A Computational Study on the Intramolecular C4-C8′ Interflavan Bond Formations of Tethered Catechin Derivatives

Abstract

Abstract The procyanidin B series is a family of dimeric flavonoids composed of catechin(s) and/or epicatechin(s) with a C4-C8′ interflavan bond. We previously reported four TMSOTf-promoted couplings for C4-C8′ interflavan bond formations by using tethered catechin(s) and/or epicatechin(s). Although one of the reactions did not provide the coupling product, the other three reactions proceeded stereoselectively at the C4-position to provide stereochemically diversified products at C3 and C3′ positions toward the procyanidin B series. Here we report computer-assisted models of transition states for the C-C bond formations to explore origins of the stereoselectivity. A systematic search of the transition states using truncated compounds provided TS-Ad, TS-Ba or TS-Cd as the most energetically favorable transition state in each of the three reactions to reproduce the C4-stereoselectivity of the experiments. Exploration of origins of the stabilized energies of TS-Ad, TS-Ba, and TS-Cd by NCIPLOT demonstrated the importance of attractive non-covalent interactions.