A computational mechanistic study on the chemo-, regio- and stereoselectivity of cycloaddition reactions leading to γ-dihydropyran and tetrahydrocarbazol compounds

Abstract

The reaction mechanisms of Danishefsky’s diene (1) with 3- and 2-substituted indoles (2 and 3) were investigated using the DFT method. Two possible approaches of the carbonyl and carbon-carbon double bond of the dienophile to Danishefsky’s diene (1) yield two types of compound, arising from the sequential [4+2] cycloaddition reaction. and hydrolysis of the silyl enol ether. Also, an acyclic hydroxyl product indicates that a stepwise mechanism of the Mukaiyama-type may be involved, when the reaction takes place in the presence of zinc chloride catalyst. In the cycloaddition reactions, while 3-substituted indole (2) tended to participate as the dienophile, 2-substituted indole (3) can react through a hetero Diels-Alder reaction. Then the chemoselectivity completely reverse in 2- and 3- substituted indoles, which energetical aspects and analysis of the Parr functions explained the chemoselectivity experimentally observed. The reactions were completely ortho regioselective with endo stereoselectivity in the zinc chloride catalyzed process. The Mukaiyama aldol reaction, as a stepwise mechanism, had a low activation energy relative to the concerted cycloaddition reactions. Moreover, analysis of the conceptual DFT reactivity indices allows the explanation of the reactivity, and the chemo- and regioselectivity.