Strategies for remote enantiocontrol in chiral gold(<scp>iii</scp>) complexes applied to catalytic enantioselective γ,δ-Diels–Alder reactions
Jolene P. Reid, Mingyou Hu, Susumu Ito, Banruo Huang, Cynthia Hong, Hengye Xiang, Matthew S. Sigman, F. Dean Toste
Abstract
The use of chiral square planar gold(iii) complexes to access enantioenriched products has rarely been applied in asymmetric catalysis. In this context, we report a mechanistic and synthetic investigation into the use of N-heterocyclic (NHC) gold(iii) complexes in γ,δ-Diels-Alder reactions of 2,4-dienals with cyclopentadiene. The optimal catalyst bearing a unique 2-chloro-1-naphthyl substituent allowed efficient synthesis of functionally rich carbocycles in good yields, diastereo- and enantioselectivities. Transition state and multivariate linear regression (MLR) analysis of both catalyst and substrate trends using molecular descriptors derived from designer parameter acquisition platforms, reveals attractive non-covalent interactions (NCIs) to be key selectivity determinates. These analyses demonstrate that a putative π-π interaction between the substrate proximal double bond and the catalyst aromatic group is an essential feature for high enantioselectivity.