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Synlett 2006(8): 1245-1249  
DOI: 10.1055/s-2006-932473
LETTER
© Georg Thieme Verlag Stuttgart · New York

Highly Enantioselective Addition of Phenylacetylene to Ketones Catalyzed by Bis(hydroxycamphorsulfonamide)-Copper(II) Complex

Lei Liua, Rui Wang*a,b, Yong-Feng Kanga,c, Hua-Qing Caia, Chao Chena
a Department of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P. R. of China
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, Gansu 730000, P. R. of China
c College of Food Science, Shanghai Fisheries University, Shanghai 200090, P. R. of China
Fax: +86(931)8912561; e-Mail: wangrui@lzu.edu.cn;
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Publication History

Received 15 November 2005
Publication Date:
10 March 2006 (online)

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Abstract

A chiral copper complex, generated from a C 2-sym­metric bis(hydroxycamphorsulfonamide) ligand (8 mol%) and Cu(OTf)2, has been discovered to effect high enantioselectivities in the addition of alkynylzinc to a series of simple ketones. The alkynylation of a variety of aromatic and aliphatic ketones resulted in excellent yields and enantioselectivities (83-98% ee). Even when the loadings of the catalyst is 5 mol%, up to 94% ee was obtained.

Key words

alkynylation - simple ketones - asymmetric catalysis - C 2-symmetric bis(hydroxycamphorsulfonamide)

11

Selected data for 9: white solid, mp 141-142 °C; [α]D 28
-51.0 (c 1.0, EtOAc). 1H NMR (200 MHz, CDCl3): δ = 0.77 (6 H, s), 0.97 (6 H, s), 1.10-1.78 (14 H, m), 2.78 (2 H, d, J = 13.8 Hz), 3.25 (2 H, d, J = 13.6 Hz), 4.03-4.08 (2 H, m), 4.30 (4 H, d, J = 5.6 Hz), 5.38 (2 H, b), 7.28-7.39 (4 H, m). 13C NMR (50 MHz, CDCl3): δ = 19.81 (2 C), 20.47 (2 C), 27.30 (2 C), 30.43 (2 C), 39.00 (2 C), 44.31 (2 C), 47.10 (2 C), 48.68 (2 C), 50.36 (2 C), 52.97 (2 C), 76.42 (2 C), 127.98 (2 C), 129.47 (2 C), 137.57 (2 C). IR (KBr): 3529, 3283, 2956, 2882, 2253, 1706, 1612, 1472, 1453, 1394, 1370, 1317, 1259, 1235, 1209, 1140, 1073, 1054, 1028, 991, 911, 883, 846, 795, 773, 733, 704 cm-1.

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Selected data for 11: white solid, mp 101-102 °C; [α]D 28
-24.0 (c 1.11, EtOH). 1H NMR (200 MHz, CDCl3): δ = 0.80 (6 H, s), 1.03 (6 H, s), 1.07-1.80 (14 H, m), 3.04 (2 H, d, J = 12.0 Hz), 3.61 (2 H, d, J = 14.0 Hz), 4.09-4.15 (2 H, m), 7.27-7.52 (4 H, m). 13C NMR (50 MHz, CDCl3): δ = 19.89 (2 C), 20.50 (2 C), 27.27 (2 C), 30.43 (2 C), 39.36 (2 C), 44.37 (2 C), 48.93 (2 C), 50.51 (2 C), 52.12 (2 C), 76.36 (2 C), 125.27 (2 C), 127.62 (2 C), 130.68 (2 C). IR (KBr): 3544, 3266, 2957, 2833, 2253, 1732, 1598, 1500, 1475, 1458, 1395, 1327, 1262, 1209, 1146, 1103, 1074, 1027, 911, 883, 800, 733, 703, 647 cm-1.

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General Procedures for Addition of Phenylacetylene to Ketones.
Compound 9 (11.36 mg, 0.02 mmol) and Cu(OTf)2 (7.2 mg, 0.02 mmol) were mixed in dry toluene (0.5 mL) under Ar atmosphere. Then, Et2Zn in toluene (1.0 M, 1.0 mL) was added. After that, phenylacetylene (108 µL) was added. After 2 h, the solution was cooled to 0 °C and treated with ketones (0.25 mmol). The resulting mixture was stirred at 0 °C for 16-60 h. After the reaction was complete (monitoring with TLC), it was quenched with aq HCl (5%). Then, the mixture was extracted with Et2O. The organic layer was washed with brine, dried over Na2SO4, and concentrated under vacuum. The residue was purified by flash column chromatography to obtain the product.