In DFT We Trust: Exhaustive Exploration of 1,3‐Dipolar Cycloadditions Between Nitrones and Levoglucosenone Exposes a Curious Case of Conformational Dynamics

Abstract

An experimental and computational study (including DFT calculations and distortion/interaction analysis) was conducted to assess the effect of the nitrone structure in the outcome of dipolar 1,3-cycloadditions with levoglucosenone, a biomass derived chiral enone. While B3LYP/6-31G* (the most popular method for modeling these reactions according to our literature search) provides qualitatively good results, large outliers were found for some systems versus experimental data. An exhaustive exploration of other levels allowed us to determine the most appropriate ones to predict simultaneously reactivity and selectivity. The systematically predicted high exo selectivity by the majority of the levels led us to reconsider our initial assignment for the reaction with the nitrone derived from piperidine, which resulted in the discovery of an interesting case of conformational dynamics.