手性助剂N-1-(1'-萘基)乙基-O-叔丁基羟胺：一种手性Weinreb酰胺等价物。

The chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine: a chiral Weinreb amide equivalent.

作者信息

Chernega Alexander N, Davies Stephen G, Goodwin Christopher J, Hepworth David, Kurosawa Wataru, Roberts Paul M, Thomson James E

机构信息

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.

出版信息

Org Lett. 2009 Aug 6;11(15):3254-7. doi: 10.1021/ol901174t.

DOI:10.1021/ol901174t

PMID:19606853

Abstract

The chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine is readily prepared from N-hydroxyphthalimide in four steps, with resolution giving access to both enantiomers in > 98% ee, on a multigram (> 25 g) scale. Conversion to a range of N-acyl derivatives, followed by highly diastereoselective alkylation (> or = 94% de) gives the corresponding chiral, 2-substituted derivatives as single diastereoisomers (> 98% de) after chromatography. Reductive cleavage with LiAlH(4) allows direct access to chiral aldehydes, and treatment with MeLi gives chiral methyl ketones in excellent enantiopurity (> or = 94% ee). The auxiliary can be recovered in > 98% ee and recycled.

摘要

手性助剂N-1-(1'-萘基)乙基-O-叔丁基羟胺可由N-羟基邻苯二甲酰亚胺经四步轻松制得，通过拆分可在多克（>25 g）规模上以>98%的对映体过量获得两种对映体。转化为一系列N-酰基衍生物，随后进行高度非对映选择性烷基化（>或=94%的非对映体过量），经色谱分离后得到相应的手性2-取代衍生物，为单一非对映异构体（>98%的非对映体过量）。用LiAlH(4)进行还原裂解可直接得到手性醛，用MeLi处理可得到对映体纯度极高（>或=94%的对映体过量）的手性甲基酮。该助剂可在>98%的对映体过量下回收并循环使用。