Understanding reactivity and regioselectivity in Diels-Alder reactions of a sugar-derived dienophile bearing two competing EWGs. An experimental and computational study

The effect of an extra EWG in the reactivity and regioselectivity in Diels-Alder reactions of beta-cyanolevoglucosenone and 4 different dienes was studied by a joint computational and experimental study. Conceptual DFT analysis successfully predicted an important enhancement in the reactivity, and correctly anticipated the regioselectivity in the reactions with isoprene. However, this static treatment failed when dealing the regiochemical preference of the reactions involving a substituted anthracene as diene. MPW1K/6-31G* calculations correctly reproduced the experimental observations. Based on the collected data, we found that when dealing with dienes and dienophiles with no clear electronically activated position, the ease of pyramidalization of the interacting atoms dictates the regioselectivity of the DA reaction. (C) 2015 Elsevier Ltd. All rights reserved.