Synlett 2015; 26(03): 318-322
DOI: 10.1055/s-0034-1379896
cluster
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed Semihydrogenation of Alkynes to Z-Alkenes

Kazuhiko Semba*
a  Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-Ku, Kyoto 615-8510, Japan
,
Ryohei Kameyama
a  Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-Ku, Kyoto 615-8510, Japan
,
Yoshiaki Nakao*
a  Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-Ku, Kyoto 615-8510, Japan
b  CREST, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan   Email: semba.kazuhiko.5n@kyoto-u.ac.jp   Email: nakao.yoshiaki.8n@kyoto-u.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 16 December 2014

Accepted after revision: 20 January 2015

Publication Date:
26 January 2015 (online)

 


Abstract

Copper-catalyzed semihydrogenation of internal alkynes has been developed. The reaction proceeds under an atmosphere of hydrogen (5 atm) at 100 °C in the presence of a readily available [(PPh3)CuCl]4 catalyst to give various Z-alkenes stereoselectively.


#

Much attention has been paid to develop copper-catalyzed reduction of unsaturated compounds such as carbonyls, imines, Michael acceptors, and alkynes due to low cost and abundance of copper as well as high chemo-, regio-, and stereoselectivities associated with copper catalysis.[1] [2] Usually, hydrosilanes are employed as a stoichiometric reducing reagent. In contrast, copper-catalyzed reduction using H2 (hydrogenation) is rare, although it is more atom-­efficient than the use of hydrosilanes. Hydrogenation of polar multiple bonds such as aldehydes, ketones, and Michael acceptors has been relatively well-studied with copper catalysis,[3] whereas that of nonpolar multiple bonds such as alkynes is limited. To the best of our knowledge, Cu2O-catalyzed semihydrogenation of terminal alkynes under an atmosphere of H2 (20 atm) has been the only precedent.[4]

Semihydrogenation of internal alkynes is an efficient method to prepare Z-alkenes, which are versatile building blocks in organic synthesis and often found in biologically active compounds. A variety of heterogeneous catalysts have been developed for this transformation.[5] Especially, the Lindlar catalyst is a well-established and effective catalyst for semihydrogenation of alkynes.[6] Nevertheless, it often suffers from Z/E isomerization, shift of double bonds, and overhydrogenation to give alkanes. Thus, uptake of H2 must be accurately monitored to control the hydrogenation. To overcome such difficulties, homogeneous catalysts such as rhodium, chromium, palladium, ruthenium, vanadium, and niobium have been developed.[7] Here, we report that [(PPh3)CuCl]4,[8] a readily available copper complex, efficiently catalyzes semihydrogenation of internal alkynes to give Z-alkenes in a highly stereoselective manner under an atmosphere of H2 (5 atm).

First, we optimized the reaction conditions employing 1-phenyl-1-hexyne (1a) as a model substrate (Table [1]). After screening a variety of reaction parameters, semihydrogenation of 1a gave (Z)-1-phenyl-1-hexene [(Z)-2a] selectively in high yield without formation of (E)-1-phenyl-1-hexene [(E)-2a] and hexylbenzene (3a) under the standard conditions: [(PPh3)CuCl]4 (2.0 mol%/Cu), LiOt-Bu (50 mol%), and i-PrOH (1.0 mmol) in toluene at 100 °C for 3 hours under an atmosphere of H2 (5 atm) (Table [1], entry 1).

Table 1 Semihydrogenation of 1a with Various Copper Catalysts

Entry

Variation from the standard conditions

Conv. of 1a (%)a

Yield of (Z)-2a + (E)-2a + 3a (%)b

Ratio of (Z)-2a/(E)-2a/3a (%)b

1

none

>99

99 (80)c

99:<1:<1

2

run for 12 h

>99

95

94:2:4

3

CuCl/Ph3P instead of [(PPh3)CuCl]4

>99

95

99:<1:<1

4

CuCl/P(o-tol)3 instead of [(PPh3)CuCl]4

<5

5

CuCl/PCy3 instead of [(PPh3)CuCl]4

>99

90

54:4:42

6

CuCl instead of [(PPh3)CuCl]4

<5

7

without [(PPh3)CuCl]4

<5

8

without LiOt-Bu

<5

9

without i-PrOH

<5

10

under N2 instead of H2

<5

11

under H2 (1.0 atm)

<5

12

Cu2O instead of [(PPh)3CuCl]4, LiOt-Bu, and i-PrOH

<5

a Determined by GC analysis with n-tridecane as an internal standard.

b Determined by 1H NMR analysis with 1,3,5-trimethoxybenzene as an internal standard.

c Isolated yield.

Notably, the selectivity is better than that reported using the Lindlar catalyst {(Z)-2a/[(Z)-2a + (E)-2a + 3a] = 91%}.[6d] Compound (Z)-2a was isolated in 80% yield after medium-pressure column chromatography on silica gel (Table [1], entry 1). Prolonging the reaction time to 12 hours slightly decreased the selectivity (Table [1], entry 2). [(PPh3)CuCl]4 generated in situ from CuCl and Ph3P showed reactivity comparable to an isolated one (Table [1], entry 3). CuBr was similarly effective as CuCl. In contrast, other copper(I) salts such as CuI, CuOAc, and CuCN showed activity far less than CuCl. The effects of phosphine ligands are summarized in entries 4–6 (Table [1]). The hydrogenation did not proceed with tri(o-tolyl)phosphine [P(o-tol)3] as a ligand or without any ligands (Table [1], entries 4 and 6). In the case of tricyclohexylphosphine (PCy3), a considerable amount of 3a was observed (Table [1], entry 5). When the reactions were performed in the absence of [(PPh3)CuCl]4, LiOt-Bu, or i-PrOH, no products were obtained (Table [1], entries 7–9). The reaction did not proceed under an N2 atmosphere instead of H2 (Table [1], entry 10), indicating that i-PrOH did not act as a hydride source. Under an atmosphere of H2 (1.0 atm), the products were not formed (Table [1], entry 11). Cu2O, which was reported to serve as a catalyst for semihydrogenation of terminal alkynes,[4] was ineffective under the present reaction conditions (Table [1], entry 12). Even in the presence of Ph3P, LiOt-Bu, and i-PrOH, Cu2O was not a good catalyst.

The scope of substrates was investigated under the optimized reaction conditions (Table [2]).[9] In the case of 1-phenyl-1-propyne (1b), (Z)-1-phenyl-1-propene [(Z)-2b] was obtained in high yield with a small amount of (E)-1-phenyl-1-propene [(E)-2b] and propylbenzene (3b) (Table [2], entry 1). The reduction of 1-phenyl-2-trimethylsilylacetylene (1c) did not proceed (Table [2], entry 2). Diphenylacetylene derivatives 1dg were efficiently semihydrogenated to give the corresponding Z-alkenes (Table [2], entries 3–6). Electron-donating and electron-withdrawing substituents on the phenyl group did not affect the yields and selectivities (Table [2], entries 4–6). The catalytic system was also effective for semihydrogenation of aliphatic alkynes 1h and 1i, giving the corresponding Z-alkenes (Z)-2h and (Z)-2i selectively (Table [2], entries 7 and 8). On the other hand, ynoate 1j and terminal alkyne 1k were not competent substrates. The reaction of 1j afforded a complex mixture (Table [2], entry 9), whereas 1k was not converted at all under the present conditions (Table [2], entry 10). With 5,7-dodecadiyne (1l), (Z)-5-dodecene was obtained selectively (Table [2], entry 11).

Zoom Image
Scheme 1 A plausible reaction mechanism

Table 2 Semihydrogenation of Various Alkynes 1

Entry

Alkyne

Conv. of 1 (%)a

Yield of (Z)-2 + (E)-2 + 3 (%)b

Ratio of (Z)-2/(E)-2/3 (%)c

1

1b

>99

(78)

96:2:2

2

1c

<5

3d

R1 = R2 = H (1d)

>99

91

96:3:1

4

R1 = R2 = Me (1e)

>99

99

98:<1:2

5

R1 = R2 = F (1f)

>99

95

98:1:1

6e,f

R1 = C(O)Oi-Pr, R2 = H (1g)

>99

52 (95)

>99:<1:<1

7

1h

>99

76

>99:<1:<1

8

1i

>99

(93)

>99:<1:<1

9

1j

>99

complex mixture

10

1k

<5

11f

1l

>99

(78)g

a Determined by GC analysis with n-tridecane as an internal standard.

b Isolated yield. Yields determined by 1H NMR analysis with 1,3,5-trimethoxybenzene as an internal standard are given in parentheses.

c Determined by 1H NMR analysis of a crude product.

d Run at 60 °C for 3 h.

e Run at 80 °C for 3 h.

f Run in 0.30 mmol scale.

g (Z)-5-Dodecene was obtained selectively.

A plausible reaction mechanism is depicted in Scheme [1]. Copper hydride 5 is generated from heterolytic cleavage of H2 by copper alkoxide 4 (step a).[10] According to the literature, syn addition of 5 across an alkyne gives alkenyl copper 6 in a stereoselective manner (step b).[11] Compound 6 is protonated by alcohol to afford (Z)-2 and regenerate 4 (step c).[12] To gain insights into the proposed reaction mechanism, semihydrogenation of 1a was performed using i-PrOD (Scheme [2]). Monodeuterated alkene (Z)-2a-d 1 was obtained regioselectively albeit with low deuterium incorporation. This result supports that i-PrOH serves as a source of hydrogen and that the addition of copper hydride 5 across 1a (step b) proceeds regioselectively. Reversibility of step a should be responsible for contamination of i-PrOH under the reaction conditions of Scheme [2] and thus the observed low deuterium content in (Z)-2a-d 1.[13]

Zoom Image
Scheme 2

In conclusion, we have established the copper-catalyzed semihydrogenation of internal alkynes. The present transformation is catalyzed by a readily available copper complex under an atmosphere of H2 (5 atm), giving Z-alkenes in high yields and selectivities. This simple catalytic system employing inexpensive metal catalyst can be an alternative to known protocols using a noble-metal catalyst such as the Lindlar catalyst.


#

Acknowledgment

This work was supported by a Grant-in-Aid for Young Scientists (B) (26810058) from MEXT and the Japan Science and Technology Corporation (CREST, ‘Establishment of Molecular Technology towards the Creation of New Functions’ Area).

Supporting Information

  • References and Notes

    • 1a For reviews on copper-catalyzed reduction of carbonyl compounds and Michael acceptors, see: Rendler S, Oestreich M. Angew. Chem. Int. Ed. 2007; 46: 498 ; and references cited therein
    • 1b Díez-González S, Nolan SP. Acc. Chem. Res. 2008; 41: 349 ; and references cited therein
    • 1c Deutsch C, Krause N, Lipshutz BH. Chem. Rev. 2008; 108: 2916 ; and references cited therein
    • 1d Lipshutz BH. Synlett 2009; 509 ; and references cited therein

      For references on copper-catalyzed semireduction of alkynes, see:
    • 2a Semba K, Fujihara T, Xu T, Terao J, Tsuji Y. Adv. Synth. Catal. 2012; 354: 1542
    • 2b Whittaker AM, Lalic G. Org. Lett. 2013; 15: 1112
    • 2c Wang G.-H, Bin H.-Y, Sun M, Chen S.-W, Liu J.-H, Zhong C.-M. Tetrahedron 2014; 70: 2175
    • 2d Cao H, Chen T, Zhou Y, Han D, Yin S.-F, Han L.-B. Adv. Synth. Catal. 2014; 356: 765

    • For the semireduction of alkynes using a stoichiometric amount of [(PPh3)CuH]6, see:
    • 2e Daeuble JF, Mcgettigan C, Stryker JM. Tetrahedron Lett. 1990; 31: 2397
    • 3a Mahoney WS, Stryker JM. J. Am. Chem. Soc. 1989; 111: 8818
    • 3b Chen J.-X, Daeuble JF, Brestensky DM, Stryker JM. Tetrahedron 2000; 56: 2153
    • 3c Chen J.-X, Daeuble JF. Tetrahedron 2000; 56: 2789
    • 3d Shimizu H, Igarashi D, Kuriyama W, Yusa Y, Sayo N, Saito T. Org. Lett. 2007; 9: 1655
    • 3e Junge K, Wendt B, Addis D, Zhou S, Das S, Fleischer S, Beller M. Chem. Eur. J. 2011; 17: 101
  • 4 Sokol’skii DV, Ualikhanova A. Russ. J. Phys. Chem. 1977; 51: 886
    • 5a Brown CA, Ahuja VK. J. Org. Chem. 1973; 38: 2226
    • 5b Brunet J.-J, Gallois P, Caubere P. J. Org. Chem. 1980; 45: 1937
    • 5c Brunet J.-J, Caubere P. J. Org. Chem. 1984; 49: 4058
    • 5d Choudary BM, Sharma GV. M, Bharathi P. Angew. Chem., Int. Ed. Engl. 1989; 28: 465
    • 5e Choi J, Yoon NM. Tetrahedron Lett. 1996; 37: 1057
    • 5f Alonso F, Osante I, Yus M. Tetrahedron 2007; 63: 93
    • 5g Mizugaki T, Murata M, Fukubayashi S, Mitsudome T, Jitsukawa K, Kaneda K. Chem. Commun. 2008; 241
    • 6a Lindlar H. Helv. Chim. Acta 1952; 35: 446
    • 6b Lindlar H, Dubuis R. Org. Synth. 1966; 46: 89
    • 6c Marvell EN, Li T. Synthesis 1973; 457
    • 6d Rajaram J, Narula AP. S, Chawla HP. S, Dev S. Tetrahedron 1983; 39: 2315
    • 7a Schrock RR, Osborn JA. J. Am. Chem. Soc. 1976; 98: 2143
    • 7b Sodeoka M, Shibasaki M. J. Org. Chem. 1985; 50: 1149
    • 7c van Laren MW, Elsevier CJ. Angew. Chem. Int. Ed. 1999; 38: 3715
    • 7d Sprengers JW, Wassenaar J, Clement ND, Cavell KJ, Elsevier CJ. Angew. Chem. Int. Ed. 2005; 44: 2026
    • 7e Belger C, Neisius NM, Plietker B. Chem. Eur. J. 2010; 16: 12214
    • 7f La Pierre HS, Arnold J, Toste FD. Angew. Chem. Int. Ed. 2011; 50: 3900
    • 7g Gianetti TL, Tomson NC, Arnold J, Bergman RG. J. Am. Chem. Soc. 2011; 133: 14904
    • 7h Chernichenko K, Madarász Á, Pápai I, Nieger M, Leskelä M, Repo T. Nat. Chem. 2013; 5: 718

    • Transfer semihydrogenation of alkynes was also reported, see:
    • 7i Trost BM, Braslau R. Tetrahedron Lett. 1989; 30: 4657
    • 7j Hauwert P, Maestri G, Sprengers JW, Catellani M, Elsevier CJ. Angew. Chem. Int. Ed. 2008; 47: 3223
    • 7k Hauwert P, Boerleider R, Warsink S, Weigand JJ, Elsevier CJ. J. Am. Chem. Soc. 2010; 132: 16900
    • 7l Hua JL. R, Liu T. J. Org. Chem. 2010; 75: 2966
    • 7m Hua JL. R. Chem. Eur. J. 2011; 17: 8462
    • 7n Shen R, Chen T, Zhao Y, Qiu R, Zhou Y, Yin S, Wang X, Goto M, Han L.-B. J. Am. Chem. Soc. 2011; 133: 17037
  • 8 Churchill MR, Kalra K. Inorg. Chem. 1974; 13: 1065
  • 9 General Procedure for the Copper-Catalyzed Semihydro­genationIn a glove box, [(PPh3)CuCl]4 (7.2 mg, 5.0 μmol), toluene (1.0 mL), LiOt-Bu (40 mg, 0.50 mmol), and i-PrOH (60 mg, 1.0 mmol) were added to a vial in this order. After being stirred for 1 min at r.t., alkyne 1 (1.0 mmol) and toluene (2.0 mL) were added to the resulting mixture. The vial was placed in an autoclave, and the autoclave was taken out of the glove box. An N2 atmosphere in the autoclave was purged by positive pressure of H2. Then, the mixture was stirred at 100 °C for 3 h under H2 (5 atm). After being cooled to r.t., H2 was released, and the mixture was diluted with EtOAc. The conversion of alkynes was determined by GC analysis with n-tridecane as an internal standard. The resulting solution was filtered through a pad of silica gel, and the filtrate was concentrated. The residue was purified by medium-pressure column chromatography on silica gel to give (Z)-2.Representative data:(Z)-2d: The reaction of 1d (180 mg, 1.0 mmol) at 60 °C followed by purification by MPLC (16 g of silica gel and Biotage® SNAP Ultra 10 g; n-hexane) gave the corresponding product (160 mg, 0.91 mmol, 91%) as a mixture of (Z)-2d,14a (E)-2d,14b and 3d 14c [(Z)-2d/(E)-2d/3d = 95:5:<1 determined by 1H NMR analysis] as a colorless oil; Rf = 0.53 (hexane). 1H NMR (CDCl3, 400 MHz): δ = 7.28–7.16 (m, 10 H), 6.60 (s, 2 H); 13C NMR (CDCl3, 101 MHz): δ = 137.2, 130.2, 128.8, 128.2, 127.1. All the resonances of 1H and 13C NMR spectra were consistent with reported values.14a (Z)-2g: The reaction of 1g (79 mg, 0.30 mmol) at 80 °C in toluene (0.80 mL) followed by purification by MPLC (16 g of silica gel and Biotage® SNAP Ultra 10 g; n-hexane–EtOAc, 99:1 to 93:7) gave the corresponding product (Z)-2g (42 mg, 0.16 mmol, 52%) as a pale yellow oil; Rf = 0.35 (n-hexane–EtOAc, 95:5). 1H NMR (CDCl3, 400 MHz): δ = 7.90 (d, J = 8.5 Hz, 2 H), 7.30 (d, J = 8.5 Hz, 2 H), 7.25–7.20 (m, 5 H), 6.71 (d, J = 12.2 Hz, 1 H), 6.61 (d, J = 12.2 Hz, 1 H), 5.24 (sept, J = 6.1 Hz, 1 H), 1.36 (d, J = 6.1 Hz, 6 H); 13C NMR (CDCl3, 101 MHz): δ = 165.9, 141.8, 136.7, 132.1, 129.4, 129.31, 129.28, 128.8, 128.7, 128.3, 127.4, 68.3, 21.9. HRMS–APCI (+): m/z [M + H]+ calcd for C18H19O2: 267.1380; found: 267.1375

    • [(PPh3)CuH]6 was synthesized from Cu(Ot-Bu) and Ph3P, see:
    • 10a Goeden GV, Caulton KG. J. Am. Chem. Soc. 1981; 103: 7354

    • For catalytic activation of H2 by copper salts, see
    • 10b Halpern J. J. Phys. Chem. 1959; 63: 398

      syn-Addition of copper hydride across internal alkynes was reported, see:
    • 11a Mankad NP, Laitar DS, Sadighi JP. Organometallics 2004; 23: 3369
    • 11b Fujihara T, Xu T, Semba K, Terao J, Tsuji Y. Angew. Chem. Int. Ed. 2011; 50: 523
  • 12 For a reference on protonation of an alkenyl copper with an alcohol, see ref. 2a
  • 13 H–D exchange between copper hydride and alcohols was reported, see ref. 2b and: Lipshutz BH, Servesko JM, Taft BR. J. Am. Chem. Soc. 2004; 126: 8352
    • 14a Yan M, Jin T, Ishikawa Y, Minato T, Fujita T, Chen L.-Y, Bao M, Asao N, Chen M.-W, Yamamoto Y. J. Am. Chem. Soc. 2012; 134: 17536
    • 14b Chen Z, Luo M, Wen Y, Luo G, Liu L. Org. Lett. 2014; 16: 3020
    • 14c Kantam ML, Kishore R, Yadav J, Sudhakar M, Venugopal A. Adv. Synth. Catal. 2012; 354: 663

  • References and Notes

    • 1a For reviews on copper-catalyzed reduction of carbonyl compounds and Michael acceptors, see: Rendler S, Oestreich M. Angew. Chem. Int. Ed. 2007; 46: 498 ; and references cited therein
    • 1b Díez-González S, Nolan SP. Acc. Chem. Res. 2008; 41: 349 ; and references cited therein
    • 1c Deutsch C, Krause N, Lipshutz BH. Chem. Rev. 2008; 108: 2916 ; and references cited therein
    • 1d Lipshutz BH. Synlett 2009; 509 ; and references cited therein

      For references on copper-catalyzed semireduction of alkynes, see:
    • 2a Semba K, Fujihara T, Xu T, Terao J, Tsuji Y. Adv. Synth. Catal. 2012; 354: 1542
    • 2b Whittaker AM, Lalic G. Org. Lett. 2013; 15: 1112
    • 2c Wang G.-H, Bin H.-Y, Sun M, Chen S.-W, Liu J.-H, Zhong C.-M. Tetrahedron 2014; 70: 2175
    • 2d Cao H, Chen T, Zhou Y, Han D, Yin S.-F, Han L.-B. Adv. Synth. Catal. 2014; 356: 765

    • For the semireduction of alkynes using a stoichiometric amount of [(PPh3)CuH]6, see:
    • 2e Daeuble JF, Mcgettigan C, Stryker JM. Tetrahedron Lett. 1990; 31: 2397
    • 3a Mahoney WS, Stryker JM. J. Am. Chem. Soc. 1989; 111: 8818
    • 3b Chen J.-X, Daeuble JF, Brestensky DM, Stryker JM. Tetrahedron 2000; 56: 2153
    • 3c Chen J.-X, Daeuble JF. Tetrahedron 2000; 56: 2789
    • 3d Shimizu H, Igarashi D, Kuriyama W, Yusa Y, Sayo N, Saito T. Org. Lett. 2007; 9: 1655
    • 3e Junge K, Wendt B, Addis D, Zhou S, Das S, Fleischer S, Beller M. Chem. Eur. J. 2011; 17: 101
  • 4 Sokol’skii DV, Ualikhanova A. Russ. J. Phys. Chem. 1977; 51: 886
    • 5a Brown CA, Ahuja VK. J. Org. Chem. 1973; 38: 2226
    • 5b Brunet J.-J, Gallois P, Caubere P. J. Org. Chem. 1980; 45: 1937
    • 5c Brunet J.-J, Caubere P. J. Org. Chem. 1984; 49: 4058
    • 5d Choudary BM, Sharma GV. M, Bharathi P. Angew. Chem., Int. Ed. Engl. 1989; 28: 465
    • 5e Choi J, Yoon NM. Tetrahedron Lett. 1996; 37: 1057
    • 5f Alonso F, Osante I, Yus M. Tetrahedron 2007; 63: 93
    • 5g Mizugaki T, Murata M, Fukubayashi S, Mitsudome T, Jitsukawa K, Kaneda K. Chem. Commun. 2008; 241
    • 6a Lindlar H. Helv. Chim. Acta 1952; 35: 446
    • 6b Lindlar H, Dubuis R. Org. Synth. 1966; 46: 89
    • 6c Marvell EN, Li T. Synthesis 1973; 457
    • 6d Rajaram J, Narula AP. S, Chawla HP. S, Dev S. Tetrahedron 1983; 39: 2315
    • 7a Schrock RR, Osborn JA. J. Am. Chem. Soc. 1976; 98: 2143
    • 7b Sodeoka M, Shibasaki M. J. Org. Chem. 1985; 50: 1149
    • 7c van Laren MW, Elsevier CJ. Angew. Chem. Int. Ed. 1999; 38: 3715
    • 7d Sprengers JW, Wassenaar J, Clement ND, Cavell KJ, Elsevier CJ. Angew. Chem. Int. Ed. 2005; 44: 2026
    • 7e Belger C, Neisius NM, Plietker B. Chem. Eur. J. 2010; 16: 12214
    • 7f La Pierre HS, Arnold J, Toste FD. Angew. Chem. Int. Ed. 2011; 50: 3900
    • 7g Gianetti TL, Tomson NC, Arnold J, Bergman RG. J. Am. Chem. Soc. 2011; 133: 14904
    • 7h Chernichenko K, Madarász Á, Pápai I, Nieger M, Leskelä M, Repo T. Nat. Chem. 2013; 5: 718

    • Transfer semihydrogenation of alkynes was also reported, see:
    • 7i Trost BM, Braslau R. Tetrahedron Lett. 1989; 30: 4657
    • 7j Hauwert P, Maestri G, Sprengers JW, Catellani M, Elsevier CJ. Angew. Chem. Int. Ed. 2008; 47: 3223
    • 7k Hauwert P, Boerleider R, Warsink S, Weigand JJ, Elsevier CJ. J. Am. Chem. Soc. 2010; 132: 16900
    • 7l Hua JL. R, Liu T. J. Org. Chem. 2010; 75: 2966
    • 7m Hua JL. R. Chem. Eur. J. 2011; 17: 8462
    • 7n Shen R, Chen T, Zhao Y, Qiu R, Zhou Y, Yin S, Wang X, Goto M, Han L.-B. J. Am. Chem. Soc. 2011; 133: 17037
  • 8 Churchill MR, Kalra K. Inorg. Chem. 1974; 13: 1065
  • 9 General Procedure for the Copper-Catalyzed Semihydro­genationIn a glove box, [(PPh3)CuCl]4 (7.2 mg, 5.0 μmol), toluene (1.0 mL), LiOt-Bu (40 mg, 0.50 mmol), and i-PrOH (60 mg, 1.0 mmol) were added to a vial in this order. After being stirred for 1 min at r.t., alkyne 1 (1.0 mmol) and toluene (2.0 mL) were added to the resulting mixture. The vial was placed in an autoclave, and the autoclave was taken out of the glove box. An N2 atmosphere in the autoclave was purged by positive pressure of H2. Then, the mixture was stirred at 100 °C for 3 h under H2 (5 atm). After being cooled to r.t., H2 was released, and the mixture was diluted with EtOAc. The conversion of alkynes was determined by GC analysis with n-tridecane as an internal standard. The resulting solution was filtered through a pad of silica gel, and the filtrate was concentrated. The residue was purified by medium-pressure column chromatography on silica gel to give (Z)-2.Representative data:(Z)-2d: The reaction of 1d (180 mg, 1.0 mmol) at 60 °C followed by purification by MPLC (16 g of silica gel and Biotage® SNAP Ultra 10 g; n-hexane) gave the corresponding product (160 mg, 0.91 mmol, 91%) as a mixture of (Z)-2d,14a (E)-2d,14b and 3d 14c [(Z)-2d/(E)-2d/3d = 95:5:<1 determined by 1H NMR analysis] as a colorless oil; Rf = 0.53 (hexane). 1H NMR (CDCl3, 400 MHz): δ = 7.28–7.16 (m, 10 H), 6.60 (s, 2 H); 13C NMR (CDCl3, 101 MHz): δ = 137.2, 130.2, 128.8, 128.2, 127.1. All the resonances of 1H and 13C NMR spectra were consistent with reported values.14a (Z)-2g: The reaction of 1g (79 mg, 0.30 mmol) at 80 °C in toluene (0.80 mL) followed by purification by MPLC (16 g of silica gel and Biotage® SNAP Ultra 10 g; n-hexane–EtOAc, 99:1 to 93:7) gave the corresponding product (Z)-2g (42 mg, 0.16 mmol, 52%) as a pale yellow oil; Rf = 0.35 (n-hexane–EtOAc, 95:5). 1H NMR (CDCl3, 400 MHz): δ = 7.90 (d, J = 8.5 Hz, 2 H), 7.30 (d, J = 8.5 Hz, 2 H), 7.25–7.20 (m, 5 H), 6.71 (d, J = 12.2 Hz, 1 H), 6.61 (d, J = 12.2 Hz, 1 H), 5.24 (sept, J = 6.1 Hz, 1 H), 1.36 (d, J = 6.1 Hz, 6 H); 13C NMR (CDCl3, 101 MHz): δ = 165.9, 141.8, 136.7, 132.1, 129.4, 129.31, 129.28, 128.8, 128.7, 128.3, 127.4, 68.3, 21.9. HRMS–APCI (+): m/z [M + H]+ calcd for C18H19O2: 267.1380; found: 267.1375

    • [(PPh3)CuH]6 was synthesized from Cu(Ot-Bu) and Ph3P, see:
    • 10a Goeden GV, Caulton KG. J. Am. Chem. Soc. 1981; 103: 7354

    • For catalytic activation of H2 by copper salts, see
    • 10b Halpern J. J. Phys. Chem. 1959; 63: 398

      syn-Addition of copper hydride across internal alkynes was reported, see:
    • 11a Mankad NP, Laitar DS, Sadighi JP. Organometallics 2004; 23: 3369
    • 11b Fujihara T, Xu T, Semba K, Terao J, Tsuji Y. Angew. Chem. Int. Ed. 2011; 50: 523
  • 12 For a reference on protonation of an alkenyl copper with an alcohol, see ref. 2a
  • 13 H–D exchange between copper hydride and alcohols was reported, see ref. 2b and: Lipshutz BH, Servesko JM, Taft BR. J. Am. Chem. Soc. 2004; 126: 8352
    • 14a Yan M, Jin T, Ishikawa Y, Minato T, Fujita T, Chen L.-Y, Bao M, Asao N, Chen M.-W, Yamamoto Y. J. Am. Chem. Soc. 2012; 134: 17536
    • 14b Chen Z, Luo M, Wen Y, Luo G, Liu L. Org. Lett. 2014; 16: 3020
    • 14c Kantam ML, Kishore R, Yadav J, Sudhakar M, Venugopal A. Adv. Synth. Catal. 2012; 354: 663

Zoom Image
Scheme 1 A plausible reaction mechanism
Zoom Image
Scheme 2