Diastereoselectivity on Intramolecular Alder‐ene Reaction of 1,6‐Dienes

• Published in: Chemphyschem Vol. 23; no. 23; pp. e202200377 - n/a
• Main Author: Cózar, Abel
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 05.12.2022; John Wiley and Sons Inc
• Subjects: activation strain model; Alnus; DFT; Dienes; energy decomposition analysis; Interaction models; intramolecular Alder-ene; Models, Molecular; Orbital stability; Polyenes; Reagents; Selectivity; Stereoselectivity; Strain energy; Substitution reactions; energy decomposition analysis; selectivity; intramolecular Alder-ene; DFT; activation strain model
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.202200377

A detailed computational study of the intramolecular Alder‐ene reaction of different 1,6‐dienes at M06‐2X(PCM)/TZ2P level of theory has been performed. We want to understand the influence of enophile‐geminal substitution pattern in the cis : trans selectivity of the cyclization process. Our analysis of the reaction coordinate by means of activation strain model of chemical reactivity (ASM‐distortion interaction model) reveals that the cis‐selectivity observed for unactivated reagents is related with high stabilizing orbital interaction and lower strain energy, consequence of an early transition structure. On the other hand, the presence of activating groups increases the asynchronicity of the transition structures and reduces the activation barrier due to more stabilizing orbital and electrostatic interactions, favoring trans‐selectivity. Computational analyses based on the activation strain‐distortion interaction model reveals that activating groups increase the trans selectivity in intramolecular ene‐Alder reactions of 1,6‐dienes due to an asynchronicity increase related with enhanced orbital and electrostatic interactions that compensate the Pauli repulsion rise.