A computational study on the stereoselective organocatalytic epoxidation of α,β-unsaturated aldehydes with hydrogen peroxide

• Published in: Organic & biomolecular chemistry 2013-11, Vol.11 (41), p.7179-7191
• Main Authors: Duarte, Filipe J S, Santos, A Gil
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c3ob41475b

The asymmetric synthesis of vicinal diols is a very important process in organic chemistry, as it allows the preparation of a large variety of useful derivatives. One of the most interesting methods to accomplish this synthesis is the asymmetric epoxidation of activated olefins, catalysed by chiral organic or organometallic catalysts. In this paper we study, with computational tools, two possible mechanisms for the asymmetric epoxidation of conjugated aldehydes with hydrogen peroxide, catalysed by chiral pyrrolidine derivatives lacking proton donor groups. Our results indicate that the mechanism that proceeds by the initial formation of an iminium intermediate is more probable than the mechanism proceeding by general base catalysis. We also conclude that besides the oxidant role of hydrogen peroxide, it also has a very important role as a co-catalyst in the initial formation of the iminium intermediates. Moreover, epoxide formation is suggested to be a two-step process that needs the explicit participation of a hydroxyl ion. In the absence of this ion, epoxidation was calculated to be a single step process that does not explain the experimental selectivity. In contrast with the currently accepted idea, the overall calculated selectivity results mainly from the iminium formation steps and from the second step of the epoxidation reaction.