NHC‐Stabilized Radicals in the Formal Hydroacylation Reaction of Alkynes

Abstract

Mechanistic details of transformations catalyzed by N‐heterocyclic carbenes (NHC) are currently of great interest, targeting questions on the active catalyst in operation and the structure and reactivity of key intermediates. These mechanistic studies are driven by the need to understand the big impact of subtle changes on the catalyst system on its reactivity, as well as to clarify the situation around the elusive intermediates in the classical catalytic cycle. In the activation process of aldehydes the formation of an enaminol structure, coined the Breslow intermediate, is widely accepted. Previously, however, we could prove that this enaminol has, besides its ionic reaction pathway, also the option to follow a radical pathway, by undergoing redox processes with the starting material. In the present study we aim to elucidate if these radical pathways are a more general phenomenon, specifically in the formal hydroacylation reaction of alkynes. The observation of radical species and computational analysis of key elemental steps in the radical and ionic pathways may lead to an onward development of chemistry based on NHC‐stabilized carbon radicals.

The Mechanism of N‐Heterocyclic Carbene Organocatalysis through a Magnifying Glass

“…These findings were consistent with a single‐electron transfer from the Breslow intermediate to the aldehyde substrate to give XI as an intermediate before the C−C bond formation. In a subsequent study, it was shown that the quantum chemically calculated and experimentally measured kinetics compare well, which provides further proof for this alternative mechanism. Accordingly, the mechanism established by Breslow can be extended by a radical pathway (Figure ).…”

“… Alternative reaction mechanism for the C−C coupling step of the benzoin condensation through a single electron transfer (Figure ) …”

NHC‐Organocatalysed Hydroacylation of Unactivated or Weakly Activated C−C Multiple Bonds and Ketones

“…The origin and reactivity of radical intermediates were analysed by EPR spectroscopy and supported by computational chemistry. This radical pathway was compared with the radicals observed in the benzoin reaction [45] …”

On the Redox Properties of the Dimers of Thiazol-2-ylidenes That Are Relevant for Radical Catalysis

“…In addition to ionic-type (2-electron) mechanisms, thiazol-2-ylidenes have also recently become privileged organocatalysts for radical transformations of aldehydes. − In these reactions, the Breslow-type enolates C – , which result from the condensation of aldehydes with NHCs in basic conditions, are able to undergo spontaneous single-electron transfer (SET) to challenging substrates ( E ox > −1.6 V vs SCE). − In the absence of aldehydes, free NHCs are milder reducing reactants. For instance, imidazol-2-ylidenes perform stoichiometric reduction of the ferrocenium cation ( E = +0.38 V vs SCE) and the trityl cation ( E = +0.27 V vs SCE) .…”