Kinetic Analysis of a Cysteine-Derived Thiyl-Catalyzed Asymmetric Vinylcyclopropane Cycloaddition Reflects Numerous Attractive Noncovalent Interactions

Kinetic
studies of a vinylcyclopropane (VCP) cycloaddition, catalyzed
by peptide-based thiyl radicals, are described. Reactions were analyzed
by using reaction progress kinetic analysis, revealing that ring-opening
of the VCP is both rate- and enantio-determining. These conclusions
are further corroborated by studies involving racemic and enantiopure
VCP starting material. Noncovalent interactions play key roles throughout:
both the peptide catalyst and VCP exhibit unproductive self-aggregation,
which appears to be disrupted by binding between the catalyst and
VCP. This in turn explains the requirement for the key catalyst feature,
a substituent at the 4-position of the proline residue, which is required
for both turnover/rate and selectivity.