Desymmetrization of cis-epoxides by chiral zeolite catalyst GTM-4: H-bond-mediated induction of enantioselectivity

We report, for the first time, the asymmetric catalytic activity of a chiral zeolite capable of enantioselectively converting an achiral reactant into chiral products. Through a combined experimental and computational study, we demonstrate that the recently discovered germanosilicate GTM-4, featuring the extra-large pore and chiral -ITV framework, promotes the enantioselective desymmetrization of cis -epoxides. GTM-4 induces enantioselectivity in the ring-opening of three structurally distinct substrates —cyclohexene oxide, cyclooctene oxide and cis -stilbene oxide— with the latter exhibiting significantly higher enantiocontrol. The size of the alcohol nucleophile further modulates the outcome, reaching an enantiomeric excess ( ee ) of up to 62% for the reaction of cis -stilbene oxide with 1-propanol, whereas cyclohexene oxide affords a maximum ee of 20%. Computational modelling provides a tentative mechanistic rationale for the emergence of chirality, revealing that strong H-bond interactions between the ≡ Ge(OH)···(OH)R pre-activated sites and the epoxide oxygen atoms, in combination with the chiral confinement imposed by the zeolite walls, bias the orientation of cis -stilbene oxide within the pores. This interaction enhances oxirane ring activation toward an S N 2 nucleophilic attack that preferentially occurs on one of the two enantiotopic carbon atoms due to steric constraints imposed by the framework walls. In contrast, although cyclohexene oxide can also engage in H-bonding, its smaller size allows greater mobility inside the -ITV channels, reducing stereocontrol. Altogether, this multidisciplinary study provides fundamental insight into how the chiral environment of GTM-4 can be harnessed to selectively express enantioselectivity during a chiral reaction, offering guidelines for the rational design of asymmetric transformations using these chiral zeolite catalysts.