Rh(II)/Pd(0) Dual-Catalyzed Regio-Divergent Three-Component Propargylic Substitution

Regio-divergent propargylic substitution to generate
functionally
diverse products from identical starting materials remains a formidable
challenge, probably due to the unpredictable regiochemical complexity.
In practically, the synthesis of α-quaternary propargylic-substituted
products is still much less developed, and preprepared nucleophiles
are generally applied in this type of reaction with propargylic substrates,
which limits the reaction efficiency and diversity of the obtained
products. Herein, we disclose unprecedented three-component propargylic
substitution of α-diazo esters with amines and propargylic carbonates
under dirhodium/palladium dual catalysis. The key to the success of
this multicomponent propargylic substitution is to avoid two-component
side reactions through a tandem process of dirhodium(II)-catalyzed
carbene insertion and palladium-catalyzed regiodivergent propargylic
substitution. The judicious selection of a diphosphine (dppf) or monophosphine
(tBuBrettphos) as the ligand is crucial
for the reaction to generate different products in a switchable way,
α-quaternary 1,3-dienyl or propargylated products, with high
regio- and chemoselectivities.