S1

(IPr)CuF-Catalyzed α-Site Regiocontrolled trans-Hydrofluorination

of Ynamides

Guohao Zhu, Shineng Qiu, Yang Xi, Yao Ding, Dongming Zhang, Rong Zhang,

Guangke He∗ and

Hongjun Zhu∗

Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Nanjing

Tech University, Nanjing 211816, People’ s Republic of China

*E-mails: hegk@njtech.edu.cn; zhuhj@njtech.edu.cn.

Spectra of compounds Z-2a-4o

Spectra of compound Z-2a p 2-4 Spectra of compound Z-2k p 33-35

Spectra of compound Z-3a p 5 Spectra of compound Z-3k p 36

Spectra of compound Z-2b p 6-8 Spectra of compound Z-2l p 37-39

Spectra of compound Z-2c p 9-11 Spectra of compound Z-3l p 40

Spectra of compound Z-2d p 12-14 Spectra of compound Z-2m p 41-43

Spectra of compound Z-2e p 15-17 Spectra of compound Z-2n p 44-46

Spectra of compound Z-2f p 18-20 Spectra of compound Z-2o p 47-49

Spectra of compound Z-2g p 21-23 Spectra of compound Z-2p p 50-52

Spectra of compound Z-2h p 24-26 Spectra of compound 4a p 53-55

Spectra of compound Z-2i p 27-29 Spectra of compound 4o p 56-58

Spectra of compound Z-2j p 30-32 Detailed discussions p 59-60

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2016

109

87

65

43

21

0pp

m

−0.0000

1.6214

3.95063.95393.97333.99053.99384.43384.45084.45454.4737

5.91546.0027

7.21347.23187.25027.25897.31207.33167.35027.44547.4641

2.10

2.09

1.00

1.362.102.10

zgh−2−176−H

170

160

150

140

130

120

110

100

9080

7060

5040

3020

100

ppm

44.0761

62.0310

76.728477.045977.3637

99.263999.3998

127.1742127.1974128.3079128.3810128.5405132.1570132.2110144.4725147.1063

154.1797

zgh−2−176−C

−30

−40

−50

−60

−70

−80

−90

−100

−110

−120

−130

−140

−150

ppm

−99.2869

zgh−2−176−F

109

87

65

43

21

0pp

m

0.0000

1.6044

4.18064.18984.19974.20384.20894.22084.23004.45764.47864.4978

6.69486.77247.26217.30637.32097.32427.32757.34787.36787.38597.44277.46107.4648

2.06

2.06

1.00

1.012.032.03

zgh−6−41(2)−H

109

87

65

43

21

0pp

m

−0.0000

1.6363

2.3356

3.93593.93943.95883.97583.97934.42574.44284.44624.4657

5.86255.9493

7.12807.14807.25847.33837.3586

3.29

2.16

2.18

1.00

2.092.19

zgh−2−158−H

170

160

150

140

130

120

110

100

9080

7060

5040

3020

100

ppm

20.1695

43.1707

61.0706

75.783976.102876.4204

98.579098.7232

127.1743127.2470128.2251136.0400136.0621143.0354145.6695

153.3398

zgh−2−158−C

−30

−40

−50

−60

−70

−80

−90

−100

−110

−120

−130

−140

−150

ppm

−99.8240

zgh−2−158−F

1110

98

76

54

32

10

ppm

−0.0000

1.5836

3.81463.94003.94703.96363.96673.97933.98624.43434.44294.45574.45884.46264.46464.47414.48275.82855.83355.91425.91936.86216.88397.26317.39177.4136

3.222.10

2.09

1.00

2.08

2.07

zgh−2−178−H

210

200

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

100

ppm

44.3281

55.2408

62.1106

76.779577.097077.4152

100.0712100.2221

113.9769

124.6053124.6629129.6482129.7229

143.3047145.9325

154.5499158.7374158.7656

zgh−2−178−C

−40

−50

−60

−70

−80

−90

−100

−110

−120

−130

−140

−150

ppm

−101.1844

zgh−2−178−F

109

87

65

43

21

0pp

m

0.0000

1.5827

3.96483.96823.98473.98784.00474.00814.44964.46644.47004.4895

5.90645.9935

7.26237.28067.30217.36487.3862

2.12

2.14

1.00

2.002.13

zgh−6−63−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

100

ppm

43.9588

62.0486

76.739377.056477.3746

97.715597.8515

128.7164129.4867129.5608130.7747130.8279132.6984132.7330144.8934147.5247153.9960

zgh−6−63−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−98.9613

zgh−6−63−F

1110

98

76

54

32

10

ppm

0.0000

1.5828

3.96583.96883.98633.98824.00564.00864.44994.47044.4898

5.89605.9834

7.26257.29897.32027.43517.4564

2.11

2.13

1.00

2.052.15

zgh−2−161−H

200

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

43.9258

62.0502

76.741177.058577.3763

97.616797.7486

120.8242120.8556129.7788129.8528131.2374131.2916131.6737144.9764147.6081153.9525

zgh−2−161−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−98.6946

zgh−2−161−F

109

87

65

43

21

0pp

m

0.0000

1.5768

3.96153.98084.00134.44954.47074.4894

5.89355.9797

6.99977.02147.04317.26227.40717.42097.42887.4425

2.10

2.15

1.00

2.05

2.20

zgh−6−64−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

44.0833

62.0768

76.740377.058877.3755

98.464598.6074

115.4007115.6148128.2607128.2941128.3466129.9232129.9993130.0774144.2729146.9043

154.2216160.5061160.5378162.9642162.9966

zgh−6−64−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−114.1784

−100.4135

zgh−6−64−F

1110

98

76

54

32

10

ppm

−0.0000

1.7066

2.5927

4.01044.03014.04834.05034.46994.49064.5098

6.03776.1270

7.27267.50527.52637.90137.9223

3.01

2.01

2.03

1.00

2.02

2.03zgh−2−180−H

200

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

26.5454

43.7797

62.0890

76.803877.122077.4406

96.479596.5977

128.1245128.2015128.6266135.1678135.1877137.4290137.4839146.1508148.7939153.6775

197.5101

zgh−2−180−C

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−96.7446

zgh−2−180−F

1110

98

76

54

32

10

ppm

−0.0000

1.6125

4.04644.04874.06614.06864.08614.08874.49614.51304.51664.5360

6.14166.2316

7.26847.55087.5730

8.16428.1865

2.08

2.11

1.00

2.07

2.05

zgh−2−164−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

43.5673

62.0575

76.731677.049277.3672

94.716694.8244

123.9102128.4866128.5652139.5730139.6247145.9779147.0727149.7137153.3479

zgh−2−164−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−95.5354

zgh−2−164−F

1110

98

76

54

32

10

ppm

−0.0000

1.5958

3.91353.93333.95324.41384.43474.45375.83535.86295.91425.94176.53106.57066.89476.92236.93436.96187.20277.22097.23887.25577.29207.31137.32997.39397.4128

2.07

2.07

1.00

0.98

1.031.032.102.13

zgh−5−174−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

43.9153

62.1076

76.775677.093177.4114

98.973099.1360

119.4508126.3261127.5851128.6554131.4584131.4922137.2174137.2293144.8673147.4659153.8592

zgh−5−174−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−103.1892

zgh−5−174−F

109

87

65

43

21

0pp

m

0.0000

1.5736

3.94413.96393.98394.43804.45534.45854.4778

6.00936.0960

7.21607.22047.22757.26027.28297.28997.3012

2.14

2.19

1.00

0.952.11

zgh−6−8−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

44.1635

62.0912

76.748677.065777.3842

94.573794.7398

123.0869123.1592125.5356127.6790127.7389132.5815

144.1283146.7406

154.2052

zgh−6−8−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−99.0002

zgh−6−8−F

109

87

65

43

21

0pp

m

0.00000.88900.90620.92371.31971.33911.35681.37391.37851.39671.41001.55342.11682.12202.13542.15352.17103.81853.83843.85834.37814.39864.41794.84624.86544.88454.92564.94474.9640

7.2613

3.30

4.65

2.09

2.13

2.09

1.00

zgh−6−2−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

13.7541

22.101923.313331.246031.2656

44.4848

62.0377

76.727377.045277.3628

101.2680101.4988

144.1145146.6589

155.0170

zgh−6−2−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−105.8722

zgh−6−2−F

109

87

65

43

21

0pp

m0.92060.93881.31501.33281.35071.37001.38871.40661.45681.47491.47681.49371.50681.51341.53101.88412.15702.17592.19392.20572.22472.24264.00264.01084.02204.03004.04294.05114.38334.40424.42375.81915.8964

7.2987

3.16

2.152.10

2.10

2.08

2.09

1.00

zgh−6−2(2)−H

109

87

65

43

21

0pp

m1.30581.31421.32371.34181.36181.37551.39221.40981.42641.44571.65702.10532.11102.12442.12992.14312.14812.16122.16683.82533.82933.84513.84693.84843.86523.86924.38484.40184.40524.42474.84614.86534.88464.92544.94474.96397.2723

3.26

4.472.59

2.19

2.10

2.09

1.00

zgh−6−75−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

13.9914

22.385823.616028.817228.836031.2668

44.4721

62.0427

76.728077.046277.3634

101.3236101.5552

144.0553146.5986

155.0363

zgh−6−75−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−105.8377

zgh−6−75−F

109

87

65

43

21

0pp

m

−0.00000.88470.90210.91921.29591.30521.31411.32291.33221.47271.49051.50871.52731.54592.14692.16572.18422.19562.21452.23284.00304.01124.02254.03044.04334.05154.38274.40084.40364.42305.81915.8964

7.2946

3.17

4.332.14

2.12

2.10

2.10

1.00

zgh−6−75(2)−H

109

87

65

43

21

0pp

m

−0.0000

1.54452.81582.83932.84992.87343.22493.23443.25903.26864.14604.15874.16824.18104.29754.31894.34014.44144.45164.46444.47464.48474.49504.50735.96506.04997.18597.20567.24377.24687.25747.26077.27727.28027.29437.31877.33727.35577.37527.48447.50257.5049

1.07

1.07

1.091.111.08

1.00

2.033.154.542.42

zgh−5−177−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

38.690538.7051

56.4175

66.8045

76.774777.092677.4107

103.1627103.3171127.4743127.5399127.5611128.5615128.5913128.6340129.0434129.2478132.0604132.1191134.7020143.4950146.1540154.2872

zgh−5−177−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−97.9325

zgh−5−177−F

109

87

65

43

21

0pp

m

0.0000

2.87533.41133.43033.45113.72913.73173.74923.7687

5.81335.90316.16506.18487.15087.16927.18757.27727.29647.31547.42517.4440

3.59

2.71

2.35

1.00

0.11

0.942.942.44

zgh−6−99−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

30.9952

41.404844.0504

76.802777.121177.4393

96.159196.3076

126.2420126.2630128.0082128.0819128.3983133.4619133.5172

146.8300149.4490

156.4090

zgh−6−99−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−97.9714

zgh−6−99−F

1110

98

76

54

32

10

ppm

0.0000

1.5514

3.04843.23913.2428

5.87175.94657.25887.26657.28507.29057.30007.30317.30627.33617.35547.36927.37327.47957.49787.5009

3.002.97

1.00

1.522.112.10

zgh−6−51−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

36.120838.4106

76.787177.105677.4232

108.1848108.3976

128.1914128.2162128.6239128.8819128.9609131.6596131.7316

146.7710149.5839

zgh−6−51−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−93.7703

zgh−6−51−F

1110

98

76

54

32

10

ppm

−0.0000

3.02473.1898

5.73125.75875.79855.82616.60546.64516.85216.87966.89186.91937.23827.25657.27447.30877.32827.34637.40867.4278

3.043.05

1.00

0.991.041.342.212.20

zgh−6−84−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

35.906638.3833

76.750277.067877.3854

108.4359108.6843119.4916119.5037126.6366128.1840128.7130134.3195134.3562136.6419136.6542146.6885149.4798

zgh−6−84−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−97.8449

zgh−6−84−F

109

87

65

43

21

0pp

m

0.0000

1.58133.91033.92563.93413.94913.95203.96073.97574.09374.11334.11744.13704.16384.33684.35884.37854.40094.44024.45554.46294.47804.48524.50106.87576.99637.40897.56837.57267.58137.5860

1.031.041.061.08

1.00

2.922.04

zgh−6−68−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

42.3683

62.8817

76.725377.042677.3607

87.556489.3416

128.5016128.5475128.8215130.0956130.1240133.2931133.4960

152.8331

168.2474168.5193

zgh−6−68−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−173.7974

zgh−6−68−F

−111

109

87

65

43

21

0pp

m

0.0000

2.8334

3.2143

6.40066.52147.26697.44867.46117.46707.47167.4958

2.97

2.89

1.00

4.90zgh−6−83−H

190

180

170

160

150

140

130

120

110

100

9080

7060

5040

3020

10pp

m

32.631132.6439

40.5523

76.745777.063577.3818

89.147090.9645

128.4942128.5388129.2263129.2380130.4496130.4791132.5484132.7452

168.6591168.9173

zgh−6−83−C

−180

−160

−140

−120

−100

−80

−60

−40

−20

0pp

m

−167.3190

zgh−6−83−F

59

Detailed discussions on the (IPr)CuF-catalyzed reaction mechanism:

The regioselectivity of the hydrofluorination was controlled by the ligand1 of the

copper-catalyst. We think that the overall regioselectivity may be controlled in the

coordination process (A→B or A’→B’), though we cannot provide any more direct

evidence. For the cone-shaped (Ph3P)3 ligand, the chelation of Cu(I) cation to the

ynamido carbonyl oxygen contributes to the regioselective attack of fluoride

nucleophile at β-carbon of ynamides.2

In contrast, the larger steric hindrance of IPr

ligand suppresses the chelation process, thus fluoride nucleophile tends to attack

α-carbon of ynamides.

References:

1. Differences between N-heterocyclic carbene and phosphine ligands: (a) R. H.

Crabtree, J. Organomet. Chem., 2005, 690, 5451-5457; (b) H. Clavier and S. P.

Nolan, Chem. Commun., 2010, 46, 841-861; (c) M. N. Hopkinson, C. Richter, M.

Schedler and F. Glorius, Nature, 2014, 510, 485-496.

2. For the chelation of the organometal reagent to the carbamoyl moiety of ynamides:

(a) Y. Fukudome, H. Naito, T. Hata and H. Urabe, J. Am. Chem. Soc., 2008, 130,

1820-1821; (b) H. Yasui, H. Yorimitsu and K. Oshima, Bull. Chem. Soc. Jpn.,

(PPh3)3 as ligand

Shape of phosphine ligand: cone-shaped

IPr as ligand

NHCs are in general more electron-donating than phosphines

Shape of NHCs ligand: fan-shaped

60

2008, 81, 373-379; (c) B. Gourdet and H. W. Lam, J. Am. Chem. Soc., 2009, 131,

3802-3803; (d) K. A. DeKorver, H. Li, A. G. Lohse, R. Hayashi, Z. Lu, Y. Zhang

and R. P. Hsung, Chem. Rev., 2010, 110, 5064-5106; (e) Y. Minko, M. Pasco, L.

Lercher, M. Botoshansky and I. Marek, Nature, 2012, 490, 522-526.