通过烯醇盐加成到酰基硅烷上合成叔β-羟基酰胺。

Synthesis of tertiary beta-hydroxy amides by enolate additions to acylsilanes.

作者信息

Lettan Robert B, Reynolds Troy E, Galliford Chris V, Scheidt Karl A

机构信息

Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.

出版信息

J Am Chem Soc. 2006 Dec 13;128(49):15566-7. doi: 10.1021/ja065605v.

DOI:10.1021/ja065605v

PMID:17147347

Abstract

The synthesis of tertiary beta-hydroxy amides from acylsilanes, acetamides, and electrophiles is described. The addition of amide enolates to acylsilanes generates beta-silyloxy homoenolate reactivity by undergoing a 1,2-Brook rearrangement. These unique nucleophiles formed in situ can then undergo smooth addition to alkyl halides, aldehydes, and ketones. Enolates derived from amides are crucial for the success of this process since ketone enolates suffer from internal return of the beta-carbanion onto the carbonyl carbon. The use of optically active amide enolates delivers beta-hydroxy amide products with good levels of diastereoselectivity (>/=10:1).

摘要

描述了由酰基硅烷、乙酰胺和亲电试剂合成叔β-羟基酰胺的方法。酰胺烯醇盐与酰基硅烷加成，通过1,2-布鲁克重排产生β-硅氧基高烯醇盐反应性。这些原位形成的独特亲核试剂随后可顺利加成到卤代烃、醛和酮上。由酰胺衍生的烯醇盐对该过程的成功至关重要，因为酮烯醇盐会出现β-碳负离子向羰基碳的内部返回。使用旋光性酰胺烯醇盐可得到具有良好非对映选择性（≥10:1）的β-羟基酰胺产物。