Asymmetric synthesis of chiral boronic esters featuring nonadjacent axial and flexible, acyclic central chirality.

ABSTRACT: Nonadjacent chirality is prevalent in pharmaceuticals and bioactive molecules, but prior studies primarily focused on constructing noncontiguous stereocenters. However, the construction of nonadjacent axial and flexible, acyclic central chirality often involves highly flexible transition states, posing challenges in achieving precise control over enantio- and diastereoselectivity. Here, extensive ligand screening, followed by structural modification and optimization, identified a bulky P,N-phosphinooxazoline (P,N-phox) ligand derived from l-serine, enabling the direct asymmetric construction of atropisomers with axial and flexible, acyclic central chirality. The reaction demonstrates broad substrate scope, accommodating diverse aryl, alkyl, and natural product-d

SUBMITTER: Zou XZ 

PROVIDER: S-EPMC12674118 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature