A DFT study of the domino inter

Abstract

The molecular mechanism of the domino inter [4 + 2]/intra [3 + 2] cycloaddition reactions of nitroalkenes with enol ethers to give nitroso acetal adducts has been characterized using density functional theory methods with the B3LYP functional and the 6-31G basis set. The presence of Lewis acid catalyst and solvent effects has been taken into account to model the experimental environment. These domino processes comprise two consecutive cycloaddition reactions: the first one is an intermolecular [4 + 2] cycloaddition of the enol ether to the nitroalkene to give a nitronate intermediate, which then affords the final nitroso acetal adduct through an intramolecular [3 + 2] cycloaddition reaction. The intermolecular [4 + 2] cycloaddition can be considered as a nucleophilic attack of the enol ether to the conjugated position of the nitroalkene, with concomitant ring closure and without intervention of an intermediate. For this cycloaddition process, the presence of the Lewis acid favors the delocalization of the negative charge that is being transferred from the enol ether to the nitroalkene and decreases the activation energy of the first cycloaddition. The [4 + 2] cycloaddition presents a total regioselectivity, while the endo/exo stereoselectivity depends on the bulk of the Lewis acid used as catalyst. Thus, for small Lewis acid catalyst, modeled by BH(3), the addition presents an endo selectivity. The [3 + 2] cycloaddition reactions present an total exo selectivity, due to the constraints imposed by the tether. Inclusion of Lewis acid catalyst and solvent effects decrease clearly the barrier for the first [4 + 2] cycloaddition relative to the second [3 + 2] one. Calculations for the activation parameters along this domino reaction allow to validate the results obtained using the potential energy barriers.