Neutral chiral bidentate tellurium-triazoles for enantioselective non-covalent chalcogen-bonding catalysis

Chalcogen-bonding (ChB) has recently garnered significant interest in the field of non-covalent catalysis, providing new possibilities through σ-hole interactions. However, the advancement of the field in enantioselective catalysis relying purely on ChB has been impeded by the inherent directionality of the interaction and presence of several σ-holes on the chalcogen atom, being particularly challenging with neutral ChB-donors. Herein, we report the design and application of chiral ChB-donors able to accomplish the still challenging asymmetric chalcogen-bonding catalysis with neutral ChB systems, reaching enantioselectivities of up to 11:89 e.r. in the anion-binding benchmark Reissert-type reaction of (iso)quinolines. Optimization of the chiral central backbone in rather simple bistriazole-bistelluride-based structures to accomplish a bidentate binding to Lewis basic substrates is performed, leading to the identification of the (R,R)-1,3-diamino cyclohexane moiety as appropriate chiral spacer. While no binding is observed for other chiral central backbones, a moderate affinity to chloride anion as model substrate is recorded for the optimized neutral ChB-donor, for which key binding features are further revealed upon computational analysis on the corresponding catalyst-chloride complex.