Inductive Diastereoselective Rationale for a Catalytic Strategy to Build Densely Chiral Five-Membered Carbocycles

We report a streamlined synthetic strategy for accessing stereocongested five-membered carbocycles from enantioenriched branched borylated 1,4-dienes. The method enables precise control over diastereoselectivity and enantiospecificity in the construction of adjacent stereocenters within the newly formed cyclic frameworks. DFT calculations provide an understanding of the origin of diastereoselection along the Cu-catalyzed borylcupration step, allowing one to establish a stereochemical model that rationalizes the key ligand-substrate and intrasubstrate interactions governing selectivity. Moreover, the resulting stereocongested cyclopentenes can be further elaborated through stereoselective alkene activation, enabling the installation of up to four contiguous stereocenters and granting access to architecturally complex, multistereogenic cyclopentane frameworks.