Asymmetric induction in methyl ketone aldol additions to α-alkoxy and α,β-bisalkoxy aldehydes:: A model for acyclic stereocontrol
Asymmetric induction in methyl ketone aldol additions to α-alkoxy and α,β-bisalkoxy aldehydes:: A model for acyclic stereocontrol
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DOI：
10.1021/ja061010o
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发表时间：
2006-07-26
影响因子：
15
通讯作者：
Siska, Sarah J.
中科院分区：
文献类型：
--
作者：
Evans, David A.;Cee, Victor J.;Siska, Sarah J.
系统地研究了在非螯合条件下，甲酮醇醛与α-烷氧基和α，β-双烷氧基醛的加成反应。与含有单一α-烷氧基立体中心的醛的加成反应通常提供符合康福斯/极性Felkin-Anh模型的产物非对映异构体。邻位不对称诱导对醛的α-烷基取代基很敏感，但对烷氧基的性质相对不敏感。在含有额外的β-烷氧基立体中心的底物上，醛的表面选择性表现出明显的依赖于α和β立体中心的相对构型。在大多数情况下，具有反关系的α-和β-烷氧基的醛表现出良好的非对映选择性，而具有同步关系的α-和β-烷氧基的醛意外地产生产物混合物。提出了一种基于康福斯类过渡态排列的立体化学模型。
A systematic study of methyl ketone aldol additions under nonchelating conditions with alpha-alkoxy and alpha,beta-bisalkoxy aldehydes is described. Additions to aldehydes containing a single alpha-alkoxy stereocenter generally provide the product diastereomers in accord with the Cornforth/polar Felkin-Anh models for carbonyl addition. Vicinal asymmetric induction is sensitive to the aldehyde alpha-alkyl substituent, but is relatively insensitive to the nature of the alkoxy protecting group. Aldehyde pi-facial selectivity in additions to substrates containing an additional beta-alkoxy-substituted stereocenter exhibits a striking dependence on the relative configuration of the alpha- and beta-stereocenters. Aldehydes with the alpha- and beta-alkoxy substituents in an anti relationship in most cases exhibit good diastereoselectivity, while aldehydes with the alpha- and beta-alkoxy substituents in a syn relationship unexpectedly give product mixtures. A stereochemical model based on Cornforth-like transition-state arrangements is proposed.