Palladium-Catalyzed, Highly Regio-, Stereo-, and Enantioselective Anti-Carboxylation of Unactivated Internal Allenes

Presented herein is the first report of a directing group-controlled, palladium-catalyzed, regio-, stereo-, and enantioselective anti-carboxylation of unactivated, internal allenes enabled via the synergistic interplay of rationally designed bidentate directing groups, palladium catalyst, and multifunctional acetate ligand. The corresponding trans allyl ester was obtained in excellent yields with exclusive delta-regioselectivity and anti-carboxypalladation stereocontrol. The pair of palladium catalysts coordinated with the bidentate directing group control regio-, and stereo- and enantioselectivity in the desired transformation. The potential of this concept has been demonstrated by the development of the first example of a chiral version of this transformation by using axial-to-central chirality transfer with high yields and good enantioselectivities. Several control experiments were conducted to validate the ligand-assisted nucleopalladation process and the rationale behind the racemization of chiral allenes. Detailed investigations, including kinetic studies, order studies, and DFT studies, were performed to elucidate the mechanism of this transformation, indicating that the anti-carboxypalladation step was the rate-limiting as well as the stereo- and enantio-determining step.