Steric Parameterization Delivers a Reciprocally Predictive Model for Substrate Reactivity and Catalyst Turnover in Rh-Catalyzed Diyne-Alkyne [2 + 2 + 2] Cycloadditions

The Rh-catalyzed [2 + 2 2] cycloaddition of diynes and alkynes is a synthetically useful transformation that rapidly constructs complex scaffolds has been used extensively for >70 years. Despite this utility, substrate reactivity issues persist, which are not mechanistically defined. Here, we provide general predictive model turnover reaction. Contrary to the proposed electronic model, predominately sterically driven process where productive proportional alkyne steric parameters. This allows priori prediction catalyst loading, turnover, reaction yield based on simple assessment parameter (e.g., A-value) alkyne. relationship reciprocal, allowing A-values be calculated from observed turnover.