Enantioselective De Novo Synthesis of a,a-Diaryl Ketones from Alkynes

Chiral a,a-diaryl ketones are structural motifs commonly present in bioactive molecules, and they are also valuable building blocks in synthetic organic chemistry. However, catalytic asymmetric synthesis of a,a-diaryl ketones bearing a tertiary stereogenic center remains largely unsolved. Herein, we report a catalytic de novo enantioselective synthesis of a,a-diaryl ketones from simple alkynes via chiral phosphoric acid (CPA) catalysis. A broad range of enolizable a,a-diaryl ketones are prepared in good yields and with excellent enantioselectivities. The described protocol also serves as an efficient deuteration method for the preparation of enantiomerically enriched deuterated a,a-diaryl ketones. Using the methodology reported, bioactive molecules, including one of the best-selling anti-breast cancer drugs, tamoxifen, are readily synthesized.

Automated summary

This study reports a simple and efficient method for the enantioselective synthesis of chiral α,α-diaryl ketones using chiral phosphoric acid catalysis, which also serves as an efficient method for the preparation of enantiomerically enriched deuterated α,α-diaryl ketones. This methodology is of great significance for the synthesis of bioactive molecules.