Asymmetric synthesis of chiral boronic esters featuring nonadjacent axial and flexible, acyclic central chirality
Year: 2025
Type: article
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–derived boronic esters, and tolerates aryl trifluoromethanesulfonates (ArOTfs) with varying electronic and steric properties. Mechanistic studies indicate a palladium(II) intermediate, with 1,2-carbon migration as the rate-determining step. Furthermore, product derivatization introduces diverse functional groups, enhancing molecular complexity and facilitating downstream transformations.
Source: Science Advances
Authors: Xi-Zhang Zou, Yu-Wen Sun, De-Wei Gao
Institutions: ShanghaiTech University, Anhui Normal University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,500
Award: G1300455179
OpenAlex ID: W4416965418