Lewis Acid-catalyzed (3 + 2) Annulation of Bicyclobutanes with Ynamides: Access to 2-amino-bicyclo[2.1.1]hexenes

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Sep 19

PMID 39296999

Authors

Deeptanu Sarkar

Shiksha Deswal

Rohan Chandra Das

Akkattu T Biju

Affiliations

Soon will be listed here.

Abstract

Strain-release driven annulations with bicyclo[1.1.0]butanes (BCBs) have become an attractive area of research for the synthesis of bioisosteric bicyclohexane derivatives, which play a vital role in drug discovery. Interestingly, the utilization of the inherent strain in BCBs for the synthesis of functionalized amino-bicyclo[2.1.1]hexenes, which may spatially mimic substituted benzenes and anilines, has received only scant attention. Herein, we report the Sc(OTf)-catalyzed (3 + 2) annulation of BCBs with ynamides for the facile synthesis of 2-amino-bicyclo[2.1.1]hexenes in one step under mild conditions. The reaction likely proceeds nucleophilic addition facilitated by the nitrogen lone pair from the alkynyl group of the ynamides to the unsubstituted side of the BCBs, followed by the annulation of the resulting enolate with the keteniminium species. For the first time, the C-C triple bond of ynamides was utilized as the coupling partner for BCBs, resulting in products adorned with a functionalizable amino group and an integrated strained alkene moiety.

Citing Articles

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PMID: 39713756 PMC: 11659875. DOI: 10.1039/d4sc07243j.

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