Estimating regio and stereoselectivity in [4+2] cycloadditions of vinyl-substituted cyclic dienes with maleic anhydride
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Updated: Jun 19, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Gaddamanugu Gayatri1, G Narahari Sastry
1Molecular Modeling Group, Organic Chemical Sciences, Indian Institute of Chemical Technology, Hyderabad-500607, India.
Abstract:
Density functional theory calculations are performed to examine the regio and stereoselective preferences in [4+2] cycloaddition reactions of vinyl cyclopentadiene (1 and 2) and vinyl heterocyclic (1-N, 1-O, 1-S, 2-N, 2-O and 2-S) systems with maleic anhydride. Stepwise and concerted pathways of model systems 1 and 2 as dienes with ethylene as dienophile reveal that the reactions proceed through asynchronous and concerted pathway. 3-Vinyl systems (2) are predicted to be more reactive compared to 2-vinyl systems (1). The regio and stereoselective preferences are evaluated based on activation energies, reaction energies, density functional based descriptors and atoms in molecules analysis. In all cases, extra-annular cycloadducts are more feasible compared to intra-annular cycloadducts. Stereoselectivity depends on the favorable secondary orbital interactions. Solvents such as water, tetrahydrofuran, acetone, and dimethyl sulphoxide are employed to understand the effects of solvents on the cycloadduct formation. The computational results thus obtained are compared with the earlier experimental observations that are available.
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