Formation of Breslow Intermediates from N‐Heterocyclic Carbenes and Aldehydes Involves Autocatalysis by the Breslow Intermediate, and a Hemiacetal. Issue 23 (2nd May 2022)

• Record Type: Journal Article
• Authors: Wessels, Alina; Klussmann, Martin; Breugst, Martin; Schlörer, Nils E.; Berkessel, Albrecht
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 23(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-02
• Subjects: Autocatalysis -- Breslow Intermediate -- Carbenes -- NMR -- Reaction Mechanisms; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202117682
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Under aprotic conditions, the stoichiometric reaction of N‐heterocyclic carbenes (NHCs) such as imidazolidin‐2‐ylidenes with aldehydes affords Breslow Intermediates (BIs), involving a formal 1, 2‐C‐to‐O proton shift. We herein report kinetic studies (NMR), complemented by DFT calculations, on the mechanism of this kinetically disfavored H‐translocation. Variable time normalization analysis (VTNA) revealed that the kinetic orders of the reactants vary for different NHC‐to‐aldehyde ratios, indicating different and ratio‐dependent mechanistic regimes. We propose that for high NHC‐to‐aldehyde ratios, the H‐shift takes place in the primary, zwitterionic NHC‐aldehyde adduct. With excess aldehyde, the zwitterion is in equilibrium with a hemiacetal, in which the H‐shift occurs. In both regimes, the critical H‐shift is auto‐catalyzed by the BI. Kinetic isotope effects observed for R‐CDO are in line with our proposal. Furthermore, we detected an H‐bonded complex of the BI with excess NHC (NMR). Abstract : Under aprotic conditions, Breslow intermediates can be generated from N‐heterocyclic carbenes such as imidazolidin‐2‐ylidenes and aldehydes. But how is the intermediary "primary adduct" (PA ) converted to the diaminoenol (BI )? Our kinetic study shows that the highly unfavorable 1, 2‐C‐to‐O H‐shift is autocatalyzed by the Breslow intermediate, and that a hemiacetal plays a crucial role in the presence of excess aldehyde.