Equivalent Atrop- and Positional Isomerism in Styrene Derivatives Prepared by Enantioselective 1,3-Diarylation

Isomerism, the ability
of a single set of atoms within
a molecule
to exist in different three-dimensional spatial arrangements connecting
through distinct bonding networks, gives rise to distinct physical,
chemical, and biological properties from a common set of atomic building
blocks. While different forms of isomerism are now well appreciated,
a rare phenomenon is the coexistence of multiple equivalent forms
of isomerism within a given pair of molecules. Here, we report that
a simple combination of palladium and amino acid cocatalysts converts ortho-alkenyl benzaldehydes into substituted styrenes possessing
equivalent atrop- and positional isomerism. Mechanistically, the reaction
proceeds through successive Mizoroki–Heck arylation promoted
by the amino acid cocatalyst. DFT calculations show that the atroposelectivity
arises from stereoselective β-H elimination in the second arylation
cycle, whereas the formation of Z products with constrained
rotation about the chiral axis is driven by the thermodynamic stability
of the Z isomer.