Pd/WingPhos-Catalyzed Synthesis of γ-Amino Alcohol Derivatives with β-Axial Stereogenicity via Desymmetrization of Allenylic Cyclic Carbonates.

Chiral γ-amino alcohols serve as pivotal scaffolds in medicinal chemistry and asymmetric catalysis. However, synthetic strategies for their construction have long been constrained to the establishment of stereogenic centers, resulting in limited stereochemical diversity that falls short of the escalating demand for functional molecular variation. To address this limitation, we have designed and synthesized a novel class of prochiral allenyl cyclic carbonates as electrophiles. By employing a Pd/WingPhos catalytic system, these electrophiles undergo efficient reaction with a wide range of amine nucleophiles─including 2-oxindoles, isatins, succinimide, quinolinones, 1-hydroxyisoquinoline, 2-hydroxypyridine, and primary/secondary sulfonamides─furnishing a series of structurally unprecedented γ-amino alcohol derivatives with β-axial stereogenicity in moderate to good yields and excellent enantioselectivities (up to 98% ee). The successful realization of this decarboxylative strategy elegantly overcomes the intrinsic limitations of conventional synthetic approaches. It not only suppresses the kinetic resolution that often arises when employing racemic allenol derivatives as nucleophiles, but also circumvents the overfunctionalization frequently encountered with prochiral bis-electrophilic allenes, thus ensuring excellent efficiency and precise stereocontrol for the allenylic substitution. Furthermore, this methodology enables the efficient construction of synthetically challenging tetrasubstituted allene frameworks with β-axial stereogenicity. The resulting γ-amino alcohol products with β-axial stereogenicity undergo diverse downstream transformations, including deprotection, cyclization with chirality transfer, oxidation, and esterification.