Substitutional control of non-statistical dynamics in the thermal deazetization of tetracyclic azo compounds

Dynamical control of reactivity for the deazetization of endo,endo-9,10-diazatetracyclo[3.3.2.0^2,4.0^6,8]dec-9-ene (3) is studied using on-the-fly quasi-classical trajectory (QCT) calculations at the density functional theory (DFT) level. Two degenerate homotropilidenes, 4 and 5, are formed simultaneously from a single transition state (TS). The ratio of the cyclohexadienyl substituted product, 4, and the dynamical product, i.e. bridgehead substituted product, 5, can be neatly controlled by tuning the topology of the potential energy surface (PES). A steep descent post-TS favors the cyclohexadienyl substituted product while a shallow descent increases the dynamical outcome. Chemical demonstration of the same is achieved by symmetrical and asymmetrical substitution of functional groups along the cleaving (C3-C4) bond. Asymmetric mono-functionalization makes the PES broader, thereby reducing the slope post-TS. This creates a favourable situation for the dynamical products, 5b-5d, to become the major ones. On the contrary, symmetric bi-functionalization makes the cyclohexadienyl substituted product, 4m-4o, overwhelmingly (>85%) predominating. As a corollary to this phenomenon, substitution of the C3-C4 bond by the heavier isotopologues of H/C restricts its motion along the IRC path by the Newtonian kinetic isotope effect. This facilitates bond-opening along the C10-C11 dynamical pathway. Hence, for isotopic substitution, the situation is reversed and the bifunctionalized 3 is more dynamically activated. Simultaneous substitution by the heavier isotopologue of C and H causes deviation from the geometric mean of individual isotopic substitution towards the dynamical product, 5. Therefore, the dynamic control in 3 becomes prominent either via functional group asymmetry or through a Newtonian kinetic isotope effect for symmetric bifunctionalization.