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

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(sp(3))-H bond insertions are realized by catalyst control. Sterically demanding dirhodium carboxylates, optimized with Rh-2(S-BTPCP)(4), favor C-H insertion into 1 degrees C-H bonds with regioselectivities reaching >95:5 (1 degrees > 2 degrees benzylic) and >90% ee. With Rh-2(S-TBPTTL)(4), preferential 2 degrees and 3 degrees 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.