Exploring the Mechanism of DABCO-Catalyzed Diastereoselective Cyclization for the Synthesis of Azetidine Nitrones.

The mechanistic details of the DABCO-catalyzed diastereoselective cyclization between β-alkyl nitroolefins and alkylidene malononitriles were elucidated by using dispersion-corrected density functional theory (DFT-D3) calculations at the M06-2X/6-311G(d,p) level with SMD solvation (dichloromethane). The reaction proceeds through four consecutive steps: (i) deprotonation and Michael addition; (ii) 1,3-proton transfer; (iii) Pinner-type cyclization; and (iv) ring contraction. Our computational results demonstrate DABCO's dual catalytic role in both proton abstraction and proton shuttle mechanisms, rationalizing the observed diastereoselectivity. The rate-determining step (ring contraction) exhibits a moderate barrier of 24.9 kcal/mol, consistent with experimental conditions, and the exclusion of alternative pathways (ΔG^‡ > 70 kcal/mol) confirms the mechanistic preference. This study provides fundamental insights into stereochemical control and establishes a theoretical framework for designing related organocatalytic transformations.