The Effect of Solvent–Substrate Noncovalent Interactions on the Diastereoselectivity in the Intramolecular Carbonyl-Ene and the Staudinger [2 + 2] Cycloaddition Reactions

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2020-10, Vol.124 (39), p.8019-8028
• Main Authors: Jain, Shailja, Vanka, Kumar
• Format: Article
• Language: English
• Subjects: A: Spectroscopy, Molecular Structure, and Quantum Chemistry
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/acs.jpca.0c05738

Noncovalent interactions (NCIs) have been identified as important contributing factors for determining selectivity in organic transformations. However, cases where NCIs between solvents and substrates are responsible for a major extent for determining selectivity are rare. The current computational study with density functional theory identifies two important transformations where this is the case: the intramolecular carbonyl-ene reaction and the Staudinger [2 + 2] cycloaddition reaction. In both cases, the role of explicit solvent molecules interacting noncovalently with the substrate has been taken into account. Calculations indicate that the diastereomeric ratio would be 95.0:5.0 for the formation of tricyclic tetrahydrofuran diastereomers via the intramolecular carbonyl-ene reaction and 94.0:6.0 for the formation of the triflone diastereomers via the Staudinger [2 + 2] cycloaddition reaction, which corroborates with the experiment. Interestingly, in both the cases, the calculations indicate that noninclusion of explicit solvent molecules would lead to only a small difference between the competing transition states, which leads to the conclusion that solvent–substrate NCIs are the major cause for diastereoselectivity in both the cases considered.