Bifunctional Brønsted Base Catalyst Enables Regio-, Diastereo-, and Enantioselective C[alpha]-Alkylation of [beta]-Tetralones and Related Aromatic-Ring-Fused Cycloalkanones

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