Synlett 2024; 35(08): 883-888
DOI: 10.1055/s-0042-1751576
new tools
Special Issue dedicated to Keith Fagnou

A Simple Tool to Benchmark Reactivity in Asymmetric Catalysis

Alberto Muñoz
,
We thank the National Institute of General Medical Sciences (NIGMS) (GM72586) for support. AM acknowledges NIGMS for a Diversity Supplement (GM72586-S1).


Dedicated to the memory of our dear friend and colleague Keith Fagnou

Abstract

Herein, we report a simple and noninvasive experimental protocol in which a series of relative reaction rates may be obtained by way of single competition experiments. This approach permits a quantitative comparison of any given number of chiral catalysts relative to a ‘benchmarking’ chiral catalyst – a particularly useful tool since catalyst design and selection have remained largely dependent on chemical intuition. We apply this benchmarking approach towards an asymmetric N-heterocyclic carbene (NHC) catalyzed intramolecular Stetter reaction as a proof-of-concept study. In doing so, we demonstrate a rapid method to assess the complex interplay between catalyst reactivity and stereoelectronic effects – an analytical approach that has heretofore not been attempted for NHCs. To showcase the generality of this method, we apply it to an enantioselective Rh(I)-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and aryl alkynes for a series of chiral phosphoramidite ligands. The results described herein demonstrate that this inexpensive and easily adoptable protocol can reveal complex yet subtle steric and stereoelectronic effects of vastly different chiral catalyst structures, which can further aid with catalyst development and selection for a clearly defined application.

Supporting Information



Publication History

Received: 15 February 2024

Accepted after revision: 06 March 2024

Article published online:
21 March 2024

© 2024. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany