Tandem Allylation/1,2-Boronate Rearrangement for the Asymmetric Synthesis of Indolines with Adjacent Quaternary Stereocenters

A three-component
coupling using lithiated indoles, boronate esters
and allylic acetates generates chiral indolines with adjacent quaternary
stereocenters. Successful stereocontrol required the use of phosphoramidite
ligands not previously described for organopalladium chemistry. Mechanistic
studies indicate a monodentate PdL intermediate, and a stepwise allylation-aryl/alkyl
migration. A protodeborylation strategy was used to install a C–H
bond in place of the C–B bond. A photoredox coupling was used
to replace C–B bond with a C–C bond in a highly diastereoselective
manner. In the specific case of methyl-vinyl ketone, a novel radical-mediated
annulation provides polycyclic products with high enantio- and diastereoselectivity.