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The first highly enantioselective iridium-catalyzed allylic alkylation that provides access to products bearing an allylic all-carbon quaternary stereogenic center has been developed. The reaction utilizes a masked acyl cyanide (MAC) reagent, which enables the one-pot preparation of α-quaternary carboxylic acids, esters, and amides with a high degree of enantioselectivity. The utility of these products is further explored through a series of diverse product transformations.

The development of the first enantio-, diastereo-, and regioselective iridium-catalyzed allylic alkylation reaction of prochiral enolates to form an all-carbon quaternary stereogenic center with an aliphatic-substituted allylic electrophile is disclosed. The reaction proceeds with good to excellent selectivity with a range of substituted tetralone-derived nucleophiles furnishing products bearing a newly formed vicinal tertiary and all-carbon quaternary stereodyad. The utility of this protocol is further demonstrated via a number of synthetically diverse product transformations.

Transition-metal-catalyzed asymmetric allylic alkylation of enolates is a powerful method for the formation of carbon− carbon bonds. Within this field, palladium-catalyzed allylic alkylation reactions have undoubtedly been the most studied. Aside from limited cases, palladium catalysts preferentially form the linear substitution product through alkylation at the less-substituted terminus of the allylic electrophile (Scheme 1). However, in contrast to palladium, most other transition metals (e.g., Mo, W, Fe, Ru, Co, Rh, Ni, Pt, and Ir) have been shown to favor the construction of the branched product, with iridium catalysts being some of the most efficient and selective. The potential application of these chiral, branched products to the synthesis of natural products and biologically active compounds has motivated the development of practical and reliable transition-metal-catalyzed methods for their construction.

This account describes our laboratory’s efforts in the development of a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic conjugate acceptors. Specifically, we highlight the study of this transformation in the following areas: (a) construction of all-carbon quaternary stereocenters, (b) elucidation of the reaction mechanism, (c) addition to heterocyclic acceptors to generate tertiary stereocenters, and (d) application in the synthesis of natural products.