Synlett 2009(14): 2295-2300  
DOI: 10.1055/s-0029-1217712
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric Synthesis of γ-Hydroxy-α,β-acetylenic Esters Catalyzed by Oxazolidine-Titanium Complex

Jincheng Mao*, Jun Guo
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Suzhou University, Suzhou 215123, P. R. of China
Fax: +86(512)65880089; e-Mail: jcmao@suda.edu.cn;
Further Information

Publication History

Received 14 April 2009
Publication Date:
03 August 2009 (online)

Abstract

An efficient catalytic system has been developed for the enantioselective reaction of alkynoates with aromatic aldehydes for the synthesis of optically active γ-hydroxy-α,β-acetylenic esters (with up to 81% isolated yield and up to 84% enantioselectivity).

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15

General Procedure for the Addition of Methyl Propiolate to Benzaldehyde All manipulations were carried out under an argon atmosphere. The ligand 2 (0.1 mmol), base (0.5 mmol), and DIMPEG (0.05 mmol) were mixed in dry toluene (2.0 mL) at r.t. Then, a solution of Me2Zn (1.2 M in toluene, 1.5 mmol) and methyl propiolate (1.5 mmol) were added in turn. After the mixture was stirred at r.t. for 7 h, Ti(Oi-Pr)4 (0.2 mmol, 60 µL) was added and the stirring continued for another 0.5 h. The yellow solution was cooled to 0 ˚C and treated with benzaldehyde (0.5 mmol, 50 µL), then the resultant mixture was allowed to warm up to r.t. naturally and stirred for 20 h. After the reaction was completed, it was cooled to 0 ˚C again and quenched by 5% aq HCl (2 mL). The mixture was extracted with EtOAc (2 × 10 mL). The organic layer was dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography (silica gel H, 10% EtOAc in PE) to give the pure product.
Methyl 4-Hydroxy-4-phenylbut-2-ynoate Yield 78%; 84% ee determined by HPLC analysis (Chiralcel OD-H column, IPA-hexane = 20:80). t R(minor) = 6.60 min, t R(major) = 7.33 min. ¹H NMR (400 MHz, CDCl3): δ = 2.67 (d, J = 6.4 Hz, 1 H), 3.80 (s, 3 H), 5.58 (d, J = 6.4 Hz, 1 H), 7.35-7.43 (m, 3 H), 7.52 (d, J = 6.8 Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 53.4, 64.4, 77.8, 87.4, 127.1, 29.22, 129.3, 138.9, 154.4.