通过催化不对称 Diels-Alder 反应构建具有卤代季碳手性中心的立体选择性。

Stereoselective construction of halogenated quaternary stereogenic centers via catalytic asymmetric Diels-Alder reaction.

机构信息

Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi 441-8580, Japan.

出版信息

J Am Chem Soc. 2010 Apr 28;132(16):5625-7. doi: 10.1021/ja1018628.

DOI:10.1021/ja1018628

PMID:20373752

Abstract

Highly enantioselective Diels-Alder reactions of alpha-halo-alpha,beta-unsaturated ketones with Lewis acid-activated chiral oxazaborolidine 1 are described. The reaction with alpha-fluoroenones provided the corresponding cyclohexane derivatives having a fluorinated quaternary stereogenic center with up to 99% de and 94% ee. The reaction with alpha-bromo cyclic enones provided the corresponding bromo bicyclic adducts with up to 99% de and 95% ee. A brominated cis-fused bicyclic adduct derived from 2-bromocyclopenten-1-one and Dane's diene was converted to the trans-fused bicyclic system via reductive alkylation with the bulky aluminum reagent aluminum tris(2,6-diphenylphenoxide) (ATPH). With this process, formal syntheses of (+)-estrone and norgestrel have been demonstrated.

摘要

高对映选择性的 Diels-Alder 反应的 α-卤代-α，β-不饱和酮与路易斯酸激活的手性恶唑硼烷 1 被描述。与α-氟烯酮的反应提供了相应的环己烷衍生物具有一个氟化的季立体中心，最高达 99%的 de 和 94%的 ee。与α-溴代环状烯酮的反应提供了相应的溴代双环加成产物，最高达 99%的 de 和 95%的 ee。一个溴化的顺式稠合双环加成产物衍生自 2-溴环戊-1-酮和 Dane 的双烯，通过用大体积的铝试剂三（2,6-二苯基苯酚）铝（ATPH）进行还原烷基化，转化为反式稠合双环体系。通过这个过程，（+）-雌酮和炔诺孕酮的正式合成已经得到了证明。