Aminocatalytic enantioselective [2 + 2] cycloaddition of Bicyclo[1.1.0]butanes and α,β-unsaturated aldehydes.

ABSTRACT: Bicyclo[1.1.0]butanes have opened a new area of chemical space for construction of bicyclo[2.1.1]hexanes - a scaffold showing promise as ortho- and meta-aryl bioisosteres. Herein, we present the first aminocatalytic concept that enables the enantioselective [2 + 2] cycloaddition of bicyclo[1.1.0]butanes with α,β-unsaturated aldehydes. The reaction is general for α,β-unsaturated aldehydes, substituted at the γ-position with aromatic functionalities, esters and ketones, by applying a secondary aminocatalyst and Yb(OTf)₃ as a Lewis acid to activate the bicyclo[1.1.0]butane. For cinnamaldehydes, bicyclo[2.1.1]hexane cycloadducts are obtained in moderate to good yields, and up to 96.5 : 3.5 e.r. Pleasingly, α,β-unsaturated aldehydes containing ester and ketone functiona

SUBMITTER: Bitsch RS 

PROVIDER: S-EPMC12360369 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature