Supporting Information - Royal Society of Chemistry · Supporting Information Copper-mediated...

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Supporting Information

Copper-mediated intramolecular aminofluorination of

1,3-dienes by using nucleophilic fluorine reagent

Zuxiao Zhang, Pinhong Chen,* and Guosheng Liu*

Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis,

Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese

Academy of Sciences, 345 Lingling Road, Shanghai, China, 200032

Email: pinhongchen@sioc.ac.cn; gliu@mail.sioc.ac.cn

Content

I. General Considerations

II. Synthesis of substrates

III. General procedure for aminofluorination of dienes

IV. Optimization of reaction conditions

V. Mechanistic Studies

VI. New compounds characterization.

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2018

I. General Considerations

All commercially available compounds were purchased from Aldrich or Alfa Aesar.

NMR spectra were recorded on a Varian Inova 400 (400 MHz for 1H; 376 MHz for 19F; 100 MHz for 13C) spectrometer. The chemical shifts (δ) are given in parts per

million relative to internal standard TMS (0 ppm for 1H) and CDCl3 (77.0 ppm for 13C). Flash column chromatography was performed on silica gel 60 (particle size

200-400 mesh ASTM, purchased from Yantai, China) and eluted with petroleum

ether/ethyl acetate. Acetonitrile was dried by refluxing over CaH2 and distillated

before use.

II. Synthesis of substrates 1. General synthesis for substrates 1a-1d and 1g-1m

Synthesis of S2: In a flame-dried round-bottom flask, the alcohol S1 (50 mmol) was dissolved in

THF (100 mL) under nitrogen, n-butyl lithium (60 mmol, 1.2 equiv) was carefully added at -78 oC.

The mixture was stirred at -78 oC for 0.5 h, then warmed to room temperature and stirred for

another 1.5 h. A solution of tosyl chloride (50 mmol, 1.0 equiv) in THF (50 mL) was added at -78

oC. Then the mixture was warmed to room temperature and stirred for 2.0 h. To another

flame-dried round-bottom, n-butyllithium (75 mmol, 1.5 equiv) was added to a solution of

diisopropylamine (75 mmol, 1.5 equiv) and THF (70 mL) at -78 oC. The mixture was stirred for

0.5 h at -78 oC and another 1.0 h at 0 oC. After that, a solution of nitrile (50 mmol, 1.0 equiv) in

THF (30 mL) was added at -78 oC. After stirring for 0.5 h, the mixture was added to the prepared

alcohol tosylate solution. The reaction was stirred at room temperature overnight, and then

quenched with NH4Cl aq. The mixture was extracted with Et2O and the combined organic phase

was dried over anhydrous Na2SO4. After concentration, the residue was purified by column

chromatography on silica gel with a gradient eluant of petroleum ether and ethyl acetate to afford

S2 as light yellow oil in 35% to 86% yield.

Synthesis of 1: In a dried round-bottom flask, a solution of nitrile S2 (1 equiv) in Et2O was added

to a mixture of lithium aluminium hydride (1.5 equiv) in anhydrous Et2O carefully under nitrogen.

The mixture was stirred at room temperature for 0.5 h and quenched with NaOH aq. The mixture

was filtered and the filtrate was concentrated in vacuo, and dissolved that in dichloromethane in a

glass flask. Et3N (1.5 equiv) and tosyl chloride (1.2 equiv) were added. The mixture was stirred

overnight and then washed with water. Then organic phase was concentrated in vacuo and the

residue was purified by column chromatography on silica gel with a gradient eluant of petroleum

ether and ethyl acetate to afford the diene substrates 1 as colorless solids.

2. General synthesis for substrates 1e-1f

In a 250 mL-flask, malonate (1 equiv) was slowly added to a mixture of sodium hydride (1.1

equiv) in THF at 0 oC under N2. The mixture was stirred for 3.5 h and then a solution of

(2E,4E)-1-bromohexa-2,4-diene in THF was carefully added. After stirring at room temperature

overnight, the mixture was carefully quenched with water and the aqueous phase was extracted

with Et2O. After concentration in vacuo, the residue S3 was dissolved in THF under N2, then

TsNHCH2OTs (4.0 equiv) and DBU (2.5 equiv) were added. The mixture was stirred at room

temperature overnight. The mixture was washed with water and the aqueous phase was extracted

with Et2O. After concentration, the residue was purified by column chromatography on silica gel

with a gradient eluant of petroleum ether and ethyl acetate to afford 1i or 1j as a white solid.

III. General procedure for aminofluorination of 1,3-dienes:

Condition A: In a dried glass tube, the diene (0.2 mmol, 1.0 equiv), CuBr2 (110 mg,

0.5 mmol, 2.5 equiv), and AgF (88 mg, 0.7 mmol, 3.5 equiv) were dissolved in

acetonitrile (1.0 mL) under N2. After the reaction mixture was stirred at room

temperature for 24 h, the solvent was removed under vacuum. The residue was

purified by column chromatography on silica gel with a gradient eluant of petroleum

ether and ethyl acetate to afford the aminofluorination product.

Condition B: In a dried glass tube, the diene (0.2 mmol, 1.0 equiv) and CuBr2 (48.4

mg, 0.22 mmol, 1.1 equiv) was dissolved in acetonitrile (1.0 mL) under N2. Then

Et3N•3HF (50 μL, 3.0 equiv) was added. After the reaction mixture was stirred at

room temperature for 24 h, the solvent was removed under vacuum. The residue was

purified by column chromatography on silica gel with a gradient eluant of petroleum

ether and ethyl acetate to afford the aminofluorination product.

IV. Optimization of reaction conditions

The reactions were carried out according to general procedure aminofluorination with

condition A in 0.1 mmol scale, results were listed in Table S1.

Table S1 Screening silver fluoride amount

Table S2 Screening different solvents

Table S3 Screening amount of CuBr2 with Et3N•3HF

V. Mechanistic Studies

1. Stepwise reaction

Contdition B: In a dried glass tube, the diene (0.1 mmol, 1.0 equiv) and CuBr2 (55 mg,

0.25 mmol, 2.5 equiv) were dissolved in acetonitrile (0.5 mL) under N2. After the

reaction mixture was stirred at room temperature for 1.0 h, AgF (44 mg, 0.35 mmol,

3.5 equiv) was added, and the mixture was stirred for another 10 h. After that, the

mixture was filtered through a short pad of silica gel, the filtrate was concentrated and

determined by 19F NMR.

Condition C: In a dried glass tube, the diene (0.1 mmol, 1.0 equiv) and CuBr2 (55 mg,

0.25 mmol, 2.5 equiv) were dissolved in acetonitrile (0.5 mL) under N2. After the

reaction mixture was stirred at room temperature for 1.0 h, the mixture was filtered

through a short pad of silica gel to remove Cu(II) salt, then AgF (44 mg, 0.35 mmol,

3.5 equiv) was added, and the mixture was stirred for another 10 h. After that, the

mixture was filtered through a short pad of silica gel, the filtrate was concentrated and

determined by 19F NMR.

Table S4 Control experiments

2. Reactions with radical scavengers

In a dried glass tube, the diene (0.1 mmol, 1.0 equiv), CuBr2 (55 mg, 0.25 mmol,

2.5 equiv), AgF (44 mg, 0.35 mmol, 3.5 equiv) and radical scavenger (0.5 equiv) were

dissolved in acetonitrile (0.5 mL) under N2. After the reaction mixture was stirred at

room temperature for 24 h. After that, the mixture was filtered through a short pad of

silica gel, the filtrate was concentrated and determined by 19F NMR. The results were

listed in Table S4.

(E)-4-(4,4-dimethyl-1-tosylpyrrolidin-2-yl)but-3-en-2-one (4) 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0

Hz, 2H), 6.77 (dd, J = 16.0, 8.4 Hz, 1H), 6.12 (d, J = 16.0 Hz, 1H),

4.16 (q, J = 8.4 Hz, 1H), 3.25 (d, J = 10.4 Hz, 1H), 3.16 (d, J = 10.4 Hz,

1H), 2.42 (s, 3H), 2.24 (s, 3H), 1.81 (dd, J = 12.8, 8.0 Hz, 1H), 1.64

(dd, J = 12.4, 8.4 Hz, 1H), 1.06 (s, 3H), 0.68 (s, 3H). HRMS (ESI) calcd. for [M+Na]+ C17

H23NO3SNa: 344.1296, found: 344.1302.

Table S4 Reactions with radical scavengers

V. New compounds characterizations N-((4E, 6E)-2,2-dimethylocta-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1a)

1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H), 7.29

(d, J = 8.0 Hz, 2H), 5.96 – 5.90 (m, 2H), 5.58 (dq, J = 13.6,

6.8 Hz 1H), 5.4 (dt, J = 15.2, 7.5 Hz, 1H), 4.37 (t, J = 6.8 Hz,

1H), 2.66 (d , J = 6.8 Hz, 2H), 2.42 (s, 3H), 1.94 (d, J = 7.6 Hz, 2H), 1.73 (d, J = 7.2 Hz, 3H), 0.84

(s, 6H). 13C NMR (100 MHz, CDCl3) δ 143.2, 136.8, 133.4, 131.3, 129.6, 127.7, 127.0, 126.7,

52.7, 42.6, 34.5, 24.9, 21.5, 18.0. HRMS (EI) calcd. for [M]+ C17H25NO2S: 307.1606, found:

307.1607.

N-((4E, 6E)-2,2-dimethylocta-4,6-dien-1-yl)-4-nitrobenzenesulfonamide (1b)

1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 8.8 Hz,

2H), 8.04 (d, J = 8.8 Hz, 2H), 5.96 – 5.90 (m, 2H),

5.59 (dq, J = 13.2, 6.4 Hz, 1H), 5.43 (dt, J = 14.0,

7.2 Hz, 1H), 5.08 (t, J = 5.6 Hz, 1H), 2.72 (d, J =

6.4 Hz, 2H), 1.94 (d, J = 6.4 Hz, 2H), 1.72 (d, J = 6.4 Hz, 3H), 0.85 (s, 6H). 13C NMR (100 MHz,

CDCl3) δ 149.9, 145.7, 133.7, 131.1, 128.2, 126.1, 124.4, 52.8, 42.6, 34.6, 24.9, 18.0. HRMS (EI)

calcd. for [M]+ C16H22N2O4S: 338.1300, found: 338.1302.

N-((4E, 6E)-2,2-dimethylocta-4,6-dien-1-yl)methanesulfonamide (1c)

1H NMR (400 MHz, CDCl3) δ 5.95 – 5.91 (m, 2H), 5.51 –

5.44 (m, 2H), 5.16 (t, J = 6.8 Hz, 1H), 2.84 (s, 3H), 2.77 (d,

J = 6.8 Hz, 2H), 1.92 (d, J = 7.6 Hz, 2H), 1.64 (d, J = 6.4 Hz, 3H), 0.82 (s, 6H). 13C NMR (100

MHz, CDCl3) δ 133.0, 131.0, 127.0, 126.3, 52.3, 42.1, 39.0, 34.2, 24.2, 17.5. HRMS (EI) calcd.

for [M]+ C11H21NO2S: 231.1293, found: 231.1294.

N-((4E, 6E)-2,2-diphenylocta-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1d)

1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.0 Hz, 2H), 7.26 –

7.17 (m, 8H), 7.04 (d, J = 8.0 Hz, 4H), 5.89 – 5.77 (m, 2H),

5.53 (dq, J = 13.6, 6.4 Hz, 1H), 4.97 (dt, J = 14.4, 7.2 Hz, 1H), 3.91 (t, J = 6.4 Hz, 1H), 3.51 (d, J

= 6.4 Hz, 2H), 2.88 (d, J = 7.6 Hz, 2H), 2.41 (s, 3H), 1.86 (d, J = 6.8 Hz, 3H). 13C NMR (100

MHz, CDCl3) δ 144.5, 143.3, 136.1, 134.4, 131.3, 129.6, 128.3, 128.0, 127.7, 127.1, 126.6, 125.3,

49.7, 49.2, 39.9, 21.4, 18.0. HRMS (EI) calcd. for [M]+ C27H29NO2S: 431.1919, found: 431.1922.

Dimethyl 2-((2E, 4E)-hexa-2,4-dien-1-yl)-2-(((4-methylphenyl)sulfonamido)methyl)malonate

1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.4 Hz,

2H),7.30 (d, J = 8.0 Hz, 2H), 6.04 – 5.92 (m, 2H), 5.64

(dq, J = 14.4, 6.8 Hz, 1H), 5.29 (dt, J = 14.8, 7.2 Hz, 1H),

5.09 (t, J = 6.8 Hz, 1H), 3.69 (s, 6H), 3.31 (d, J = 6.8 Hz, 2H), 2.68 (d, J = 7.6 Hz, 2H), 2.42 (s,

3H), 1.71 (d, J = 6.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.5, 143.8, 137.3, 135.8, 131.2,

130.1, 129.8, 127.4, 123.3, 58.8, 53.1, 45.9, 35.9, 21.8, 18.3. HRMS (ESI) calcd. for [M+Na]+

C19H25NO6SNa: 418.1295, found: 438.1300.

Diethyl 2-((2E, 4E)-hexa-2,4-dien-1-yl)-2-(((4-methylphenyl)sulfonamido)methyl)malonate

1H NMR (400 MHz, CDCl3) δ 7.21 (d, J = 8.4 Hz, 2H), 7.29 (d,

J = 8.4 Hz, 2H), 6.04 – 5.91 (m, 2H), 5.60 (dq, J = 13.6, 6.8 Hz,

1H), 5. 28 (dt, J = 11.2, 7.6 Hz, 1H), 5.12 (t, J = 6.8 Hz, 1H), 4.15 (q, J = 7.2 Hz, 4H), 3.29 (d, J =

6.8 Hz, 2H), 2.67 (d, J = 7.6 Hz, 2H), 2.41 (s, 3H), 1.71 (d, J = 6.4 Hz, 3H), 1.23 (t, J = 6.8 Hz,

6H). 13C NMR (100 MHz, CDCl3) δ 169.8, 143.4, 136.8, 135.3, 130.8, 129.7, 129.3, 127.0, 123.1,

61.8, 58.1, 45.6, 35.5, 21.5, 18.0, 13.9. HRMS calcd. for [M+Na]+ C21H29NO6SNa: 446.1608,

found: 446.1613.

N-((1-((2E, 4E)-hexa-2,4-dien-1-yl)cyclohexyl)methyl)-4-methylbenzenesulfonamide (1g)

(d, J = 8.4 Hz, 2H), 5.96 – 5.92 (m, 2H), 5.56 (dq, J = 13.6,

6.4 Hz, 1H), 5.36 (dt, J = 14.8, 6.8 Hz,1H), 4.70 – 4.55 (m,

1H), 2.72 (d, J = 6.8 Hz, 2H), 2.42 (s, 3H), 2.00 (d, J = 6.4 Hz, 2H), 1.73 (d, J = 6.4 Hz, 3H), 1.37

– 1.35 (m, 6H), 1.26 – 1.23 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 143.2, 136.8, 133.4, 131.3,

129.6, 127.7, 127.1, 126.4, 49.3, 39.1, 36.8, 33.3, 25.9, 21.5, 21.2, 18.0. HRMS (EI) calcd. for

[M]+ C20H29NO2S: 347.1919, found: 347.1921.

N-((4E, 6E)-2,2-dimethylnona-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1h)

1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.4 Hz, 2H),

7.73 (d, J = 8.4 Hz, 2H), 5.97 – 5.93 (m, 2H), 5.64 – 5.60

(m, 1H), 5.45 – 5.41 (m, 1H), 4.46 (t, J = 6.6 Hz, 1H), 2.66

(d, J = 6.8 Hz, 2H), 2.43 (s, 3H), 2.06 (dq, J = 7.6, 7.6 Hz, 2H), 1.95 (d, J = 7.2 Hz, 2H), 1.00 (t, J

= 7.6 Hz, 3H), 0.84 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 143.1, 136.8, 134.7, 133.4, 129.5,

128.9, 126.9, 126.8, 52.6, 42.5, 34.5, 25.4, 24.8, 21.4, 13.4. HRMS (EI) calcd. For [M]+

C18H27NO2S: 321.1763, found: 321.1760.

N-((4E, 6E)-2,2-dimethyldeca-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1i)

7.29 (d, J = 8.0 Hz, 2H), 5.98 – 5.89 (m, 2H), 5.57 – 5.52

(m, 1H), 5.45 – 5.40 (m, 1H), 5.18 (t, J = 6.4 Hz, 1H), 2.66 (d, J = 7.2 Hz, 2H), 2.40 (s, 3H), 2.04

(q, J = 7.2 Hz, 2H), 1.94 (d, J = 8.0 Hz, 2H), 1.41 (tq, J = 7.2, 7.2 Hz, 2H), 0.90 (t, J = 7.6 Hz,

3H), 0.82 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 143.0, 136.9, 133.4, 132.9, 130.1, 129.5, 127.0,

126.9, 52.7, 42.5, 34.6, 34.5, 24.8, 22.4, 21.4, 13.6. HRMS (EI) calcd. For [M]+ C19H29NO2S:

335.1919, found: 335.1917.

N-((4E, 6E)-2,2-dimethyldodeca-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1j)

7.24 (d, J = 8.4 Hz, 2H), 5.96 – 5.92 (m, 2H), 5.60 – 5.54

(m, 1H), 5.45 – 5.40 (m, 1H), 4.54 (t, J = 6.8 Hz, 1H), 2.66 (d, J = 6.8 Hz, 2H), 2.40 (s, 3H), 2.03

(q, J = 6.8 Hz, 2H), 1.89 (d, J = 7.2 Hz, 2H), 1.40 – 1.25 (m, 6H), 0.84 (t, J = 6.4 Hz, 3H), 0.76 (s,

6H). 13C NMR (100 MHz, CDCl3) δ 143.0, 136.9, 133.6, 129.8, 129.7, 129.6, 127.1, 126.8, 52.7,

42.7, 34.6, 32.6, 31.4, 28.9, 24.9, 22.5, 21.5, 14.0. HRMS (EI) calcd. for [M]+ C21H33NO2S:

363.2232, found: 363.2229.

N-((4E, 6E)-8-methoxy-2,2-dimethylocta-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1k)

7.31 (d, J = 8.4 Hz, 2H), 6.13 (dd, J = 14.4, 10.4 Hz,

1H), 6.00 (dd, J = 14.4, 10.4 Hz, 1H), 5.65 – 5.58 (m, 2H), 4.63 (t, J = 6.8 Hz, 1H), 3.93 (d, J =

6.0 Hz, 2H), 3.33 (s, 3H), 2.67 (d, J = 6.8 Hz, 2H), 2.42, (s, 3H), 1.98 (d, J = 8.0 Hz, 2H), 0.84 (s,

6H). 13C NMR (100 MHz, CDCl3) δ 143.3, 136.9, 132.7, 132.6, 130.2, 129.7, 127.7, 127.0, 72.7,

57.9, 52.8, 42.6, 34.6, 24.8, 21.5. HRMS (EI) calcd. for [M]+ C18H27NO3S: 337.1712, found:

337.1709.

(E)-N-(2,2-dimethylhepta-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1l)

(d, J = 8.0 Hz, 2H), 6.28 (dt, J = 16.8, 10.8 Hz, 1H), 5.99

(dd, J = 14.4, 10.4 Hz, 1H), 5.59 (dt , J = 14.4, 7.6 Hz, 1H),

5.11 (d, J = 16.8 Hz, 1H), 4.99 (d, J = 10.0 Hz, 1H), 4.73 (t, J = 7.6 Hz, 1H), 2.69 (d, J = 6.8 Hz,

2H), 2.43 (s, 3H), 1.98 (d, J = 7.6 Hz, 2H), 0.87 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 143.3,

136.9, 134.0, 131.8, 129.6, 127.0, 115.6, 52.7, 42.5, 34.6, 24.8, 21.5. Known compound, the data

is consistent with literature.S1

(E)-N-(2,2-dimethylhepta-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1m)

1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.0 Hz , 2H), 7.30

(d, J = 8.0 Hz, 2H), 6.22 (t, J = 10.8 Hz, 1H), 5.75 (d, J =

10.4 Hz, 1H), 5.44 (dt, J = 14.4, 7.6 Hz, 1H), 4.66 (t, J = 6.4

Hz, 1H) , 2.67 (d, J = 7.2 Hz, 2H), 2.42 (s, 3H), 1.98 (d, J = 7.6 Hz, 2H), 1.76 (s, 3H), 1.73 (s, 3H),

0.84 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 143.1, 136.9, 133.5, 129.8, 129.6, 127.0, 126.6, 124.8,

52.7, 42.8, 34.5, 25.8, 24.8, 21.4, 18.1. HRMS (EI) calcd. for [M]+ C18H27NO2S: 321.1763, found:

321.1764.

N-((4E, 6E)-2,2-dimethyl-7-phenylhepta-4,6-dien-1-yl)-4-methylbenzenesulfonamide (1n)

(d, J = 7.2 Hz, 2H), 7.32 – 7.28 (m, 4H), 7.23 (t, J = 7.6 Hz,

1H), 6.74 (dd, J = 15.6, 10.4 Hz, 1H), 6.46 (d, J = 15.6 Hz, 1H), 6.20 (dd, J = 14.8, 10.4 Hz, 1H),

5.74 (dt, J = 15.6, 8.0 Hz, 1H), 4.69 (t, J = 6.8 Hz, 1H), 2.71 (d, J = 6.8 Hz, 2H), 2.40 (s, 3H), 2.06

(d, J = 7.6 Hz, 2H), 0.89 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 143.3, 137.4, 136.9, 133.6, 130.8,

130.5, 129.7, 128.8, 128.5, 127.3, 127.0, 126.1, 52.7, 42.8, 34.8, 25.0, 21.5. HRMS (EI) calcd. for

[M]+ C22H27NO2S: 369.1762, found: 369.1765.

(E)-2-(3-fluorobut-1-en-1-yl)-4,4-dimethyl-1-tosylpyrrolidine (2a)

1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0

Hz, 2H), 5.72 – 5.68 (m, 2H), 5.00 – 4.94 (dm, J = 47.6 Hz, 1H), 4.10 –

4.06 (m, 1H), 3.20 – 3.13 (m, 2H), 2.41 (s, 3H), 1.77 (dd, J = 15.6, 7.6

Hz, 1H), 1.56 (dd, J = 13.2, 8.4 Hz, 1H), 1.35 (dd, J = 23.6, 6.0 Hz, 3H),

1.04 (s, 3H), 0.72 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -167.6 –

-167.8 (m). 13C NMR (100 MHz, CDCl3) δ 143.2, 135.5, 133.5 (d, J = 11.0 Hz), 130.5 (d, J = 19.7

Hz), 129.4, 127.4, 89.8 (d, J = 162.3 Hz), 61.2, 60.8, 47.3 (d, J = 1.5 Hz), 37.6, 26.3, 25.9, 21.4,

20.9 (d, J = 23.9 Hz).

HRMS (ESI) calcd. for [M+Na]+ C17H24FNO2SNa: 348.1404, found: 348.1397.

(E)-2-(3-fluorobut-1-en-1-yl)-4,4-dimethyl-1-((4-nitrophenyl)sulfonyl)pyrrolidine (2b)

1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 8.8 Hz, 2H), 8.00 (d, J = 8.8 Hz, 2H), 5.79 – 5.71 (m,

1H), 5.55 – 5.49 (m, 1H), 5.04 – 4.89 (dm, J = 48.4 Hz, 1H), 4.28 – 4.24 (m, 1H), 3.38 (d, J =

10.0 Hz, 1H), 3.15 (d, J = 9.6 Hz, 1H), 1.89 – 1.84 (m, 1H), 1.58 – 1.50 (m, 1H), 1.41 (dd, J =

23.6, 6.0 Hz, 3H), 1.09 (s, 3H), 0.89 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -168.1 – 168.5 (m). 13C NMR (100 MHz, CDCl3) δ 149.8, 145.4, 132.3 (d, J = 10.6 Hz), 132.0 (d, J = 19.3 Hz), 128.5

(d, J = 8.3 Hz), 124.1, 88.8 (d, J = 163.5 Hz), 61.2, 61.0, 47.3, 37.9, 25.9, 25.8, 21.0 (d, J = 23.9

Hz). HRMS (ESI) calcd. for [M+Na]+ C16H21FN2O4SNa: 379.1098, found: 379.1115;

(E)-2-(3-fluorobut-1-en-1-yl)-4,4-dimethyl-1-(methylsulfonyl)pyrrolidine (2c)

1H NMR (400 MHz, CDCl3) δ 5.81 – 5.71 (m, 2H), 5.13 (dt, J = 48.4,

6.0 Hz, 1H), 4.35 – 4.33 (m, 1H), 3.40 (dd, J = 10.0, 1.2 Hz, 1H), 3.08

(d, J = 10.0 Hz, 1H), 2.86 (s, 3H), 1.99 – 1.94 (m, 1H), 1.62 – 1.57 (m,

1H), 1.40 (dd, J = 23.6, 6.4 Hz, 3H), 1.11 (s, 3H), 1.09 (s, 3H). 19F

NMR (376 MHz, CDCl3) δ -168.9 – -169.2 (m). 13C NMR (100 MHz,

CDCl3) δ 132.5 (d, J = 11.1 Hz), 132.1 (d, J = 18.6 Hz), 88.8 (d, J = 163.6 Hz), 60.6, 60.5, 47.6,

40.3, 37.9, 26.0, 21.1 (d, J = 23.1 Hz). HRMS (ESI) calcd. for [M+Na]+ C11H20FNO2SNa:

272.10910, found: 272.1092.

(E)-2-(3-fluorobut-1-en-1-yl)-4,4-diphenyl-1-tosylpyrrolidine (2d)

1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.0 Hz, 2H), 7.16 – 7.08

(m, 12H), 5.65 – 5.56 (m, 1H), 5.43 – 5.36 (m, 1H), 4.94 – 4.79 (dm,

J = 48.4 Hz, 1H), 4.16 – 4.01 (m, 3H), 2.75 (dd, J = 12.8, 7.6 Hz, 1H),

2.44 (dd, J = 12.8, 7.6 Hz, 1H), 2.36 (s, 3H), 1.25 (dd, J = 23.2, 6.4

Hz, 3H). 19F NMR (376 MHz, CDCl3) δ -168.3 – -168.6 (m). 13C

NMR (100 MHz, CDCl3) δ 144.8, 144.3, 143.0, 132.3 (d J = 11.2 Hz), 131.5 (d, J = 20.1 Hz),

129.3, 128.4, 128.3, 127.2, 127.1, 126.6, 126.5, 126.4, 126.3, 89.4 (d, J = 126.8 Hz), 60.1, 57.8,

52.5, 45.1, 21.3, 20.7 (d, J = 23.8 Hz). HRMS (ESI) calcd. for [M+H]+ C27H29NO2FS: 450.1897,

found: 450.1888.

Dimethyl (E)-5-(3-fluorobut-1-en-1-yl)-1-tosylpyrrolidine-3,3-dicarboxylate (2e)

1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.0 Hz, 2H), 7.27 (d, J

= 8.0 Hz, 2H), 5.72 – 5.66 (m, 2H), 5.04 – 5.88 (dm, J = 48.0 Hz,

1H), 4.17 – 4.13 (m, 1H), 4.00 (d, J = 10.8 Hz, 1H), 3.83 (d, J =

11.2 Hz, 1H), 3.67 (s, 3H), 3.54 (s, 3H), 2.52 (dd, J = 13.2, 8.0 Hz,

1H), 2.38 (s, 3H), 2.21 (dd, J = 13.2, 6.4 Hz, 1H), 1.33 (dd, J =

24.0, 6.8 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ -173.2 – -173.4 (m). 13C NMR (100 MHz,

CDCl3) δ 169.4, 169.1, 143.8, 134.8, 132.0 (d, J = 19.7 Hz), 131.3 (d, J = 11.2 Hz), 129.6, 127.7,

89.6 (d, J = 163.2 Hz), 60.4, 58.2, 53.9 (d, J = 5.9 Hz), 53.2, 39.5, 29.7, 21.5, 21.0 (d, J = 23.8 Hz).

HRMS (ESI) calcd. for [M+Na]+ C19H24NO6FSNa: 436.1201, found: 436.1199.

Diethyl (E)-5-(3-fluorobut-1-en-1-yl)-1-tosylpyrrolidine-3,3-dicarboxylate (2f)

J = 8.4 Hz, 2H), 5.71 – 5.58 (m, 2H), 5.08 – 4.92 (dm, J = 48.0

Hz, 1H), 4.21 – 4.12 (m, 2H), 4.08 – 4.00 (m, 2H), 3.89 – 3.86

(m, 1H), 2.57 (dd, J = 13.2, 8.0 Hz, 1H), 2.42 (s, 3H), 2.24 (dd,

J = 12.8, 6.4 Hz, 1H), 1.39 (dd, J = 23.2, 6.4 Hz, 3H), 1.24 (t, J

= 7.2 Hz, 3H), 1.19 (t, J = 7.2 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ -168.6 – -169.0 (m). 13C

NMR (100 MHz, CDCl3) δ 169.0, 168.7, 143.6, 134.9, 131.9 (d, J = 20.1 Hz), 131.3 (d, J = 11.1

Hz), 129.5, 127.7, 89.6 (d, J = 162.9 Hz), 62.2, 60.5, 58.3, 53.8, 53.7, 39.5, 21.5, 20.9 (d, J = 23.8

Hz), 13.8, 13.7. HRMS (ESI) calcd. for [M+Na]+ C21H28NO6FSNa: 464.1514, found: 464.1513.

(E)-3-(3-fluorobut-1-en-1-yl)-2-tosyl-2-azaspiro[4.5]decane (2g)

1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4

Hz, 2H), 5.71 – 5.68 (m, 2H), 5.09 – 5.95 (dm, J = 46.8 Hz, 1H), 4.03 –

3.99 (m, 1H), 3.33 (d, J = 10.4 Hz, 1H), 3.16 (d, J = 10.4 Hz, 1H), 2.41

(s, 3H), 1.83 (dd, J = 12.8, 6.4 Hz, 1H), 1.53 (dd, J = 12.8, 8.4 Hz, 1H),

1.40 (dd, J = 23.6, 6.4 Hz, 3H), 1.43 – 1.25 (m, 8H), 0.99 – 0.92 (m,

2H). 19F NMR (376 MHz, CDCl3) δ -167.3 – 167.7 (m). 13C NMR (100

MHz, CDCl3) δ 143.2, 133.7 (d, J = 10.4 Hz), 13.4 (d, J = 20.1 Hz), 129.4, 127.5, 127.4, 89.8 (d, J

= 162.1 Hz), 60.1, 58.7, 45.3, 41.4, 36.3, 34.5, 25.8, 23.6, 22.9, 21.4, 21.1 (d, J = 23.8 Hz). HRMS

calcd. for [M+H]+ C20H29FNO2S: 366.1898, found: 366.1892.

(E)-2-(3-fluoropent-1-en-1-yl)-4,4-dimethyl-1-tosylpyrrolidine (2h)

1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 2H), 7.30 (d, J =

8.4 Hz, 2H), 5.72 – 5.65 (m, 2H), 4.76 (dq, J = 48.4, 6.0 Hz, 1H),

4.14 – 4.07 (m, 1H), 3.20 – 3.14 (m, 2H), 2.41 (s, 3H), 1.78 – 1.73

(m, 3H), 1.57 (dd, J = 12.8, 8.4 Hz, 1H), 1.05 (s, 3H), 0.95 (t, J = 7.6

Hz, 3H), 0.73 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -175.6 – -175.8 (m). 13C NMR (100 MHz,

CDCl3) δ 143.2, 134.3 (d, J = 11.2 Hz), 129.4, 129.3 (d, J = 20.1 Hz), 127.5, 127.4, 94.6 (d, J =

166.6 Hz), 61.2, 60.9, 47.4, 37.6, 28.3 (d, J = 23.1 Hz), 26.4, 26.0, 21.4, 8.9 (d, J = 5.2 Hz).

HRMS (ESI) calcd. for [M+Na]+ C18H26FNO2SNa: 362.1560, found: 362.1571.

(E)-2-(3-fluorohex-1-en-1-yl)-4,4-dimethyl-1-tosylpyrrolidine (2i)

1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 2H), 7.30 (d, J

= 8.0 Hz, 2H), 5.70 – 5.57 (m, 2H), 4.86 – 4.72 (dm, J = 49.2 Hz,

1H), 4.09 – 4.03 (m, 1H), 3.16 – 3.09 (m, 2H), 2.42 (s, 3H), 1.78

(dd, J = 12.4, 7.6 Hz, 1H), 1.64 – 1.25 (m, 4H), 1.57 (dd, J = 12.4,

8.0 Hz, 1H), 1.05 (s, 3H), 0.94 (t, J = 7.2 Hz, 3H), 0.74 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -174.8 – -175.2 (m). 13C NMR (100 MHz, CDCl3) δ 143.2, 135.6,

134.1 (d, J = 11.2 Hz), 129.5 (d, J = 20.1 Hz), 129.4, 127.5, 93.3 (d, J = 165.3 Hz), 61.2, 60.9,

47.4, 37.6, 37.4 (d, J = 22.1 Hz), 26.4, 26.0, 21.5. 18.0 (d, J = 4.7 Hz), 13.8. HRMS (ESI) calcd.

for [M+Na]+ C19H28FNO2S: 376.1717, found: 376.1725.

(E)-2-(3-fluorooct-1-en-1-yl)-4,4-dimethyl-1-tosylpyrrolidine (2j) 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 2H), 7.30 (d,J = 8.0 Hz, 2H), 5.70 – 5.65 (m,

2H), 4.89 – 4.75 (dm, J = 48.4 Hz, 1H), 4.12 – 4.08 (m, 1H), 3.21 –

3.14 (m, 2H), 2.41 (s, 3H), 1.74 (dd, J = 12.8, 8.0 Hz, 1H), 1.68 –

1.52 (m, 2H), 1.57 (dd, J = 12.4, 8.0 Hz, 1H), 1.43 – 1.23 (m, 6H),

1.05 (s, 3H), 0.90 (t, J = 6.4 Hz, 3H), 0.74 (s, 3H). 19F NMR (376

MHz, CDCl3) δ -174.6 – -174.8 (m). 13C NMR (100 MHz, CDCl3)

δ 143.2, 135.6, 134.1 (d, J = 10.9 Hz), 129.6 (d, J = 19.8 Hz), 129.4,

127.5, 92.7 (d, J = 165.2 Hz), 61.2, 60.9, 47.4, 37.6, 35.3 (d, J = 22.0 Hz), 31.5, 26.4, 26.0, 24.4 (d,

J = 4.6 Hz), 22.5, 21.5, 14.0. HRMS (ESI) calcd. for [M+Na]+ C21H32FNO2SNa: 404.2030, found:

404.2038.

(E)-2-(3-fluoro-4-methoxybut-1-en-1-yl)-4,4-dimethyl-1-tosylpyrrolidine (2k)

J = 8.0 Hz, 2H), 5.86 – 5.80 (m, 1H), 5.73 – 5.64 (m, 1H), 5.08

– 4.95 (dm, J = 49.6 Hz, 1H), 4.14 (q, J = 8.0 Hz, 1H), 3.52 (d,

J = 5.2 Hz, 1H), 3.48 – 3.45 (m, 1H), 3.41 (s, 3H), 3.21 – 3.15

(m, 2H), 2.43 (s, 3H), 1.78 (dd, J = 12.4, 7.6 Hz, 1H), 1.58 (dd,

J = 12.8, 8.0 Hz, 1H), 1.05 (s, 3H), 0.73 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -182.4 – -182.6

(m). 13C NMR (100 MHz, CDCl3) δ 143.3, 135.8 (d, J = 10.4 Hz), 135.5, 129.5, 127.5, 125.6 (d, J

= 19.0 Hz), 91.3 (d, J = 170.3 Hz), 74.6 (d, J = 22.4 Hz), 61.2, 60.8, 59.3, 47.2, 37.7, 26.4, 26.0,

21.5. HRMS (ESI) calcd. for [M+Na]+ C18H26FNO3SNa: 378.1510, found: 378.1519.

(E)-2-(1-bromo-3-phenylallyl)-4,4-dimethyl-1-tosylpyrrolidine (3n)

1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 8.0 Hz, 2H), 7.33 – 7.22

(m, 5H), 7.16 (d, J = 8.0 Hz, 2H), 6.30 (d, J = 15.6 Hz, 1H), 6.06 (dd,

J = 16.0, 8.4 Hz, 1H), 4.23 – 4.19 (m, 1H), 4.07 (t, J = 7.6 Hz, 1H),

3.41 (d, J = 12.4 Hz, 1H), 2.94 (d, J = 12.4 Hz, 1H), 2.34 (s, 3H), 2.12

(dd, J = 14.0, 4.0 Hz, 1H), 1.84 (dd, J = 14.0, 8.0 Hz, 1H), 1.11 (s,

3H), 1.07 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 143.2, 136.8, 135.9, 134.9, 129.3, 128.5, 128.1,

127.7, 126.6, 124.6, 65.9, 55.5, 49.7, 45.4, 32.8, 27.7, 26.5, 21.4. HRMS calcd. for [M+H]+

C17H25NO3S: 323.1628, found: 324.1534.

Reference: [1] H. Yamamoto, I.Sasaki, S. Shiomi, N. Yamasaki and H. Imagawa, Org. Lett., 2012, 14, 2266.

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