Recovering the causal kinetic-thermodynamic relationship in asynchronous reactions.

Kinetic-thermodynamic relationships underpin the interpretation and design of reactivity, yet strongly asynchronous reactions often display weak, erratic, or even inverted responses. Such behaviour is often interpreted as anomalous or even 'anti-thermodynamic', appearing to violate the expected monotonic relationship between reaction energy and barrier. We show that the standard practice of directly correlating activation barriers with overall reaction energies in asynchronous systems conflates energetically distinct phases into a single apparent step; the resulting negative or arbitrarily large gradients are artefacts of representation rather than evidence of exotic reactivity. By decoupling the reaction phases, we recover the underlying energy-barrier relationships in concerted asynchronous reactions, rendering them directly comparable to synchronous cases. We rationalise these spurious gradients by showing how differences in the energetic responses of the primary and secondary stages distort the overall energy-barrier relationship. Across representative systems, including 1,2-hydride shifts, a (3 + 2) ynolate-nitrone cycloaddition and a gold(i)-mediated 6-endo-dig cyclisation, we recover physically meaningful kinetic-thermodynamic relationships by isolating reaction phases through constrained internal coordinates. This framework shows that even highly asynchronous reactions obey well-defined thermodynamic relationships once their constituent processes are properly resolved. The resulting diagnostic provides a practical means to assess synchronicity experimentally and to extract the relative energetics of constituent reaction stages.