氮杂螺环化合物的多样性导向合成。

Diversity-oriented synthesis of azaspirocycles.

作者信息

Wipf Peter, Stephenson Corey R J, Walczak Maciej A A

机构信息

Department of Chemistry, Center for Chemical Methodologies & Library Development, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

出版信息

Org Lett. 2004 Aug 19;6(17):3009-12. doi: 10.1021/ol0487783.

DOI:10.1021/ol0487783

PMID:15330670

Abstract

Multicomponent condensation of N-diphenylphosphinoylimines, alkynes, zirconocene hydrochloride, and diiodomethane provides a rapid access to omega-unsaturated dicyclopropylmethylamines. These novel building blocks are converted into heterocyclic 5-azaspiro[2.4]heptanes, 5-azaspiro-[2.5]octanes, and 5-azaspiro[2.6]nonanes by means of selective ring-closing metathesis, epoxide opening, or reductive amination. The resulting functionalized pyrrolidines, piperidines, and azepines are scaffolds of considerable relevance for chemistry-driven drug discovery.

摘要

N-二苯基膦酰亚胺、炔烃、二氯二茂锆和二碘甲烷的多组分缩合反应能够快速合成ω-不饱和二环丙基甲胺。通过选择性闭环复分解反应、环氧化合物开环反应或还原胺化反应，这些新型结构单元可转化为杂环5-氮杂螺[2.4]庚烷、5-氮杂螺[2.5]辛烷和5-氮杂螺[2.6]壬烷。由此得到的功能化吡咯烷、哌啶和氮杂䓬是化学驱动药物发现中具有重要意义的骨架结构。