Mechanism Switch in Mannich‐Type Reactions: ELF and NCI Topological Analyses of the Reaction between Nitrones and Lithium Enolates. Issue 19 (27th May 2015)

• Record Type: Journal Article
• Authors: Roca‐López, David; Polo, Victor; Tejero, Tomás; Merino, Pedro
• Is Part Of: European journal of organic chemistry. Issue 19(2015)
• Page Start: 4143
• Page End: 4152
• Publication Date: 2015-05-27
• Subjects: Reaction mechanisms -- Mannich reaction -- Nitrones -- Enolates; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201500447
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: The mechanism of the addition of lithium enolates derived from esters, ketones and aldehydes to nitrones (Mannich‐type reaction) has been studied using DFT methods. While the reactions with α‐methoxy and α‐methyl enolates takes place through a stepwise mechanism, consisting of an initial nucleophilic attack of the enolate to the nitrone carbon followed by a second nucleophilic attack of the nitrone oxygen to the formed carbonyl group, the reaction with α‐unsusbtituted enolates takes place through a one‐step mechanism. The IRC analysis shows the presence of a hidden intermediate in agreement with one kinetic step two stages process. The topological analysis of the electronic localization function (ELF) confirms that only when the first C–C bond is formed, does the C–O bond formation begin. The NCI analyses, are also in agreement with the formation of intermediates for α‐methoxy and α‐methyl enolates and a highly asynchronous one‐step process in the case of α‐unsusbtituted enolates. Abstract : Depending on the type of enolate the reaction mechanism changes from one‐step to stepwise.