stoltz2.caltech.eduSupporting Information for Duquette, Cusumano, Lefoulon, Moore, and Stoltz S1...

Supporting Information for Duquette, Cusumano, Lefoulon, Moore, and Stoltz

S1

Supporting Information for

Probing Trends in Enantioinduction via Substrate Design: Palladium-

Catalyzed Decarboxylative Allylic Alkylation of a-Enaminones

Douglas C. Duquette, Alexander Q. Cusumano, Louise Lefoulon, Jared T. Moore, and Brian M.

Stoltz*

Warren and Katharine Schlinger Laboratory of Chemistry and Chemical Engineering, Division

of Chemistry and Chemical Engineering, California Institute of Technology, MC 101-20,

Pasadena, California 91125, United States

[email protected]

Table of Contents:

Materials and Methods ................................................................................................................................................. S2

List of Abbreviations .................................................................................................................................................... S3

General Procedure for Pd-Catalyzed Allylic Alkylation Reactions ............................................................................ S4

Determination of Enantiomeric Excess ..................................................................................................................... S13

Synthesis of Allylic Alkylation Substrates ................................................................................................................ S16

Derivatization of Enaminone Products ...................................................................................................................... S27

References ................................................................................................................................................................. S32

NMR and IR Spectra of New Compounds ................................................................................................................ S33


S2

Materials and Methods

Unless otherwise stated, reactions were performed in flame-dried glassware under an argon

or nitrogen atmosphere using dry, deoxygenated solvents. Reactions were heated by pre-heated oil

bath unless otherwise specified. Solvents were dried by passage through an activated alumina

column under argon.1 Acetone was used directly from a Sigma-Aldrich ACS reagent grade bottle.

Brine solutions are saturated aqueous solutions of sodium chloride. Reagents were purchased from

Sigma-Aldrich, Acros Organics, Strem, or Alfa Aesar and used as received unless otherwise stated.

The (S)-t-BuPHOX (L1) ligand was prepared by known methods.2 Reaction progress was

monitored by thin-layer chromatography (TLC) or Agilent 1290 UHPLC-MS. TLC was performed

using E. Merck silica gel 60 F254 precoated glass plates (0.25 mm) and visualized by UV

fluorescence quenching or KMnO4 staining. Silicycle SiliaFlash® P60 Academic Silica gel

(particle size 40–63 nm) was used for flash column chromatography. 1H NMR spectra were

recorded on Varian Inova 500 MHz, Varian 400 MHz, and Bruker 400 MHz spectrometers and

are reported relative to residual CHCl3 (δ 7.26 ppm). 13C NMR spectra were recorded on a Varian

Inova 500 MHz spectrometer (125 MHz), a Varian 400 MHz spectrometer (100 MHz), and Bruker

400 MHz spectrometers (100 MHz) and are reported relative to CHCl3 (δ 77.16 ppm). Data for 1H

NMR are reported as follows: chemical shift (δ ppm) (multiplicity, coupling constant (Hz),

integration). Multiplicities are reported as follows: s = singlet, d = doublet, t = triplet, q = quartet,

p = pentet, sept = septuplet, m = multiplet, dm = doublet of multiplets, br s = broad singlet, br d =

broad doublet, app = apparent. Data from 13C NMR spectra are reported in terms of chemical

shifts (δ ppm). IR spectra were obtained by use of a Perkin Elmer Spectrum BXII spectrometer

using thin films deposited on NaCl plates and reported in frequency of absorption (cm-1). Optical

rotations were measured with a Jasco P-2000 polarimeter operating on the sodium D-line (589

nm), using a 100 mm path-length cell and are reported as: [α]D25 (concentration in g/100 mL,

solvent, ee). Analytical chiral HPLC was performed with an Agilent 1100 Series HPLC utilizing

a Chiralpak (AD, AD- H, or AS) or Chiralcel (OD-H, OJ-H, or OB-H) columns (4.6 mm x 25 cm)

obtained from Daicel Chemical Industries, Ltd. Analytical chiral SFC was performed with a

Mettler SFC supercritical CO2 analytical chromatography system with Chiralpak AD-H column,

OD-H column, and OJ-H column obtained from Daicel Chemical Industries, Ltd. High resolution

mass spectra (HRMS) were obtained from the Caltech Mass Spectral Facility (GC-EI+, EI+, or

FAB+) or Agilent 6200 Series TOF with an Agilent G1978A Multimode source in electrospray


S3

ionization (ESI+), atmospheric pressure chemical ionization (APCI+), or mixed ionization mode

(MM: ESI-APCI+).

List of Abbreviations:

ee – enantiomeric excess, SFC – supercritical fluid chromatography, TLC – thin-layer

chromatography, IPA – isopropanol, NBS – N-bromosuccinimide,


S4

General Procedure A: Palladium-Catalyzed Allylic Alkylation Reactions

In a glove box under an atmosphere of N2, Pd2(dmdba)3 (29.7 mg, 23.3 µmol, 5 mol %) and (S)-t-

BuPHOX ligand (22.5 mg, 58.2 µmol, 12.5 mol %) were dissolved in EtOAc (12 mL). The catalyst

mixture was let stir at 40 ºC in a pre-heated vial block for 30 minutes. At this point, a solution of

allyl b-ketoester (1, 130 mg, 0.465 mmol, 1.00 equiv) in EtOAc (2.0 mL, final concentration of

0.033 M with respected to 1) was added. The reaction mixture was sealed, removed from the glove

box and stirred at 40 °C in a pre-heated vial block until the reaction was complete as indicated by

TLC analysis (typically around 9-12 hours). The reaction mixture was filtered through a short plug

of silica, being eluted with additional EtOAc (25 mL). The filtrate was concentrated in vacuo and

purified by flash column chromatography to afford the desired enaminone product 2.

Note: After pre-complexation of catalyst the reaction mixture is red/brown in color, which changes

immediately to light green upon addition of substrate. Upon completion, the reaction returns to

the original red/brown color.

(S)-6-allyl-6-methyl-2-morpholinocyclohex-2-en-1-one (2a)

Prepared according to general procedure A using substrate 1a. The product was purified by flash

column chromatography (SiO2, 5–10% acetone in hexanes) to yield enaminone 2a as a colorless

oil (104 mg, 0.442 mmol, 95% yield). Rf = 0.22 (20% acetone in hexanes); 1H NMR (500 MHz,

CDCl3) δ 5.88 (t, J = 4.5 Hz, 1H), 5.78 – 5.69 (m, 1H), 5.06 – 5.02 (m, 2H), 3.80 (ddd, J = 5.7,

3.5, 2.2 Hz, 4H), 2.82 (dt, J = 9.9, 4.6 Hz, 2H), 2.73 – 2.67 (m, 2H), 2.48 – 2.38 (m, 2H), 2.34

(ddd, J = 13.8, 7.2, 1.1 Hz, 1H), 2.23 (dd, J = 13.7, 7.7 Hz, 1H), 1.88 (dt, J = 13.8, 6.0 Hz, 1H),

1.73 (ddd, J = 13.9, 6.9, 5.7 Hz, 1H), 1.09 (s, 3H).; 13C NMR (125 MHz, CDCl3) δ 200.4, 145.5,

134.0, 125.0, 118.1, 66.9, 50.5, 45.4, 41.2, 33.2, 21.9, 21.8; IR (Neat Film, NaCl): 2960, 2918,

O

OR1

O Pd2(dmdba)3 (5 mol%)

EtOAc, 40 ºC, 9 h

OR1N N

OO

(S)–2(±)–1

R2R2

(S)-t-BuPHOX (12.5 mol%)

OMe

NO


S5

2853, 2813, 1679, 1615, 1447, 1376, 1262, 1208, 1120, 1099, 1001, 990, 915 cm-1; HRMS (ESI-

APCI) m/z: [M+H]+ Calc’d for C14H22NO2 236.1645; Found 236.1641; [α]25 –315.66 (c 13.57,

CHCl3, 99% ee).

(S)-6-allyl-6-ethyl-2-morpholinocyclohex-2-en-1-one (2b)

Prepared according to general procedure A using substrate 1b. The product was purified by flash

column chromatography (SiO2, 5–10% acetone in hexanes) to yield enaminone 2b as a colorless

oil (116 mg, 0.465 mmol, 99% yield). Rf = 0.25 (40% Et2O in hexanes); 1H NMR (500 MHz,

CDCl3) δ 5.83 (t, J = 4.4 Hz, 1H), 5.73 – 5.66 (m, 1H), 5.04 – 5.02 (m, 1H), 5.01 – 4.99 (m, 1H),

3.79 – 3.77 (m, 4H), 2.80 – 2.74 (m, 2H), 2.70 (ddd, J = 11.6, 7.4, 4.2 Hz, 2H), 2.40 (tdd, J = 5.9,

4.5, 1.4 Hz, 2H), 2.34 (ddt, J = 14.0, 6.9, 1.3 Hz, 1H), 2.23 (ddt, J = 14.0, 7.9, 1.1 Hz, 1H), 1.81

(t, J = 6.2 Hz, 2H), 1.59 (qd, J = 7.5, 1.3 Hz, 2H), 0.80 (t, J = 7.5 Hz, 3H).; 13C NMR (125 MHz,

CDCl3) δ 200.2, 146.0, 134.4, 124.8, 117.9, 67.0, 50.6, 48.6, 38.8, 30.4, 27.0, 21.8, 8.4; IR (Neat

Film, NaCl): 2962, 2933, 2854, 2814, 1678, 1616, 1447, 1377, 1263, 1208, 1120, 1070, 1099, 998

cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C15H24NO2 250.1802; Found 250.1813; [α]25

5.52 (c 7.45, CHCl3, 98% ee).

(S)-6-allyl-6-(((tert-butyldimethylsilyl)oxy)methyl)-2-morpholinocyclohex-2-en-1-one (2c)

Prepared according to general procedure A using substrate 1c. The product was purified by flash

column chromatography (SiO2, 20% acetone in hexanes) to yield enaminone 2c (164 mg, 0.445

mmol, 96% yield) as a pale tan oil; Rf = 0.33 (20% EtOAc in hexanes); 1H NMR (500 MHz,

CDCl3) δ 5.87 (t, J = 4.6 Hz, 1H), 5.74 – 5.66 (m, 1H), 5.04 – 5.00 (m, 2H), 3.78 (t, J = 4.6 Hz,

4H), 3.68 (d, J = 9.7 Hz, 1H), 3.62 (d, J = 9.7 Hz, 1H), 2.74 (t, J = 4.7 Hz, 4H), 2.43 – 2.38 (m,

3H), 2.26 (ddt, J = 13.8, 7.8, 1.1 Hz, 1H), 1.96 (ddd, J = 13.3, 7.1, 6.0 Hz, 1H), 1.89 (dt, J = 13.7,

5.9 Hz, 1H), 0.85 (s, 9H), 0.01 (s, 3H), 0.01 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 198.8, 146.4,

134.1, 125.1, 118.0, 67.0, 66.1, 51.0, 50.5, 37.2, 28.5, 26.0, 21.7, 18.3, -5.4, -5.5; IR (Neat Film,

OEt

NO

ON

O OTBS


S6

NaCl): 2953, 2855, 1677, 1639, 1615, 1472, 1463, 1447, 1378, 1299, 1262, 1208, 1121, 973, 917

cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C20H36NO3Si 366.2459; Found 366.2466; [α]25

–111.67 (c 10.25, CHCl3, 99% ee).

(S)-6-allyl-6-(2-((tert-butyldimethylsilyl)oxy)ethyl)-2-morpholinocyclohex-2-en-1-one (2d)

Prepared according to general procedure A using substrate 1d. The product was purified by flash

column chromatography (SiO2, 20% acetone in hexanes) to yield enaminone 2d (165 mg, 0.432

mmol, 93% yield) as a colorless oil; Rf = 0.31 (20% EtOAc in hexanes); 1H NMR (500 MHz,

CDCl3) δ 5.87 (s, 1H), 5.74 (dddd, J = 16.5, 10.5, 7.8, 6.9 Hz, 1H), 5.08 – 5.01 (m, 2H), 3.85 –

3.76 (m, 4H), 3.70 (ddd, J = 10.2, 8.4, 6.1 Hz, 1H), 3.57 (ddd, J = 10.3, 8.6, 5.9 Hz, 1H), 2.82 –

2.68 (m, 4H), 2.51 – 2.35 (m, 3H), 2.27 (dd, J = 14.0, 7.8 Hz, 1H), 1.92 – 1.82 (m, 3H), 1.75 (ddd,

J = 14.0, 8.4, 5.9 Hz, 1H), 0.87 (s, 9H), 0.03 (s, 3H), 0.02 (s, 3H); 13C NMR (125 MHz, CDCl3) δ

199.6, 145.8, 134.2, 125.0, 118.3, 67.0, 59.5, 50.6, 47.8, 39.5, 37.0, 31.3, 26.1, 21.9, 18.4, -5.1, -

5.2; IR (Neat Film, NaCl): 2953, 2928, 2855, 2817, 1679, 1616, 1448, 1262, 1207, 1121, 1098,

1030, 977, 914 cm-1; HRMS (APCI) m/z: [M+H]+ calc’d for C21H38NO3Si 380.2615; Found

380.2618; [α]25 –9.38 (c 3.48, CHCl3, 99% ee).

Methyl (R)-3-(1-allyl-3-morpholino-2-oxocyclohex-3-en-1-yl)propanoate (2e)

Prepared according to general procedure A using substrate 1e. The product was purified by flash

column chromatography (SiO2, 5–50% EtOAc in hexanes) to yield enaminone 2e (140 mg, 0.456

mmol, 98% yield) as a colorless oil; Rf = 0.31 (20% EtOAc in hexanes); Rf = 0.40 (50% EtOAc in

hexanes); 1H NMR (500 MHz, CDCl3) δ 5.86 (t, J = 4.4 Hz, 1H), 5.73 – 5.65 (m, 1H), 5.07 – 5.02

(m, 2H), 3.77 (td, J = 4.8, 1.1 Hz, 4H), 3.63 (s, 3H), 2.77 – 2.70 (m, 4H), 2.43 (td, J = 5.9, 4.1 Hz,

2H), 2.35 – 2.28 (m, 2H), 2.26 – 2.16 (m, 2H), 1.93 (dddd, J = 14.1, 11.2, 5.4, 1.0 Hz, 1H), 1.86 –

ON

OOTBS

ON

OCO2Me


S7

1.80 (m, 3H); 13C NMR (125 MHz, CDCl3) δ 199.1, 174.0, 145.7, 133.3, 125.0, 118.6, 66.8, 51.6,

50.4, 47.8, 38.9, 30.6, 29.2, 28.8, 21.6; IR (Neat Film, NaCl): 2950, 2853, 1735, 1676, 1617, 1437,

1375, 1263, 1207, 1174, 1119 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C17H26NO4

308.1856; Found 308.1859; [α]25 34.36 (c 16.49, CHCl3, 97% ee).

(R)-6-allyl-2-morpholino-6-(3-oxobutyl)cyclohex-2-en-1-one (2f)

Prepared according to general procedure A using substrate 1f. The product was purified by flash

column chromatography (SiO2, 20–50% EtOAc in hexanes) to yield enaminone 2f (122 mg, 0.419


CDCl3) δ 5.89 (t, J = 4.5 Hz, 1H), 5.69 (ddt, J = 16.6, 10.4, 7.3 Hz, 1H), 5.08 – 5.03 (m, 2H), 3.79

(t, J = 4.7 Hz, 4H), 2.78 (dt, J = 11.6, 4.7 Hz, 2H), 2.70 (dt, J = 11.5, 4.7 Hz, 2H), 2.50 – 2.43 (m,

3H), 2.32 (tdd, J = 9.5, 6.7, 3.9 Hz, 2H), 2.25 (ddt, J = 14.0, 7.6, 1.2 Hz, 1H), 2.12 (s, 3H), 1.89 –

1.75 (m, 4H); 13C NMR (125 MHz, CDCl3) δ 208.6, 199.6, 145.9, 133.6, 118.7, 67.0, 50.7, 47.9,

39.3, 38.4, 31.0, 30.2, 30.2, 28.0, 21.8; IR (Neat Film, NaCl): 2921, 2853, 2814, 1716, 1674, 1615,

1446, 1369, 1262, 1206, 1167, 1119, 978, 922 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for

C17H26NO3 292.1907; Found 292.1914; [α]25 15.98 (c 10.28, CHCl3, 94% ee).

(R)-3-(1-allyl-3-morpholino-2-oxocyclohex-3-en-1-yl)propanenitrile (2g)

Prepared according to general procedure A using substrate 1g. The product was purified by flash

column chromatography (SiO2, 5–50% EtOAc in hexanes) to yield enaminone 2g (217 mg, 0.465



– 3.74 (m, 4H), 2.82 (ddd, J = 11.7, 5.3, 3.4 Hz, 2H), 2.65 (ddd, J = 11.6, 5.9, 3.4 Hz, 2H), 2.54 –

2.24 (m, 6H), 2.07 (ddd, J = 14.0, 10.2, 5.9 Hz, 1H), 1.92 – 1.83 (m, 2H), 1.78 (ddd, J = 14.1, 10.2,

ON

O

MeO

ON

OCN


S8

5.8 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 198.5, 145.7, 132.4, 125.4, 120.1, 119.5, 77.4, 77.2,

76.9, 66.9, 50.5, 48.0, 48.0, 38.8, 30.5, 30.3, 21.6, 12.3; IR (Neat Film, NaCl): 2929, 2854, 1675,

1448, 1263, 1205, 1118, 1000, 924 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C16H23N2O2

275.1754; Found 275.1753; [α]25 29.26 (c 11.02, CHCl3, 94% ee).

(S)-6-allyl-6-benzyl-2-morpholinocyclohex-2-en-1-one (2h)

Prepared according to general procedure A using substrate 1h. The product was purified by flash

column chromatography (SiO2, 5–20% acetone in hexanes) to yield enaminone 2h (217 mg, 0.442

mmol, 95% yield) as a colorless oil; Rf = 0.20 (40% Et2O in hexanes; 1H NMR (500 MHz, CDCl3)

δ 7.25 – 7.17 (m, 3H), 7.15 – 7.09 (m, 2H), 5.88 (t, J = 4.5 Hz, 1H), 5.77 (dddd, J = 16.9, 10.2,

8.0, 6.6 Hz, 1H), 5.11 – 5.02 (m, 2H), 3.80 (dd, J = 5.2, 4.2 Hz, 4H), 3.07 (d, J = 13.5 Hz, 1H),

2.80 – 2.70 (m, 5H), 2.47 – 2.39 (m, 3H), 2.15 (ddt, J = 14.0, 8.0, 1.1 Hz, 1H), 1.80 (dt, J = 13.9,

5.8 Hz, 1H), 1.75 – 1.69 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 199.2, 146.3, 137.6, 134.1, 130.9,

128.1, 126.5, 125.2, 118.6, 67.0, 50.6, 49.9, 40.7, 39.8, 29.8, 21.9; IR (Neat Film, NaCl): 2919,

2854, 2814, 1675, 1614, 1447, 1263, 1205, 1119, 981, 923 cm-1; HRMS (ESI-APCI) m/z: [M+H]+

calc’d for C20H26NO2 312.1958; Found 312.1967; [α]25 –95.78 (c 4.69, CHCl3, 96% ee).

(S)-6-allyl-6-(4-methoxybenzyl)-2-morpholinocyclohex-2-en-1-one (2i)

Prepared according to general procedure A using substrate 1i. The product was purified by flash

column chromatography (SiO2, 5–20% acetone in hexanes) to yield enaminone 2i (159 mg, 0.465

mmol, 99% yield) as a colorless oil; Rf = 0.17 (40% Et2O in hexanes); 1H NMR (500 MHz, CDCl3)

δ 7.05 – 7.02 (m, 2H), 6.79 – 6.76 (m, 2H), 5.87 (t, J = 4.5 Hz, 1H), 5.76 (dddd, J = 16.8, 10.2,

8.0, 6.6 Hz, 1H), 5.09 – 5.01 (m, 2H), 3.80 (t, J = 4.7 Hz, 4H), 3.77 (s, 3H), 3.01 (d, J = 13.8 Hz,

1H), 2.75 (q, J = 4.9 Hz, 4H), 2.66 (d, J = 13.8 Hz, 1H), 2.45 – 2.40 (m, 3H), 2.13 (ddt, J = 13.9,

8.0, 1.1 Hz, 1H), 1.80 (dt, J = 13.8, 5.9 Hz, 1H), 1.71 (dt, J = 13.9, 6.5 Hz, 1H); 13C NMR (125

OBn

NO

ON

OOMe


S9

MHz, CDCl3) δ 199.3, 158.3, 146.3, 134.1, 131.8, 129.5, 125.3, 118.5, 113.5, 67.0, 55.3, 55.2,

50.6, 50.0, 39.9, 39.8, 29.7, 21.9; IR (Neat Film, NaCl): 2930, 2853, 1675, 1611, 1512, 1447, 1263,

1248, 1205, 1178, 1119, 1035, 981, 923 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for

C21H28NO3 342.2064; Found 342.2064; [α]25 –316.96 (c 12.93, CHCl3, 95% ee).

(S)-6-allyl-2-morpholino-6-(4-(trifluoromethyl)benzyl)cyclohex-2-en-1-one (2j)

Prepared according to general procedure A using substrate 1j. The product was purified by flash

column chromatography (SiO2, 5–20% acetone in hexanes) to yield enaminone 2j (154 mg, 0.406

mmol, 87% yield) as a pale yellow oil; Rf = 0.20 (40% Et2O in hexanes); 1H NMR (500 MHz,

CDCl3) δ 7.49 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H), 5.88 (t, J = 4.5 Hz, 1H), 5.77 (dddd, J

= 17.0, 10.1, 7.8, 6.8 Hz, 1H), 5.13 (ddt, J = 10.1, 2.0, 1.0 Hz, 1H), 5.08 (dq, J = 16.9, 1.5 Hz, 1H),

3.84 – 3.77 (m, 4H), 3.20 (d, J = 13.5 Hz, 1H), 2.83 – 2.76 (m, 2H), 2.75 – 2.68 (m, 3H), 2.51 –

2.35 (m, 3H), 2.22 (dd, J = 14.0, 7.8 Hz, 1H), 1.79 (dt, J = 13.8, 5.3 Hz, 1H), 1.70 (ddd, J = 14.0,

8.4, 5.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 198.6, 146.2, 142.1, 133.5, 131.2, 128.7 (q, J =

32.3 Hz), 127.7, 125.5, 125.3, 124.9 (q, J = 3.8 Hz), 123.3, 119.1, 66.9, 50.6, 50.0, 40.4, 39.8,

29.9, 21.8; 19F NMR (470 MHz, CDCl3) δ 62.4; IR (Neat Film, NaCl): 2928, 2855, 2817, 1678,


calc’d for C21H25NO2F 380.1832; Found 380.1835; [α]25 –22.43 (c 8.54, CHCl3, 92% ee).

(S)-6-methyl-6-(2-methylallyl)-2-morpholinocyclohex-2-en-1-one (2k)

Prepared according to general procedure A using substrate 1k. The product was purified by flash

column chromatography (20% EtOAc in hexanes) to afford enaminone 2k as a colorless oil (25

mg, 100 µmol 92% yield); 1H NMR (500 MHz, CDCl3) δ 5.89 (t, J = 4.5 Hz, 1H), 4.82 (dt, J =

2.9, 1.5 Hz, 1H), 4.65 (dq, J = 1.9, 0.9 Hz, 1H), 3.84 – 3.76 (m, 4H), 2.91 (ddd, J = 11.5, 6.1, 3.4

Hz, 2H), 2.64 (ddd, J = 10.2, 4.7, 2.1 Hz, 2H), 2.51 (dd, J = 13.5, 1.1 Hz, 1H), 2.45 – 2.40 (m,

ON

OCF3

OMe

NO

Me


S10

2H), 2.18 (dd, J = 13.6, 0.8 Hz, 1H), 1.90 (ddd, J = 13.7, 7.0, 5.8 Hz, 1H), 1.72 – 1.67 (m, 1H),

1.66 (s, 3H), 1.10 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 199.1, 145.6, 138.9, 125.1, 116.7, 67.0,

50.5, 46.1, 45.6, 32.8, 22.5, 21.8; IR (Neat Film, NaCl) 2931, 2855, 1679, 1263, 1120cm-1; HRMS

(ESI) m/z: [M+H]+ calc’d for C14H21NClO2 270.1261; Found 270.1259; [α]25 –7.5 (c 0.8, CHCl3,

99% ee).

(S)-6-(2-chloroallyl)-6-methyl-2-morpholinocyclohex-2-en-1-one (2l)

Prepared according to general procedure A using substrate 1l. The product was purified by flash

column chromatography (20% EtOAc in hexanes) to afford enaminone 2l as a colorless oil (25

mg, 93 µmol, 58% yield); 1H NMR (500 MHz, CDCl3) δ 5.91 (t, J = 4.5 Hz, 1H), 5.28 (d, J = 0.7

Hz, 1H), 5.15 (s, 1H), 3.84 – 3.78 (m, 4H), 2.93 – 2.88 (m, 2H), 2.85 (dd, J = 14.3, 0.9 Hz, 1H),

2.71 – 2.65 (m, 2H), 2.53 (d, J = 14.3 Hz, 1H), 2.46 (dtd, J = 5.3, 4.3, 2.6 Hz, 2H), 2.03 (ddd, J =

13.6, 7.4, 6.2 Hz, 1H), 1.84 – 1.79 (m, 1H), 1.17 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 199.1,

145.6, 138.9, 125.1, 116.7, 67.0, 50.5, 46.1, 45.6, 32.8, 22.5, 21.8; IR (Neat Film, NaCl) 2931,

2855, 1679, 1263, 1120cm-1; HRMS (ESI) m/z: [M+H]+ calc’d for C14H21NClO2 270.1261; Found

270.1259; [α]25 –7.5 (c 0.8, CHCl3, 99% ee).

(S)-6-allyl-6-methyl-2-(piperidin-1-yl)cyclohex-2-en-1-one (2m)

Prepared according to general procedure A using substrate 1m. The product was purified by flash

column chromatography (SiO2, 10–20% acetone in hexanes) to yield enaminone 2m (107 mg,

0.459 mmol, 99% yield) as a colorless oil; Rf = 0.37 (40% Et2O in hexanes); 1H NMR (500 MHz,


(dt, J = 10.8, 5.2 Hz, 2H), 2.60 (dt, J = 11.2, 5.2 Hz, 2H), 2.45 – 2.30 (m, 3H), 2.21 (dd, J = 13.8,

7.6 Hz, 1H), 1.84 (dt, J = 12.7, 6.0 Hz, 1H), 1.72 – 1.61 (m, 5H), 1.55 – 1.41 (m, 2H), 1.07 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 200.8, 147.0, 134.4, 124.6, 118.0, 51.6, 45.5, 41.4, 33.4, 26.1, 24.5,

OMe

NO

Cl

OMe

N


S11

22.1, 22.0; IR (Neat Film, NaCl): 2931, 2852, 2798, 1680, 1613, 1451, 1384, 1217, 1093, 996,

913 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C15H24NO 234.1852; Found 234.1847; [α]25

–172.28 (c 6.64, CHCl3, 99% ee).

(S)-6-allyl-3,6-dimethyl-2-morpholinocyclohex-2-en-1-one (2n)

Prepared according to general procedure A using substrate 1n. The product was purified by flash

column chromatography (SiO2, 10–20% Et2O in hexanes) to yield enaminone 2n (60.2 mg, 0.241

mmol, 52% yield) as a pale yellow oil; Rf = 0.35 (29% Et2O in hexanes); 1H NMR (500 MHz,

CDCl3) δ 5.72 (ddt, J = 16.8, 10.2, 7.4 Hz, 1H), 5.06 – 5.01 (m, 2H), 3.71 – 3.66 (m, 4H), 2.95 –

2.87 (m, 4H), 2.42 – 2.30 (m, 2H), 2.29 – 2.24 (m, 1H), 2.20 – 2.16 (m, 1H), 1.99 (s, 2H), 1.82

(ddd, J = 13.7, 6.4, 5.6 Hz, 1H), 1.67 (ddd, J = 13.6, 7.2, 5.6 Hz, 1H), 1.03 (s, 3H).; 13C NMR (125

MHz, CDCl3) δ 202.0, 153.4, 141.6, 134.3, 118.0, 77.4, 77.2, 76.9, 68.1, 50.6, 44.9, 41.3, 32.5,

28.7, 21.8, 19.8; IR (Neat Film, NaCl): 2912, 2847, 1664, 1452, 1374, 1294, 1259, 1190, 1114,

988, 911 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C15H24NO2 250.1802; Found 250.1803;

[α]25 30.71 (c 3.52, CHCl3, 90% ee).

(S)-3-allyl-3-methyl-[1,1'-bi(cyclohexan)]-6-en-2-one (2o)

Prepared according to general procedure A using substrate 1o. The product was purified by flash

column chromatography (SiO2, 5% Et2O in hexanes) to yield enaminone 2o (11 mg, 47 µmol, 93%

yield) as a pale yellow oil; Rf = 0.43 (5% Et2O in hexanes); 1H NMR (500 MHz, CDCl3) δ 6.50

(td, J = 4.1, 1.0 Hz, 1H), 5.73 (ddt, J = 16.8, 10.3, 7.4 Hz, 1H), 5.07 – 5.01 (m, 2H), 2.55 – 2.48

(m, 1H), 2.41 – 2.27 (m, 3H), 2.17 (ddt, J = 13.7, 7.6, 1.2 Hz, 1H), 1.94 – 1.79 (m, 1H), 1.77 –

1.60 (m, 6H), 1.34 (qt, J = 12.5, 3.2 Hz, 2H), 1.20 – 1.11 (m, 1H), 1.09 – 0.96 (m, 5H); 13C NMR

(125 MHz, CDCl3) δ 203.2, 143.4, 140.5, 134.5, 117.9, 44.4, 41.4, 36.4, 33.3, 33.1, 32.7, 26.9,

26.9, 26.6, 23.0, 22.0; IR (Neat Film, NaCl): 2922, 2849, 1669, 1448, 1175, 911 cm-1; HRMS

OMe

NO

Me

OMe


S12

(ESI-APCI) m/z: [M+H]+ calc’d for C16H25O 233.1900; Found 233.1892; [α]25 –1.176 (c 0.43,

CHCl3, 72% ee).

(R)-5-allyl-5-methyl-2-morpholinocyclopent-2-en-1-one (2p)

Prepared according to general procedure A using substrate 1p. The product was purified by flash

column chromatography (SiO2, 10% acetone in hexanes) to yield enaminone 2p (97 mg, 0.438

mmol, 94% yield) as a pale tan oil; Rf = 0.23 (20% acetone in hexanes); 1H NMR (500 MHz,

CDCl3) δ 6.54 – 6.48 (m, 1H), 5.85 (ddt, J = 17.2, 10.5, 5.6 Hz, 1H), 5.27 (dq, J = 17.2, 1.6 Hz,

1H), 5.20 (dq, J = 10.5, 1.3 Hz, 1H), 4.64 – 4.52 (m, 2H), 2.59 – 2.50 (m, 1H), 2.50 – 2.40 (m,

2H), 2.38 – 2.26 (m, 1H), 1.92 – 1.81 (m, 1H), 1.80 – 1.60 (m, 5H), 1.55 (s, 1H), 1.40 – 1.22 (m,

5H), 1.21 – 1.04 (m, 2H), 1.04 – 0.92 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 209.1, 149.3, 133.9,

131.6, 118.2, 66.7, 48.6, 46.8, 42.7, 37.2, 24.0; IR (Neat Film, NaCl): 2960, 2913, 2853, 1703,

1611, 1451, 1380, 1261, 1120, 1020, 993 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for

C13H20NO2 222.1489; Found 222.1490; [α]25 –263.53 (c 6.76, CHCl3, 83% ee).

Large Scale Palladium-Catalyzed Allylic Alkylation Reactions

An oven-dried round bottom flask charged with a stir bar was cycled into a glove box under an

atmosphere of N2. To the flask were then added Pd2(dmdba)3 (78.5 mg, 61.5 µmol, 0.5 mol %)

and (S)-t-BuPHOX ligand (62.0 mg, 0.160 mmol, 1.3 mol %). The flask was then sealed with a

rubber septum and removed from the glovebox. A nitrogen line was then affixed and remained

throughout the course of the reaction. EtOAc (32 mL) was then added to the flask and the catalyst

mixture was let stir at 40 ºC in a pre-heated oil bath (ca. 30 minutes). At this point, a solution of

allyl b-ketoester (1, 3.44 g, 12.3 mmol, 1.00 equiv) in EtOAc (5.3 mL, final concentration of 0.33

M with respect to 1) was added. The reaction mixture was stirred at 40 °C in a pre-heated oil bath

O

NO Me

O

OMe

O Pd2(dmdba)3 (0.5 mol%)

EtOAc, 40 ºC, 9 h

OMe

N NOO

(S)-2a(±)-1a

(S)-t-BuPHOX (1.3 mol%)

93% yield, 98% ee[12.3 mmol scale]


S13

until the reaction was complete as indicated by TLC analysis (20% acetone/hexanes). The reaction

mixture was concentrated in vacuo and the crude material was purified by flash column

chromatography (SiO2, 5–10% acetone in hexanes) to yield enaminone 2a as a colorless oil (2.69

g, 11.4 mmol, 93% yield, 98% ee). Rf = 0.22 (20% acetone in hexanes). Characterization data

provided above.


S14

Determination of Enantiomeric Excess

compound assay methodand conditions

retention timeof major isomer

(min)

retention timeof minor isomer

(min)%eeentry

1 SFC, 5% iPrOH in CO22.5 mL/min, AD-H col.

5.91 5.62 99

OMe

NO

2a

2 HPLC, 5% iPrOH in hexanes1 mL/min, OD-H col.

8.77 9.14 98

OEt

NO

2b

3 SFC, 3% iPrOH in CO22.5 mL/min, AD-H col.

4.45 3.95 99

ON

O

2c

4 SFC, 2% iPrOH in CO22.5 mL/min, OD-H col.

3.59 4.10 99

ON

O

2d

5 SFC, 10% MeOH in CO25 mL/min, AD-H col.

3.43 1.75 97

ON

O

2e

6 SFC, 10% iPrOH in CO25 mL/min, AD-H col.

2.27 1.81 94

ON

O

2f

CO2Me

OTBS

OTBS

MeO


S15



(min)


(min)%eeentry

7 SFC, 10% iPrOH in CO25 mL/min, AD-H col.

2.19 2.40 94

ON

O

2g

8 SFC, 8% MeOH in CO25 mL/min, OJ-H col.

2.41 2.63 96

OBn

NO

2h

9 SFC, 5% MeOH in CO25 mL/min, OD-H col.

6.29 6.99 95

2i

CN

ON

OOMe

10 SFC, 5% iPrOH in CO25 mL/min, OJ-H col.

3.88 4.52 92

2j

ON

OCF3

13 HPLC, 3% EtOH in hexanes1 mL/min, AD col.

9.01 9.84 99

OMe

N

2m

12 SFC, 5% iPrOH in hexanes2.5 mL/min, OD-H col.

10.2 9.4 99

OMe

NO

2l

11 SFC, 5% iPrOH in hexanes2.5 mL/min, AD-H col.

8.6 7.8 99

OMe

NO

2k

Me

Cl


S16



(min)


(min)%eeentry

14 HPLC, 1.5% iPrOH in hexanes1 mL/min, OD-H col.

8.99 8.40 90

ON

O

2n

15

HPLC, 3% iPrOH in hexanes1 mL/min, OD-H col.

14.22 17.7 83

2p

O

NO

16

SFC, 10% iPrOH in CO22.5 mL/min, AD col.

3.08 3.52 72

O

2o


S17

Synthesis of Allylic Alkylation Substrates

Allyl 1-methyl-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1a)

General procedure B: To a solution of diisopropylamine (1.77 mL, 12.7 mmol, 1.29 equiv) in

THF (50 mL) at 0 ºC was dropwise added a solution of n-butyllithium in hexanes (5.51 mL, 2.19

M, 12.1 mmol, 1.22 equiv). The solution was stirred for 30 minutes at 0 ºC, then cooled to –78 °C.

To the reaction was then dropwise added a solution of 2-morpholinocyclohex-2-en-1-one3 (1.79

g, 9.88 mmol, 1.00 equiv) in THF (8.0 mL, 1.2 M) at –78 ºC. The mixture was stirred for 90

minutes, quenched with saturated aqueous NH4Cl (50 mL) and water (50 mL), diluted with EtOAc

(100 mL) and the phases were separated. The aqueous portion was again extracted with EtOAc

(100 mL). The combined organic fractions were dried over Na2SO4, filtered, and concentrated in

vacuo to yield the crude b-ketoester as a pale-yellow oil [confirmed to be the desired acylated

compound by crude 1H NMR analysis]. A portion (531 mg, 2.00 mmol, 1.00 equiv) of this crude

intermediate was taken up in acetone (10 mL, 0.20 M). Potassium carbonate (553 mg, 4.00 mmol,

2.0 equiv) and MeI (149 µL, 2.40 mmol, 1.20 equiv) were then added. The reaction mixture was

heated to 50 °C for 10 hours. Upon completion, the reaction mixture was cooled to room

temperature, filtered using a fritted funnel, and rinsed with 10 mL Et2O. The filtrate was

concentrated in vacuo and purified by flash column chromatography (SiO2, 4–8% acetone in

hexanes) to yield enaminone 1a (347 mg, 1.24 mmol, 62% yield over 2 steps) as a pale yellow oil;

Rf = 0.45 (50% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) δ 5.87 – 5.73 (m, 2H), 5.27 (dq,

J = 17.2, 1.5 Hz, 1H), 5.21 (dq, J = 10.4, 1.2 Hz, 1H), 4.61 – 4.53 (m, 2H), 3.81 (ddd, J = 11.3,

6.3, 3.1 Hz, 2H), 3.76 (ddd, J = 11.3, 6.4, 2.9 Hz, 2H), 2.99 – 2.96 (m, 2H), 2.63 – 2.55 (m, 2H),

2.54 – 2.49 (m, 1H), 2.47 – 2.42 (m, 1H), 2.36 (dtd, J = 19.1, 5.4, 3.1 Hz, 1H), 1.84 (ddd, J = 13.6,

9.7, 5.6 Hz, 1H), 1.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 193.9, 172.4, 146.4, 131.6, 124.0

118.9, 66.9, 66.0, 54.2, 50.0, 33.3, 22.7, 20.6; IR (Neat Film, NaCl): 3447 (broad), 2955, 2855,

2067, 1733, 1695, 1617, 1450, 1378, 1264, 1248, 1222, 1175, 1145, 1119, 1020, 992, 948 cm-1;

HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C15H22NO4 280.1543; Found 280.1554.

ON

O ON

O

1a

MeO

O1) LDA, THF, –78 ºC;then, allyl chloroformate

2) MeI, K2CO3,acetone, 50 ºC


S18

Allyl 1-ethyl-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1b)

Prepared according to general procedure B using ethyl iodide. The product was purified by flash

column chromatography (SiO2, 4–20% EtOAc in hexanes) to yield enaminone 1b (468 mg, 1.60

mmol, 74% yield over 2 steps) as a pale-yellow oil. Rf = 0.53 (50% EtOAc in hexanes); 1H NMR

(400 MHz, CDCl3) δ 5.83 (ddt, J = 17.2, 10.4, 5.8 Hz, 1H), 5.73 (ddd, J = 4.5, 3.5, 1.2 Hz, 1H),

5.27 (dq, J = 17.2, 1.5 Hz, 1H), 5.21 (dq, J = 10.4, 1.2 Hz, 1H), 4.57 (dq, J = 5.8, 1.5 Hz, 2H), 3.80

(ddd, J = 11.4, 6.4, 3.1 Hz, 1H), 3.75 (ddd, J = 11.3, 6.3, 3.0 Hz, 1H), 2.97 – 2.93 (m, 2H), 2.60 –

2.52 (m, 3H), 2.44 – 2.33 (m, 2H), 1.95 (dq, J = 13.9, 7.5 Hz, 1H), 1.86 (ddd, J = 13.0, 9.6, 5.4

Hz, 1H), 1.78 (dq, J = 13.9, 7.5 Hz, 1H), 0.92 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ

193.6, 171.3, 146.8, 131.7, 128.2, 123.5, 119.0, 67.0, 65.8, 57.9, 50.0, 29.8, 27.0, 22.6, 9.1; IR

(Neat Film, NaCl): 2961, 2855, 1732, 1694, 1617, 1448, 1378, 1300, 1264, 1220, 1167, 1120, 957,

934 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C16H24NO4 294.1700; Found 294.1690.

Allyl 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3-morpholino-2-oxocyclohex-3-ene-1-

carboxylate (1d)

Synthesized according to general procedure B using (2-bromoethoxy)(tert-butyl)dimethylsilane

and cesium carbonate in place of potassium carbonate. The product was purified by flash column

chromatography (SiO2, 5–20% EtOAc in hexanes) to yield enaminone 1d (184 mg, 0.434 mmol,

49% yield over 2 steps) as a pale tan oil; Rf = 0.23 (20% EtOAc in hexanes); 1H NMR (500 MHz,

CDCl3) δ 5.83 (ddt, J = 17.2, 10.4, 5.9 Hz, 1H), 5.78 – 5.70 (m, 1H), 5.27 (dq, J = 17.2, 1.5 Hz,

1H), 5.21 (dq, J = 10.5, 1.2 Hz, 1H), 4.60 – 4.52 (m, 2H), 3.82 – 3.66 (m, 6H), 2.96 – 2.29 (m,

2H), 2.59 – 2.46 (m, 4H), 2.38 (dtd, J = 19.0, 5.5, 2.9 Hz, 1H), 2.14 (ddd, J = 13.8, 7.6, 6.1 Hz,

1H), 1.98 – 1.89 (m, 2H), 0.86 (s, 9H), 0.02 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 193.3, 171.0,

146.5, 131.7, 123.7, 119.1, 66.9, 66.0, 59.7, 56.5, 50.0, 36.8, 30.8, 26.0, 22.7, 18.4, -5.2; IR (Neat

ON

OEt

O

O

ON

OO

O

OTBS


S19

Film, NaCl): 2955, 2928, 2855, 1733, 1695, 1616, 1447, 1378, 1263, 1209, 1120, 1100, 981, 935

cm-1; HRMS (ESI) m/z: [M+H]+ calc’d for C22H38NO5Si 424.2514; Found 424.2521.

Allyl 1-(3-methoxy-3-oxopropyl)-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1e)

Prepared according to general procedure B using methyl acrylate. The product was purified by

flash column chromatography (SiO2, 10–20% acetone in hexanes) to yield enaminone 1e (223 mg,

0.635 mmol, 58% yield over 2 steps) as a yellow oil; Rf = 0.42 (50% EtOAc in hexanes); 1H NMR

(500 MHz, CDCl3) δ 5.80 (ddt, J = 17.3, 10.4, 5.9 Hz, 1H), 5.73 – 5.67 (m, 1H), 5.25 (dd, J = 17.2,

1.5 Hz, 1H), 5.19 (dd, J = 10.4, 1.3 Hz, 1H), 4.60 – 4.48 (m, 2H), 3.76 (ddd, J = 11.3, 6.4, 3.1 Hz,

2H), 3.71 (ddd, J = 11.4, 6.4, 3.0 Hz, 2H), 2.92 (ddd, J = 11.7, 6.3, 3.0 Hz, 2H), 2.56 – 2.41 (m,

4H), 2.40 – 2.27 (m, 3H), 2.18 (ddd, J = 14.0, 10.6, 5.6 Hz, 1H), 2.04 (ddd, J = 14.1, 10.8, 5.4 Hz,

1H), 1.84 (ddd, J = 14.5, 9.8, 6.1 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 193.1, 173.4, 170.9,

146.6, 131.4, 123.3, 119.2, 66.8, 66.1, 56.7, 51.7, 49.8, 30.7, 29.5, 28.9, 22.5; IR (Neat Film,

NaCl): 2953, 2854, 2820, 1733, 1694, 1616, 1447, 1377, 1264, 1209, 1177, 1120, 983, 957 cm-1;

HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C18H26NO6 352.1755; Found 352.1771.

Allyl 3-morpholino-2-oxo-1-(3-oxobutyl)cyclohex-3-ene-1-carboxylate (1f)

Prepared according to general procedure B using methyl vinyl ketone. The product was purified

by flash column chromatography (SiO2, 20–65% EtOAc in hexanes) to yield enaminone 1f (537

mg, 1.60 mmol, 74% yield over 2 steps) as a pale yellow oil that solidified on storage at –20 °C;

Rf = 0.28 (50% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) δ 5.81 (ddt, J = 17.2, 10.4, 5.9

Hz, 1H), 5.75 – 5.69 (m, 1H), 5.26 (dq, J = 17.2, 1.5 Hz, 1H), 5.20 (dq, J = 10.4, 1.2 Hz, 1H), 4.59

– 4.49 (m, 2H), 3.77 (ddd, J = 11.4, 6.4, 3.1 Hz, 2H), 3.72 (ddd, J = 11.3, 6.4, 3.0 Hz, 2H), 2.93

(ddd, J = 11.9, 6.3, 3.1 Hz, 2H), 2.60 (ddd, J = 17.7, 10.3, 5.5 Hz, 1H), 2.57 – 2.49 (m, 2H), 2.52

ON

OO

O

CO2Me

ON

OO

O

MeO


S20

– 2.39 (m, 2H), 2.41 – 2.35 (m, 1H), 2.36 – 2.32 (m, 1H), 2.10 (s, 4H), 1.98 (ddd, J = 14.1, 10.3,

5.3 Hz, 1H), 1.84 (ddd, J = 9.7, 8.1, 4.9 Hz, 1H);13C NMR (125 MHz, CDCl3) δ 207.7, 193.4,

171.2, 146.7, 131.4, 123.5, 119.3, 66.9, 66.0, 56.7, 49.9, 38.9, 31.1, 30.0, 30.0, 27.7, 22.6; IR (Neat

Film, NaCl): 2956, 2854, 1721, 1615, 1447, 1372, 1299, 1264, 1209, 1179, 1120, 1095, 982, 939

cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C18H26NO5 336.1805; Found 336.1803.

Allyl 1-(2-cyanoethyl)-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1g)

Prepared according to general procedure B using acrylonitrile. The product was purified by flash

column chromatography (SiO2, 10–20% acetone in hexanes) to yield enaminone 1g (247 mg, 0.776

mmol, 71% yield over 2 steps) as a colorless oil; Rf = 0.29 (50% EtOAc in hexanes); 1H NMR

(500 MHz, CDCl3) δ 5.83 (ddt, J = 16.5, 10.4, 6.0 Hz, 1H), 5.76 (t, J = 4.3 Hz, 1H), 5.29 (dq, J =

17.1, 1.4 Hz, 1H), 5.25 (dq, J = 10.4, 1.2 Hz, 1H), 4.64 – 4.56 (m, 2H), 3.79 (ddd, J = 11.4, 6.4,

3.1 Hz, 2H), 3.73 (ddd, J = 11.4, 6.4, 3.0 Hz, 2H), 2.95 (ddd, J = 11.8, 6.4, 3.1 Hz, 2H), 2.60 –

2.49 (m, 4H), 2.45 – 2.38 (m, 3H), 2.21 (ddd, J = 14.0, 9.5, 5.9 Hz, 1H), 2.07 (ddd, J = 14.0, 9.5,

6.3 Hz, 1H), 1.92 – 1.86 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 192.7, 170.2, 146.6, 131.1, 123.7,

119.9, 119.4, 66.8, 66.5, 56.5, 49.8, 31.1, 30.2, 22.5, 13.3; IR (Neat Film, NaCl): 2956, 2854, 2247,


calc’d for C17H23N2O4 319.1652, Found 319.1668.

Allyl 1-benzyl-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1h)

Prepared according to general procedure B using benzyl bromide. The product was purified by

flash column chromatography (SiO2, 4–10% acetone in hexanes) to yield enaminone 1h (498 mg,

1.40 mmol, 65% yield over 2 steps) as a colorless oil; Rf = 0.23 (20% acetone in hexanes); 1H

NMR (500 MHz, CDCl3) δ 7.26 – 7.19 (m, 3H), 7.19 – 7.14 (m, 2H), 5.79 (ddt, J = 17.3, 10.4, 5.9

Hz, 1H), 5.71 (ddd, J = 4.5, 3.3, 1.3 Hz, 1H), 5.26 (dq, J = 17.2, 1.5 Hz, 1H), 5.21 (dq, J = 10.4,

ON

OO

O

CN

ON

OBn

O

O


S21

1.2 Hz, 1H), 3.82 (ddd, J = 11.4, 6.4, 3.0 Hz, 2H), 3.77 (ddd, J = 11.3, 6.4, 2.9 Hz, 2H), 3.26 (d, J

= 13.7 Hz, 1H), 3.14 (d, J = 13.7 Hz, 1H), 2.96 (ddd, J = 11.7, 6.4, 3.0 Hz, 2H), 2.58 – 2.51 (m,

3H), 2.40 – 2.27 (m, 2H), 1.80 – 1.74 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 192.6, 170.5, 146.8,

136.4, 131.5, 130.7, 128.2, 128.2, 126.9, 123.9, 119.2, 66.9, 66.1, 58.7, 49.9, 39.8, 30.0, 22.7; IR

(Neat Film, NaCl): 2956, 2854, 1734, 1691, 1615, 1447, 1377, 1263, 1207, 1176, 1118, 1085, 980,

937 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C21H26NO4 356.1856; Found 356.1857.

Allyl 1-(4-methoxybenzyl)-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1i)

Prepared according to general procedure B using p-methoxybenzyl chloride. The product was

purified by flash column chromatography (SiO2, 5–10% acetone in hexanes) to yield enaminone

1i (86 mg, 0.22 mmol, 21% yield over 2 steps) as a pale yellow oil; Rf = 0.72 (20% Et2O in

CH2Cl2); 1H NMR (500 MHz, CDCl3) δ 7.09 (d, J = 8.6 Hz, 2H), 6.78 (d, J = 8.7 Hz, 2H), 5.80

(ddt, J = 17.2, 10.4, 5.9 Hz, 1H), 5.72 (t, J = 4.3 Hz, 1H), 5.26 (dq, J = 17.2, 1.5 Hz, 1H), 5.22 (dq,

J = 10.4, 1.2 Hz, 1H), 4.53 (dq, J = 5.9, 1.4 Hz, 2H), 3.82 (ddd, J = 11.4, 6.4, 3.0 Hz, 2H), 3.79 –

3.75 (m, 5H), 3.19 (d, J = 13.9 Hz, 1H), 3.10 (d, J = 13.9 Hz, 1H), 2.96 (ddd, J = 11.6, 6.5, 3.1 Hz,

2H), 2.59 – 2.49 (m, 3H), 2.38 – 2.28 (m, 2H), 1.76 (ddd, J = 14.2, 10.4, 6.2 Hz, 1H); 13C NMR

(125 MHz, CDCl3) δ 192.7, 170.6, 158.6, 146.8, 131.7, 131.6, 128.3, 123.9, 119.2, 113.6, 66.9,

66.1, 58.8, 55.3, 50.0, 38.9, 30.0, 22.7; IR (Neat Film, NaCl): 2954, 2853, 1734, 1691, 1612, 1512,

1445, 1262, 1248, 1208, 1178, 1119, 1034, 981, 938 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d

for C22H28NO5 386.1962; found 386.1948.

ON

OO

O

OMe


S22

Allyl 3-morpholino-2-oxo-1-(4-(trifluoromethyl)benzyl)cyclohex-3-ene-1-carboxylate (1j)

Prepared according to general procedure B using p-trifluoromethylbenzyl bromide. The product

was purified by flash column chromatography (SiO2, 2:1:1–2:2:1 hexanes:DCM:acetone) to yield

enaminone 1j (276 mg, 0.652 mmol, 60% yield over 2 steps) as a pale yellow oil; Rf = 0.78 (20%

Et2O in CH2Cl2); 1H NMR (500 MHz, CDCl3) δ 7.50 (d, J = 7.8 Hz, 2H), 7.32 (d, J = 7.5 Hz, 2H),

5.80 – 5.69 (m, 2H), 5.28 – 5.18 (m, 2H), 4.51 (dq, J = 5.9, 1.5 Hz, 2H), 3.83 (ddd, J = 11.4, 6.4,

3.0 Hz, 2H), 3.77 (ddd, J = 11.4, 6.4, 2.9 Hz, 2H), 3.29 (d, J = 13.6 Hz, 1H), 3.19 (d, J = 13.6 Hz,

1H), 2.97 (ddd, J = 11.8, 6.4, 3.0 Hz, 2H), 2.59 – 2.50 (m, 3H), 2.38 – 2.32 (m, 2H), 1.78 (ddd, J

= 14.2, 10.4, 6.2 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 192.3, 170.3, 146.8, 140.7, 131.3, 131.2,

129.2 (q, J = 32.4 Hz), 125.3, 125.1 (q, J = 3.8 Hz), 123.8, 123.3, 119.5, 66.9, 66.3, 58.7, 49.9,

39.6, 30.4, 22.7; 19F NMR (470 MHz, CDCl3) δ 62.5; IR (Neat Film, NaCl): 2957, 2855, 1732,

1694, 1618, 1447, 1418, 1323, 1263, 1209, 1162, 1116, 1066, 1019, 981, 938 cm-1; HRMS (ESI-

APCI) m/z: [M+H]+ calc’d for C22H25NO4F 424.1730; Found 424.1737.

2-Methylallyl 1-methyl-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1k)

Prepared according to general procedure B using 2-methylallyl cyanoformate (SI3, vida infra).

The product was purified by flash column chromatography (20–24% EtOAc/hexanes) to yield

enaminone 1k as a slightly yellow oil (808 mg, 2.76 mmol, 56% yield over 2 steps). 1H NMR (500

MHz, CDCl3) δ 5.79 (ddd, J = 4.9, 3.5, 1.1 Hz, 1H), 4.92 (d, J = 10.9 Hz, 2H), 4.50 (d, J = 12.7

Hz, 1H), 3.82 (ddd, J = 11.4, 6.4, 3.0 Hz, 2H), 3.77 (ddd, J = 11.3, 6.4, 2.9 Hz, 2H), 3.00 (ddd, J

= 11.1, 4.9, 2.0 Hz, 2H), 2.61 – 2.51 (m, 3H), 2.47 (dddd, J = 13.5, 5.1, 3.1, 1.2 Hz, 1H), 2.39 (dtd,

J = 19.0, 5.4, 3.1 Hz, 1H), 1.87 (ddd, J = 13.5, 9.7, 5.6 Hz, 1H), 1.71 (s, 3H), 1.41 (s, 3H); 13C

NMR (125 MHz, CDCl3) δ 193.7, 172.3, 146.3, 139.4, 123.9, 113.5, 68.4, 66.8, 54.1, 49.8, 33.3,

ON

OO

O

CF3

ON

OMe

O

O

Me


S23

22.6, 20.6, 19.5; IR (Neat Film, NaCl) 2936, 2854, 1737, 1694, 1615, 1450, 1175, 1119, cm-1;

HRMS (ESI) m/z: [M+H]+ calc’d for C16H24NO4 294.1700; found 294.1705.

2-Chloroallyl 1-methyl-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1l)

Prepared according to general procedure B using 2-chloroallyl cyanoformate (SI1, vida infra). The

product was purified by flash column chromatography (20–22% EtOAc/hexanes) to yield

enaminone 1l as a slightly yellow oil (470 mg, 1.50 mmol, 37% yield over 2 steps); 1H NMR (500

MHz, CDCl3) δ 5.82 (ddd, J = 5.0, 3.6, 1.0 Hz, 1H), 5.44 (dt, J = 1.8, 1.2 Hz, 1H), 5.40 (d, J = 1.7

Hz, 1H), 4.72 (ddd, J = 13.5, 1.2, 0.6 Hz, 1H), 4.63 (ddd, J = 13.5, 1.2, 0.6 Hz, 1H), 3.83 (ddd, J

= 11.4, 6.4, 3.1 Hz, 2H), 3.78 (ddd, J = 11.3, 6.3, 3.0 Hz, 2H), 3.00 (ddd, J = 9.6, 6.2, 3.1 Hz, 2H),

2.65 – 2.50 (m, 3H), 2.51 – 2.46 (m, 1H), 2.41 (dtd, J = 19.0, 5.4, 3.3 Hz, 1H), 1.89 (ddd, J = 13.5,

9.4, 5.5 Hz, 1H), 1.43 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 193.5, 171.9, 146.3, 135.4, 124.3,

115.8, 66.9, 66.7, 54.2, 49.9, 33.3, 22.6, 20.6; IR (Neat Film, NaCl) 2954, 2855, 1741, 1693, 1450,

1377 cm-1; HRMS (ESI) m/z: [M+H]+ calc’d for C15H21NClO4 314.1154; Found 314.1156.

Allyl 1-methyl-2-oxo-3-(piperidin-1-yl)cyclohex-3-ene-1-carboxylate (1m)

Prepared according to general procedure B using 2-(piperidin-1-yl)cyclohex-2-en-1-one.3 The

product was purified by flash column chromatography (SiO2, 8–16% Et2O in hexanes) to yield

enaminone 1m (427 mg, 1.54 mmol, 59% yield over 2 steps) as a pale tan oil; Rf = 0.32 (40% Et2O

in hexanes; 1H NMR (500 MHz, CDCl3) δ 5.77 (ddt, J = 17.2, 10.4, 5.7 Hz, 1H), 5.69 (ddd, J =

4.8, 3.5, 1.0 Hz, 1H), 5.21 (dd, J = 17.2, 1.5 Hz, 1H), 5.14 (dd, J = 10.5, 1.3 Hz, 1H), 4.55 – 4.47

(m, 2H), 2.81 (ddd, J = 11.2, 7.2, 3.6 Hz, 2H), 2.46 (dddt, J = 18.1, 9.2, 5.4, 3.3 Hz, 3H), 2.37

(dddd, J = 13.6, 5.1, 3.2, 1.1 Hz, 1H), 2.29 (dtd, J = 19.0, 5.4, 3.2 Hz, 1H), 1.77 (ddd, J = 13.4,

9.6, 5.6 Hz, 1H), 1.65 – 1.53 (m, 4H), 1.46 – 1.41 (m, 2H), 1.31 (s, 3H); 13C NMR (125 MHz,

CDCl3) δ 194.0, 172.3, 147.7, 131.8, 123.5, 118.7, 65.8, 54.2, 51.0, 33.4, 26.0, 24.5, 22.8, 20.7;

ON

OMe

O

O

Cl

ON

MeO

O


S24

IR (Neat Film, NaCl): 2934, 2851, 2802, 1735, 1696, 1613, 1452, 1387, 1248, 1222, 1175, 1110,

987, 943 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C16H24NO3 278.1751; Found 278.1747.

Allyl 1,4-dimethyl-3-morpholino-2-oxocyclohex-3-ene-1-carboxylate (1n)

Prepared according to general procedure B using 3-methyl-2-morpholinocyclohex-2-en-1-one.4

The product was purified by flash column chromatography (SiO2, 5–20% EtOAc in hexanes) to

yield enaminone 1n (772 mg, 2.63 mmol, 74% yield over 2 steps) as a pale yellow oil; Rf = 0.34

(20% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) δ 5.82 (ddt, J = 17.2, 10.5, 5.6 Hz, 1H),

5.24 (dq, J = 17.2, 1.6 Hz, 1H), 5.18 (dq, J = 10.4, 1.3 Hz, 1H), 4.58 (ddt, J = 13.3, 5.5, 1.5 Hz,

1H), 4.53 (ddt, J = 13.3, 5.6, 1.4 Hz, 1H), 3.70 – 3.63 (m, 4H), 2.99 – 2.90 (m, 2H), 2.90 – 2.81

(m, 2H), 2.49 (dddd, J = 19.2, 9.8, 5.3, 1.1 Hz, 1H), 2.38 (ddd, J = 13.6, 5.2, 3.6 Hz, 1H), 2.28

(dddd, J = 19.1, 5.6, 3.6, 0.9 Hz, 1H), 1.95 (s, 3H), 1.79 (ddd, J = 13.6, 9.7, 5.5 Hz, 1H), 1.33 (s,

3H); 13C NMR (125 MHz, CDCl3) δ 194.8, 172.5, 153.2, 142.1, 131.8, 118.4, 67.9, 65.7, 53.9,

50.3, 32.3, 29.2, 20.5, 19.6; IR (Neat Film, NaCl): 2935, 2848, 1734, 1680, 1452, 1375, 1259,

1190, 1168, 1114, 1070, 989 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C16H24NO4 294.1700; Found 294.1701.

Allyl 3-methyl-2-oxo-[1,1'-bi(cyclohexan)]-6-ene-3-carboxylate (1o)

Prepared according to general procedure B using [1,1'-bi(cyclohexan)]-6-en-2-one.5 The product

was purified by flash column chromatography (SiO2, 10% Et2O in DCM) to yield enone 1o (51

mg, 0.185 mmol, 30% yield over 2 steps) as a pale yellow oil; Rf = 0.33 (10% Et2O in hexanes); 1H NMR (500 MHz, CDCl3) δ 6.51 (dt, J = 4.4, 2.2 Hz, 1H), 5.84 (ddt, J = 17.2, 10.5, 5.6 Hz, 1H),

5.26 (dd, J = 17.2, 1.5 Hz, 1H), 5.20 (dd, J = 10.4, 1.4 Hz, 1H), 4.57 (tt, J = 5.5, 1.4 Hz, 2H), 2.57

– 2.42 (m, 3H), 2.35 – 2.27 (m, 1H), 1.89 – 1.80 (m, 1H), 1.77 – 1.61 (m, 6H), 1.37 (s, 3H), 1.36

– 1.29 (m, 2H), 1.19 – 1.07 (m, 2H), 1.02 – 0.93 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 196.8,

ON

OMe

O

O

Me

OMe

O

O


S25

172.8, 144.2, 140.9, 131.9, 118.5, 65.8, 53.6, 36.8, 33.4, 32.8, 32.3, 26.9, 26.8, 26.5, 23.6, 20.6;

IR (Neat Film, NaCl): 2925, 2851, 1734, 1684, 1379, 1351, 1299, 1247, 1167, 1110, 981, 935 cm-

1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C17H25O3 277.1798; Found 277.1791.

Allyl 1-methyl-3-morpholino-2-oxocyclopent-3-ene-1-carboxylate (1p)

Prepared according to general procedure B using 2-morpholinocyclopent-2-en-1-one.6 The

product was purified by flash column chromatography (SiO2, 2–10% EtOAc in DCM) to yield

enaminone 1p (151 mg, 0.570 mmol, 21% yield over 2 steps) as a pale orange oil; Rf = 0.33 (10%

EtOAc in CH2Cl2); 1H NMR (500 MHz, CDCl3) δ 6.39 (t, J = 3.2 Hz, 1H), 5.85 (ddt, J = 17.2,

10.5, 5.5 Hz, 1H), 5.27 (dq, J = 17.2, 1.6 Hz, 1H), 5.20 (dq, J = 10.5, 1.3 Hz, 1H), 4.58 (dt, J =

5.5, 1.5 Hz, 2H), 3.79 (ddd, J = 5.2, 3.9, 0.8 Hz, 4H), 3.19 – 3.15 (m, 2H), 3.05 – 3.01 (m, 3H),

2.38 (dd, J = 18.2, 3.2 Hz, 1H), 1.42 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 201.8, 171.6, 148.6,

131.9, 131.8, 118.3, 66.6, 65.9, 54.1, 48.5, 37.8, 21.1; IR (Neat Film, NaCl): 2962, 2933, 2855,

1740, 1707, 1612, 1452, 1379, 1263, 1178, 1120, 1068, 1022, 994 cm-1; HRMS (ESI-APCI) m/z:

[M+H]+ calc’d for C14H20NO4 266.1387; Found 266.1391.

Allyl 1-(((tert-butyldimethylsilyl)oxy)methyl)-3-morpholino-2-oxocyclohex-3-ene-1-

carboxylate (1c)

To a solution of diisopropylamine (1.77 mL, 12.7 mmol, 1.29 equiv) in THF (50 mL) at 0 ºC was

dropwise added a solution of n-butyllithium in hexanes (5.51 mL, 2.19 M, 12.1 mmol, 1.22 equiv).

The solution was stirred for 30 minutes at 0 ºC, then cooled to –78 °C. To the reaction was then

dropwise added a solution of 2-morpholinocyclohex-2-en-1-one3 (1.79 g, 9.88 mmol, 1.00 equiv)

in THF (8.0 mL, 1.2 M) at –78 ºC. The mixture was stirred for 90 minutes, quenched with saturated

aqueous NH4Cl (50 mL) and water (50 mL), diluted with EtOAc (100 mL) and the phases were

separated. The aqueous portion was again extracted with EtOAc (100 mL). The combined organic

O

NMe

O

OO

ON

OO

O

OTBS


S26

fractions were dried over Na2SO4, filtered, and concentrated in vacuo to yield the crude b-ketoester

as a pale-yellow oil [confirmed to be the desired acylated compound by crude 1H NMR analysis].

A portion (218 mg, 0.822 mmol, 1.00 equiv) of this crude intermediate was dissolved in THF (1.6

mL, 0.5 M) and cooled to 0 °C. Potassium carbonate (247 mg, 2.47 mmol, 3.0 equiv) and 37%

aqueous formaldehyde (156 µL, 5.67 mmol, 6.9 equiv) were added. The reaction was warmed to

23 °C and stirred for 4 hours. Upon completion, the reaction mixture was extracted with EtOAc (2

x 5 mL). The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo,

and purified by flash column chromatography (SiO2, 20–35% acetone in hexanes) to yield 133 mg

of a pale-yellow oil. This intermediate alcohol was taken up in CH2Cl2 (4.5 mL, 0.1 M) and TBSCl

(75 mg, 0.49 mmol, 1.1 equiv) and imidazole (61 mg, 0.90 mmol, 2.0 equiv) were added. The

reaction mixture was stirred for 8 hours, concentrated in vacuo and purified by column

chromatography (SiO2, 20–35% EtOAc in hexanes) to yield enaminone 1c (106 mg, 0.257 mmol,

29% yield over 3 steps) as a pale yellow oil; Rf = 0.25 (25% EtOAc in hexanes); 1H NMR (500

MHz, CDCl3) δ 5.88 – 5.80 (m, 2H), 5.27 (dq, J = 17.2, 1.5 Hz, 1H), 5.20 (dq, J = 10.4, 1.3 Hz,

1H), 4.60 (ddt, J = 13.2, 5.8, 1.4 Hz, 1H), 4.54 (ddt, J = 13.2, 5.7, 1.4 Hz, 1H), 4.08 (d, J = 9.8 Hz,

1H), 3.88 (d, J = 9.8 Hz, 1H), 3.83 – 3.73 (m, 4H), 2.91 – 2.85 (m, 2H), 2.68 – 2.58 (m, 3H), 2.55

– 2.49 (m, 1H), 2.44 – 2.36 (m, 1H), 2.02 (ddd, J = 13.8, 10.0, 5.8 Hz, 1H), 0.85 (s, 9H), 0.03 (s,

3H), 0.03 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 192.0, 169.6, 146.7, 131.7, 125.0, 118.8, 66.9,

66.6, 66.0, 65.4, 59.9, 50.0, 29.8, 28.0, 25.9, 25.8, 22.5, 18.3, -5.5; IR (Neat Film, NaCl): 2955,

2929, 2894, 2856, 1734, 1690, 1616, 1462, 1448, 1379, 1262, 1217, 1120, 964 cm-1; HRMS

(APCI) m/z: [M+H]+ calc’d for C21H36NO5Si 410.2357; found 410.2342.

2-chloroallyl carbonocyanidate (SI1)

Prepared according to literature precedent.7 Product vacuum distilled (62–65°C, 20 torr) to afford

the product (SI2) as a clear oil (6.13 g, 90% yield). 1H NMR (500 MHz, CDCl3) δ 5.62 – 5.59

(m, 1H), 5.57 (d, J = 2.1 Hz, 1H), 4.88 (d, J = 0.9 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ

143.5, 132.9, 118.5, 108.9, 69.7; IR (Neat Film, NaCl) 2249, 1759, 1640, 1230, 1180, 918 cm-1;

NC O

O

Cl


S27

Anal. Calc’d for C5H4NO2Cl: C, 41.26%; H, 2.77%; N, 9.62%; Cl, 24.36%; Found: C, 41.22%;

H, 2.79%, N, 9.49%; Cl, 24.18%.

2-methylallyl carbonochloridate (SI2)

Prepared as reported for the 2-chloroallyl substrate from the report by Stoltz and coworkers.7 The

product was vacuum distilled (45–47 °C, 20 torr) to provide the product (SI2) as a clear oil (7.48

g, 60% yield). Spectral data matches that reported in the literature.8 1H NMR (500 MHz, CDCl3)

δ 5.10 – 5.07 (m, 1H), 5.07 – 5.04 (m, 1H), 4.71 (s, 2H), 1.81 (s, 3H); 13C NMR (125 MHz, CDCl3)

δ 150.4, 137.9, 115.8, 75.0, 19.2.

2-methylallyl carbonocyanidate (SI3)

Prepared according to procedure for cyanoformate SI1 from chloroformate SI2. Product vacuum

distilled (60°C, 35 torr) to afford the product (SI3) as a clear oil (3.61 g, 81% yield). 1H NMR (500

MHz, CDCl3) δ 5.12 – 5.06 (m, 2H), 4.73 (s, 2H), 1.81 (s, 3H); 13C NMR (125 MHz, CDCl3) δ

144.1, 137.2, 116.4, 109.3, 72.0, 19.3; IR (Neat Film, NaCl) 2246, 1762, 1227, 1242, 918 cm-1;

Anal. Calc’d for C6H7NO2: C, 57.59%; H, 5.64%; N, 11.19%; Found: C, 57.59%; H, 5.49%; N,

11.11%.

Cl O

O

NC O

O


S28

Derivatization of Enaminone Products

(S)-6-allyl-2-hydroxy-6-methylcyclohex-2-en-1-one (3)

Enaminone 2a (297 mg, 1.26 mmol) was diluted in MeOH/H2O (4:1). HCl (0.1 mL, 12 M aqueous)

was added by syringe. The reaction mixture was stirred at 60 °C under nitrogen for 2 h. The mixture

was cooled to room temperature and partitioned between H2O and CH2Cl2. The aqueous layer was

extracted with CH2Cl2 two additional times. The combined organic layers were dried over Na2SO4,

filtered, and concentrated. The residue was purified by flash column chromatography (1–2%

EtOAc/hexanes) to give diketone 3 (166 mg, 1.00 mmol, 79% yield) as a yellow oil. 1H NMR (300

MHz, CDCl3) δ 6.07 (s, 1H), 6.02 (t, J = 4.6 Hz, 1H), 5.68 (dddd, J = 16.4, 10.6, 7.6, 7.2 Hz, 1H),

5.09 – 4.99 (m, 2H), 2.38 – 2.30 (m, 3H), 2.18 (ddt, J = 13.8, 7.6, 1.1 Hz, 1H), 1.95 – 1.86 (m,

1H), 1.72 (ddd, J = 13.7, 6.5, 5.5 Hz, 1H), 1.10 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 200.3, 145.6,

133.5, 118.7, 117.0, 44.1, 41.1, 33.6, 21.8, 20.4; IR (Neat Film, NaCl): 3428, 3076, 2975, 2935,

1721, 1640, 1455, 1217 cm-1; HRMS (FAB+) m/z: [M+H–H2]+ calc’d for C10H13O2 165.0916;

Found 165.0916; [α]25 –5.95 (c 4.45, CHCl3).

(S)-6-allyl-6-methyl-2-(phenylamino)cyclohex-2-en-1-one (4)

Compound 2a (52 mg, 0.21 mmol, 1.0 equiv) was dissolved in toluene (1.3 mL, 0.16 M). p-

Toluenesulfonic acid monohydrate (39 mg, 0.21 mmol, 1.0 equiv) and aniline (20 µL, 0.22 mmol,

1.0 equiv) were then added to the solution of 2a. The mixture was heated to 50°C for 3.5 h. The

reaction mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3 (3x). The

organic layer was then dried over Na2SO4, filtered, and concentrated in vacuo. The crude was

purified by flash column chromatography (2% EtOAc in hexanes) to yield compound 4 (18 mg,

75 µmol, 35% yield). 1H NMR (500 MHz, CDCl3) δ 7.28 – 7.24 (m, 2H), 7.05 – 7.02 (m, 2H),

6.91 (tt, J = 7.4, 1.1 Hz, 1H), 6.34 (t, J = 4.7 Hz, 1H), 5.76 (ddt, J = 16.5, 10.5, 7.4 Hz, 1H), 5.12

– 5.06 (m, 2H), 2.52 – 2.40 (m, 3H), 2.26 (ddt, J = 13.8, 7.6, 1.2 Hz, 1H), 1.98 (ddd, J = 13.6, 6.8,

OMe

HO

OPhHN

Me


S29

5.4 Hz, 1H), 1.80 (ddd, J = 13.6, 6.8, 5.3 Hz, 1H), 1.17 (s, 3H) (N–H not observed in CDCl3); 13C

NMR (125 MHz, CDCl3) δ 200.0, 142.3, 134.8, 134.0, 133.9, 121.1, 118.8, 118.5, 115.0, 44.4,

41.5, 33.1, 22.2, 21.0; IR (Neat Film, NaCl): 3364, 2926, 1668, 1634, 1600, 1515, 1442, 1306,

1203, 1014, 997, 916, 750, 691 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C16H20NO 242.1539; Found 242.1535; [α]25 –4.72 (c 2.18, CHCl3).

(S)-2-allyl-2-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (5)

To a solution of enaminone 2a (118 mg, 0.500 mmol, 1.00 equiv) toluene (2 mL, 0.25 M), p-

toluenesulfonic acid monohydrate (95 mg, 0.50 mmol, 1.0 equiv) and phenyl hydrazine (54 mg,

0.50 mmol, 1.0 equiv) were added. The reaction was heated to 60 °C and stirred for 4 hours, cooled

to room temperature, diluted with saturated aqueous NH4Cl (1 mL), and extracted with EtOAc (3x

5 mL). The combined organic fractions were dried over Na2SO4, filtered, and concentrated in

vacuo. The crude intermediate was taken up in 5 mL 4:1 AcOH:12 M HCl (0.1 M) and stirred for

2 hours at ambient temperature. Ice (ca. 10 g) was then added. The ice/reaction mixture was

quenched with 5.0 M NaOH until a pH of 9–10 was achieved. The mixture was extracted with

EtOAc (3x 20 mL). The combined organic fractions were dried over Na2SO4, filtered, and

concentrated in vacuo. The product was purified by column chromatography (SiO2, 5–15% EtOAc

in hexanes) to yield indole 5 (120 mg, 0.500 mmol, 99% yield over 2 steps) as a yellow oil; Rf =

0.54 (20% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) δ 9.75 (s, 1H), 7.66 (dt, J = 8.1, 1.0

Hz, 1H), 7.49 (dt, J = 8.4, 0.9 Hz, 1H), 7.38 (ddd, J = 8.3, 7.0, 1.1 Hz, 1H), 7.16 (ddd, J = 8.0, 6.9,

1.0 Hz, 1H), 5.87 (ddt, J = 16.6, 10.4, 7.4 Hz, 1H), 5.15 – 5.10 (m, 2H), 3.10 – 2.98 (m, 2H), 2.57

(dd, J = 13.8, 7.2 Hz, 1H), 2.38 (ddt, J = 13.8, 7.5, 1.2 Hz, 1H), 2.24 (ddd, J = 13.6, 7.1, 5.2 Hz,

1H), 2.05 (ddd, J = 13.6, 6.9, 5.2 Hz, 1H), 1.29 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 196.3,

138.7, 134.4, 130.3, 128.0, 126.9, 125.9, 121.4, 120.4, 118.3, 112.9, 45.5, 41.5, 35.7, 22.1, 18.4;

IR (Neat Film, NaCl): 3279, 3076, 2963, 2926, 1638, 1573, 1545, 1473, 1331, 1224, 1014, 992,

977, 916 cm-1; HRMS (ESI-APCI) m/z: [M+H]+ calc’d for C16H18NO 240.1383; Found 240.1383;

[α]25 –131.65 (c 7.84, CHCl3).

OMeH

N


S30

Ethyl (S)-6-allyl-1-(4-methoxyphenyl)-6-methyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-

carboxylate (6)

Enaminone 2a (31 mg, 0.13 mmol, 1.0 equiv) and ethyl (Z)-2-chloro-2-(2-(4-

methoxyphenyl)hydrazono)acetate9 (73, 50 mg, 0.19 mmol, 1.5 equiv) were dissolved in toluene

(1.4 mL). Then, triethylamine (0.15 mL, 0.11 mmol, 0.83 equiv) was added. The reaction mixture

was heated at the reflux for 17 h. The reaction mixture was then cooled to ambient temperature,

quenched with water, and extracted with ethyl acetate. The organic layer was washed with brine

and dried over Na2SO4, filtered, and concentrated in vacuo. The product was purified by flash

column chromatography (5–15% EtOAc/hexanes) to give the compound 6 as a yellow-orange oil

(22 mg, , 6.0 µmol, 46% yield); 1H NMR (500 MHz, CDCl3) δ 7.36 (d, J = 8.9 Hz, 2H), 6.94 (d, J

= 8.9 Hz, 2H), 5.80 – 5.72 (m, 1H), 5.12 – 5.05 (m, 2H), 4.44 (q, J = 7.1 Hz, 2H), 3.85 (s, 3H),

3.18 – 3.06 (m, 2H), 2.42 (ddt, J = 13.8, 7.1, 1.2 Hz, 1H), 2.27 (ddt, J = 13.7, 7.6, 1.1 Hz, 1H),

2.13 (ddd, J = 14.0, 6.6, 5.4 Hz, 1H), 1.98 (ddd, J = 14.0, 7.3, 5.6 Hz, 1H), 1.42 (t, J = 7.1 Hz,

3H), 1.17 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 192.7, 162.3, 160.1, 140.0, 135.2, 133.6, 132.9,

132.8, 127.1, 118.8, 113.8, 61.3, 55.7, 46.7, 40.8, 34.9, 21.6, 19.0, 14.6; IR (Neat Film, NaCl):

2917, 2357, 2340, 1691, 1515, 1301, 1251, 1195, 1127, 1026, 935 cm-1; HRMS (ESI-APCI) m/z:

[M+H]+ calc’d for C21H25N2O4 369.1809; Found 369.1791; [α]25 –7.56 (c 0.45, CHCl3).

(S)-6-allyl-3-bromo-6-methyl-2-morpholinocyclohex-2-en-1-one (SI4)

Enaminone 2a (120 mg, 0.51 mmol, 1.0 equiv) was dissolved in CH2Cl2 (4.5 mL, 0.1 M). The

reaction mixture was cooled to –78 °C. A solution of NBS (91 mg, 0.51 mmol, 1.0 equiv) in

CH2Cl2 (4.5 mL) was added dropwise to the reaction by syringe. The reaction mixture was stirred

OMe

NN

EtO2C

MeO

OMe

NO

Br


S31

at –78 °C for 25 min. The solution was quenched with a solution of 10% K2CO3 (3 mL). The

mixture was warmed to room temperature and extracted with 3 x CH2Cl2. The organic layers were

combined, dried, filtered and concentrated. The residue was purified by flash column

chromatography (3% EtOAc/hexanes) to give the desired compound as a yellow oil (96 mg, 0.31

mmol, 60% yield). 1H NMR (500 MHz, CDCl3) δ 5.68 (ddt, J = 16.7, 10.2, 7.4 Hz, 1H), 5.10 –

5.01 (m, 2H), 3.71 (ddd, J = 5.3, 3.8, 1.3 Hz, 4H), 3.06 – 2.99 (m, 2H), 2.97 – 2.92 (m, 2H), 2.93

– 2.83 (m, 2H), 2.28 (ddt, J = 13.8, 7.3, 1.2 Hz, 1H), 2.21 (ddt, J = 13.8, 7.5, 1.2 Hz, 1H), 1.88

(ddd, J = 13.8, 6.3, 5.7 Hz, 1H), 1.74 (ddd, J = 13.9, 7.2, 5.8 Hz, 1H), 1.07 (s, 3H); 13C NMR (125

MHz, CDCl3) δ 199.4, 143.8, 141.9, 133.5, 118.7, 67.7, 50.2, 45.8, 40.9, 33.7, 33.3, 21.5; IR (Neat

Film, NaCl) 2958, 2851, 1678, 1606, 1451, 1261, 1212, 1113, 1049, 920 cm-1; HRMS (ESI-APCI)

m/z: [M+H]+ calc’d for C14H21BrNO2 314.0750; Found 314.0742; [α]25 –1.56 (c 1.68, CHCl3).

(S)-4-allyl-4-methyl-2-morpholino-5,6-dihydro-[1,1'-biphenyl]-3(4H)-one (7)

Compound SI4 (54 mg, 0.17 mmol, 1.0 equiv) was dissolved in DME (7 mL) and 1 M K3PO4

(0.72 mL, 4.5 equiv). Phenylboronic acid (29 mg, 0.24 mmol, 1.5 equiv) and PdCl2(dppf) (26 mg,

32 µmol, 0.19 equiv) were added to the reaction mixture. The mixture was heated to 60 °C under

nitrogen for 2h. The reaction mixture was cooled to room temperature and then extracted with

diethyl ether (3x). The combined organic layer was dried with Na2SO4, filtered and concentrated

in vacuo. The reaction mixture was purified by flash column chromatography (SiO2, 3–6%

EtOAc/hexanes) to give the product as bright yellow-orange oil (51 mg, 0.16 mmol, 96% yield). 1H NMR (500 MHz, CDCl3) δ 7.40 – 7.36 (m, 2H), 7.33 – 7.29 (m, 1H), 7.26 – 7.22 (m, 2H), 6.93

– 6.82 (m, 1H), 5.79 (ddt, J = 16.6, 10.3, 7.4 Hz, 1H), 5.11 – 5.05 (m, 2H), 3.53 (t, J = 4.6 Hz,

4H), 2.73 – 2.61 (m, 6H), 2.40 – 2.29 (m, 2H), 1.96 (dt, J = 13.7, 5.8 Hz, 1H), 1.85 (ddd, J = 13.5,

6.9, 6.1 Hz, 1H), 1.15 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 202.7, 145.7, 141.2, 140.5, 134.2,

129.8, 128.2, 127.9, 118.2, 115.4, 67.5, 51.2, 44.8, 41.4, 32.2, 29.0, 21.9; IR (Neat Film, NaCl):

2916, 2850, 2358, 1669, 1457, 1374, 1261, 1210, 1112, 1029, 978, 757, 698 cm-1; HRMS (ESI-

APCI) m/z: [M+H]+ calc’d for C20H26NO2 312.1958; Found 312.1968; [α]25 0.00 (c 0.76, CHCl3).

OMe

NO

Ph


S32

References 1) Pangborn, A. M.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers, F. J. Safe and

Convenient Procedure for Solvent Purification. Organometallics 1996, 15, 1518–1520.

2) (a) Tani, K.; Behenna, D. C.; McFadden, R. M.; Stoltz, B. M. Org. Lett. 2007, 9, 2529–

2531. (b) Krout, M. R.; Mohr, J. T.; Stoltz, B. M. Org. Synth. 2009, 86, 181–193.

3) Tobias, M. A.; Strong, J. G.; Napier, R. P. J. Org. Chem. 1970, 35, 1709–1711.

4) Di-methyl ref

5) Prepared from 2-iodocyclohexenone and cyclohexylmagnesium bromide following the

procedure from the following publication: Barriault, L.; Thomas, J. D. O.; Clément, R. J.

Org. Chem. 2003, 68, 2317–2323.

6) Sato, K.; Inoue, S.; Kitagawa, T.; Takahashi, T. J. Org. Chem. 1973, 38, 551–554.

7) White, D. E.; Stewart, I. C.; Grubbs, R. H.; Stoltz, B. M. J. Am Chem. Soc. 2008, 130,

810–811.

8) Ghosh, S.; Chaudhuri, S.; Bisai, A. Chem. Eur. J. 2015, 21, 17479–17484.

9) Pinto, D. J. P.; Orwat, M. J.; Koch, S.; Rossi, K. A.; Alexander, R. S.; Smallwood, A.;

Wong, P. C.; Rendina, A. R.; Luettgen, J. M.; Knabbs, R. M.; He, K.; Xin, B.; Wexler, R.

R.; Lam, P. Y. S. J. Med. Chem. 2007, 50, 5339–5356.


S33

01

23

45

67

89

10

ppm

3.12

1.09

1.08

1.08

1.01

2.06

2.09

2.05

2.06

2.14

0.99

1.00

1.93

1.37

1.82

1.83

1.83

1.84

1.85

1.85

1.86

1.87

2.38

2.39

2.42

2.43

2.43

2.46

2.46

2.47

2.51

2.55

2.55

2.56

2.56

2.58

2.96

2.99

3.74

3.76

3.76

3.77

3.77

3.78

3.79

3.80

3.80

3.81

3.81

3.82

3.82

4.55

4.56

4.56

4.56

4.57

4.57

4.57

4.58

4.58

4.58

4.59

5.20

5.20

5.20

5.21

5.22

5.22

5.22

5.25

5.25

5.28

5.28

5.29

5.29

5.79

5.80

5.81

5.81

5.82

5.82

5.83

5.83

5.85

ON

O

1a

Me

O

O

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1a

.

Spectral Data for New Compounds


S34

020406080100120140160180200220

ppm

20.6

22.7

33.3

50.0

54.2

66.0

66.9

118.9

124.0

131.6

146.4

172.4

193.9

Infrared spectrum (Thin Film, NaCl) of compound 1a.

13C NMR (125 MHz, CDCl3) of compound 1a.


S35

01

23

45

67

89

10

ppm

3.01

1.14

1.08

1.14

2.03

3.04

2.02

2.00

2.00

2.01

0.99

1.00

1.06

1.00

0.90

0.92

0.93

1.76

1.78

1.79

1.80

1.84

1.85

1.86

1.86

1.88

1.89

1.93

1.95

1.96

1.97

2.39

2.40

2.40

2.40

2.41

2.41

2.53

2.54

2.54

2.55

2.55

2.56

2.56

2.57

2.58

2.93

2.94

2.94

2.95

2.95

2.96

2.97

2.97

3.73

3.74

3.75

3.75

3.76

3.76

3.77

3.77

3.78

3.79

3.80

3.80

3.81

3.81

3.82

3.83

5.20

5.20

5.21

5.22

5.22

5.22

5.25

5.26

5.29

5.29

5.29

5.80

5.82

5.84

5.86

1 H N

MR

(400

MH

z, C

DC

l 3) o

f com

poun

d 1b

.

ON

O

1b

EtO

O


S36

020406080100120140160180200220

ppm

9.1

22.6

27.0

29.8

50.0

57.9

65.8

67.0

119.0

123.5

131.7

146.8

171.3

193.6

Infrared spectrum (Thin Film, NaCl) of compound 1b.

13C NMR (100 MHz, CDCl3) of compound 1b.


S37

01

23

45

67

89

10

ppm

2.89

2.95

9.19

1.00

1.04

1.02

3.05

1.99

4.11

1.01

1.01

1.01

1.03

0.96

0.99

1.96

0.03

0.03

0.85

2.03

2.60

2.60

2.61

2.61

2.62

2.62

2.63

2.63

2.63

2.63

2.86

2.87

2.87

2.88

2.88

2.89

2.90

3.74

3.76

3.76

3.77

3.77

3.78

3.78

3.78

3.79

3.80

3.80

3.81

3.87

3.89

4.07

4.09

4.55

4.55

4.55

4.56

4.56

4.56

4.58

4.58

4.58

4.59

4.59

4.59

5.19

5.19

5.21

5.21

5.22

5.26

5.26

5.29

5.29

5.81

5.82

5.82

5.82

5.82

5.83

5.83

5.83

5.83

5.83

5.84

5.84

5.87

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1c

.

O

O

ON

O

1cOTBS


S38

020406080100120140160180200220

ppm

-5.5

-5.5

18.3

22.4

25.9

25.9

25.9

28.0

50.0

59.9

65.4

66.0

66.9

118.8

125.0

131.8

146.7

169.6

192.0

Infrared spectrum (Thin Film, NaCl) of compound 1c.

13C NMR (100 MHz, CDCl3) of compound 1c.


S39

01

23

45

67

89

10

ppm

6.00

9.07

2.05

1.05

1.03

4.01

1.99

6.02

2.00

0.98

0.99

0.91

1.04

0.02

0.86

1.92

1.93

1.94

1.94

1.94

1.95

1.96

1.97

1.98

2.12

2.13

2.13

2.14

2.16

2.16

2.53

2.54

2.55

2.55

2.55

2.56

2.56

2.57

2.58

2.58

2.93

2.94

2.94

3.68

3.69

3.69

3.71

3.72

3.73

3.73

3.74

3.75

3.75

3.75

3.76

3.77

3.77

3.78

3.79

3.80

3.80

3.80

4.55

4.55

4.55

4.56

4.56

4.56

4.56

4.57

4.57

4.58

5.20

5.20

5.22

5.22

5.26

5.26

5.29

5.29

5.80

5.82

5.84

5.86

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1d

.

O

O

ON

O

1dOTBS


S40

020406080100120140160180200220

ppm

-5.2

18.4

22.7

26.0

30.8

36.8

50.0

56.5

59.7

66.0

66.9

119.1

123.7

131.7

146.5

171.0

193.3

Infrared spectrum (Thin Film, NaCl) of compound 1d.

13C NMR (100 MHz, CDCl3) of compound 1d.


S41

01

23

45

67

89

10

ppm

1.09

1.06

1.07

3.04

4.07

2.00

3.00

2.00

2.01

1.99

0.95

0.97

0.98

0.93

2.05

2.06

2.07

2.16

2.17

2.18

2.31

2.32

2.33

2.34

2.37

2.38

2.39

2.41

2.43

2.45

2.50

2.51

2.51

2.52

2.52

2.53

2.54

2.54

2.90

2.91

2.91

2.92

2.92

2.93

2.94

2.94

3.62

3.70

3.71

3.71

3.72

3.73

3.73

3.74

3.75

3.75

3.76

3.76

3.78

4.52

4.53

4.53

4.53

4.54

4.54

4.54

4.55

4.55

4.56

5.18

5.18

5.20

5.20

5.23

5.23

5.27

5.27

5.69

5.70

5.70

5.71

5.71

5.77

5.79

5.80

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1e

.

O

O

ON

O

1eCO

2Me


S42

020406080100120140160180200220

ppm

22.5

28.9

29.5

30.7

49.8

51.7

56.7

66.1

66.8

66.8

119.2

123.3

131.4

146.6

170.9

173.4

193.1

Infrared spectrum (Thin Film, NaCl) of compound 1e.

13C NMR (100 MHz, CDCl3) of compound 1e.


S43

01

23

45

67

89

10

ppm

1.12

1.13

4.02

1.00

1.05

2.01

2.09

1.03

2.00

2.04

2.05

2.05

0.99

1.01

1.02

1.00

1.86

1.98

2.00

2.01

2.07

2.08

2.09

2.10

2.34

2.35

2.35

2.37

2.37

2.37

2.38

2.46

2.47

2.48

2.51

2.51

2.51

2.52

2.53

2.53

2.53

2.54

2.54

2.54

2.55

2.55

2.92

2.92

2.93

2.93

3.71

3.72

3.72

3.73

3.74

3.74

3.75

3.76

3.77

3.77

3.78

4.53

4.53

4.54

4.54

4.54

4.55

4.55

4.56

4.56

4.56

5.19

5.19

5.21

5.21

5.24

5.24

5.28

5.28

5.71

5.72

5.72

5.73

5.78

5.80

5.82

5.84

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1f

.

O

O

ON

O

1fMeO


S44

020406080100120140160180200220

ppm

22.6

27.7

30.0

30.0

31.1

38.9

49.9

49.9

56.7

66.0

66.9

119.3

123.5

131.4

146.7

171.2

193.4

207.7

Infrared spectrum (Thin Film, NaCl) of compound 1f.

13C NMR (100 MHz, CDCl3) of compound 1f.


S45

01

23

45

67

89

10

ppm

1.00

1.05

1.07

3.02

4.06

2.00

1.97

1.99

2.00

0.95

0.98

0.98

1.00

1.90

2.07

2.08

2.09

2.10

2.19

2.20

2.21

2.38

2.39

2.40

2.40

2.42

2.42

2.42

2.43

2.44

2.45

2.52

2.52

2.53

2.53

2.54

2.54

2.55

2.56

2.57

2.57

2.93

2.94

2.94

2.95

2.95

2.96

2.97

2.97

3.72

3.73

3.74

3.74

3.75

3.75

3.77

3.77

3.78

3.79

3.79

3.80

3.80

4.58

4.59

4.59

4.60

4.60

4.60

4.61

4.61

4.61

5.23

5.24

5.25

5.26

5.27

5.27

5.31

5.31

5.76

5.80

5.82

5.83

5.85

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1g

.

O

O

ON

O

1gCN


S46

020406080100120140160180200220

ppm

13.3

22.5

30.2

31.1

49.8

56.5

66.5

66.8

119.4

119.9

123.7

131.1

146.6

170.2

192.7

Infrared spectrum (Thin Film, NaCl) of compound 1g.

13C NMR (125 MHz, CDCl3) of compound 1g.


S47

01

23

45

67

89

10

ppm

1.02

2.01

2.99

1.95

1.01

1.00

1.97

2.00

1.98

0.94

0.97

0.98

0.94

2.01

2.99

2.34

2.35

2.35

2.35

2.51

2.51

2.52

2.52

2.53

2.53

2.54

2.54

2.55

2.95

2.95

2.96

2.96

2.97

2.98

3.13

3.15

3.24

3.27

3.74

3.75

3.76

3.76

3.77

3.77

3.78

3.79

3.80

3.81

3.82

3.82

3.83

3.83

3.84

3.85

5.20

5.20

5.22

5.22

5.24

5.24

5.27

5.28

5.71

5.71

5.72

5.72

5.76

5.78

5.79

5.82

7.16

7.16

7.16

7.17

7.17

7.18

7.20

7.21

7.22

7.22

7.23

7.23

7.23

7.24

7.24

7.25

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1h

.

O

O

ON

O

1h


S48

020406080100120140160180200220

ppm

22.7

30.0

39.7

49.9

58.7

66.1

66.9

119.2

123.9

126.9

128.2

130.7

131.5

136.4

146.8

170.5

170.5

192.6

Infrared spectrum (Thin Film, NaCl) of compound 1h.

13C NMR (100 MHz, CDCl3) of compound 1h.


S49

01

23

45

67

89

10

ppm

1.00

2.04

3.00

2.00

1.02

1.02

5.08

2.04

2.03

0.98

1.10

0.95

1.01

2.07

2.01

2.33

2.33

2.34

2.34

2.34

2.35

2.35

2.36

2.36

2.51

2.52

2.52

2.52

2.53

2.54

2.54

2.55

2.55

2.95

2.95

2.96

2.96

2.97

2.98

3.08

3.11

3.17

3.20

3.75

3.75

3.76

3.77

3.77

3.77

3.78

3.79

3.80

3.81

3.82

3.82

3.83

3.83

3.84

4.52

4.52

4.52

4.52

4.53

4.53

4.53

4.54

5.20

5.21

5.21

5.22

5.23

5.23

5.24

5.25

5.28

5.28

5.28

5.72

5.77

5.79

5.81

5.83

6.77

6.79

7.08

7.10

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1i

.

O

O

ON

O

1i

OMe


S50

020406080100120140160180200220

ppm

22.7

30.0

38.9

50.0

55.3

58.8

66.1

66.9

113.6

119.2

123.9

128.3

131.6

131.7

146.9

158.6

170.6

192.7

Infrared spectrum (Thin Film, NaCl) of compound 1i.

13C NMR (100 MHz, CDCl3) of compound 1i.


S51

01

23

45

67

89

10

ppm

1.00

2.03

3.04

2.00

1.01

1.03

2.03

2.05

2.03

2.01

1.95

2.04

2.11

2.34

2.35

2.36

2.37

2.37

2.38

2.38

2.38

2.51

2.51

2.52

2.52

2.52

2.53

2.53

2.54

2.54

2.55

2.96

2.96

2.97

2.97

2.98

2.99

2.99

3.18

3.20

3.27

3.30

3.75

3.75

3.76

3.76

3.77

3.77

3.78

3.79

3.81

3.81

3.82

3.83

3.83

3.84

3.84

4.50

4.50

4.50

4.51

4.51

4.51

4.52

4.52

5.20

5.20

5.20

5.21

5.22

5.22

5.22

5.23

5.25

5.25

5.25

5.72

7.31

7.33

7.33

7.49

7.50

7.50

7.51

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1j

.

O

O

ON

O

1j

CF3


S52

020406080100120140160180200220

ppm

22.7

30.4

39.6

49.9

58.7

66.3

66.9

119.5

123.3

123.8

125.0

125.1

125.1

125.1

128.8

129.1

129.3

129.6

131.2

131.2

140.7

146.8

170.3

192.4

Infrared spectrum (Thin Film, NaCl) of compound 1j.

13C NMR (125 MHz, CDCl3) of compound 1j.


S53

-180-160-140-120-100-80-60-40-20020

ppm

-62.5

19F NMR (470 MHz, CDCl3) of compound 1j.


S54

01

23

45

67

89

10

ppm

2.99

2.92

1.00

1.02

1.01

3.04

2.00

2.03

2.01

2.06

2.02

1.04

1.41

1.71

1.72

1.84

1.86

1.86

1.87

1.88

1.88

1.89

1.90

2.41

2.41

2.45

2.46

2.46

2.46

2.48

2.49

2.49

2.49

2.52

2.53

2.56

2.57

2.57

2.58

2.59

2.59

2.60

2.60

2.60

2.61

2.98

2.98

2.99

2.99

3.00

3.00

3.01

3.02

3.02

3.75

3.75

3.76

3.77

3.77

3.78

3.78

3.79

3.80

3.81

3.82

3.82

3.83

3.83

3.84

3.84

4.51

4.52

4.52

4.52

4.91

4.93

5.78

5.78

5.79

5.79

5.79

5.80

5.80

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1k

.

O

O

ON

O

1k

Me

Me


S55

020406080100120140160180200220

ppm

19.5

20.6

22.6

33.3

49.8

54.1

66.8

68.4

113.5

123.9

139.4

146.3

172.3

193.7

Infrared spectrum (Thin Film, NaCl) of compound 1k.

13C NMR (125 MHz, CDCl3) of compound 1k.


S56

01

23

45

67

89

10

ppm

3.01

1.03

1.01

1.04

3.04

2.00

2.06

2.07

1.05

0.99

1.02

1.01

1.01

1.43

1.89

1.90

1.91

2.43

2.47

2.59

2.59

2.60

2.60

2.61

2.61

2.61

2.61

2.62

2.63

2.63

2.98

2.98

2.99

2.99

3.01

3.01

3.75

3.76

3.77

3.77

3.78

3.78

3.79

3.80

3.80

3.81

3.82

3.82

3.83

3.83

3.84

3.85

4.62

4.62

4.62

4.62

4.64

4.65

4.65

4.65

4.65

4.70

4.71

4.71

4.71

4.73

4.73

4.73

4.73

5.40

5.40

5.44

5.44

5.44

5.44

5.45

5.45

5.81

5.81

5.81

5.82

5.82

5.83

5.83

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1l

.

O

O

ON

O

1l

Me

Cl


S57

020406080100120140160180200220

ppm

20.6

22.6

33.3

49.9

54.2

66.7

66.9

115.7

115.8

124.3

135.4

146.3

171.9

193.5

Infrared spectrum (Thin Film, NaCl) of compound 1l.

13C NMR (125 MHz, CDCl3) of compound 1l.


S58

01

23

45

67

89

10

ppm

3.02

2.06

3.99

1.07

1.07

1.05

3.07

2.00

2.00

0.99

1.06

1.00

1.00

1.37

1.48

1.48

1.49

1.51

1.61

1.61

1.62

1.62

1.63

1.63

1.63

1.64

1.64

1.64

1.64

1.65

1.65

1.65

1.66

1.66

1.67

1.67

1.68

1.81

1.82

1.82

1.83

1.84

1.84

1.85

2.37

2.42

2.48

2.48

2.49

2.49

2.49

2.50

2.50

2.51

2.51

2.52

2.52

2.85

2.86

2.87

2.88

4.55

4.56

4.56

4.56

4.57

4.57

4.57

4.57

4.58

5.19

5.19

5.21

5.21

5.21

5.25

5.25

5.28

5.29

5.73

5.73

5.74

5.74

5.74

5.75

5.80

5.82

5.84

5.86

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1m

.

O

OMeO

N

1m


S59

020406080100120140160180200220

ppm

20.7

22.8

24.5

26.0

33.4

51.0

54.2

65.8

118.7

123.5

131.8

147.7

172.6

194.3

Infrared spectrum (Thin Film, NaCl) of compound 1m.

13C NMR (125 MHz, CDCl3) of compound 1m.


S60

01

23

45

67

89

10

ppm

3.00

1.09

3.10

1.07

1.06

1.11

2.01

2.09

4.10

1.00

1.01

0.95

0.97

0.95

1.33

1.76

1.77

1.78

1.78

1.79

1.80

1.80

1.82

1.95

1.95

1.96

2.30

2.30

2.30

2.31

2.36

2.37

2.37

2.38

2.39

2.39

2.40

2.40

2.84

2.86

2.87

2.87

2.87

2.92

2.92

2.93

2.95

3.65

3.65

3.66

3.66

3.66

3.67

3.68

4.53

4.53

4.54

4.54

4.55

4.55

4.56

4.56

4.57

4.57

4.58

4.58

5.17

5.17

5.17

5.19

5.19

5.19

5.19

5.22

5.22

5.25

5.25

5.26

5.26

5.79

5.80

5.80

5.81

5.82

5.84

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1n

.

O

O

ON

O

1n

Me

Me


S61

020406080100120140160180200220

ppm

19.6

20.5

29.2

32.3

50.3

53.9

65.7

67.9

118.4

131.8

142.1

153.2

172.5

194.8

Infrared spectrum (Thin Film, NaCl) of compound 1n.

13C NMR (125 MHz, CDCl3) of compound 1n.


S62

01

23

45

67

89

10

ppm

1.09

2.30

2.09

3.01

6.08

1.23

1.13

3.15

2.01

1.00

1.04

0.95

1.00

0.96

1.07

1.08

1.10

1.10

1.12

1.13

1.15

1.32

1.32

1.34

1.35

1.37

1.62

1.62

1.65

1.65

1.67

1.69

1.69

1.69

1.70

1.70

1.70

1.70

1.71

1.71

1.72

1.72

1.72

1.73

1.73

1.75

1.75

1.76

1.84

1.85

1.86

2.33

2.45

2.46

2.47

2.47

2.48

2.48

2.53

2.54

4.56

4.56

4.56

4.57

4.57

4.58

4.58

4.58

4.59

5.19

5.19

5.21

5.21

5.25

5.25

5.28

5.28

5.82

5.84

5.85

6.50

6.50

6.51

6.51

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1o

.

O

O

O

1o


S63

020406080100120140160180200220

ppm

20.6

23.6

26.5

26.8

26.9

32.3

32.8

33.4

36.8

53.6

65.8

118.5

131.9

140.9

144.2

172.8

196.8

Infrared spectrum (Thin Film, NaCl) of compound 1o.

13C NMR (125 MHz, CDCl3) of compound 1o.


S64

01

23

45

67

89

10

ppm

3.00

1.00

3.00

2.01

4.01

2.03

1.02

1.08

1.03

1.00

1.42

2.36

2.36

2.39

2.40

3.01

3.01

3.01

3.02

3.03

3.04

3.05

3.15

3.16

3.16

3.16

3.17

3.17

3.18

3.19

3.19

3.78

3.78

3.79

3.79

3.79

3.80

3.80

4.57

4.57

4.58

4.58

4.58

4.59

5.19

5.19

5.20

5.20

5.21

5.21

5.22

5.22

5.25

5.25

5.25

5.26

5.28

5.29

5.29

5.29

5.81

5.82

5.83

5.83

5.83

5.84

5.85

5.86

5.86

5.87

5.87

5.87

5.88

5.89

6.39

6.39

6.40

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 1p

.

O

NO

OO

1p


S65

020406080100120140160180200220

ppm

21.1

37.8

48.5

54.1

65.9

66.6

118.3

131.8

131.9

148.6

171.6

201.8

Infrared spectrum (Thin Film, NaCl) of compound 1p.

13C NMR (125 MHz, CDCl3) of compound 1p.


S66

01

23

45

67

89

10

ppm

3.01

1.01

1.03

1.01

1.02

2.00

2.00

2.01

4.04

2.00

0.97

1.00

1.09

1.09

1.71

1.72

1.73

1.74

1.74

1.75

1.85

1.86

1.88

1.89

2.20

2.22

2.23

2.23

2.24

2.25

2.32

2.32

2.33

2.33

2.35

2.36

2.40

2.41

2.41

2.42

2.42

2.42

2.42

2.43

2.43

2.44

2.44

2.69

2.70

2.71

2.71

2.71

2.72

2.80

2.81

2.82

2.84

2.85

3.79

3.79

3.80

3.80

3.81

3.81

3.81

5.03

5.03

5.04

5.05

5.05

5.05

5.06

5.06

5.06

5.06

5.71

5.73

5.73

5.74

5.74

5.87

5.88

5.89

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2a

.

OMe

NO

2a


S67

020406080100120140160180200220

ppm

21.8

21.9

33.2

41.2

45.4

50.5

66.9

118.1

125.0

134.0

145.5

200.4

Infrared spectrum (Thin Film, NaCl) of compound 2a.

13C NMR (125 MHz, CDCl3) of compound 2a.


S68

01

23

45

67

89

10

ppm

3.01

2.00

2.00

1.00

1.00

2.00

2.01

2.00

4.00

0.98

1.00

1.00

1.00

0.79

0.80

0.82

1.56

1.56

1.58

1.58

1.59

1.60

1.61

1.61

1.80

1.81

1.82

2.20

2.22

2.23

2.23

2.23

2.25

2.25

2.25

2.32

2.32

2.33

2.33

2.34

2.36

2.38

2.39

2.39

2.40

2.40

2.41

2.41

2.41

2.42

2.42

2.69

2.70

2.70

2.71

2.71

2.72

2.75

2.76

2.76

2.77

2.77

2.78

3.77

3.77

3.78

3.78

3.78

3.79

3.79

4.99

5.00

5.00

5.00

5.00

5.01

5.01

5.02

5.03

5.03

5.03

5.82

5.83

5.84

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2b

.

OEt

NO

2b


S69

020406080100120140160180200220

ppm

8.4

21.8

27.0

30.4

38.8

48.6

50.6

67.0

117.9

124.8

134.4

146.0

200.2

Infrared spectrum (Thin Film, NaCl) of compound 2b.

13C NMR (125 MHz, CDCl3) of compound 2b.


S70

01

23

45

67

89

10

ppm

2.83

2.92

9.00

1.01

1.00

1.00

3.05

4.00

1.01

1.04

3.92

2.00

0.98

0.94

0.01

0.01

0.85

1.88

1.89

1.90

1.92

1.93

1.95

1.95

1.96

1.98

2.24

2.25

2.26

2.26

2.27

2.27

2.28

2.28

2.28

2.38

2.39

2.39

2.40

2.40

2.40

2.41

2.41

2.41

2.42

2.42

2.42

2.43

2.43

2.43

2.43

2.73

2.74

2.75

3.61

3.63

3.67

3.69

3.78

3.79

3.79

5.00

5.00

5.00

5.00

5.01

5.01

5.02

5.03

5.03

5.03

5.03

5.04

5.04

5.67

5.68

5.69

5.69

5.69

5.71

5.73

5.73

5.86

5.87

5.88

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2c

.

ON

O

2c

OTBS


S71

020406080100120140160180200220

ppm

-5.5

-5.5

-5.5

18.3

21.7

25.9

25.9

28.5

37.2

50.5

51.0

66.1

67.0

118.0

125.1

134.1

146.5

198.8

Infrared spectrum (Thin Film, NaCl) of compound 2c.

13C NMR (125 MHz, CDCl3) of compound 2c.


S72

01

23

45

67

89

10

ppm

2.78

2.87

9.04

1.00

3.01

1.00

3.00

3.93

0.99

1.03

4.01

2.00

1.00

0.94

0.02

0.03

0.87

1.75

1.77

1.77

1.78

1.83

1.84

1.84

1.85

1.85

1.86

1.87

1.87

1.87

1.88

1.88

1.88

1.89

1.89

2.27

2.28

2.28

2.29

2.30

2.36

2.37

2.39

2.40

2.42

2.43

2.43

2.44

2.44

2.44

2.45

2.45

2.75

2.76

2.77

3.56

3.56

3.56

3.57

3.58

3.58

3.59

3.67

3.68

3.69

3.69

3.70

3.70

3.71

3.79

3.80

3.81

5.02

5.02

5.03

5.04

5.04

5.04

5.05

5.06

5.06

5.06

5.06

5.07

5.86

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2d

.

ON

O

2d

OTBS


S73

020406080100120140160180200220

ppm

-5.2

-5.1

18.4

21.9

26.1

31.3

37.0

39.5

47.8

50.6

59.5

67.0

118.3

125.0

134.2

145.8

199.7

Infrared spectrum (Thin Film, NaCl) of compound 2d.

13C NMR (125 MHz, CDCl3) of compound 2d.


S74

01

23

45

67

89

10

ppm

3.04

1.11

2.09

2.05

2.07

4.03

3.05

4.00

2.02

1.01

1.00

1.80

1.80

1.81

1.81

1.82

1.82

1.83

1.83

1.83

1.85

1.85

1.86

1.86

1.92

1.93

1.94

2.19

2.19

2.21

2.21

2.22

2.24

2.25

2.26

2.29

2.30

2.30

2.30

2.30

2.31

2.31

2.31

2.32

2.32

2.33

2.33

2.42

2.42

2.43

2.43

2.44

2.44

2.45

2.72

2.73

2.74

2.75

3.63

3.63

3.76

3.77

3.77

3.78

3.78

3.78

5.02

5.03

5.03

5.03

5.04

5.05

5.05

5.05

5.06

5.06

5.07

5.07

5.07

5.85

5.86

5.87

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2e

.

ON

O

2e

OMe

O


S75

020406080100120140160180200220

ppm

21.6

28.8

29.2

30.6

38.9

47.8

50.4

51.6

66.8

118.6

125.0

133.3

145.7

174.0

199.1

Infrared spectrum (Thin Film, NaCl) of compound 2e.

13C NMR (125 MHz, CDCl3) of compound 2e.


S76

01

23

45

67

89

10

ppm

4.13

3.00

1.06

2.04

3.11

2.01

2.00

4.01

2.00

1.00

0.99

1.78

1.79

1.79

1.80

1.80

1.81

1.81

1.82

1.83

1.83

1.83

1.84

1.85

1.86

1.86

2.12

2.24

2.25

2.25

2.25

2.26

2.27

2.27

2.31

2.31

2.31

2.32

2.32

2.32

2.33

2.35

2.35

2.36

2.43

2.44

2.44

2.45

2.45

2.46

2.46

2.47

2.47

2.69

2.70

2.71

2.72

2.73

2.76

2.77

2.78

2.78

2.79

3.78

3.79

3.80

5.04

5.04

5.05

5.06

5.06

5.06

5.07

5.07

5.08

5.08

5.67

5.69

5.70

5.88

5.89

5.89

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2f

.

ON

O

2f

Me

O


S77

020406080100120140160180200220

ppm

21.8

28.0

30.2

31.0

38.4

39.3

47.9

50.7

67.0

118.7

125.5

133.6

145.9

199.6

208.6

Infrared spectrum (Thin Film, NaCl) of compound 2f.

13C NMR (125 MHz, CDCl3) of compound 2f.


S78

01

23

45

67

89

10

ppm

1.16

2.03

1.17

6.27

2.00

2.02

4.01

2.04

1.00

0.95

1.77

1.78

1.78

1.79

1.80

1.81

1.85

1.86

1.86

1.87

1.87

1.88

1.89

2.06

2.06

2.08

2.10

2.26

2.27

2.28

2.29

2.29

2.30

2.30

2.31

2.31

2.33

2.35

2.35

2.37

2.45

2.46

2.47

2.49

2.63

2.64

2.64

2.65

2.65

2.66

2.66

2.67

2.80

2.81

2.81

2.82

2.83

2.83

2.84

2.84

2.85

3.76

3.77

3.77

3.78

3.78

3.79

5.07

5.07

5.10

5.10

5.11

5.11

5.13

5.13

5.62

5.64

5.65

5.89

5.90

5.91

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2g

.

ON

O

2g

CN


S79

020406080100120140160180200220

ppm

12.3

21.6

30.3

30.5

38.8

48.0

50.5

66.9

119.5

120.1

125.4

132.4

145.7

198.5

Infrared spectrum (Thin Film, NaCl) of compound 2g.

13C NMR (125 MHz, CDCl3) of compound 2g.


S80

01

23

45

67

89

10

ppm

1.05

1.10

1.13

3.01

5.01

1.05

4.01

2.05

1.00

0.97

1.99

3.00

1.72

1.73

1.74

1.75

1.79

1.80

1.82

2.13

2.15

2.16

2.18

2.40

2.41

2.41

2.42

2.42

2.42

2.43

2.43

2.43

2.44

2.44

2.44

2.46

2.71

2.73

2.74

2.74

2.75

2.75

2.76

2.77

3.06

3.09

3.79

3.80

3.81

3.81

5.03

5.03

5.06

5.06

5.07

5.07

5.07

5.07

5.09

5.09

5.09

5.76

5.78

5.87

5.88

5.89

7.11

7.12

7.12

7.13

7.13

7.13

7.19

7.20

7.20

7.20

7.22

7.22

7.22

7.23

7.24

7.24

7.25

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2h

.

OBn

NO

2h


S81

020406080100120140160180200220

ppm

21.8

29.8

39.8

40.7

49.9

50.6

67.0

118.6

125.2

126.5

128.1

128.1

130.9

130.9

134.1

137.6

146.3

199.2

Infrared spectrum (Thin Film, NaCl) of compound 2h.

13C NMR (125 MHz, CDCl3) of compound 2h.


S82

01

23

45

67

89

10

ppm

1.07

1.02

1.00

3.00

1.02

4.00

1.00

2.98

3.98

2.00

0.95

0.99

1.92

2.00

1.70

1.71

1.71

1.73

1.74

1.77

1.78

1.79

1.81

2.11

2.12

2.13

2.13

2.14

2.15

2.15

2.15

2.40

2.40

2.41

2.41

2.41

2.42

2.42

2.43

2.43

2.43

2.44

2.45

2.65

2.68

2.74

2.75

2.76

2.77

2.77

2.99

3.02

3.77

3.79

3.80

3.81

5.01

5.02

5.02

5.05

5.05

5.05

5.06

5.06

5.06

5.06

5.08

5.08

5.08

5.08

5.75

5.76

5.77

5.77

5.86

5.87

5.88

6.77

6.77

6.78

6.79

7.03

7.03

7.04

7.04

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2i

.

ON

O

2i

OMe


S83

020406080100120140160180200220

ppm

21.9

29.7

39.8

39.9

49.9

50.6

55.3

67.0

113.5

118.5

125.3

129.5

131.8

134.1

146.3

158.3

199.3

Infrared spectrum (Thin Film, NaCl) of compound 2i.

13C NMR (125 MHz, CDCl3) of compound 2i.


S84

01

23

45

67

89

10

ppm

1.07

1.06

1.03

3.05

2.90

1.99

1.00

3.87

0.95

1.00

0.97

0.93

2.01

1.91

1.70

1.71

1.71

1.73

1.77

1.78

1.79

1.81

2.20

2.21

2.22

2.23

2.24

2.37

2.38

2.38

2.39

2.39

2.39

2.40

2.40

2.41

2.41

2.41

2.42

2.42

2.44

2.45

2.69

2.70

2.71

2.71

2.72

2.72

2.74

2.77

2.78

2.78

2.79

2.80

2.80

3.19

3.21

3.80

3.80

3.80

3.81

3.81

3.81

3.82

5.06

5.07

5.10

5.10

5.11

5.12

5.12

5.13

5.14

5.14

5.76

5.78

5.78

5.87

5.88

5.89

7.25

7.26

7.26

7.48

7.49

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2j

.

ON

O

2j

CF3


S85

020406080100120140160180200220

ppm

21.8

29.9

39.8

40.4

50.0

50.6

66.9

119.1

123.3

125.0

125.4

125.5

131.2

133.5

142.1

146.2

198.6

Infrared spectrum (Thin Film, NaCl) of compound 2j.

13C NMR (125 MHz, CDCl3) of compound 2j.


S86

-180-160-140-120-100-80-60-40-20020

ppm

-62.4

19F NMR (470 MHz, CDCl3) of compound 2j.


S87

01

23

45

67

89

10

ppm

3.00

2.97

1.00

1.00

1.00

2.00

1.00

2.01

1.99

4.07

1.02

1.03

1.01

1.10

1.66

1.68

1.69

1.70

1.71

1.88

1.88

1.90

1.90

1.91

1.91

2.16

2.16

2.19

2.19

2.41

2.42

2.42

2.42

2.42

2.43

2.43

2.43

2.44

2.44

2.44

2.50

2.50

2.52

2.53

2.63

2.63

2.64

2.64

2.65

2.66

2.66

2.66

2.89

2.90

2.90

2.91

2.91

2.92

2.93

3.77

3.78

3.78

3.79

3.80

3.80

3.80

3.80

3.81

3.82

3.82

3.83

4.64

4.65

4.65

4.65

4.65

4.65

4.82

4.82

4.82

4.82

5.88

5.89

5.90

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2k

.

OMe

NO

2k

Me


S88

020406080100120140160180200220

ppm

21.9

23.3

24.7

33.3

44.9

44.9

45.6

50.5

67.0

115.0

115.0

115.0

125.0

142.4

145.6

200.3

Infrared spectrum (Thin Film, NaCl) of compound 2k.

13C NMR (125 MHz, CDCl3) of compound 2k.


S89

01

23

45

67

89

10

ppm

3.01

1.00

1.05

2.02

1.02

2.05

1.05

2.07

4.04

1.05

1.03

1.08

1.17

1.80

1.81

1.82

1.83

2.01

2.02

2.02

2.03

2.05

2.05

2.44

2.45

2.45

2.46

2.46

2.46

2.46

2.47

2.47

2.47

2.48

2.52

2.55

2.66

2.66

2.67

2.67

2.68

2.68

2.68

2.69

2.69

2.69

2.70

2.84

2.84

2.87

2.87

2.88

2.89

2.89

2.89

2.90

2.90

2.91

2.92

2.92

3.78

3.79

3.79

3.80

3.80

3.81

3.81

3.81

3.82

3.82

3.83

3.83

5.15

5.15

5.15

5.16

5.27

5.28

5.28

5.28

5.91

5.91

5.92

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2l

.

OMe

NO

2l

Cl


S90

020406080100120140160180200220

ppm

21.8

22.5

32.8

45.6

46.1

50.5

67.0

116.7

125.1

138.9

145.6

199.1

Infrared spectrum (Thin Film, NaCl) of compound 2l.

13C NMR (125 MHz, CDCl3) of compound 2l.


S91

01

23

45

67

89

10

ppm

2.92

2.01

4.91

1.00

1.00

2.98

1.95

1.98

1.98

1.00

1.00

1.07

1.47

1.49

1.50

1.63

1.64

1.64

1.65

1.66

1.67

1.68

1.70

1.71

1.83

1.84

1.86

2.19

2.21

2.22

2.23

2.31

2.32

2.33

2.35

2.36

2.37

2.39

2.40

2.41

2.42

2.43

2.44

2.57

2.58

2.60

2.61

2.62

2.68

2.69

2.70

2.72

2.73

5.01

5.02

5.02

5.04

5.69

5.71

5.71

5.72

5.73

5.74

5.74

5.75

5.76

5.78

5.83

5.84

5.85

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2m

.

OMe

N

2m


S92

020406080100120140160180200220

ppm

21.9

21.9

22.1

22.1

24.5

26.1

33.4

41.4

41.4

45.5

51.6

118.0

124.7

134.4

147.0

200.8

Infrared spectrum (Thin Film, NaCl) of compound 2m.

13C NMR (100 MHz, CDCl3) of compound 2m.


S93

01

23

45

67

89

10

ppm

3.01

1.02

1.01

3.01

1.01

1.01

2.00

4.00

4.10

2.00

0.96

1.03

1.65

1.66

1.67

1.67

1.68

1.68

1.70

1.79

1.80

1.80

1.82

1.82

1.83

1.83

1.99

2.18

2.19

2.19

2.20

2.20

2.24

2.25

2.26

2.26

2.26

2.34

2.34

2.35

2.35

2.35

2.36

2.36

2.36

2.36

2.37

2.37

2.37

2.37

2.38

2.89

2.90

2.91

2.91

2.92

2.93

3.67

3.68

3.69

5.01

5.01

5.01

5.02

5.03

5.04

5.04

5.04

5.04

5.04

5.05

5.05

5.05

5.06

5.06

5.06

5.69

5.71

5.71

5.72

5.72

5.74

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2n

.

OMe

NO

Me

2n


S94

020406080100120140160180200220

ppm

19.76

21.82

28.66

32.46

41.29

44.93

50.64

68.07

118.03

134.34

141.60

153.45

202.05

Infrared spectrum (Thin Film, NaCl) of compound 2n.

13C NMR (125 MHz, CDCl3) of compound 2n.


S95

01

23

45

67

89

10

ppm

5.00

1.02

2.00

6.06

1.03

1.02

3.05

0.96

2.00

0.94

0.95

1.00

1.03

1.03

1.05

1.06

1.16

1.33

1.36

1.62

1.62

1.63

1.63

1.64

1.65

1.65

1.65

1.68

1.69

1.70

1.70

1.71

1.71

1.72

1.72

1.72

1.73

1.73

1.74

1.74

1.75

1.85

1.85

1.87

1.88

2.17

2.19

2.29

2.30

2.33

2.33

2.33

2.34

2.34

2.34

2.35

2.35

2.35

2.36

2.36

5.01

5.01

5.02

5.04

5.04

5.04

5.05

5.05

5.05

5.05

5.05

5.06

5.06

5.70

5.72

5.73

6.49

6.50

6.50

6.50

6.51

6.51

O 2o

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2o

.


S96

020406080100120140160180200220

ppm

22.0

23.0

26.5

26.9

26.9

32.7

33.0

33.3

36.4

41.4

44.4

117.9

134.6

140.5

143.4

203.2

Infrared spectrum (Thin Film, NaCl) of compound 2o.

13C NMR (100 MHz, CDCl3) of compound 2o.


S97

01

23

45

67

89

10

ppm

3.00

1.03

2.08

1.04

2.03

2.08

4.03

2.05

1.00

1.02

1.09

2.13

2.15

2.17

2.18

2.21

2.22

2.22

2.23

2.47

2.47

2.47

2.50

2.51

3.01

3.02

3.02

3.03

3.04

3.06

3.07

3.08

3.08

3.09

3.76

3.77

3.78

4.99

5.00

5.01

5.01

5.02

5.02

5.04

5.05

5.05

5.05

5.57

5.57

5.59

5.59

5.59

5.59

5.60

5.61

5.61

5.62

5.62

5.63

5.63

5.64

5.64

5.64

5.66

5.66

6.25

6.25

6.26

6.26

O

NO

2p

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 2p

.


S98

020406080100120140160180200220

ppm

24.0

37.2

42.7

42.7

46.8

48.6

66.7

118.2

131.6

133.9

149.3

209.1

Infrared spectrum (Thin Film, NaCl) of compound 2p.



S99

01

23

45

67

89

10

ppm

3.50

1.04

1.03

1.11

3.11

2.11

1.00

0.93

0.74

1.10

1.69

1.70

1.71

1.72

1.74

1.74

1.76

1.86

1.88

1.88

1.90

1.91

1.93

1.95

2.14

2.17

2.19

2.19

2.19

2.21

2.21

2.22

2.31

2.32

2.32

2.32

2.33

2.33

2.33

2.34

2.34

2.34

2.35

2.35

2.35

2.35

2.36

2.36

2.36

2.37

2.37

5.00

5.00

5.01

5.01

5.01

5.03

5.03

5.04

5.04

5.04

5.06

5.06

5.06

5.07

5.07

5.07

5.08

5.64

5.64

5.66

5.67

5.67

5.69

5.69

5.73

6.01

6.02

6.04

6.07

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 3.

OMe

HO

3


S100

020406080100120140160180200220

ppm

20.36

21.79

33.58

41.07

44.07

116.96

118.74

133.51

145.57

200.31

Infrared spectrum (Thin Film, NaCl) of compound 3.



S101

01

23

45

67

89

10

ppm

3.00

1.00

0.96

1.16

3.34

2.30

1.10

1.21

0.99

2.11

2.15

1.17

1.80

1.81

1.81

1.82

1.96

1.96

1.97

2.25

2.26

2.28

2.43

2.44

2.44

2.45

2.45

2.45

2.45

2.46

2.46

2.46

2.46

2.46

2.47

2.47

2.47

2.47

2.48

2.48

2.49

5.07

5.07

5.07

5.08

5.09

5.09

5.09

5.09

5.11

5.11

5.11

5.11

5.73

5.75

5.77

5.79

6.33

6.34

6.34

6.89

6.91

6.91

6.91

6.92

7.02

7.03

7.03

7.03

7.04

7.04

7.04

7.04

7.25

7.25

7.25

7.26

7.26

7.26

7.27

7.28

7.28

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 4.

OMe

PhHN

4


S102

020406080100120140160180200220

ppm

21.0

22.2

33.1

41.5

44.4

115.0

118.5

118.5

118.7

118.8

121.1

129.3

129.3

134.0

134.7

142.3

200.0


13C NMR (125 MHz, CDCl3) of compound 4.


S103

01

23

45

67

89

10

ppm

3.00

1.02

1.01

1.01

1.01

2.02

2.00

1.02

1.00

1.00

1.00

1.00

1.00

1.29

2.04

2.05

2.05

2.07

2.07

2.08

2.22

2.23

2.23

2.24

2.25

2.26

2.36

2.37

2.39

2.40

2.55

2.57

2.58

2.59

3.01

3.02

3.03

3.04

3.04

3.05

3.05

3.07

5.10

5.11

5.11

5.12

5.12

5.13

5.13

5.14

5.14

5.14

5.14

5.84

5.87

5.88

5.90

7.14

7.14

7.15

7.16

7.16

7.17

7.17

7.36

7.36

7.38

7.38

7.38

7.39

7.39

7.48

7.48

7.48

7.49

7.50

7.50

7.65

7.65

7.66

7.67

7.67

7.67

9.75

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 5.

OMe

5

H N


S104

020406080100120140160180200220

ppm

18.4

22.1

35.7

41.5

45.5

112.9

118.3

120.4

121.4

125.9

127.0

128.0

130.3

134.4

138.7

196.3




S105

01

23

45

67

89

10

ppm

2.92

3.02

0.97

0.99

1.00

0.99

2.01

3.01

2.03

2.04

1.00

2.11

2.01

1.17

1.41

1.42

1.44

1.96

1.96

1.97

1.98

1.99

1.99

2.00

2.10

2.12

2.12

2.13

2.13

2.14

2.15

2.25

2.27

2.28

2.28

2.28

2.29

2.30

2.30

2.40

2.40

2.41

2.41

2.42

2.42

2.43

2.44

3.10

3.11

3.11

3.11

3.12

3.12

3.13

3.14

3.85

4.42

4.44

4.45

4.46

5.06

5.06

5.06

5.07

5.09

5.09

5.09

5.09

5.10

5.10

5.11

5.11

5.11

5.11

5.73

5.75

5.75

5.76

5.77

5.79

6.93

6.95

7.35

7.37

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 6.

OMe

6

NN

MeO

2C

MeO


S106

020406080100120140160180200220

ppm

14.3

14.6

18.6

21.6

34.9

40.8

46.7

55.7

60.5

61.3

113.8

118.8

127.1

132.8

132.9

133.6

135.2

140.0

160.0

162.3

192.7




S107

01

23

45

67

89

10

ppm

3.00

1.00

1.05

2.04

6.06

4.09

2.06

1.01

1.07

2.02

1.03

2.05

1.15

1.85

1.86

1.86

1.95

1.96

1.98

2.33

2.33

2.34

2.34

2.34

2.35

2.35

2.36

2.63

2.65

2.65

2.66

2.66

2.68

2.68

2.69

2.69

2.70

2.70

2.71

2.71

2.72

3.52

3.53

3.54

5.06

5.06

5.06

5.08

5.08

5.08

5.09

5.09

5.10

5.10

5.10

5.10

5.76

5.78

5.79

6.82

6.83

6.84

6.84

7.23

7.24

7.24

7.24

7.24

7.25

7.25

7.25

7.26

7.31

7.32

7.33

7.36

7.36

7.37

7.38

7.38

7.38

7.39

7.40

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d 7.

OMe

NO

7Ph


S108

020406080100120140160180200220

ppm

21.9

29.0

32.2

41.4

44.8

51.2

67.5

115.4

118.2

127.9

128.0

128.2

129.8

134.2

140.5

141.2

145.7

202.7




S109

01

23

45

67

89

10

ppm

1.97

0.99

1.00

4.88

4.88

5.57

5.57

5.60

5.60

5.60

5.61

5.61

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d SI

1 .

NCO

Cl

O

SI1


S110

020406080100120140160180200220

ppm

69.7

108.9

118.5

118.5

132.9

143.5

Infrared spectrum (Thin Film, NaCl) of compound SI1.

13C NMR (125 MHz, CDCl3) of compound SI1.


S111

01

23

45

67

89

10

ppm

2.97

2.00

2.00

1.81

1.81

1.82

4.73

4.74

5.08

5.08

5.09

5.09

5.09

5.09

1 H N

MR

(500

MH

z, C

DC

l 3) o

f com

poun

d SI

3.

NCO

Me

O

SI3


S112

020406080100120140160180200220

ppm

19.3

72.0

109.3

116.4

116.4

137.2

144.1

Infrared spectrum (Thin Film, NaCl) of compound SI3.

13C NMR (125 MHz, CDCl3) of compound SI3.

Date post:	22-Mar-2021
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