Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis

• DOI: 10.1126/sciadv.adg7754
• Publication Date: 2023-06-16T17:58:40Z
• Authors: Hong-Fu Liu; Liang Long; Zhi-Qiang Zhu; Teng-Fei Wu; Yi-Rui Zhang; Han-Peng Pan; Ai-Jun Ma; Jin-Bao Peng; Yong-Heng Wang; Hao Gao; Xiang-Zhi Zhang
• Keywords: Phosphoric acid; Racemization; Alkyne

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products medicinally relevant molecules. Nevertheless, general broadly applicable methods enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to easy racemization. Here, we report a visible light photoactivation phosphoric acid–catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, Hantzsch ester expeditious α,α-diarylketones with excellent yields enantioselectivities. In reaction, three chemical bonds, including C═O, C─C, C─H, formed, providing de novo chiral α,α-diarylketones. Moreover, this protocol provides convenient practical method synthesize or modify complex bioactive molecules, efficient routes florylpicoxamid BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, substituents all play crucial roles in stereocontrol reaction.