Post on 06-Aug-2020
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.