N-Heterocyclic carbene (NHC) catalysis has emerged as a powerful stratagem in organic synthesis to construct complex molecules primarily by polarity reversal (umpolung) approaches. These unique Lewis bases have been used to generate acyl anions, enolates, and homoenolates in catalytic fashion. Recently, a new strategy has emerged that dramatically expands the synthetic utility of carbene catalysis by leveraging additional activation modes: cooperative catalysis. The careful selection and balance of cocatalysts have led to enhanced reactivity, increased yields, and improved stereoselectivity. In certain cases, these catalytic additives have changed the regioselectivity or diastereoselectivity. This Minireview highlights new advances in NHC cooperative catalysis and surveys the evolution of this field.

Cooperative Catalysis and Activation with N-Heterocyclic Carbenes

First reported less than a decade ago, the α,β-unsaturated acyl azolium has emerged as a central reactive intermediate for reaction discovery using N-heterocyclic carbene catalysis. In this Perspective, an introduction to the four main reactivity patterns accessible from this intermediate is provided. The Perspective is handled in a largely chronological fashion, with an emphasis on alternate approaches to the key intermediate and first-in-class reaction cascades. Finally, a brief discussion of emerging trends in this field of catalysis is presented. Although not exhaustive, the Perspective provides an overview of this active area of research and serves as a guide for future investigations.

N-Heterocyclic Carbene Catalysis via the α,β-Unsaturated Acyl Azolium

ConspectusThis Account is aimed at highlighting the recent developments in the N-heterocyclic carbene (NHC)-catalyzed generation of α,β-unsaturated acylazolium intermediates and their subsequent reactivity with (bis)nucleophiles thereby shedding light on the power of this NHC-bound intermediate in organocatalysis. This key intermediate can be generated by the addition of NHCs to α,β-unsaturated aldehyde or acid derivatives. A wide variety of bisnucleophiles can add across the α,β-unsaturated acylazoliums to form various five and six-membered heterocycles and carbocycles. Moreover, suitably substituted nucleophiles can add to this intermediate and result in valuable products following cascade processes. Employing chiral NHCs in the process can result in the enantioselective synthesis of valuable compounds.In 2013, we developed a unified strategy for the enantioselective synthesis of dihydropyranones and dihydropyridinones by the NHC-catalyzed formal [3 + 3] annulation of 2-bromoenals with readily available...

NHC-Catalyzed Generation of α,β-Unsaturated Acylazoliums for the Enantioselective Synthesis of Heterocycles and Carbocycles.

N‐Heterocyclic Carbene Organocatalysis: Activation Modes and Typical Reactive Intermediates

Die Katalyse mit N-heterocyclischen Carbenen (NHC) hat sich in der organischen Synthese zu einer leistungsfahigen Strategie entwickelt, um komplexe Molekule hauptsachlich durch Umpolungsverfahren aufzubauen. Diese einzigartigen Lewis-Basen wurden verwendet, um Acylanionen, Enolate und Homoenolate katalytisch zu generieren. Kurzlich wurde eine neue Strategie entwickelt, mit der die Anwendbarkeit der Carbenkatalyse bei Synthesen durch den wirksamen Einsatz zusatzlicher Aktivierungsarten erheblich erweitert werden konnte: die kooperative Katalyse. Durch die sorgfaltige Auswahl von Cokatalysatoren konnen Reaktivitaten, Ausbeuten und Stereoselektivitaten verbessert werden. In einigen Fallen haben diese katalytischen Additive die Regioselektivitat oder Diastereoselektivitat verandert. In diesem Kurzaufsatz werden die neuesten Fortschritte bei der kooperativen Katalyse mit NHCs herausgestellt und die Gesamtentwicklung des Gebiets betrachtet.

Wang

Papers

Enantioselective Synthesis of Bicyclic Î´-Lactones via N-Heterocyclic Carbene-Catalyzed Cascade Reaction