2-取代-5-卤代-2,3-二氢-4(H)-嘧啶-4-酮的合成及其在对映选择性合成α-取代β-氨基酸中利用Sonogashira偶联反应的衍生化。

Synthesis of 2-substituted-5-halo-2,3-dihydro-4(H)-pyrimidin-4-ones and their derivatization utilizing the Sonogashira coupling reaction in the enantioselective synthesis of alpha-substituted beta-amino acids.

作者信息

Díaz-Sánchez Blanca R, Iglesias-Arteaga Martín A, Melgar-Fernández Roberto, Juaristi Eusebio

机构信息

Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000 México, D.F., Mexico.

出版信息

J Org Chem. 2007 Jun 22;72(13):4822-5. doi: 10.1021/jo0705115. Epub 2007 May 25.

DOI:10.1021/jo0705115

PMID:17523668

Abstract

A convenient, one-pot procedure for the synthesis of 1-benzoyl-2(S)-substituted-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones by tandem decarboxylation/beta-iodination of the corresponding 6-carboxy-perhydropyrimidin-4-ones was developed. In addition, several 1-benzoyl-2(S)-substituted-5-bromo-2,3-dihydro-4(H)-pyrimidin-4-ones were readily prepared by bromination of 1-benzoyl-2(S)-substituted-2,3-dihydro-4(H)-pyrimidin-4-ones. Subsequently, Sonogashira coupling of the halogenated heterocyclic enones with various terminal alkynes produced 1-benzoyl-2(S)-isopropyl-5-alkynyl-2,3-dihydro-4(H)-pyrimidin-4-ones in good yields. Hydrogenation of the unsaturated C-C moieties in the Sonogashira products followed by acid hydrolysis afforded highly enantioenriched alpha-substituted beta-amino acids.

摘要

开发了一种便捷的一锅法，通过相应的6-羧基全氢嘧啶-4-酮的串联脱羧/β-碘化反应合成1-苯甲酰基-2(S)-取代-5-碘-2,3-二氢-4(H)-嘧啶-4-酮。此外，通过1-苯甲酰基-2(S)-取代-2,3-二氢-4(H)-嘧啶-4-酮的溴化反应，可轻松制备几种1-苯甲酰基-2(S)-取代-5-溴-2,3-二氢-4(H)-嘧啶-4-酮。随后，卤代杂环烯酮与各种末端炔烃进行Sonogashira偶联反应，以良好的产率生成1-苯甲酰基-2(S)-异丙基-5-炔基-2,3-二氢-4(H)-嘧啶-4-酮。对Sonogashira产物中不饱和C-C部分进行氢化，然后进行酸水解，得到高度对映体富集的α-取代β-氨基酸。