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

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.