Selective C(sp³)–H Bond Insertion in Carbene/Alkyne Metathesis Reactions. Enantioselective Construction of Dihydroindoles

Abstract

A general access to chiral dihydroindole derivatives in high yields is achieved by C–H functionalization in a highly site- and enantioselective cascade reaction of propargyl diazoacetates. Highly site-selective intramolecular C(sp3)–H bond insertions are realized by catalyst control. Sterically demanding dirhodium carboxylates, optimized with Rh2(S-BTPCP)4, favor C–H insertion into 1° C–H bonds with regioselectivities reaching >95:5 (1° > 2° benzylic) and >90% ee. With Rh2(S-TBPTTL)4, preferential 2° and 3° C–H bond insertion occurs due to the configuration of catalyst and electronic effects. The chiral dirhodium catalyst not only promotes carbene/alkyne metathesis (CAM) to generate the donor/donor carbene intermediate, but is also responsible for the observed asymmetric induction in the terminating C–H bond insertion reaction.