Pd-catalyzed enantioselective allylic substitution: new strategic options for the total synthesis of natural products.

TLDR: The enantioselective version of palladium-catalyzed allylic substitution, sometimes referred to as AAA (asymmetric allylic alkylation), has emerged as a powerful synthetic tool and has recently proven to be of particular value as they react with cyclic substrates of type 1 and 2.

Abstract: The enantioselective version of palladium-catalyzed allylic substitution, sometimes referred to as AAA (asymmetric allylic alkylation), has emerged as a powerful synthetic tool.[1] Since the first report of a stoichiometric AAA reaction in the 1970s,[2] it took almost 20 years of research until effective catalytic systems based on chiral ligands were developed. The major challenge in conducting such reactions enantioselectively arises from the fact that both the departure of the allylic leaving group, resulting in the formation of a cationic p-allyl–Pd complex and, in most cases, the attack of the nucleophile occur on the p face of the substrate opposite to the metal. Asymmetric induction therefore proceeds remote to the employed chiral ligands. However, some particularly successful concepts to address this issue have been devised, and over 100 catalysts have been developed.[3] Besides high levels of asymmetric induction, advantages of the AAA methodology are a broad tolerance towards functional groups and, in contrast to many other catalytic asymmetric methods, a great flexibility in the bond type to be formed. For instance, H, O, N, S, P, and C nucleophiles can be employed. Among the many new opportunities thus arising for the synthetic chemist,[4] AAA reactions of cyclic substrates of type 1 and 2 have recently proven to be of particular value as they