75
7.91
7.91
7.94
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.7
0
30.8
635
.29
48.8
9
62.9
665
.19
76.3
376
.75
77.1
8
120.
3112
1.04
127.
8912
8.14
128.
4313
2.52
133.
6213
5.35
136.
77
157.
82
169.
40
195.
72
NHS
O O
EtO2C
O
NHS
O O
EtO2C
O
63
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.04
1.00
1.00
2.03
0.98
4.08
1.04
1.01
2.03
1.29
1.31
1.34
3.72
3.78
4.02
4.08
4.25
4.28
4.29
4.30
4.31
4.33
4.34
4.35
4.36
4.38
4.39
4.40
4.42
6.20
7.29
7.30
7.32
7.33
7.35
7.36
7.38
7.38
7.40
7.41
7.44
7.46
7.49
7.58
7.60
7.63
7.79
7.81
7.82
7.83
7.89
7.89
7.92
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
0
48.6
9
63.4
464
.72
64.7
5
76.3
376
.75
77.1
7
111.
1611
1.49
118.
3211
8.64
123.
7512
3.88
127.
8712
8.50
131.
3913
1.42
133.
7713
5.15
139.
7613
9.88
163.
5816
6.98
168.
80
195.
30
NHS
O O
EtO2C
OF
NHS
O O
EtO2C
OF
64
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.00
1.00
1.00
2.00
0.97
2.00
2.00
0.99
1.01
2.00
0.00
1.29
1.32
1.34
3.70
3.76
4.04
4.10
4.25
4.28
4.29
4.30
4.31
4.32
4.34
4.35
4.36
4.37
4.38
4.39
4.40
4.43
6.19
7.44
7.46
7.49
7.58
7.58
7.60
7.61
7.61
7.62
7.63
7.69
7.69
7.74
7.75
7.76
7.89
7.90
7.92
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
1
48.6
9
63.4
664
.78
76.3
376
.76
77.1
8
122.
7412
4.28
127.
8812
8.50
130.
9813
3.77
133.
8713
5.14
138.
6613
9.76
168.
77
195.
32
NHS
O O
EtO2C
OCl
NHS
O O
EtO2C
OCl
65
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
1.00
1.00
2.04
0.98
2.01
1.03
5.06
-0.0
0
1.29
1.31
1.34
3.73
3.79
4.10
4.16
4.27
4.28
4.30
4.31
4.32
4.33
4.36
4.38
4.39
4.40
4.42
4.43
4.44
6.29
7.44
7.47
7.49
7.58
7.59
7.61
7.63
7.89
7.90
7.91
7.91
7.93
7.95
7.98
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.56
48.59
63.54
65.07
76.31
76.73
77.16
120.77
121.36
121.41
121.46
121.51
122.48
124.39
127.72
127.77
127.81
127.87
127.90
128.51
133.84
134.70
135.07
135.14
135.58
136.02
137.73
138.69
168.63
195.23
NHS
O O
EtO2C
OF3C
NHS
O O
EtO2C
OF3C
66
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.00
1.01
1.01
2.05
1.00
5.09
3.00
-0.0
0
1.28
1.31
1.33
3.75
3.81
4.02
4.08
4.24
4.27
4.28
4.29
4.30
4.31
4.33
4.35
4.37
4.39
4.40
4.41
4.42
4.43
4.46
6.25
7.44
7.47
7.49
7.54
7.58
7.61
7.63
7.85
7.88
7.90
7.93
-50-40-30-20-100102030405060708090100110120130140150160170180190200210220230240f1 (ppm)
13.52
48.56
63.49
64.81
76.31
76.73
77.16
114.66
116.15
118.11
121.56
122.98
123.47
125.01
127.89
128.50
133.70
133.79
135.12
139.42
152.44
152.46
152.49
152.51
168.64
195.19
NHS
O O
EtO2C
OF3CO
NHS
O O
EtO2C
OF3CO
67
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.28
1.01
2.06
1.00
0.97
3.08
3.09
2.05
-0.0
0
1.23
1.25
1.27
3.58
3.64
4.20
4.22
4.24
4.25
4.26
4.28
4.28
4.30
4.32
4.33
4.34
4.36
4.47
4.53
6.33
7.36
7.38
7.40
7.41
7.42
7.43
7.45
7.48
7.50
7.59
7.61
7.64
7.64
7.65
7.65
7.65
7.66
7.67
7.69
7.70
7.92
7.92
7.95
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.4
3
45.3
345
.36
63.1
964
.25
64.3
0
76.3
276
.75
77.1
7
117.
6911
7.75
120.
5712
0.85
122.
5612
2.79
127.
8712
8.49
133.
0313
3.12
133.
7313
5.33
137.
7713
7.80
155.
9515
9.36
168.
32
195.
94
NHS
O O
EtO2C
O
F
NHS
O O
EtO2C
O
F
68
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.04
1.00
1.00
2.02
0.98
2.04
4.04
2.01
0.00
1.28
1.31
1.33
3.70
3.76
4.02
4.08
4.24
4.27
4.28
4.29
4.30
4.31
4.33
4.33
4.35
4.36
4.37
4.38
4.39
4.42
6.20
7.27
7.43
7.46
7.49
7.52
7.54
7.55
7.56
7.57
7.58
7.58
7.58
7.59
7.60
7.62
7.63
7.64
7.67
7.88
7.89
7.91
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
1
48.6
1
63.4
364
.20
76.3
176
.73
77.1
6
122.
2512
7.85
128.
5012
9.19
131.
2513
3.36
133.
7513
4.48
135.
1713
9.36
168.
83
195.
28
NHS
O O
EtO2C
O
Cl
NHS
O O
EtO2C
O
Cl
69
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
1.00
1.03
2.00
1.00
2.02
1.02
3.08
2.02
1.03
1.02
1.00
0.00
1.28
1.30
1.32
3.72
3.77
4.18
4.24
4.26
4.27
4.28
4.29
4.30
4.32
4.34
4.35
4.36
4.37
4.38
4.39
4.42
6.28
7.41
7.43
7.46
7.55
7.57
7.60
7.64
7.66
7.69
7.72
7.74
7.89
7.92
7.97
8.00
8.12
8.15
8.21
8.24
8.40
8.43
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
6
48.5
7
63.2
465
.21
76.3
476
.77
77.1
9
119.
4212
2.86
125.
1412
7.85
128.
1212
8.36
128.
4612
9.12
130.
7613
3.67
134.
6013
5.29
135.
43
169.
26
195.
58
NHS
O O
EtO2C
O
NHS
O O
EtO2C
O
70
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.05
3.02
1.00
1.00
2.05
0.96
2.26
3.04
3.03
0.00
1.27
1.30
1.32
2.41
3.67
3.73
4.04
4.10
4.25
4.26
4.27
4.28
4.29
4.31
4.32
4.33
4.34
4.35
4.36
4.38
6.09
7.24
7.27
7.62
7.63
7.65
7.66
7.67
7.69
7.70
7.70
7.70
7.71
7.72
7.79
7.81
7.81
7.82
7.83
7.83
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
0
21.3
7
48.7
0
63.1
065
.21
76.3
076
.72
77.1
5
121.
5012
3.95
127.
9812
9.13
130.
4313
2.86
133.
2913
5.26
136.
6514
4.67
169.
33
195.
22
NHS
O O
EtO2CO
NHS
O O
EtO2CO
71
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.10
1.00
1.00
2.02
1.97
0.97
2.01
5.00
3.03
1.00
2.00
-0.0
0
1.26
1.29
1.31
3.63
3.68
4.01
4.07
4.27
4.28
4.29
4.31
4.32
4.33
5.12
6.10
6.97
7.00
7.25
7.33
7.34
7.35
7.36
7.37
7.38
7.38
7.40
7.40
7.62
7.63
7.64
7.68
7.68
7.69
7.70
7.70
7.80
7.82
7.86
7.88
7.89
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
2
29.3
5
48.5
0
63.0
865
.27
69.8
976
.30
76.7
376
.93
77.1
5
114.
5012
1.50
123.
9512
7.13
127.
9612
8.38
128.
5813
0.24
130.
4213
3.27
135.
2613
5.65
136.
68
162.
99
169.
39
194.
02
NHS
O O
EtO2CO
OBn
NHS
O O
EtO2CO
OBn
72
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.03
1.00
1.00
2.05
0.93
2.00
3.04
1.05
2.04
-0.0
0
1.28
1.30
1.32
3.66
3.72
4.04
4.10
4.26
4.27
4.28
4.29
4.30
4.31
4.33
4.34
4.35
4.36
4.37
4.38
6.12
7.09
7.10
7.10
7.13
7.15
7.15
7.21
7.64
7.65
7.65
7.66
7.70
7.71
7.72
7.72
7.80
7.83
7.92
7.93
7.94
7.94
7.95
7.96
7.97
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.59
48.61
63.20
65.13
76.34
76.76
77.19
115.49
115.78
121.48
123.96
130.54
130.55
130.68
131.77
131.81
133.39
135.23
136.52
164.17
167.57
169.19
194.09
NHS
O O
EtO2CO
F
NHS
O O
EtO2CO
F
73
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.06
1.00
1.00
2.03
0.97
8.09
0.00
1.27
1.30
1.32
3.65
3.71
4.03
4.09
4.25
4.26
4.28
4.29
4.30
4.31
4.32
4.34
4.35
4.36
4.37
4.38
6.12
7.58
7.61
7.62
7.64
7.65
7.66
7.68
7.71
7.72
7.75
7.78
7.80
7.82
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.63
48.64
63.27
65.06
76.36
76.78
77.20
121.51
123.95
128.99
129.36
130.58
131.80
133.44
133.98
135.18
136.44
169.15
194.74
NHS
O O
EtO2CO
Br
NHS
O O
EtO2CO
Br
74
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.07
1.01
2.89
1.00
2.01
0.95
2.98
1.00
1.99
2.02
0.00
1.29
1.31
1.34
3.72
3.78
3.95
4.07
4.13
4.24
4.27
4.28
4.29
4.30
4.32
4.33
4.34
4.35
4.37
4.38
4.39
4.40
4.43
6.10
7.27
7.64
7.65
7.66
7.68
7.71
7.72
7.82
7.83
7.85
7.95
7.96
7.98
7.98
8.11
8.11
8.13
8.14
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
1
49.0
252
.19
63.2
865
.03
76.2
876
.70
77.1
2
121.
5712
3.88
127.
7912
9.63
130.
5713
3.38
134.
3313
5.31
136.
4713
8.38
165.
6216
9.08
195.
22
NHS
O O
EtO2CO
CO2Me
NHS
O O
EtO2CO
CO2Me
75
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.00
0.99
1.00
2.03
0.94
5.02
1.00
2.00
-0.0
0
1.29
1.31
1.34
3.72
3.78
4.06
4.12
4.25
4.27
4.29
4.30
4.31
4.32
4.33
4.34
4.36
4.37
4.38
4.39
4.40
4.43
6.10
7.63
7.64
7.65
7.66
7.68
7.69
7.70
7.71
7.73
7.75
7.82
7.84
7.85
8.01
8.04
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.60
48.86
63.34
65.01
76.28
76.70
77.12
121.26
121.57
123.88
124.88
125.46
125.51
125.56
125.61
127.23
128.25
130.61
133.42
134.19
134.62
135.06
135.34
135.51
136.46
137.93
169.00
194.81
NHS
O O
EtO2CO
CF3
NHS
O O
EtO2CO
CF3
76
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.06
1.00
1.00
2.06
0.95
3.02
1.01
2.01
2.00
0.00
1.30
1.33
1.35
3.75
3.81
4.07
4.12
4.26
4.29
4.30
4.31
4.32
4.34
4.35
4.36
4.37
4.39
4.40
4.41
4.42
4.44
6.09
7.27
7.67
7.69
7.72
7.72
7.73
7.73
7.74
7.83
7.85
8.07
8.08
8.10
8.10
8.30
8.30
8.32
8.32
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
2
48.9
8
63.4
564
.95
76.2
876
.70
77.1
3
121.
6112
3.67
123.
8412
8.99
130.
7013
3.48
135.
3613
6.37
139.
65
150.
45
168.
85
194.
33
NHS
O O
EtO2CO
NO2
NHS
O O
EtO2CO
NO2
77
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
2.98
1.00
1.00
2.05
0.97
2.26
1.04
4.03
1.02
-0.0
0
1.30
1.32
1.35
2.53
3.62
3.68
4.02
4.08
4.26
4.28
4.29
4.30
4.31
4.33
4.34
4.35
4.36
4.37
4.38
4.40
6.11
7.22
7.25
7.26
7.28
7.38
7.38
7.40
7.43
7.43
7.60
7.61
7.63
7.64
7.65
7.66
7.66
7.68
7.69
7.81
7.83
7.83
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
4
21.1
8
51.0
7
63.1
365
.36
76.2
876
.71
77.1
3
121.
5212
3.89
125.
5212
8.68
130.
4213
1.94
131.
9713
3.28
135.
3213
5.45
136.
6813
8.78
169.
36
198.
88
NHS
O O
EtO2CO
NHS
O O
EtO2CO
78
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.09
1.01
2.97
1.00
2.02
0.92
2.01
1.00
3.01
2.05
-0.0
0
1.27
1.29
1.31
3.70
3.77
3.85
3.88
4.09
4.11
4.17
4.22
4.24
4.25
4.26
4.28
4.29
4.30
4.30
4.32
4.33
4.34
4.36
4.38
6.09
6.95
6.98
6.98
6.99
7.01
7.03
7.04
7.51
7.51
7.62
7.63
7.64
7.69
7.70
7.70
7.71
7.71
7.72
7.79
7.81
7.81
7.84
7.84
7.86
7.87
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
3
54.1
255
.25
62.9
165
.60
76.3
676
.79
77.2
1
111.
4212
0.48
121.
3812
4.09
125.
4213
0.30
130.
5013
3.30
134.
6913
5.16
136.
86
159.
15
169.
63
196.
50
NHS
O O
EtO2CO
OMe
NHS
O O
EtO2CO
OMe
79
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
1.04
1.00
2.02
0.92
0.98
1.25
4.00
1.00
1.03
0.00
1.28
1.31
1.33
3.63
3.64
3.69
3.70
4.10
4.12
4.16
4.18
4.25
4.27
4.28
4.29
4.30
4.31
4.32
4.34
4.35
4.36
4.37
4.38
7.10
7.11
7.13
7.13
7.14
7.15
7.17
7.17
7.24
7.24
7.27
7.29
7.29
7.55
7.56
7.56
7.57
7.57
7.57
7.58
7.58
7.59
7.59
7.60
7.61
7.62
7.62
7.64
7.65
7.66
7.68
7.69
7.70
7.71
7.71
7.81
7.81
7.83
7.84
7.91
7.91
7.93
7.94
7.96
7.96
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
0
53.3
653
.47
63.1
465
.14
65.1
9
76.2
776
.69
77.1
2
116.
3011
6.61
121.
5212
3.56
123.
7212
3.97
124.
3912
4.44
130.
3613
0.39
130.
4613
3.34
135.
1813
5.39
135.
5113
6.41
160.
3716
3.75
169.
29
193.
5219
3.57
NHS
O O
EtO2CO
F
NHS
O O
EtO2CO
F
80
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.02
1.00
1.00
1.99
0.97
3.01
4.00
1.00
-0.0
0
1.32
1.35
1.37
3.66
3.72
4.11
4.17
4.28
4.29
4.31
4.32
4.33
4.34
4.35
4.37
4.37
4.39
4.40
4.41
6.09
7.33
7.33
7.34
7.35
7.35
7.36
7.37
7.42
7.42
7.43
7.44
7.60
7.60
7.61
7.61
7.63
7.63
7.63
7.64
7.65
7.68
7.70
7.80
7.82
7.83
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
5
52.4
4
63.3
365
.29
76.3
076
.72
77.1
4
121.
5112
3.91
126.
8112
9.51
130.
5113
0.56
131.
2813
2.51
133.
3613
5.29
136.
5013
6.68
169.
03
197.
80
NHS
O O
EtO2CO
Cl
NHS
O O
EtO2CO
Cl
81
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.00
1.00
1.00
2.00
0.98
2.04
1.00
4.00
1.00
-0.02
1.32
1.34
1.37
3.62
3.68
4.05
4.11
4.28
4.30
4.31
4.32
4.34
4.35
4.36
4.37
4.39
4.39
4.41
4.43
6.08
7.25
7.27
7.28
7.29
7.31
7.31
7.33
7.34
7.34
7.35
7.37
7.37
7.39
7.40
7.42
7.48
7.49
7.51
7.52
7.58
7.59
7.59
7.60
7.61
7.61
7.62
7.63
7.65
7.65
7.66
7.67
7.78
7.78
7.81
7.81
7.81
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.70
51.93
63.39
65.21
76.31
76.73
77.15
118.77
121.51
123.88
127.29
128.97
130.52
132.22
133.36
133.76
135.31
136.50
139.01
168.95
198.75
NHS
O O
EtO2CO
Br
NHS
O O
EtO2CO
Br
82
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.06
3.00
1.00
1.00
2.00
0.96
2.01
4.98
1.01
0.00
1.27
1.30
1.32
2.38
3.69
3.75
4.06
4.12
4.25
4.26
4.27
4.28
4.29
4.31
4.32
4.33
4.34
4.35
4.36
4.38
6.11
7.27
7.31
7.34
7.36
7.39
7.42
7.59
7.60
7.61
7.62
7.63
7.64
7.65
7.66
7.68
7.68
7.69
7.70
7.71
7.72
7.72
7.74
7.80
7.83
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
2
20.9
4
48.8
6
63.1
365
.19
76.3
476
.76
77.1
9
121.
4812
3.99
125.
0912
8.34
128.
3713
0.47
133.
3513
4.43
135.
2713
5.31
136.
6513
8.33
169.
30
195.
82
NHS
O O
EtO2CO
NHS
O O
EtO2CO
83
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
1.00
2.91
1.02
2.00
0.87
0.98
1.00
2.00
3.01
1.00
-0.0
0
1.28
1.31
1.33
3.68
3.74
3.84
4.04
4.10
4.23
4.26
4.27
4.28
4.29
4.31
4.32
4.33
4.34
4.35
4.37
4.38
4.39
4.41
6.08
7.12
7.13
7.13
7.15
7.15
7.16
7.16
7.33
7.36
7.38
7.44
7.45
7.45
7.46
7.48
7.48
7.63
7.64
7.65
7.67
7.70
7.71
7.82
7.84
7.84
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
2
48.8
9
55.1
6
63.1
765
.18
76.2
776
.70
77.1
2
111.
9412
0.29
120.
5212
1.53
123.
9212
9.44
130.
4813
3.31
135.
3113
6.62
159.
63
169.
24
195.
50
NHS
O O
EtO2CO
OMe
NHS
O O
EtO2CO
OMe
84
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.04
1.00
1.00
2.03
0.85
1.02
4.01
2.01
1.00
-0.0
0
1.29
1.31
1.33
3.66
3.72
4.02
4.08
4.23
4.26
4.27
4.28
4.29
4.31
4.32
4.33
4.34
4.36
4.37
4.38
4.39
4.42
6.07
7.27
7.33
7.35
7.38
7.63
7.64
7.65
7.66
7.66
7.67
7.69
7.70
7.71
7.72
7.72
7.73
7.73
7.74
7.74
7.82
7.84
7.85
8.03
8.03
8.04
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
2
48.7
7
63.2
965
.00
76.2
876
.71
77.1
3
121.
5712
2.80
123.
8912
6.39
130.
0713
0.57
130.
9013
3.38
135.
3213
6.48
136.
97
169.
06
194.
36
NHS
O O
EtO2CO
Br
NHS
O O
EtO2CO
Br
85
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.05
1.00
1.01
1.99
0.88
10.0
4
0.98
-0.0
0
1.29
1.32
1.34
3.85
3.91
4.19
4.25
4.28
4.29
4.30
4.31
4.32
4.33
4.35
4.36
4.37
4.38
4.39
4.41
4.43
6.15
7.26
7.61
7.72
7.72
7.75
7.75
7.83
7.85
7.87
7.88
7.90
7.95
7.96
8.41
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
4
48.8
7
63.1
965
.27
76.2
876
.70
77.1
3
121.
5612
3.08
124.
0012
6.72
127.
5112
8.41
128.
6412
9.28
130.
0013
0.49
132.
0413
2.64
133.
3313
5.37
135.
6013
6.71
169.
32
195.
55
NHS
O O
EtO2CO
NHS
O O
EtO2CO
86
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.05
1.02
1.00
2.05
0.94
0.99
0.98
4.01
1.02
0.00
1.29
1.32
1.34
3.57
3.63
3.93
3.98
4.23
4.26
4.27
4.28
4.29
4.30
4.31
4.32
4.33
4.34
4.35
4.36
4.37
4.38
4.39
4.42
6.07
6.56
6.56
6.57
6.58
7.24
7.25
7.27
7.59
7.59
7.60
7.60
7.62
7.63
7.64
7.65
7.66
7.70
7.71
7.81
7.81
7.83
7.84
7.84
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.5
9
48.1
5
63.2
664
.87
76.2
876
.70
77.1
3
112.
3511
7.93
121.
4812
3.94
130.
4713
3.32
135.
2113
6.53
146.
7715
1.37
169.
05
184.
31
NHS
O O
EtO2CO
O
NHS
O O
EtO2CO
O
87
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
1.00
1.00
2.01
0.95
0.98
4.97
1.02
0.00
1.28
1.31
1.33
3.63
3.68
4.01
4.07
4.26
4.27
4.28
4.29
4.30
4.32
4.32
4.34
4.35
4.36
4.37
4.38
6.09
7.11
7.13
7.13
7.14
7.64
7.65
7.66
7.68
7.69
7.70
7.70
7.70
7.71
7.71
7.72
7.72
7.73
7.79
7.80
7.82
7.82
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
1
48.8
6
63.2
765
.16
76.3
576
.78
77.2
0
121.
4512
4.01
128.
1013
0.54
132.
7613
3.41
134.
5713
5.21
136.
4714
2.17
169.
04
188.
27
NHS
O O
EtO2CO
S
NHS
O O
EtO2CO
S
88
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.07
1.00
1.00
2.06
0.99
1.00
3.07
6.10
1.01
-0.0
0
1.29
1.32
1.34
3.39
3.44
3.81
3.86
4.23
4.25
4.26
4.27
4.28
4.30
4.31
4.32
4.33
4.34
4.36
4.37
4.38
6.08
6.68
6.74
7.27
7.36
7.37
7.39
7.39
7.40
7.41
7.51
7.52
7.54
7.59
7.61
7.62
7.64
7.65
7.66
7.69
7.70
7.80
7.83
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.6
2
50.0
9
63.1
565
.13
76.3
076
.72
76.9
277
.15
121.
4812
3.92
124.
7212
8.16
128.
7213
0.42
130.
7213
3.29
133.
6113
5.23
136.
6414
4.34
169.
20
195.
37
NHS
O O
EtO2CPh
O
NHS
O O
EtO2CPh
O
89
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.08
1.01
1.00
2.06
0.99
2.01
1.06
2.01
3.13
1.03
-0.0
1
1.29
1.32
1.34
3.37
3.43
3.81
3.87
4.23
4.25
4.26
4.28
4.29
4.31
4.32
4.34
4.35
4.37
4.38
4.40
5.99
7.25
7.35
7.37
7.40
7.44
7.45
7.46
7.47
7.48
7.49
7.53
7.53
7.56
7.59
7.59
7.61
7.62
7.63
7.64
7.65
7.66
7.68
7.68
7.79
7.82
-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.61
54.39
63.42
64.66
76.29
76.72
77.14
86.60
93.14
118.92
121.54
123.83
128.40
130.57
130.91
132.84
133.37
135.21
136.10
168.68
182.20
NHS
O O
EtO2CPh
O
NHS
O O
EtO2CPh
O
NHS
O O
EtO2CPh
O
90
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.05
3.01
1.00
2.01
1.00
2.01
3.10
2.01
2.06
-0.0
1
1.38
1.41
1.43
1.47
1.49
4.23
4.26
4.28
4.31
4.39
4.42
4.44
4.46
6.15
7.26
7.44
7.45
7.47
7.57
7.59
7.60
7.60
7.61
7.62
7.63
7.63
7.78
7.78
7.78
7.79
7.79
7.80
7.81
7.81
7.81
7.90
7.91
7.93
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.7
214
.38
49.9
4
63.1
8
68.6
276
.29
76.7
177
.13
121.
3112
6.08
128.
2712
8.49
130.
2413
2.35
133.
3313
5.43
136.
93
168.
81
200.
78
NHS
O O
EtO2C
O
NHS
O O
EtO2C
O
91
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
3.00
2.01
1.00
0.95
2.00
2.03
1.00
1.00
2.03
-0.0
0
1.31
1.33
1.36
3.88
4.34
4.37
4.39
4.41
5.57
5.73
5.99
6.93
6.96
7.27
7.67
7.68
7.69
7.70
7.70
7.71
7.72
7.81
7.82
7.84
7.88
7.88
7.90
7.91
7.96
7.99
7.99
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.62
55.27
63.48
66.04
66.34
76.28
76.70
77.12
90.75
93.41
113.75
121.25
126.84
126.91
130.91
131.81
131.86
133.01
133.26
135.71
164.37
167.45
189.87
190.14
NHS
O O
EtO2C
O
F
OMe
NHS
O O
EtO2C
O
F
OMe
92
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
1.01
1.09
2.02
0.09
0.96
2.05
0.88
1.00
1.02
1.03
3.02
1.01
1.01
-0.0
11.
291.
321.
341.
461.
471.
491.
491.
511.
521.
532.
142.
162.
182.
202.
232.
252.
872.
912.
922.
932.
942.
952.
982.
993.
783.
793.
833.
844.
264.
274.
284.
294.
314.
324.
344.
354.
364.
374.
394.
405.
857.
197.
217.
257.
287.
307.
337.
457.
467.
487.
487.
507.
517.
607.
617.
627.
637.
637.
657.
667.
687.
707.
727.
727.
797.
817.
988.
01
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.5
9
23.0
8
28.4
8
55.9
5
63.1
6
69.1
676
.28
76.7
077
.12
121.
6512
3.87
126.
5512
7.23
128.
4513
0.52
131.
5413
3.54
133.
8413
5.22
135.
4514
3.61
169.
90
196.
25
NHS
O O
EtO2C
O
NHS
O O
EtO2C
O
93
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.06
1.02
1.00
2.02
0.96
1.00
1.02
2.02
3.16
2.02
2.04
0.00
1.33
1.35
1.38
2.88
2.95
2.97
2.99
3.02
3.20
3.22
3.24
3.27
4.32
4.35
4.37
4.40
5.86
6.88
6.96
7.02
7.27
7.44
7.46
7.49
7.55
7.57
7.60
7.62
7.63
7.65
7.65
7.67
7.68
7.70
7.70
7.73
7.73
7.76
7.79
7.81
7.86
7.86
7.89
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.82
42.89
63.72
67.85
76.30
76.73
77.15
121.35
124.42
128.31
128.36
130.51
130.83
132.72
133.38
135.31
136.89
137.15
139.74
168.64
189.98
NHS
O O
EtO2C
Ph
O
NHS
O O
EtO2C
Ph
O
94
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
2.00
0.98
2.01
3.05
1.00
1.00
2.02
0.02
1.34
1.36
1.39
4.37
4.38
4.38
4.39
4.40
4.41
4.43
4.43
4.44
4.45
4.45
4.47
6.01
7.28
7.49
7.52
7.54
7.54
7.66
7.69
7.71
7.74
7.74
7.75
7.76
7.77
7.78
7.78
7.87
7.87
7.88
7.89
7.89
7.90
7.96
8.09
8.09
8.12
8.12
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.52
64.08
67.90
68.22
68.25
68.56
76.27
76.70
77.12
111.52
115.10
118.67
121.62
126.68
126.75
128.52
130.04
130.07
130.10
130.12
130.84
130.88
130.92
131.48
133.26
134.89
136.32
165.20
165.23
165.30
165.32
187.08
187.46
187.50
187.89
SNH
O O
EtO2C
O
PhFF
3ax'
SNH
O O
EtO2C
O
PhFF
3ax'
95
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.01
1.04
3.00
1.06
2.02
2.00
0.97
5.03
1.00
0.99
0.97
-0.0
0
1.32
1.34
1.36
2.31
2.33
2.34
2.45
2.48
2.50
2.52
2.64
2.66
2.68
2.70
2.72
4.19
4.21
4.22
4.23
4.25
4.26
4.27
4.28
4.30
4.30
4.31
4.34
4.35
5.84
7.13
7.15
7.16
7.18
7.19
7.23
7.25
7.26
7.27
7.35
7.38
7.46
7.60
7.62
7.65
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.7
9
21.5
3
30.6
1
41.6
7
63.2
4
68.4
876
.32
76.7
477
.17
120.
8812
4.70
125.
9012
8.11
128.
1413
1.11
132.
3513
8.13
139.
9314
4.33
169.
68NH
SO O
4
EtO2C
NHS
O O
4
EtO2C
96
NS
OO
O
PhEtO2C
5
NS
OO
O
PhEtO2C
5
97
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.00
1.00
1.00
2.01
1.00
4.03
1.00
1.00
1.00
-0.03
1.00
1.02
1.05
2.95
2.99
3.74
3.79
3.99
4.01
4.02
4.04
4.05
4.06
4.07
4.08
4.10
4.10
4.11
4.12
4.14
4.15
4.16
4.18
7.19
7.19
7.21
7.22
7.22
7.22
7.24
7.24
7.25
7.64
7.64
7.64
7.64
7.65
7.65
7.70
7.70
7.72
7.73
7.73
7.74
7.76
7.76
7.83
7.84
7.86
7.86
7.92
7.92
7.92
8.00
8.00
8.03
-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
13.37
45.86
63.12
68.62
76.34
76.76
77.19
118.01
121.67
121.74
123.19
123.99
127.99
130.82
133.54
133.64
133.95
135.76
138.31
167.91
188.33
6
NS
O O
OEtO2C
6
NS
O O
OEtO2C
98
9. The structure of 3ka and 3aw’ by X-ray diffraction analysis
NHS
O O
O
3kaEtO2C
Table S3. Crystal data and structure refinement for (S)-3ka (CCDC 1522074)Empirical formula C22H19NO5SFormula weight 409.44Temperature / K 105.8Crystal system orthorhombicSpace group P212121 a / Å, b / Å, c / Å 8.8173(4), 14.3926(7), 15.3659(7)α/°, β/°, γ/° 90.00, 90.00, 90.00 Volume / Å3 1950.00(15)Z 4 ρcalc / mg mm-3 1.395μ / mm-1 1.775F(000) 856Crystal size / mm3 0.25 × 0.24 × 0.232Θ range for data collection 8.42 to 141.9°Index ranges -10 ≤ h ≤ 9, -17 ≤ k ≤ 17, -17 ≤ l ≤ 18Reflections collected 6453Independent reflections 3678[R(int) = 0.0210 (inf-0.9Å)]Data/restraints/parameters 3678/0/264Goodness-of-fit on F2 1.061Final R indexes [I>2σ (I) i.e. Fo>4σ (Fo)] R1 = 0.0271, wR2 = 0.0686Final R indexes [all data] R1 = 0.0275, wR2 = 0.0689Largest diff. peak/hole / e Å-3 0.330/-0.306Flack Parameters 0.003(12)Completeness 0.989
99
Crystal structure for 3aw’ ( CCDC 1536298)
3aw’from different perspective
NS
O O
EtO2C
O
Me
Et
SR
3aw'
