Sequential Visible-Light Photoactivation and Palladium Catalysis Enabling Enantioselective [4+2] Cycloadditions

Catalytic asymmetric cycloadditions
of reactive ketene intermediates provide new opportunities for the
production of chiral heterocyclic molecules. Though known for over
100 years, ketenes still remain underexplored in the field of transition-metal
(TM)-catalyzed asymmetric cycloadditions because (1) ketenes, as highly
electron-deficient species, are possibly unstable to low-valence TMs
(i.e., decarbonylation or aggregation) and (2) the conventional thermal
synthesis of ketenes from acyl chlorides and amines may be incompatible
with TM catalysis (i.e., reactive acyl chloride and amine hydrochloride
byproducts). Herein, we detail the unprecedented asymmetric [4+2]
cycloaddition of vinyl benzoxazinanones with a variety of ketene intermediates
via sequential visible-light photoactivation and palladium catalysis.
It is well demonstrated that the traceless and transient generation
of ketenes from α-diazoketones through visible-light-induced
Wolff rearrangement is important for the success of present cycloaddition.
Furthermore, chiral palladium catalysts with a new, chiral hybrid
P, S ligand enable asymmetric cycloaddition with high reaction selectivity
and enantiocontrol.