FULL PAPER DOI: 10.1002/asia.201402643
Copper(I)-Catalyzed Regioselective Addition of Nucleophilic Silicon Across Terminal and Internal Carbon–Carbon Triple Bonds Chinmoy K. Hazra,[a, b] Carolin Fopp,[a] and Martin Oestreich*[a] Abstract: The copper(I) alkoxide-catalyzed release of a silicon-based cuprate reagent from a silicon–boron pronucleophile is applied to the addition across carbon–carbon triple bonds. Commercially available CuBr·Me2S was found to be a general precatalyst
that secures high regiocontrol for both aryl- and alkyl-substituted terminal as well as internal alkynes. The solvent Keywords: alkynes · copper · regioselectivity · silicon · silylmetalation
Introduction
carbon–silicon bond-forming reactions were (re-)investigated using this approach, namely 1,4-[10] and 1,2-addition,[11, 12] as well as allylic substitution reactions.[13] Loh and co-workers had also elaborated a procedure for the addition across selected terminal alkynes in which the steric demand of a monodentate phosphine ligand secures high branched selectivity (Scheme 1, top).[14] Later, Hoveyda and co-workers
A silicon atom attached to an alkene is an often used linchpin in synthetic chemistry, and improved methods for the preparation of vinylic silanes are, despite several general procedures known today, still welcome.[1] A convenient way to access these building blocks is by regiocontrolled addition of a silicon–metal bond across a terminal carbon–carbon triple bond, typically with the newly formed bonds in syn relationship. Conversely, electronically and sterically unbiased internal alkynes with no directing group continue to be a challenging class of substrates. Silicon-based cuprates are reagents of choice to achieve that transformation,[2] and (R3Si)2CuLi·LiCN used to be the standard source of the silicon nucleophile.[3] Protocols catalytic in copper rely on either R3SiMgMe[4] or (R3Si)2Zn[5] as precursors of anionic silicon.[6] Zincates R3SiZnR2Li and (R3Si)3ZnLi in the presence of a copper catalyst[7] as well as novel dianion-type zincates R3SiZnR(OR)2Mg2Cl alone[8] do also transfer silicon groups onto carbon–carbon triple bonds. Recently, a new approach to the catalytic generation of silicon-based copper reagents emerged.[9] The silicon nucleophile is released from a bench-stable pronucleophile by transmetalation of its silicon–boron bond with a copper(I) alkoxide, a process that is believed to proceed through a sbond metathesis. In a short period of time, all fundamental
Scheme 1. Regioselective addition of catalytically generated silicon-based cuprates across terminal alkynes: branched-selective (top, Loh and coworkers, 2011)[14] and linear-selective (bottom, Hoveyda and co-workers, 2013).[15] Mes = mesityl, pin = pinacolato.
[a] Dr. C. K. Hazra, C. Fopp, Prof. Dr. M. Oestreich Institut fr Chemie, Technische Universitt Berlin Strasse des 17. Juni 115, 10623 Berlin (Germany) Fax: (+ 49) 30-314-28829 E-mail: [email protected]
disclosed the corresponding linear-selective addition, employing an N-heterocyclic carbene as a supporting ligand (Scheme 1, bottom).[15] Aside from these reports, the related 1,4-addition to acceptor-substituted triple bonds was independently published by four laboratories this year (not shown).[16] We report here a general method for the linearselective addition without added ligand. Moreover, the same setup also allows for regioselective addition across internal alkynes.
[b] Dr. C. K. Hazra NRW Graduate School of Chemistry Organisch-Chemisches Institut Westflische Wilhelms-Universitt Mnster Corrensstrasse 40, 48149 Mnster (Germany) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201402643.
Chem. Asian J. 2014, 9, 3005 – 3010
greatly influences the regioisomeric ratio, favoring the linear regioisomer with terminal acceptors. This facile protocol even allows for the transformation of internal acceptors with remarkable levels of regio- and diastereocontrol.
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Results and Discussion
ity was excellent for 1 a!3 a (aryl substitution) but poor for 2 a!4 a (alkyl substitution). Changing the solvent from THF to, for example, 1,2-dichloroethane then greatly improved the b/a ratio of the latter (b:a = 93:7, entry 4) while maintaining the high regiocontrol of the former (b:a = 99:1, entry 3). The base also had an influence, and Cs2CO3 was superior to NaOMe in several control experiments; therefore, the remaining experiments collected in Table 1 were performed with Cs2CO3 as base and various copper(I) salts in three different solvents (entries 5–18). It is clear from this data that there is no obvious trend, and the poor regiocontrol seen for 2 a with CuCN in THF (entries 2 and 6) as well as the inverted regioselectivity for 1 a with CuBr in THF (entry 9) remain unexplained. The b-selectivity is generally high but b/a ratios and yields were best with CuBr·Me2S as a copper source, and b:a = 99:1 for 1 a!3 a (entry 17) and b:a = 93:7 for 2 a!4 a (entry 14) were obtained in THF and DCE, respectively. We then subjected six more examples with electronically modified aryl rings to the optimized procedure (1 b–1 g, Table 2). These reacted cleanly no matter what the X group was, thereby affording the linear vinylic silanes b-E-3 b–3 g as single regio- and diastereomers. With no phosphine or Nheterocyclic carbene ligand at the copper(I) catalyst as in previous studies, the b-regioisomer is highly favored, and similar results were achieved with CuCN as the copper source. A terminal carbon–carbon triple bond with an isopropenyl instead of an aryl group yielded, depending on the solvent, the linear vinylic silane with b:a > 99:1 and 93:7, respectively (5!6, Scheme 2).
We had used the copper(I)-catalyzed transmetalation approach in the racemic variants of 1,2-additions[11a, 12a] and allylic substitution[13a] without any additional ligands. Reaction times increased significantly in the presence of both phosphines[13a] and N-heterocyclic carbenes[11a, 12b, 13b] as supporting ligands, particularly documented by the enantioselective procedures recently developed by us.[12b, 13b] For that reason, and in contrast to the work of Hoveyda and co-workers[15] (cf. Scheme 1, bottom), we decided to investigate the related addition across terminal carbon–carbon triple bonds without the addition of ligands. Screening of copper source/base/solvent combinations with and without an alcohol as additive required the variation of four parameters, and selected results are summarized in Table 1. The reactions in the abTable 1. Screening of copper source/base/solvent combinations for the regioselective addition of nucleophilic silicon across terminal triple bonds.
Entry
R
Catalyst
Solvent
t [h]
b/a ratio[a]
Yield [%][b]
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu
CuCN CuCN CuCN CuCN CuCN CuCN CuI CuI CuBr CuBr CuCl CuCl CuBr·Me2S CuBr·Me2S CuBr·Me2S CuBr·Me2S CuBr·Me2S CuBr·Me2S
THF THF DCE DCE THF THF THF THF THF THF THF THF THF THF DCM DCM DCE DCE
7 8 5 6 8 8 8 8 8 10 8 8 10 8 12 10 12 10
99:1 50:50 99:1 93:7 99:1 66:34 97:3 88:12 36:64 92:8 99:1 87:13 96:4 93:7 94:6 85:15 99:1 92:8
91 99 94[c] 67[c] 95 50 80 76 93 81 99 77 86 89 79 72 96 76
Table 2. Linear-selective addition across aryl-substituted terminal alkynes.
[a] Determined by GLC and 1H NMR analysis prior to purification. [b] Yield determined by GLC analysis using tetracosane as internal standard. [c] Combined yield of analytically pure regioisomers after purification by flash column chromatography on silica gel. DCM = dichloromethane, DCE = 1,2-dichloroethane.
sence of MeOH were generally slower, and we believe that residual MeOH (in NaOMe) or traces of H2O serve as proton sources at small scale. We also tested representative aryl- and alkyl-substituted alkynes 1 a and 2 a, hoping that one catalyst system would work for both. Our search for the optimal setup commenced with CuCN/NaOMe/THF, added MeOH, and a slight excess of Me2PhSiBpin[17] that had served us well before (entries 1 and 2).[12a] The regioselectiv-
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b/a ratio[a]
Yield [%][b]
1 a (X = H) 1 b (X = Me) 1 c (X = OMe) 1 d (X = Br) 1 e (X = F)
99:1 99:1 99:1 99:1 99:1
89 96 93 88 85
6
1f
99:1
83
7
1g
99:1
91
Entry
Terminal alkyne
1 2 3 4 5
Vinylic silane
[a] Determined by GLC and 1H NMR analysis prior to purification. [b] Combined yield of analytically pure regioisomers after purification by flash column chromatography on silica gel.
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Table 4. Screening of copper source/base/solvent combinations for the regioselective addition of nucleophilic silicon across an internal triple bond.
Scheme 2. Linear-selective addition across an enyne to yield a 1,3-diene.
Application of the CuBr·Me2S/Cs2CO3 combination in THF to a handful of typical alkyl-substituted alkynes 2 a–2 d was reasonably successful (Table 3, entries 1–4). The b/ a ratios were not as good as in Hoveydas case,[15] but increased steric bulk at the terminus also secured excellent regiocontrol (2 d!4 d, entry 4). Replacement of the tBu by a Me3Si group had the same beneficial effect (2 e!4 e, entry 5).
b/a ratio[a]
Yield [%][b]
2a
93:7
65
2
2b
88:12
85
3
2c
86:14
80
4
2d
99:1
84
5
2e
98:2[c]
85
Terminal alkyne
1
Vinylic silane
Base
Solvent
t [h]
b/a ratio[a]
Yield [%][b]
1 2 3 4 5 6
CuCN CuCN CuBr CuBr·Me2S CuBr·Me2S CuBr·Me2S
NaOMe Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3
THF THF THF THF DCM DCE
12 12 12 12 12 8
80:20 81:19 82:18 83:17 98:2 85:15
74 99 83 82 92 85
ry to a-selective platinum- and palladium-catalyzed hydrosilylation of the same class of compounds.[22] We chose the conversion of 1-phenylprop-1-yne into the corresponding 1,2-disubstituted vinylic silane as a model reaction (7 a!8 a, Table 4). The standard CuCN/NaOMe/THF combination was moderately selective (entry 1), yet substantially exceeding the regioselectivity we had found with the copper(I)-catalyzed methodology using (Me2PhSi)2Zn as the source of the silicon nucleophile (b:a = 62:38 with Et instead of Me).[5] A screening of copper(I) salts with Cs2CO3 as base and THF as solvent led to no improvement (entries 2–4). However, the solvent emerged as crucial again, and DCM but not DCE resulted in synthetically useful regioselectivity in favor of the b-isomer (entries 5 and 6). With the optimal solvent for internal acceptors at hand, we probed the electronic effect of an X substituent in the para position of the aryl group (X = CF3, CN, and OMe). For the electron-withdrawing CF3 and CN groups, the desired addition across the triple bond occurred with good regio- and diastereoselectivity (7 b!8 b and 7 c!8 c, Scheme 3), but the substrate with the electron-donating OMe group reacted sluggishly with partial decomposition (not shown). A CN group in the ortho position that could potentially coordinate to the copper(I) catalyst was also tolerated (7 d!8 d and 7 e!8 e, Scheme 3). As electron-deficient aryl groups facilitate the addition of the silicon nucleophile, we included heteroaryl groups (pyridin-2-yl and pyrazin-2-yl) into this survey, thereby creating a more pronounced electronic bias. Both heterocycles allowed for regioselective addition across the internal carbon–carbon triple bond (7 f–7 h!8 f–8 h, Scheme 3).
[a] Determined by GLC and 1H NMR analysis prior to purification. [b] Combined yield of analytically pure regioisomers after purification by flash column chromatography on silica gel. [c] E/Z = 94:6.
The results obtained with terminal carbon–carbon triple bonds illustrate that relatively simple catalyst systems lead to excellent to good regioselectivities, and it was this simplicity that prompted us to also test the related internal acceptors. These substrates are extremely challenging,[18] and there is, to date, essentially no solution to the problem using stoichiometric or catalytic silicon-based cuprates.[1] We had reported promising regioselectivity (b:a = 92:8) for two 1phenylalk-1-ynes using [(Et2N)Ph2Si]2Zn together with CuI as a catalyst several years ago.[5] Electronically biased systems equipped with an electron-withdrawing group, usually carbonyl or carboxyl, do indeed react with superb regiocontrol,[16] but these 1,4-additions are cognate to those of a,bunsaturated acceptors.[10] That b-selectivity is complementa-
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Catalyst
[a] Determined by GLC and 1H NMR analysis prior to purification. [b] Yield determined by GLC analysis using tetracosane as internal standard.
Table 3. Linear-selective addition across alkyl- and silyl-substituted terminal alkynes.
Entry
Entry
Conclusions The present contribution completes the existing methodology of copper(I)-catalyzed conversion of carbon–carbon triple bonds into the vinylic silane motif using silicon–boron
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0.28 mmol, 2.5 equiv), Me2PhSiBpin (72 mg, 0.28 mmol, 2.5 equiv), MeOH (12 mg, 0.37 mmol, 3.4 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using cyclohexane as eluent afforded the title compound (E)-8 a (16 mg, 58 %, b:a = 98:2, E/Z > 95:5) as a colorless oil. Rf = 0.24 (cyclohexane). GLC (FS-SE-54): tR = 19.3 min. 1 H NMR (500 MHz, CDCl3): d = 0.44 (s, 6 H), 1.94 (d, J = 1.7 Hz, 3 H), 6.81 (q, J = 1.7 Hz, 1 H), 7.20–7.25 (m, 1 H), 7.29–7.40 (m, 7 H), 7.55– 7.61 ppm (m, 2 H). 13C NMR (126 MHz, CDCl3): d = 3.3, 16.8, 126.8, 127.8, 127.9, 128.2, 129.1, 129.2, 134.2, 138.3, 138.4, 139.0 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.2 ppm. IR (ATR): n˜ = 3051 (w), 3021 (w), 2955 (w), 1596 (w), 1489 (m), 1247 (s), 1110 (s), 961 (m), 810 (s), 770 (s), 728 (s), 694 cm1 (s). HRMS (EI) exact mass for [M] + (C17H20Si): calcd m/z 252.1329, found 252.1321. The regioselectivity and double bond geometry were assigned by comparison with reported 1H NMR spectra of the title compound and known isomers.[24] (E)-DimethylACHTUNGRE(phenyl)(1-(4-(trifluoromethyl)phenyl)hex-1-en-2-yl)silane (8 b) Prepared from 1-(hex-1-yn-1-yl)-4-(trifluoromethyl)benzene (7 b, 24 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.2 mg, 6.0 mmol, 5.0 mol %), Cs2CO3 (90 mg, 0.28 mmol, 2.5 equiv), Me2PhSiBpin (73 mg, 0.28 mmol, 2.5 equiv), MeOH (12 mg, 0.37 mmol, 3.4 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using cyclohexane as eluent afforded the title compound (E)-8 b (34 mg, 85 %, b:a = 92:8, E/ Z > 95:5) as a colorless oil. Rf = 0.48 (cyclohexane). GLC (FS-SE-54): tR = 20.7 min. 1H NMR (400 MHz, CDCl3): d = 0.47 (s, 6 H), 0.78 (t, J = 7.3 Hz, 3 H), 1.17–1.34 (m, 4 H), 2.30–2.34 (m, 2 H), 6.79 (s, 1 H), 7.34– 7.40 (m, 5 H), 7.55–7.59 ppm (m, 4 H). 13C NMR (101 MHz, CDCl3): d = 2.3, 13.9, 23.1, 30.7, 32.0, 125.2 (q, J = 3.8 Hz), 127.0 (q, J = 271.6 Hz), 128.0, 128.6 (q, J = 31.5 Hz), 128.9, 129.2, 134.2, 138.1, 138.4, 142.1, 146.6 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.5 ppm. 19F NMR (471 MHz, CDCl3): d = 62.4 ppm. IR (ATR): n˜ = 3070 (vw), 3052 (vw), 3010 (vw), 2958 (w), 2931 (w), 2862 (vw), 1615 (w), 1428 (w), 1322 (vs), 1248 (m), 1163 (s), 1122 (s), 1107 (s), 1066 (s), 1016 (m), 813 (s), 772 (m), 730 (m), 699 cm1 (s). HRMS (EI) exact mass for [M] + (C21H25F3Si): calcd m/z 362.1672, found 362.1671.
Scheme 3. Regio- and diastereoselective addition across internal alkynes.
reagents.[14–16, 23] By ligand control, terminal alkynes were transformed regioselectively into the branched[14] (a-selectivity) and linear[15] (b-selectivity) vinylic silanes, respectively before (Scheme 1). Recently, propiolic acid and aldehyde derivatives were also successfully engaged in this chemistry, selectively producing b-regioisomers in conjugate additions.[16] Our work demonstrates that simple copper(I) salt/ solvent combinations lead to synthetically useful b/a ratios for aryl- and alkyl-substituted terminal alkynes. Moreover, even internal alkynes do react with unprecedented levels of regiocontrol.
(E)-4-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)benzonitrile (8 c) Prepared from 4-(hex-1-yn-1-yl)benzonitrile (7 c, 22 mg, 0.12 mmol, 1.0 equiv), using CuBr·Me2S (1.4 mg, 6.8 mmol, 6.8 mol %), Cs2CO3 (94 mg, 0.29 mmol, 2.4 equiv), Me2PhSiBpin (72 mg, 0.27 mmol, 2.3 equiv), MeOH (11 mg, 0.33 mmol, 2.7 equiv), and DCM (3 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 c (36 mg, 94 %, b:a = 97:3, E/Z > 95:5) as a colorless oil. Rf = 0.57 (cyclohexane/ethyl acetate 90:10). GLC (FS-SE-54): tR = 24.4 min. 1 H NMR (400 MHz, CDCl3): d = 0.46 (s, 6 H), 0.77 (t, J = 7.2 Hz, 3 H), 1.16–1.32 (m, 4 H), 2.29–2.33 (m, 2 H), 6.75 (s, 1 H), 7.32–7.40 (m, 5 H), 7.54–7.57 (m, 2 H), 7.60–7.62 ppm (m, 2 H); 13C NMR (126 MHz, CDCl3): d = –2.4, 13.8, 23.0, 30.7, 31.9, 110.2, 119.2, 128.0, 129.3, 129.4, 132.1, 134.2, 137.7, 138.1, 143.3, 148.1 ppm; 29Si NMR (99 MHz, CDCl3): d = –6.3 ppm. IR (ATR): n˜ = 3066 (w), 3012 (vw), 2951 (w), 1425 (m), 1245 (s), 1106 (s), 1048 (m), 814 (vs), 787 (vs), 726 (vs), 694 cm1 (vs); HRMS (EI) exact mass for [M] + (C21H25NSi): calcd m/z 319.1751, found 319.1766.
Experimental Section Typical Procedure for the Silylcupration of Internal Alkynes with Me2PhSiBpin A flame-dried Schlenk tube is successively charged with CuBr·Me2S (5.0 mol %) and Cs2CO3 (2.5 equiv). The corresponding solvent (0.33 m) is added, and the resulting suspension is maintained at room temperature for 30 min and subsequently cooled to 0 8C. At this temperature, Me2PhSiBpin (2.5 equiv) is added, and the reaction mixture is stirred for another 20 min, followed by addition of MeOH (3.0 equiv) and the corresponding alkyne (7 a–7 h, 1.0 equiv), either neat or dissolved in the corresponding solvent (0.11 m). The reaction mixture is allowed to slowly warm to room temperature and maintained at this temperature until analysis of an aliquot by thin-layer chromatography (TLC) or gas-liquid chromatography (GLC) indicates complete conversion of the alkyne substrate (6–14 h). The reaction mixture is filtrated through a small pad of silica gel using tert-butyl methyl ether and concentrated under reduced pressure. Purification of the residue by flash column chromatography on silica gel using mixtures of cyclohexane and ethyl acetate as eluents affords the analytically pure vinylic silanes 8 a–8 h as colorless oils. The b:a and E/Z ratios are determined by GLC and 1H NMR analysis prior to purification.
(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)pent-1-en-1-yl)benzonitrile (8 d) Prepared from 2-(pent-1-yn-1-yl)benzonitrile (7 d, 17 mg, 0.10 mmol, 1.0 equiv), using CuBr·Me2S (1.2 mg, 6.0 mmol, 6.0 mol %), Cs2CO3 (90 mg, 0.28 mmol, 2.8 equiv), Me2PhSiBpin (60 mg, 0.22 mmol, 2.2 equiv), MeOH (11 mg, 0.34 mmol, 3.4 equiv), and DCM (3 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 d (30 mg, 98 %, b:a = 97:3, E/Z > 95:5) as a colorless oil. Rf = 0.42 (cyclohexane:ethyl acetate 95:5). GLC (FS-SE-54): tR = 22.8 min. 1 H NMR (500 MHz, CDCl3): d = 0.51 (s, 6 H), 0.74 (t, J = 7.3 Hz, 3 H), 1.24–1.32 (m, 2 H), 2.21–2.24 (m, 2 H), 6.98 (br s, 1 H), 7.30–7.40 (m, 5 H), 7.54 (td, J = 7.7, 1.0 Hz, 1 H), 7.61–7.64 (m, 2 H), 7.66 ppm (dd, J = 7.7,
(E)-DimethylACHTUNGRE(phenyl)(1-phenylprop-1-en-2-yl)silane (8 a) Prepared from prop-1-yn-1-ylbenzene (7 a, 13 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.2 mg, 6.0 mmol, 5.0 mol %), Cs2CO3 (91 mg,
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(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)pyrazine (8 h)
1.0 Hz, 1 H). 13C NMR (126 MHz, CDCl3): d = 2.4, 14.4, 23.1, 33.3, 112.4, 118.1, 127.1, 128.0, 129.3 (2C), 132.3, 132.9, 134.2, 135.9, 138.0, 142.6, 148.9 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.2 ppm. IR (ATR): n˜ = 2958 (m), 2931 (w), 2871 (w), 2224 (w), 1592 (w), 1467 (m), 1427 (m), 1377 (w), 1306 (w), 1248 (s), 1111 (s), 1010 (m), 812 (vs), 758 (vs), 731 (vs), 699 cm1 (vs). HRMS (EI) exact mass for [M] + (C20H23NSi): calcd m/z 305.1594, found 305.1690.
Prepared from 2-(hex-1-yn-1-yl)pyrazine (7 h, 18 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.6 mg, 7.8 mmol, 7.1 mol %), Cs2CO3 (91 mg, 0.28 mmol, 2.5 equiv), Me2PhSiBpin (73 mg, 0.28 mmol, 2.5 equiv), MeOH (11 mg, 0.34 mmol, 3.1 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 h (30 mg, 93 %, b:a = 94:6, E/Z > 95:5) as a colorless oil. Rf = 0.24 (cyclohexane:ethyl acetate = 90:10). GLC (FS-SE-54): tR = 21.9 min. 1 H NMR (500 MHz, CDCl3): d = 0.41 (s, 6 H), 0.89 (t, J = 7.4 Hz, 3 H), 1.30–1.38 (m, 2 H), 1.44–1.50 (m, 2 H), 2.39–2.42 (m, 2 H), 7.11 (br s, 1 H), 7.21–7.22 (m, 3 H), 7.44–7.45 (m, 2 H), 8.15–8.17 (m, 2 H), 8.35 ppm (br s, 1 H). 13C NMR (126 MHz, CDCl3): d = 0.3, 14.1, 22.7, 32.7, 39.9, 127.5, 128.2, 133.4, 136.7, 140.7, 141.9, 142.7, 144.7, 151.8, 152.4 ppm. 29Si NMR (99 MHz, CDCl3): d = 11.0 ppm. IR (ATR): n˜ = 3050 (w), 2955 (m), 2927 (m), 2857 (m), 1599 (w), 1520 (m), 1458 (m), 1427 (m), 1393 (s), 1243 (s), 1150 (s), 1109 (s), 1056 (m), 1017 (s), 813 (vs), 772 (vs), 730 (s), 699 cm1 (vs). HRMS (ESI) exact mass for [M+H] + (C18H25N2Si): calcd m/z 297.1782, found 297.1791.
(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)benzonitrile (8 e) Prepared from 2-(hex-1-yn-1-yl)benzonitrile (7 e, 20 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.7 mg, 8.3 mmol, 7.5 mol %), Cs2CO3 (0.11 g, 0.33 mmol, 3.0 equiv), Me2PhSiBpin (97 mg, 0.37 mmol, 3.4 equiv), MeOH (11 mg, 0.35 mmol, 3.2 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 e (29 mg, 83 %, b:a = 89:11, E/Z > 95:5) as a colorless oil. Rf = 0.57 (cyclohexane/ethyl acetate 90:10). GLC (FS-SE-54): tR = 24.4 min. 1 H NMR (500 MHz, CDCl3): d = 0.46 (s, 6 H), 0.77 (t, J = 7.2 Hz, 3 H), 1.17–1.32 (m, 4 H), 2.29–2.32 (m, 2 H), 6.76 (s, 1 H), 7.32–7.34 (m, 2 H), 7.37–7.39 (m, 3 H), 7.55–7.56 (m, 2 H), 7.60–7.61 ppm (m, 2 H). 13C NMR (126 MHz, CDCl3): d = 2.4, 13.8, 23.0, 30.7, 31.9, 110.2, 119.2, 127.8, 128.0, 129.3, 129.4, 131.9, 132.1, 134.2, 137.7, 138.1, 143.2, 148.1 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.3 ppm. IR (ATR): n˜ = 3067 (vw), 2954 (w), 2926 (w), 2226 (m), 1727 (w), 1601 (w), 1497 (vw), 1460 (vw), 1426 (m), 1247 (s), 1108 (s), 909 (vw), 812 (vs), 791 (vs), 729 (vs), 697 cm1 (vs). HRMS (EI) exact mass for [M] + (C21H25NSi): calcd m/z 319.1751, found 319.1748.
Acknowledgements C.K.H. thanks the NRW Graduate School of Chemistry for a predoctoral fellowship (2010–2013). M.O. is indebted to the Einstein Foundation (Berlin) for an endowed professorship.
(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)pyridine (8 f) Prepared from 2-(hex-1-yn-1-yl)pyridine (7 f, 18 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.4 mg, 6.8 mmol, 6.2 mol %), Cs2CO3 (0.10 g, 0.32 mmol, 2.9 equiv), Me2PhSiBpin (66 mg, 0.25 mmol, 2.3 equiv), MeOH (11 mg, 0.35 mmol, 3.2 equiv), and DCM (3 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 f (28 mg, 85 %, b:a > 97:3, E/Z = 95:5) as a colorless oil. Rf = 0.35 (cyclohexane/ethyl acetate 90:10). GLC (FS-SE-54): tR = 21.7 min. 1 H NMR (500 MHz, CDCl3): d = 0.47 (s, 6 H), 0.78 (t, J = 7.2 Hz, 3 H), 1.19–1.34 (m, 4 H), 2.56–2.59 (m, 2 H), 6.83 (s, 1 H), 7.08–7.11 (m, 1 H), 7.23–7.25 (m, 1 H), 7.34–7.37 (m, 3 H), 7.56–7.60 (m, 2 H), 7.62 (td, J = 7.7, 1.9 Hz, 1 H), 8.60–8.61 ppm (m, 1 H). 13C NMR (126 MHz, CDCl3): d = 2.5, 13.9, 23.2, 30.6, 31.9, 121.4, 123.9, 127.9, 129.1, 134.3, 136.0, 138.5, 138.6, 148.6, 149.4, 157.2 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.3 ppm. IR (ATR): n˜ = 3066 (w), 3002 (w), 2954 (m), 2926 (m), 2855 (m), 1581 (s), 1459 (m), 1424 (s), 1294 (vw), 1246 (s), 1148 (m), 1110 (s), 1027 (m), 896 (w), 816 (vs), 771 (vs), 730 (vs), 697 cm1 (vs). HRMS (EI) exact mass for [M] + (C19H25NSi): calcd m/z 295.1751, found 295.1740.
[1] For an authoritative review, see: D. S. W. Lim, E. A. Anderson, Synthesis 2012, 983 – 1010 and references therein. [2] For a review, see: A. Barbero, F. J. Pulido, Acc. Chem. Res. 2004, 37, 817 – 825. [3] a) I. Fleming, F. Roessler, J. Chem. Soc. Chem. Commun. 1980, 276 – 277; b) I. Fleming, T. W. Newton, F. Roessler, J. Chem. Soc. Perkin Trans. 1 1981, 2527 – 2532. [4] H. Hayami, M. Sato, S. Kanemoto, Y. Morizawa, K. Oshima, H. Nozaki, J. Am. Chem. Soc. 1983, 105, 4491 – 4492. [5] G. Auer, M. Oestreich, Chem. Commun. 2006, 311 – 313. [6] For a review, see: A. Weickgenannt, M. Oestreich, Chem. Eur. J. 2010, 16, 402 – 412. [7] a) Y. Okuda, K. Wakamatsu, W. Tckmantel, K. Oshima, H. Nozaki, Tetrahedron Lett. 1985, 26, 4629 – 4632; b) K. Wakamatsu, T. Nonaka, Y. Okuda, W. Tckmantel, K. Oshima, K. Utimoto, H. Nozaki, Tetrahedron 1986, 42, 4427 – 4436. [8] S. Nakamura, M. Uchiyama, T. Ohwada, J. Am. Chem. Soc. 2004, 126, 11146 – 11147. [9] a) For a general review of silicon – boron bond activation, see: M. Oestreich, E. Hartmann, M. Mewald, Chem. Rev. 2013, 113, 402 – 441; b) for a brief review of silicon – boron bond activation through transmetalation, see: E. Hartmann, M. Oestreich, Chim. Oggi 2011, 29, 34 – 36. [10] a) K.-s. Lee, A. H. Hoveyda, J. Am. Chem. Soc. 2010, 132, 2898 – 2900; b) H. Y. Harb, K. D. Collins, J. V. Garcia Altur, S. Bowker, L. Campbell, D. J. Procter, Org. Lett. 2010, 12, 5446 – 5449; c) K.-s. Lee, H. Wu, F. Haeffner, A. H. Hoveyda, Organometallics 2012, 31, 7823 – 7826; d) V. Pace, J. P. Rae, H. Y. Harb, D. J. Procter, Chem. Commun. 2013, 49, 5150 – 5152; e) V. Pace, J. P. Rae, D. J. Procter, Org. Lett. 2014, 16, 476 – 479. [11] a) C. Kleeberg, E. Feldmann, E. Hartmann, D. J. Vyas, M. Oestreich, Chem. Eur. J. 2011, 17, 13538 – 13543 (racemic); b) V. Cirriez, C. Rasson, T. Hermant, J. Petrignet, J. Daz lvarez, K. Robeyns, O. Riant, Angew. Chem. Int. Ed. 2013, 52, 1785 – 1788; Angew. Chem. 2013, 125, 1829 – 1832 (enantioselective). [12] a) D. J. Vyas, R. Frçhlich, M. Oestreich, Org. Lett. 2011, 13, 2094 – 2097 (racemic); b) A. Hensel, K. Nagura, L. B. Delvos, M. Oestreich, Angew. Chem. Int. Ed. 2014, 53, 4964 – 4967; Angew. Chem.
(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)-5-methylpyridine (8 g) Prepared from 2-(hex-1-yn-1-yl)-5-methylpyridine (7 g, 20 mg, 0.12 mmol, 1.0 equiv), using CuBr·Me2S (1.2 mg, 6.0 mmol, 5.0 mol %), Cs2CO3 (91 mg, 0.28 mmol, 2.3 equiv), Me2PhSiBpin (73 mg, 0.28 mmol, 2.3 equiv), MeOH (13 mg, 0.39 mmol, 3.3 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 g (32 mg, 93 %, b:a 95:5, E/Z 95:5) as a colorless oil. Rf = 0.23 (cyclohexane:ethyl acetate = 95:5). GLC (FS-SE-54): tR = 22.9 min. 1 H NMR (500 MHz, CDCl3): d = 0.47 (s, 6 H), 0.79 (t, J = 7.2 Hz, 3 H), 1.19–1.32 (m, 4 H), 2.32 (s, 3 H), 2.54–2.57 (m, 2 H), 6.82 (s, 1 H), 7.17 (d, J = 8.0 Hz, 1 H), 7.34–7.46 (m, 3 H), 7.45 (dd, J = 8.1, 2.1 Hz, 1 H), 7.57– 7.59 (m, 2 H), 8.44 ppm (br s, 1 H). 13C NMR (126 MHz, CDCl3): d = 2.5, 13.9, 18.4, 23.2, 30.6, 31.8, 123.4, 127.9, 129.1, 130.9, 134.3, 136.7, 138.3, 138.5, 147.7, 149.6, 154.2 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.3 ppm. IR (ATR): n˜ = 3068 (vw), 3049 (vw), 2998 (w), 2955 (m), 2927 (m), 2857 (w), 1596 (w), 1553 (w), 1482 (m), 1427 (m), 1378 (m), 1247 (s), 1111 (s), 1027 (m), 815 (vs), 768 (vs), 729 (vs), 698 cm1 (vs). HRMS (ESI) exact mass for [M+H] + (C20H28NSi): calcd m/z 310.1986, found 310.1992.
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[13]
[14] [15] [16]
[17] [18]
[19]
[20] For a remarkable syn- and regioselective platinum-catalyzed hydrosilylation of an internal alkyne directed by a tethered alkene, see: Y. Kawasaki, Y. Ishikawa, K. Igawa, K. Tomooka, J. Am. Chem. Soc. 2011, 133, 20712 – 20715. [21] For anti- and regioselective hydrosilylation of internal alkynes electronically not biased by a carbonyl/carboxyl group, see: a) B. M. Trost, Z. T. Ball, J. Am. Chem. Soc. 2001, 123, 12726 – 12727; b) B. M. Trost, Z. T. Ball, J. Am. Chem. Soc. 2005, 127, 17644 – 17655. [22] For syn- and regioselective hydrosilylation of electronically biased internal alkynes, see: a) D. A. Rooke, E. M. Ferreira, J. Am. Chem. Soc. 2010, 132, 11926 – 11928; b) D. A. Rooke, E. M. Ferreira, Angew. Chem. Int. Ed. 2012, 51, 3225 – 3230; Angew. Chem. 2012, 124, 3279 – 3284 (both platinum-catalyzed); c) Y. Sumida, T. Kato, S. Yoshida, T. Hosoya, Org. Lett. 2012, 14, 1552 – 1555 (palladium-catalyzed). [23] For the preparation of vinylic silanes from alkynes involving oxidative addition of the silicon-boron bond to low-valent transition metals, see: a) Ref. 9 a; b) for an account article, see: T. Ohmura, M. Suginome, Bull. Chem. Soc. Jpn. 2009, 82, 29 – 49; for selected original publications, see: c) M. Suginome, H. Nakamura, Y. Ito, Chem. Commun. 1996, 2777 – 2778; d) S.-y. Onozawa, Y. Hatanaka, M. Tanaka, Chem. Commun. 1997, 1229 – 1230; e) T. Ohmura, K. Oshima, M. Suginome, Chem. Commun. 2008, 1416 – 1418; f) T. Ohmura, K. Oshima, H. Taniguchi, M. Suginome, J. Am. Chem. Soc. 2010, 132, 12194 – 12196; g) T. Ohmura, K. Oshima, M. Suginome, Angew. Chem. Int. Ed. 2011, 50, 12501 – 12504; Angew. Chem. 2011, 123, 12709 – 12712. [24] a) I. Fleming, M. Rowley, Tetrahedron 1989, 45, 413 – 424; b) A. Ch ned , I. Fleming, R. Salmon, M. C. West, J. Organomet. Chem. 2003, 686, 84 – 93. Received: June 10, 2014 Published online: July 25, 2014
2014, 126, 5064 – 5067 (enantioselective); c) T. Mita, M. Sugawara, K. Saito, Y. Sato, Org. Lett. 2014, 16, 3028 – 3031 (enantioselective). a) D. J. Vyas, M. Oestreich, Angew. Chem. Int. Ed. 2010, 49, 8513 – 8515; Angew. Chem. 2010, 122, 8692 – 8694 (racemic); b) L. B. Delvos, D. J. Vyas, M. Oestreich, Angew. Chem. Int. Ed. 2013, 52, 4650 – 4653; Angew. Chem. 2013, 125, 4748 – 4751 (enantioselective); c) M. Takeda, R. Shintani, T. Hayashi, J. Org. Chem. 2013, 78, 5007 – 5017 (enantioselective); d) C. K. Hazra, M. Oestreich, Eur. J. Org. Chem. 2013, 4903 – 4908 (diastereoselective). P. Wang, X.-L. Yeo, T. P. Loh, J. Am. Chem. Soc. 2011, 133, 1254 – 1256. F. Meng, H. Jang, A. H. Hoveyda, Chem. Eur. J. 2013, 19, 3204 – 3214. a) S. Vercruysse, L. Cornelissen, F. Nahra, L. Collard, O. Riant, Chem. Eur. J. 2014, 20, 1834 – 1838; b) J. A. Calderone, W. L. Santos, Angew. Chem. Int. Ed. 2014, 53, 4154 – 4158; Angew. Chem. 2014, 126, 4238 – 4242; c) R. T. H. Linstadt, C. A. Peterson, D. J. Lippincott, C. I. Jette, B. H. Lipshutz, Angew. Chem. Int. Ed. 2014, 53, 4159 – 4163; Angew. Chem. 2014, 126, 4243 – 4247; d) Y.-H. Xu, L.-H. Wu, J. Wang, T.-P. Loh, Chem. Commun. 2014, 50, 7195 – 7197. M. Suginome, T. Matsuda, Y. Ito, Organometallics 2000, 19, 4647 – 4649. The regioselective transformation of internal triple bonds into 1,2disubstituted vinylic silanes is accomplished in a few cases by transition metal-catalyzed hydrosilylation, and the seminal works are collected in Refs. [19–21]. For syn- and regioselective platinum-catalyzed hydrosilylation of various internal alkynes, see: a) A. Hamze, O. Provot, M. Alami, J.D. Brion, Org. Lett. 2005, 7, 5625 – 5628; b) A. Hamze, O. Provot, J.D. Brion, M. Alami, Synthesis 2007, 2025 – 2036; c) G. BerthonGelloz, J.-M. Schumers, G. De Bo, I. E. Mark, J. Org. Chem. 2008, 73, 4190 – 4197.
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Copper(I)-Catalyzed Regioselective Addition of Nucleophilic Silicon Across Terminal and Internal Carbon–Carbon Triple Bonds Chinmoy K. Hazra,[a, b] Carolin Fopp,[a] and Martin Oestreich*[a] Abstract: The copper(I) alkoxide-catalyzed release of a silicon-based cuprate reagent from a silicon–boron pronucleophile is applied to the addition across carbon–carbon triple bonds. Commercially available CuBr·Me2S was found to be a general precatalyst
that secures high regiocontrol for both aryl- and alkyl-substituted terminal as well as internal alkynes. The solvent Keywords: alkynes · copper · regioselectivity · silicon · silylmetalation
Introduction
carbon–silicon bond-forming reactions were (re-)investigated using this approach, namely 1,4-[10] and 1,2-addition,[11, 12] as well as allylic substitution reactions.[13] Loh and co-workers had also elaborated a procedure for the addition across selected terminal alkynes in which the steric demand of a monodentate phosphine ligand secures high branched selectivity (Scheme 1, top).[14] Later, Hoveyda and co-workers
A silicon atom attached to an alkene is an often used linchpin in synthetic chemistry, and improved methods for the preparation of vinylic silanes are, despite several general procedures known today, still welcome.[1] A convenient way to access these building blocks is by regiocontrolled addition of a silicon–metal bond across a terminal carbon–carbon triple bond, typically with the newly formed bonds in syn relationship. Conversely, electronically and sterically unbiased internal alkynes with no directing group continue to be a challenging class of substrates. Silicon-based cuprates are reagents of choice to achieve that transformation,[2] and (R3Si)2CuLi·LiCN used to be the standard source of the silicon nucleophile.[3] Protocols catalytic in copper rely on either R3SiMgMe[4] or (R3Si)2Zn[5] as precursors of anionic silicon.[6] Zincates R3SiZnR2Li and (R3Si)3ZnLi in the presence of a copper catalyst[7] as well as novel dianion-type zincates R3SiZnR(OR)2Mg2Cl alone[8] do also transfer silicon groups onto carbon–carbon triple bonds. Recently, a new approach to the catalytic generation of silicon-based copper reagents emerged.[9] The silicon nucleophile is released from a bench-stable pronucleophile by transmetalation of its silicon–boron bond with a copper(I) alkoxide, a process that is believed to proceed through a sbond metathesis. In a short period of time, all fundamental
Scheme 1. Regioselective addition of catalytically generated silicon-based cuprates across terminal alkynes: branched-selective (top, Loh and coworkers, 2011)[14] and linear-selective (bottom, Hoveyda and co-workers, 2013).[15] Mes = mesityl, pin = pinacolato.
[a] Dr. C. K. Hazra, C. Fopp, Prof. Dr. M. Oestreich Institut fr Chemie, Technische Universitt Berlin Strasse des 17. Juni 115, 10623 Berlin (Germany) Fax: (+ 49) 30-314-28829 E-mail: [email protected]
disclosed the corresponding linear-selective addition, employing an N-heterocyclic carbene as a supporting ligand (Scheme 1, bottom).[15] Aside from these reports, the related 1,4-addition to acceptor-substituted triple bonds was independently published by four laboratories this year (not shown).[16] We report here a general method for the linearselective addition without added ligand. Moreover, the same setup also allows for regioselective addition across internal alkynes.
[b] Dr. C. K. Hazra NRW Graduate School of Chemistry Organisch-Chemisches Institut Westflische Wilhelms-Universitt Mnster Corrensstrasse 40, 48149 Mnster (Germany) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201402643.
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greatly influences the regioisomeric ratio, favoring the linear regioisomer with terminal acceptors. This facile protocol even allows for the transformation of internal acceptors with remarkable levels of regio- and diastereocontrol.
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Results and Discussion
ity was excellent for 1 a!3 a (aryl substitution) but poor for 2 a!4 a (alkyl substitution). Changing the solvent from THF to, for example, 1,2-dichloroethane then greatly improved the b/a ratio of the latter (b:a = 93:7, entry 4) while maintaining the high regiocontrol of the former (b:a = 99:1, entry 3). The base also had an influence, and Cs2CO3 was superior to NaOMe in several control experiments; therefore, the remaining experiments collected in Table 1 were performed with Cs2CO3 as base and various copper(I) salts in three different solvents (entries 5–18). It is clear from this data that there is no obvious trend, and the poor regiocontrol seen for 2 a with CuCN in THF (entries 2 and 6) as well as the inverted regioselectivity for 1 a with CuBr in THF (entry 9) remain unexplained. The b-selectivity is generally high but b/a ratios and yields were best with CuBr·Me2S as a copper source, and b:a = 99:1 for 1 a!3 a (entry 17) and b:a = 93:7 for 2 a!4 a (entry 14) were obtained in THF and DCE, respectively. We then subjected six more examples with electronically modified aryl rings to the optimized procedure (1 b–1 g, Table 2). These reacted cleanly no matter what the X group was, thereby affording the linear vinylic silanes b-E-3 b–3 g as single regio- and diastereomers. With no phosphine or Nheterocyclic carbene ligand at the copper(I) catalyst as in previous studies, the b-regioisomer is highly favored, and similar results were achieved with CuCN as the copper source. A terminal carbon–carbon triple bond with an isopropenyl instead of an aryl group yielded, depending on the solvent, the linear vinylic silane with b:a > 99:1 and 93:7, respectively (5!6, Scheme 2).
We had used the copper(I)-catalyzed transmetalation approach in the racemic variants of 1,2-additions[11a, 12a] and allylic substitution[13a] without any additional ligands. Reaction times increased significantly in the presence of both phosphines[13a] and N-heterocyclic carbenes[11a, 12b, 13b] as supporting ligands, particularly documented by the enantioselective procedures recently developed by us.[12b, 13b] For that reason, and in contrast to the work of Hoveyda and co-workers[15] (cf. Scheme 1, bottom), we decided to investigate the related addition across terminal carbon–carbon triple bonds without the addition of ligands. Screening of copper source/base/solvent combinations with and without an alcohol as additive required the variation of four parameters, and selected results are summarized in Table 1. The reactions in the abTable 1. Screening of copper source/base/solvent combinations for the regioselective addition of nucleophilic silicon across terminal triple bonds.
Entry
R
Catalyst
Solvent
t [h]
b/a ratio[a]
Yield [%][b]
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu Ph nBu
CuCN CuCN CuCN CuCN CuCN CuCN CuI CuI CuBr CuBr CuCl CuCl CuBr·Me2S CuBr·Me2S CuBr·Me2S CuBr·Me2S CuBr·Me2S CuBr·Me2S
THF THF DCE DCE THF THF THF THF THF THF THF THF THF THF DCM DCM DCE DCE
7 8 5 6 8 8 8 8 8 10 8 8 10 8 12 10 12 10
99:1 50:50 99:1 93:7 99:1 66:34 97:3 88:12 36:64 92:8 99:1 87:13 96:4 93:7 94:6 85:15 99:1 92:8
91 99 94[c] 67[c] 95 50 80 76 93 81 99 77 86 89 79 72 96 76
Table 2. Linear-selective addition across aryl-substituted terminal alkynes.
[a] Determined by GLC and 1H NMR analysis prior to purification. [b] Yield determined by GLC analysis using tetracosane as internal standard. [c] Combined yield of analytically pure regioisomers after purification by flash column chromatography on silica gel. DCM = dichloromethane, DCE = 1,2-dichloroethane.
sence of MeOH were generally slower, and we believe that residual MeOH (in NaOMe) or traces of H2O serve as proton sources at small scale. We also tested representative aryl- and alkyl-substituted alkynes 1 a and 2 a, hoping that one catalyst system would work for both. Our search for the optimal setup commenced with CuCN/NaOMe/THF, added MeOH, and a slight excess of Me2PhSiBpin[17] that had served us well before (entries 1 and 2).[12a] The regioselectiv-
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b/a ratio[a]
Yield [%][b]
1 a (X = H) 1 b (X = Me) 1 c (X = OMe) 1 d (X = Br) 1 e (X = F)
99:1 99:1 99:1 99:1 99:1
89 96 93 88 85
6
1f
99:1
83
7
1g
99:1
91
Entry
Terminal alkyne
1 2 3 4 5
Vinylic silane
[a] Determined by GLC and 1H NMR analysis prior to purification. [b] Combined yield of analytically pure regioisomers after purification by flash column chromatography on silica gel.
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Table 4. Screening of copper source/base/solvent combinations for the regioselective addition of nucleophilic silicon across an internal triple bond.
Scheme 2. Linear-selective addition across an enyne to yield a 1,3-diene.
Application of the CuBr·Me2S/Cs2CO3 combination in THF to a handful of typical alkyl-substituted alkynes 2 a–2 d was reasonably successful (Table 3, entries 1–4). The b/ a ratios were not as good as in Hoveydas case,[15] but increased steric bulk at the terminus also secured excellent regiocontrol (2 d!4 d, entry 4). Replacement of the tBu by a Me3Si group had the same beneficial effect (2 e!4 e, entry 5).
b/a ratio[a]
Yield [%][b]
2a
93:7
65
2
2b
88:12
85
3
2c
86:14
80
4
2d
99:1
84
5
2e
98:2[c]
85
Terminal alkyne
1
Vinylic silane
Base
Solvent
t [h]
b/a ratio[a]
Yield [%][b]
1 2 3 4 5 6
CuCN CuCN CuBr CuBr·Me2S CuBr·Me2S CuBr·Me2S
NaOMe Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3
THF THF THF THF DCM DCE
12 12 12 12 12 8
80:20 81:19 82:18 83:17 98:2 85:15
74 99 83 82 92 85
ry to a-selective platinum- and palladium-catalyzed hydrosilylation of the same class of compounds.[22] We chose the conversion of 1-phenylprop-1-yne into the corresponding 1,2-disubstituted vinylic silane as a model reaction (7 a!8 a, Table 4). The standard CuCN/NaOMe/THF combination was moderately selective (entry 1), yet substantially exceeding the regioselectivity we had found with the copper(I)-catalyzed methodology using (Me2PhSi)2Zn as the source of the silicon nucleophile (b:a = 62:38 with Et instead of Me).[5] A screening of copper(I) salts with Cs2CO3 as base and THF as solvent led to no improvement (entries 2–4). However, the solvent emerged as crucial again, and DCM but not DCE resulted in synthetically useful regioselectivity in favor of the b-isomer (entries 5 and 6). With the optimal solvent for internal acceptors at hand, we probed the electronic effect of an X substituent in the para position of the aryl group (X = CF3, CN, and OMe). For the electron-withdrawing CF3 and CN groups, the desired addition across the triple bond occurred with good regio- and diastereoselectivity (7 b!8 b and 7 c!8 c, Scheme 3), but the substrate with the electron-donating OMe group reacted sluggishly with partial decomposition (not shown). A CN group in the ortho position that could potentially coordinate to the copper(I) catalyst was also tolerated (7 d!8 d and 7 e!8 e, Scheme 3). As electron-deficient aryl groups facilitate the addition of the silicon nucleophile, we included heteroaryl groups (pyridin-2-yl and pyrazin-2-yl) into this survey, thereby creating a more pronounced electronic bias. Both heterocycles allowed for regioselective addition across the internal carbon–carbon triple bond (7 f–7 h!8 f–8 h, Scheme 3).
[a] Determined by GLC and 1H NMR analysis prior to purification. [b] Combined yield of analytically pure regioisomers after purification by flash column chromatography on silica gel. [c] E/Z = 94:6.
The results obtained with terminal carbon–carbon triple bonds illustrate that relatively simple catalyst systems lead to excellent to good regioselectivities, and it was this simplicity that prompted us to also test the related internal acceptors. These substrates are extremely challenging,[18] and there is, to date, essentially no solution to the problem using stoichiometric or catalytic silicon-based cuprates.[1] We had reported promising regioselectivity (b:a = 92:8) for two 1phenylalk-1-ynes using [(Et2N)Ph2Si]2Zn together with CuI as a catalyst several years ago.[5] Electronically biased systems equipped with an electron-withdrawing group, usually carbonyl or carboxyl, do indeed react with superb regiocontrol,[16] but these 1,4-additions are cognate to those of a,bunsaturated acceptors.[10] That b-selectivity is complementa-
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Catalyst
[a] Determined by GLC and 1H NMR analysis prior to purification. [b] Yield determined by GLC analysis using tetracosane as internal standard.
Table 3. Linear-selective addition across alkyl- and silyl-substituted terminal alkynes.
Entry
Entry
Conclusions The present contribution completes the existing methodology of copper(I)-catalyzed conversion of carbon–carbon triple bonds into the vinylic silane motif using silicon–boron
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0.28 mmol, 2.5 equiv), Me2PhSiBpin (72 mg, 0.28 mmol, 2.5 equiv), MeOH (12 mg, 0.37 mmol, 3.4 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using cyclohexane as eluent afforded the title compound (E)-8 a (16 mg, 58 %, b:a = 98:2, E/Z > 95:5) as a colorless oil. Rf = 0.24 (cyclohexane). GLC (FS-SE-54): tR = 19.3 min. 1 H NMR (500 MHz, CDCl3): d = 0.44 (s, 6 H), 1.94 (d, J = 1.7 Hz, 3 H), 6.81 (q, J = 1.7 Hz, 1 H), 7.20–7.25 (m, 1 H), 7.29–7.40 (m, 7 H), 7.55– 7.61 ppm (m, 2 H). 13C NMR (126 MHz, CDCl3): d = 3.3, 16.8, 126.8, 127.8, 127.9, 128.2, 129.1, 129.2, 134.2, 138.3, 138.4, 139.0 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.2 ppm. IR (ATR): n˜ = 3051 (w), 3021 (w), 2955 (w), 1596 (w), 1489 (m), 1247 (s), 1110 (s), 961 (m), 810 (s), 770 (s), 728 (s), 694 cm1 (s). HRMS (EI) exact mass for [M] + (C17H20Si): calcd m/z 252.1329, found 252.1321. The regioselectivity and double bond geometry were assigned by comparison with reported 1H NMR spectra of the title compound and known isomers.[24] (E)-DimethylACHTUNGRE(phenyl)(1-(4-(trifluoromethyl)phenyl)hex-1-en-2-yl)silane (8 b) Prepared from 1-(hex-1-yn-1-yl)-4-(trifluoromethyl)benzene (7 b, 24 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.2 mg, 6.0 mmol, 5.0 mol %), Cs2CO3 (90 mg, 0.28 mmol, 2.5 equiv), Me2PhSiBpin (73 mg, 0.28 mmol, 2.5 equiv), MeOH (12 mg, 0.37 mmol, 3.4 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using cyclohexane as eluent afforded the title compound (E)-8 b (34 mg, 85 %, b:a = 92:8, E/ Z > 95:5) as a colorless oil. Rf = 0.48 (cyclohexane). GLC (FS-SE-54): tR = 20.7 min. 1H NMR (400 MHz, CDCl3): d = 0.47 (s, 6 H), 0.78 (t, J = 7.3 Hz, 3 H), 1.17–1.34 (m, 4 H), 2.30–2.34 (m, 2 H), 6.79 (s, 1 H), 7.34– 7.40 (m, 5 H), 7.55–7.59 ppm (m, 4 H). 13C NMR (101 MHz, CDCl3): d = 2.3, 13.9, 23.1, 30.7, 32.0, 125.2 (q, J = 3.8 Hz), 127.0 (q, J = 271.6 Hz), 128.0, 128.6 (q, J = 31.5 Hz), 128.9, 129.2, 134.2, 138.1, 138.4, 142.1, 146.6 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.5 ppm. 19F NMR (471 MHz, CDCl3): d = 62.4 ppm. IR (ATR): n˜ = 3070 (vw), 3052 (vw), 3010 (vw), 2958 (w), 2931 (w), 2862 (vw), 1615 (w), 1428 (w), 1322 (vs), 1248 (m), 1163 (s), 1122 (s), 1107 (s), 1066 (s), 1016 (m), 813 (s), 772 (m), 730 (m), 699 cm1 (s). HRMS (EI) exact mass for [M] + (C21H25F3Si): calcd m/z 362.1672, found 362.1671.
Scheme 3. Regio- and diastereoselective addition across internal alkynes.
reagents.[14–16, 23] By ligand control, terminal alkynes were transformed regioselectively into the branched[14] (a-selectivity) and linear[15] (b-selectivity) vinylic silanes, respectively before (Scheme 1). Recently, propiolic acid and aldehyde derivatives were also successfully engaged in this chemistry, selectively producing b-regioisomers in conjugate additions.[16] Our work demonstrates that simple copper(I) salt/ solvent combinations lead to synthetically useful b/a ratios for aryl- and alkyl-substituted terminal alkynes. Moreover, even internal alkynes do react with unprecedented levels of regiocontrol.
(E)-4-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)benzonitrile (8 c) Prepared from 4-(hex-1-yn-1-yl)benzonitrile (7 c, 22 mg, 0.12 mmol, 1.0 equiv), using CuBr·Me2S (1.4 mg, 6.8 mmol, 6.8 mol %), Cs2CO3 (94 mg, 0.29 mmol, 2.4 equiv), Me2PhSiBpin (72 mg, 0.27 mmol, 2.3 equiv), MeOH (11 mg, 0.33 mmol, 2.7 equiv), and DCM (3 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 c (36 mg, 94 %, b:a = 97:3, E/Z > 95:5) as a colorless oil. Rf = 0.57 (cyclohexane/ethyl acetate 90:10). GLC (FS-SE-54): tR = 24.4 min. 1 H NMR (400 MHz, CDCl3): d = 0.46 (s, 6 H), 0.77 (t, J = 7.2 Hz, 3 H), 1.16–1.32 (m, 4 H), 2.29–2.33 (m, 2 H), 6.75 (s, 1 H), 7.32–7.40 (m, 5 H), 7.54–7.57 (m, 2 H), 7.60–7.62 ppm (m, 2 H); 13C NMR (126 MHz, CDCl3): d = –2.4, 13.8, 23.0, 30.7, 31.9, 110.2, 119.2, 128.0, 129.3, 129.4, 132.1, 134.2, 137.7, 138.1, 143.3, 148.1 ppm; 29Si NMR (99 MHz, CDCl3): d = –6.3 ppm. IR (ATR): n˜ = 3066 (w), 3012 (vw), 2951 (w), 1425 (m), 1245 (s), 1106 (s), 1048 (m), 814 (vs), 787 (vs), 726 (vs), 694 cm1 (vs); HRMS (EI) exact mass for [M] + (C21H25NSi): calcd m/z 319.1751, found 319.1766.
Experimental Section Typical Procedure for the Silylcupration of Internal Alkynes with Me2PhSiBpin A flame-dried Schlenk tube is successively charged with CuBr·Me2S (5.0 mol %) and Cs2CO3 (2.5 equiv). The corresponding solvent (0.33 m) is added, and the resulting suspension is maintained at room temperature for 30 min and subsequently cooled to 0 8C. At this temperature, Me2PhSiBpin (2.5 equiv) is added, and the reaction mixture is stirred for another 20 min, followed by addition of MeOH (3.0 equiv) and the corresponding alkyne (7 a–7 h, 1.0 equiv), either neat or dissolved in the corresponding solvent (0.11 m). The reaction mixture is allowed to slowly warm to room temperature and maintained at this temperature until analysis of an aliquot by thin-layer chromatography (TLC) or gas-liquid chromatography (GLC) indicates complete conversion of the alkyne substrate (6–14 h). The reaction mixture is filtrated through a small pad of silica gel using tert-butyl methyl ether and concentrated under reduced pressure. Purification of the residue by flash column chromatography on silica gel using mixtures of cyclohexane and ethyl acetate as eluents affords the analytically pure vinylic silanes 8 a–8 h as colorless oils. The b:a and E/Z ratios are determined by GLC and 1H NMR analysis prior to purification.
(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)pent-1-en-1-yl)benzonitrile (8 d) Prepared from 2-(pent-1-yn-1-yl)benzonitrile (7 d, 17 mg, 0.10 mmol, 1.0 equiv), using CuBr·Me2S (1.2 mg, 6.0 mmol, 6.0 mol %), Cs2CO3 (90 mg, 0.28 mmol, 2.8 equiv), Me2PhSiBpin (60 mg, 0.22 mmol, 2.2 equiv), MeOH (11 mg, 0.34 mmol, 3.4 equiv), and DCM (3 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 d (30 mg, 98 %, b:a = 97:3, E/Z > 95:5) as a colorless oil. Rf = 0.42 (cyclohexane:ethyl acetate 95:5). GLC (FS-SE-54): tR = 22.8 min. 1 H NMR (500 MHz, CDCl3): d = 0.51 (s, 6 H), 0.74 (t, J = 7.3 Hz, 3 H), 1.24–1.32 (m, 2 H), 2.21–2.24 (m, 2 H), 6.98 (br s, 1 H), 7.30–7.40 (m, 5 H), 7.54 (td, J = 7.7, 1.0 Hz, 1 H), 7.61–7.64 (m, 2 H), 7.66 ppm (dd, J = 7.7,
(E)-DimethylACHTUNGRE(phenyl)(1-phenylprop-1-en-2-yl)silane (8 a) Prepared from prop-1-yn-1-ylbenzene (7 a, 13 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.2 mg, 6.0 mmol, 5.0 mol %), Cs2CO3 (91 mg,
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(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)pyrazine (8 h)
1.0 Hz, 1 H). 13C NMR (126 MHz, CDCl3): d = 2.4, 14.4, 23.1, 33.3, 112.4, 118.1, 127.1, 128.0, 129.3 (2C), 132.3, 132.9, 134.2, 135.9, 138.0, 142.6, 148.9 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.2 ppm. IR (ATR): n˜ = 2958 (m), 2931 (w), 2871 (w), 2224 (w), 1592 (w), 1467 (m), 1427 (m), 1377 (w), 1306 (w), 1248 (s), 1111 (s), 1010 (m), 812 (vs), 758 (vs), 731 (vs), 699 cm1 (vs). HRMS (EI) exact mass for [M] + (C20H23NSi): calcd m/z 305.1594, found 305.1690.
Prepared from 2-(hex-1-yn-1-yl)pyrazine (7 h, 18 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.6 mg, 7.8 mmol, 7.1 mol %), Cs2CO3 (91 mg, 0.28 mmol, 2.5 equiv), Me2PhSiBpin (73 mg, 0.28 mmol, 2.5 equiv), MeOH (11 mg, 0.34 mmol, 3.1 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 h (30 mg, 93 %, b:a = 94:6, E/Z > 95:5) as a colorless oil. Rf = 0.24 (cyclohexane:ethyl acetate = 90:10). GLC (FS-SE-54): tR = 21.9 min. 1 H NMR (500 MHz, CDCl3): d = 0.41 (s, 6 H), 0.89 (t, J = 7.4 Hz, 3 H), 1.30–1.38 (m, 2 H), 1.44–1.50 (m, 2 H), 2.39–2.42 (m, 2 H), 7.11 (br s, 1 H), 7.21–7.22 (m, 3 H), 7.44–7.45 (m, 2 H), 8.15–8.17 (m, 2 H), 8.35 ppm (br s, 1 H). 13C NMR (126 MHz, CDCl3): d = 0.3, 14.1, 22.7, 32.7, 39.9, 127.5, 128.2, 133.4, 136.7, 140.7, 141.9, 142.7, 144.7, 151.8, 152.4 ppm. 29Si NMR (99 MHz, CDCl3): d = 11.0 ppm. IR (ATR): n˜ = 3050 (w), 2955 (m), 2927 (m), 2857 (m), 1599 (w), 1520 (m), 1458 (m), 1427 (m), 1393 (s), 1243 (s), 1150 (s), 1109 (s), 1056 (m), 1017 (s), 813 (vs), 772 (vs), 730 (s), 699 cm1 (vs). HRMS (ESI) exact mass for [M+H] + (C18H25N2Si): calcd m/z 297.1782, found 297.1791.
(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)benzonitrile (8 e) Prepared from 2-(hex-1-yn-1-yl)benzonitrile (7 e, 20 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.7 mg, 8.3 mmol, 7.5 mol %), Cs2CO3 (0.11 g, 0.33 mmol, 3.0 equiv), Me2PhSiBpin (97 mg, 0.37 mmol, 3.4 equiv), MeOH (11 mg, 0.35 mmol, 3.2 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 e (29 mg, 83 %, b:a = 89:11, E/Z > 95:5) as a colorless oil. Rf = 0.57 (cyclohexane/ethyl acetate 90:10). GLC (FS-SE-54): tR = 24.4 min. 1 H NMR (500 MHz, CDCl3): d = 0.46 (s, 6 H), 0.77 (t, J = 7.2 Hz, 3 H), 1.17–1.32 (m, 4 H), 2.29–2.32 (m, 2 H), 6.76 (s, 1 H), 7.32–7.34 (m, 2 H), 7.37–7.39 (m, 3 H), 7.55–7.56 (m, 2 H), 7.60–7.61 ppm (m, 2 H). 13C NMR (126 MHz, CDCl3): d = 2.4, 13.8, 23.0, 30.7, 31.9, 110.2, 119.2, 127.8, 128.0, 129.3, 129.4, 131.9, 132.1, 134.2, 137.7, 138.1, 143.2, 148.1 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.3 ppm. IR (ATR): n˜ = 3067 (vw), 2954 (w), 2926 (w), 2226 (m), 1727 (w), 1601 (w), 1497 (vw), 1460 (vw), 1426 (m), 1247 (s), 1108 (s), 909 (vw), 812 (vs), 791 (vs), 729 (vs), 697 cm1 (vs). HRMS (EI) exact mass for [M] + (C21H25NSi): calcd m/z 319.1751, found 319.1748.
Acknowledgements C.K.H. thanks the NRW Graduate School of Chemistry for a predoctoral fellowship (2010–2013). M.O. is indebted to the Einstein Foundation (Berlin) for an endowed professorship.
(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)pyridine (8 f) Prepared from 2-(hex-1-yn-1-yl)pyridine (7 f, 18 mg, 0.11 mmol, 1.0 equiv), using CuBr·Me2S (1.4 mg, 6.8 mmol, 6.2 mol %), Cs2CO3 (0.10 g, 0.32 mmol, 2.9 equiv), Me2PhSiBpin (66 mg, 0.25 mmol, 2.3 equiv), MeOH (11 mg, 0.35 mmol, 3.2 equiv), and DCM (3 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 f (28 mg, 85 %, b:a > 97:3, E/Z = 95:5) as a colorless oil. Rf = 0.35 (cyclohexane/ethyl acetate 90:10). GLC (FS-SE-54): tR = 21.7 min. 1 H NMR (500 MHz, CDCl3): d = 0.47 (s, 6 H), 0.78 (t, J = 7.2 Hz, 3 H), 1.19–1.34 (m, 4 H), 2.56–2.59 (m, 2 H), 6.83 (s, 1 H), 7.08–7.11 (m, 1 H), 7.23–7.25 (m, 1 H), 7.34–7.37 (m, 3 H), 7.56–7.60 (m, 2 H), 7.62 (td, J = 7.7, 1.9 Hz, 1 H), 8.60–8.61 ppm (m, 1 H). 13C NMR (126 MHz, CDCl3): d = 2.5, 13.9, 23.2, 30.6, 31.9, 121.4, 123.9, 127.9, 129.1, 134.3, 136.0, 138.5, 138.6, 148.6, 149.4, 157.2 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.3 ppm. IR (ATR): n˜ = 3066 (w), 3002 (w), 2954 (m), 2926 (m), 2855 (m), 1581 (s), 1459 (m), 1424 (s), 1294 (vw), 1246 (s), 1148 (m), 1110 (s), 1027 (m), 896 (w), 816 (vs), 771 (vs), 730 (vs), 697 cm1 (vs). HRMS (EI) exact mass for [M] + (C19H25NSi): calcd m/z 295.1751, found 295.1740.
[1] For an authoritative review, see: D. S. W. Lim, E. A. Anderson, Synthesis 2012, 983 – 1010 and references therein. [2] For a review, see: A. Barbero, F. J. Pulido, Acc. Chem. Res. 2004, 37, 817 – 825. [3] a) I. Fleming, F. Roessler, J. Chem. Soc. Chem. Commun. 1980, 276 – 277; b) I. Fleming, T. W. Newton, F. Roessler, J. Chem. Soc. Perkin Trans. 1 1981, 2527 – 2532. [4] H. Hayami, M. Sato, S. Kanemoto, Y. Morizawa, K. Oshima, H. Nozaki, J. Am. Chem. Soc. 1983, 105, 4491 – 4492. [5] G. Auer, M. Oestreich, Chem. Commun. 2006, 311 – 313. [6] For a review, see: A. Weickgenannt, M. Oestreich, Chem. Eur. J. 2010, 16, 402 – 412. [7] a) Y. Okuda, K. Wakamatsu, W. Tckmantel, K. Oshima, H. Nozaki, Tetrahedron Lett. 1985, 26, 4629 – 4632; b) K. Wakamatsu, T. Nonaka, Y. Okuda, W. Tckmantel, K. Oshima, K. Utimoto, H. Nozaki, Tetrahedron 1986, 42, 4427 – 4436. [8] S. Nakamura, M. Uchiyama, T. Ohwada, J. Am. Chem. Soc. 2004, 126, 11146 – 11147. [9] a) For a general review of silicon – boron bond activation, see: M. Oestreich, E. Hartmann, M. Mewald, Chem. Rev. 2013, 113, 402 – 441; b) for a brief review of silicon – boron bond activation through transmetalation, see: E. Hartmann, M. Oestreich, Chim. Oggi 2011, 29, 34 – 36. [10] a) K.-s. Lee, A. H. Hoveyda, J. Am. Chem. Soc. 2010, 132, 2898 – 2900; b) H. Y. Harb, K. D. Collins, J. V. Garcia Altur, S. Bowker, L. Campbell, D. J. Procter, Org. Lett. 2010, 12, 5446 – 5449; c) K.-s. Lee, H. Wu, F. Haeffner, A. H. Hoveyda, Organometallics 2012, 31, 7823 – 7826; d) V. Pace, J. P. Rae, H. Y. Harb, D. J. Procter, Chem. Commun. 2013, 49, 5150 – 5152; e) V. Pace, J. P. Rae, D. J. Procter, Org. Lett. 2014, 16, 476 – 479. [11] a) C. Kleeberg, E. Feldmann, E. Hartmann, D. J. Vyas, M. Oestreich, Chem. Eur. J. 2011, 17, 13538 – 13543 (racemic); b) V. Cirriez, C. Rasson, T. Hermant, J. Petrignet, J. Daz lvarez, K. Robeyns, O. Riant, Angew. Chem. Int. Ed. 2013, 52, 1785 – 1788; Angew. Chem. 2013, 125, 1829 – 1832 (enantioselective). [12] a) D. J. Vyas, R. Frçhlich, M. Oestreich, Org. Lett. 2011, 13, 2094 – 2097 (racemic); b) A. Hensel, K. Nagura, L. B. Delvos, M. Oestreich, Angew. Chem. Int. Ed. 2014, 53, 4964 – 4967; Angew. Chem.
(E)-2-(2-(DimethylACHTUNGRE(phenyl)silyl)hex-1-en-1-yl)-5-methylpyridine (8 g) Prepared from 2-(hex-1-yn-1-yl)-5-methylpyridine (7 g, 20 mg, 0.12 mmol, 1.0 equiv), using CuBr·Me2S (1.2 mg, 6.0 mmol, 5.0 mol %), Cs2CO3 (91 mg, 0.28 mmol, 2.3 equiv), Me2PhSiBpin (73 mg, 0.28 mmol, 2.3 equiv), MeOH (13 mg, 0.39 mmol, 3.3 equiv), and DCM (4 mL). Purification by flash column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate as eluent afforded the title compound (E)-8 g (32 mg, 93 %, b:a 95:5, E/Z 95:5) as a colorless oil. Rf = 0.23 (cyclohexane:ethyl acetate = 95:5). GLC (FS-SE-54): tR = 22.9 min. 1 H NMR (500 MHz, CDCl3): d = 0.47 (s, 6 H), 0.79 (t, J = 7.2 Hz, 3 H), 1.19–1.32 (m, 4 H), 2.32 (s, 3 H), 2.54–2.57 (m, 2 H), 6.82 (s, 1 H), 7.17 (d, J = 8.0 Hz, 1 H), 7.34–7.46 (m, 3 H), 7.45 (dd, J = 8.1, 2.1 Hz, 1 H), 7.57– 7.59 (m, 2 H), 8.44 ppm (br s, 1 H). 13C NMR (126 MHz, CDCl3): d = 2.5, 13.9, 18.4, 23.2, 30.6, 31.8, 123.4, 127.9, 129.1, 130.9, 134.3, 136.7, 138.3, 138.5, 147.7, 149.6, 154.2 ppm. 29Si NMR (99 MHz, CDCl3): d = 6.3 ppm. IR (ATR): n˜ = 3068 (vw), 3049 (vw), 2998 (w), 2955 (m), 2927 (m), 2857 (w), 1596 (w), 1553 (w), 1482 (m), 1427 (m), 1378 (m), 1247 (s), 1111 (s), 1027 (m), 815 (vs), 768 (vs), 729 (vs), 698 cm1 (vs). HRMS (ESI) exact mass for [M+H] + (C20H28NSi): calcd m/z 310.1986, found 310.1992.
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[13]
[14] [15] [16]
[17] [18]
[19]
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