Assembly of four diverse heterocyclic libraries enabled by prins cyclization, Au-catalyzed enyne cycloisomerization, and automated amide synthesis

Jiayue Cui, David I. Chai, Christopher Miller, Jason Hao, Christopher Thomas, Jingqi Wang, Karl A. Scheidt, Sergey A. Kozmin*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We describe a unified synthetic strategy for efficient assembly of four new heterocyclic libraries. The synthesis began by creating a range of structurally diverse pyrrolidinones or piperidinones. Such compounds were obtained in a simple one-flask operation starting with readily available amines, ketoesters, and unsaturated anhydrides. The use of tetrahydropyran-containing ketoesters, which were rapidly assembled by our Prins cyclization protocol, enabled efficient fusion of pyran and piperidinone cores. A newly developed Au(I)-catalyzed cycloisomerization of alkyne-containing enamides further expanded heterocyclic diversity by providing rapid entry into a wide range of bicyclic and tricyclic dienamides. The final stage of the process entailed diversification of each of the initially produced carboxylic acids using a fully automated platform for amide synthesis, which delivered 1872 compounds in high diastereomeric and chemical purity.

Original languageEnglish (US)
Pages (from-to)7435-7470
Number of pages36
JournalJournal of Organic Chemistry
Volume77
Issue number17
DOIs
StatePublished - Sep 7 2012

ASJC Scopus subject areas

  • Organic Chemistry

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