Bifunctional Brønsted Base Catalyst Enables Regio-, Diastereo-, and Enantioselective Cα -Alkylation of β-Tetralones and Related Aromatic-Ring-Fused Cycloalkanones

Abstract

The catalytic asymmetric synthesis of both α-substituted and α,α-disubstituted (quaternary) β-tetralones through direct α-functionalization of the corresponding β-tetralone precursor remains elusive. A designed Brønsted base-squaramide bifunctional catalyst promotes the conjugate addition of either unsubstituted or α-monosubstituted β-tetralones to nitroalkenes. Under these reaction conditions, not only enolization, and thus functionalization, occurs at the α-carbon atom of the β-tetralone exclusively, but adducts including all-carbon quaternary centers are also formed in highly diastereo- and enantioselective manner.

Keywords: Brønsted bases; heterocycles; organocatalysis; polycycles; synthetic methods.