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

Abstract

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.

A Brief Introduction to Chemical Reaction Optimization

“…Therefore, precise kinetic parameters cannot be elucidated, but the plots required are simple to construct and easy to interpret, which allows easy determination of this kinetic information. Because of its systematic approach to analysis, RPKA has been widely adopted in process chemistry settings and reported in several applications. − …”

Visible-light mediated catalytic asymmetric radical deuteration at non-benzylic positions

“…Motivated by the growing interest in merging asymmetric organocatalysis with photocatalysis [25][26][27][28][29][30][31][32] and in view of the paucity of practical methods for asymmetric radical deuterations, we recently questioned whether a photocatalytic radical deuteration could be achieved in a highly enantioselective and cost-effective fashion. In particular, we hypothesized that a combination of chiral thiols with deuterium oxide (D 2 O) might be a potential solution, given the widespread use of achiral thiols as a catalyst for non-asymmetric radical deuteration 4,[33][34][35][36] and the encouraging stereocontrol that chiral thiol catalysts exerted in a handful of prior work [37][38][39][40] . Additionally, the following features make this strategy promising: 1) uncatalyzed background deuteration-a common issue when carbon anions are involved-would be inhibited as prochiral carbon radicals are virtually unreactive towards D 2 O due to the high bond dissociation energy (BDE) of the O-D bond (119 kcal/mol for HO-H bond) 24,41 , 2) deuterium atom would be covalently bonded to the chiral thiol catalyst through facile in-situ hydrogen/deuterium exchange 4 , thereby enhancing enantiofacial discrimination for the deuteration event.…”

Facile Synthesis of Gradient Polycarbonate–Polyester Terpolymers from Monomer Mixtures Mediated by an Asymmetric Chromium Complex

“…complexes have been explored for the synthesis of block copolymers through bridging ROCOP and ROP reactions, ,,,− among which salen-Cr complexes exhibit wide monomer scope, good activity, high selectivity, and reliable molecular weight controllability. − Hence, Cr complexes were chosen as ideal candidates. Noncovalent interactions played a remarkable role in the catalytic activity and monomer recognition, − among which the N–H bond of rigid o -aminophenolate moieties in catam ligands endowed metal complexes with a high catalytic activity for cyclic ester polymerization. − Therefore, we designed a novel Cr complex 1 chelated with an asymmetric ligand (containing one salen bond and one catam bond, Scheme b) for the preparation of gradient terpolymers from cyclohexene oxide (CHO), CO 2 , and ε-caprolactone (ε-CL). The reaction process and the relationship of chain configurations with reaction conditions were investigated in detail.…”