Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes

作者：Chernega Alexander N; Davies Stephen G^*; Fletcher Ai M; Goodwin Christopher J; Hepworth David; Prasad R Shyam; Roberts Paul M; Savory Edward D; Smith Andrew D; Thomson James E

来源：Tetrahedron, 2010, 66(23): 4167-4194.

DOI：10.1016/j.tet.2010.03.105

• Weinreb amide
• Glycolate enolate
• Diastereoselective alkylation
• Aldol reaction

Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates alpha-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH(4) to give enantiopure alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes in good yield.

• 出版日期2010-6-5