Atherton–Todd Reaction-Guided Enantioselective Synthesis of Axially Chiral Olefins via Bifunctional Phosphonium Salt-Regulating Ketone-Enol Tautomerism

• Published in: ACS catalysis 2023-10, Vol.13 (19), p.13077-13088
• Main Authors: Fang, Siqiang, He, Jiajia, Liu, Zanjiao, Su, Zhishan, Guo, Fengyuan, Wang, Tianli
• Format: Article
• Language: English
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.3c03304

Atropisomerically enriched olefin scaffolds are of great importance in many fields of chemistry. Although several synthetic routes to these axial molecules have been reported, alternative, powerful catalytic strategies are still highly demanded in this area. Here, we present an unprecedented organocatalytic method toward the atroposelective assembly of axially chiral olefins with phosphorus unit via bifunctional phosphonium salt-catalyzed Atherton–Todd reaction of ketones. This protocol provides a concise and efficient avenue to allow access to atropisomeric olefins with excellent stereoselectivities (up to 99:1 e.r.). Moreover, experimental studies and density functional theory (DFT) calculations revealed that this atroposelective Atherton–Todd coupling proceeded through a dynamic kinetic resolution (DKR) process by phosphonium-controlled ketone-enol tautomerism and also provided insights into the origins of stereoselectivities in the formation of chiral axis. This catalytic strategy offering a convenient and pragmatic route to enantioenriched axial olefins has never been disclosed, providing a platform for exploring the potential applications of atropisomeric olefin-containing phosphorus molecules.