Lewis acid-catalyzed (3 + 2) annulation of bicyclobutanes with ynamides: access to 2-amino-bicyclo[2.1.1]hexenes.

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)₃-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 via nucleophilic addition facilitated by the nitrogen lone pair from the alkynyl group of the ynamides to the unsubstituted side of the BCBs

SUBMITTER: Sarkar D 

PROVIDER: S-EPMC11404026 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature