Understanding the influence of Lewis acids in the regioselectivity of the Diels–Alder reactions of 2-methoxy-5-methyl-1,4-benzoquinone: A DFT study

The mechanisms of the Diels–Alder (DA) reactions of 2-methoxy-5-methyl-1,4-benzoquinone 1 with 2- methyl-1,3-butadiene 2, in the absence and in the presence of LA catalysts, have been studied using the DFT method at the B3LYP/6-31G(d) level of theory. The uncatalyzed DA reactions between 1 and 2 take place via synchronous concerted TSs. The large activation barrier as well as the low stereo and regioselectivity associated with the uncatalyzed process are in clear agreement with the non-polar character of the cycloaddition. Coordination of the LA catalysts, BF3 or SnCl4, to the oxygen atoms of the benzoquinone 1 produces a large acceleration of the reaction, which can be associated with the large polar character of the cycloaddition. The different coordination modes of BF3 and SnCl4 LA catalysts to the oxygen atoms of benzoquinone 1 allow explaining the reverse para/meta regioselectivity observed in these LA-catalyzed DA reactions. The analysis based on the global and local electrophilicity indices of the reagents correctly explains the polar nature of the title reactions, as well as the change of regioselectivity experimentally observed.We acknowledge support from FONDECYT Grant No. 1070715. J.S.D. acknowledges MECESUP fellowship No. 0408. L.R.D. thanks the Spanish Government for financial support through project CTQ2006-14297/BQU