Asymmetric Three-Component Reaction for the Synthesis of Tetrasubstituted Allenoates via Allenoate-Copper Intermediates

A catalytic asymmetric three-component reaction of alpha-diazoesters with terminal alkynes and isatins was achieved. This one-pot synthesis gave rise to axially chiral tetrasubstituted allenoates bearing a stereogenic center. The chiral guanidinium salt/CuBr/YBr3 catalytic system proved efficient and highly diastereo-and enantioselective for a wide range of alkynes, aromatic alpha-diazoesters, and isatins under mild reaction conditions. This approach enables a Cu(I)-involved asymmetric multicomponent reaction (AMCR) of alpha-diazo compounds and gives solid experimental evidence for the formation of allenoate-Cu(I) intermediates in C-H insertion of alpha-diazoesters to terminal alkynes. We also found that additional acids improved the catalyst efficiency of guanidinium salt/CuCl in the direct enantioselective C-H insertion of alpha-aryl diazoesters. Mechanism studies suggest that the combined-acid systems (Lewis acid combined with assisted Lewis acid or Bronsted acid combined with assisted Lewis acid) bring out higher reactivity by associative interaction and allow for an equally effective asymmetric environment.