# Carbon and Heteroatom Activation via N‐Heterocyclic Carbene‐Bound Dearomative Intermediates for Stereoselective Annulation Reactions

## TL;DR

This review discusses how N-heterocyclic carbenes activate carbon and heteroatoms in aromatic compounds to create stereoselective cyclic molecules.

## Contribution

The paper provides a comprehensive overview of NHC-bound dearomative intermediates for carbon and heteroatom activation since 2013.

## Key findings

- NHC-bound dearomative intermediates enable stereoselective annulation reactions.
- o-QDMs, o-QMs, and aza-analogs are key intermediates for activating aromatic compounds.
- These methods synthesize enantioenriched cyclic molecules efficiently.

## Abstract

N‐Heterocyclic carbene (NHC) organocatalysis has long been recognized as a powerful and versatile method for the implementation of (asymmetric) transformations enabling the formation of C─C and C–heteroatom bonds. A number of NHC‐bound active ionic species have been classically established for activation of carbon atoms as either nucleophiles or electrophiles at diverse positions, such as (aza)Breslow intermediates, homoenolate equivalents, azolium (di)enolates, simple acyl (imidoyl) azoliums, and α,β‐unsaturated/alkynyl acyl azoliums. Within this realm, the past decade has witnessed a blossoming interest in the deployment of NHC‐tethered dearomative intermediates for the activation of both carbon atoms and heteroatoms in aromatic compounds. Accordingly, functionalization of benzylic carbon atoms was made possible through catalyst‐bound o‐quinodimethanes (o‐QDMs), while remote activation of oxygen and nitrogen atoms was effectively achieved through NHC‐bound o‐quinone methides (o‐QMs) and aza‐analogs (aza‐o‐QMs), along with aza‐fulvene type intermediates and triaza‐diene species. Aim of this review is to provide an overview of the most relevant literature on the development of NHC‐bound dearomative intermediates for carbon and heteroatom activation since 2013, with emphasis on their applications for stereoselective annulation reactions.

Use of N‐heterocyclic carbenes (NHCs) to activate carbon and heteroatoms in aromatic compounds is reviewed based on key dearomative NHC‐bound intermediates, i.e., ortho‐quinodimethanes (o‐QDMs), ortho‐quinone methides (o‐QMs) and aza‐analogs (aza‐o‐QMs), aza‐fulvene and triaza‐diene intermediates. Their formation and reactivity in stereoselective annulation reactions for the synthesis of enantioenriched (hetero)cyclic molecules are discussed.