关于 N-1-(1'-萘基)乙基-O-叔丁基羟胺酸酯衍生的烯醇盐的烷基化中立体选择性的起源：手性 Weinreb 酰胺等价物。

On the origins of diastereoselectivity in the alkylation of enolates derived from N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxamates: chiral Weinreb amide equivalents.

机构信息

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

出版信息

J Org Chem. 2010 Feb 19;75(4):1214-27. doi: 10.1021/jo902499s.

DOI:10.1021/jo902499s

PMID:20095549

Abstract

The stereochemical outcome observed upon alkylation of enolates derived from N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxamates (chiral Weinreb amide equivalents) may be rationalized by a chiral relay mechanism. Deprotonation with KHMDS leads to a nonchelated (Z)-enolate in which the oxygen atoms adopt an anti-periplanar conformation. The configuration of the N-1-(1'-naphthyl)ethyl group dictates the conformation of the O-tert-butyl group and the configuration adopted by the adjacent pyramidal nitrogen atom. Highly diastereoselective enolate alkylation then proceeds anti to both the bulky tert-butyl group (sterically driven) and the N-lone pair (stereoelectronically driven).

摘要

通过 N-1-(1'-萘基)乙基-O-叔丁基羟胺酯（手性 Weinreb 酰胺等价物）衍生的烯醇化物的烷基化反应观察到的立体化学结果可以通过手性接力机制来合理化。用 KHMDS 进行脱质子化会导致非螯合的（Z）-烯醇化物，其中氧原子采用反式稠合构象。N-1-(1'-萘基)乙基基团的构型决定了 O-叔丁基基团的构象和相邻的三角锥形氮原子的构型。然后，高非对映选择性的烯醇化物烷基化反应反式进行，既受到叔丁基基团的位阻（位阻驱动），也受到 N-孤对电子的立体电子驱动。