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

N-heterocyclic carbene (NHC) catalysis has emerged as a powerful strategy in organic synthesis. In recent years a number of reviews have been published on NHC-catalyzed transformations involving Breslow intermediates, acyl azoliums, α,β-unsaturated acyl azoliums, homoenolate equivalents, and azolium enolates. However, the azolium dienolate intermediates generated by NHCs have been employed in asymmetric synthesis only very recently, especially in cycloadditions dealing with remote functionalization. This Minireview highlights all the developments and the new advances in NHC-catalyzed asymmetric cycloaddition reactions involving azolium dienolate intermediates.

N-Heterocyclic Carbene Catalysis via Azolium Dienolates: An Efficient Strategy for Remote Enantioselective Functionalizations.

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

Introduction: Spirooxindole, a unique and versatile scaffold, has been widely studied in some fields such as pharmaceutical chemistry and synthetic chemistry. Especially in the application of medicine, quite a few compounds featuring spirooxindole motif have displayed excellent and broad pharmacological activities. Many identified candidate molecules have been used in clinical trials, showing promising prospects.Areas covered: This article offers an overview of different applications and developments of spirooxindoles (including the related natural products and their derivatives) in the process of drug innovation, including such as in anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, antimalarial, and antiviral activities. Furthermore, the crucial structure-activity relationships, molecular mechanisms, pharmacokinetic properties, and main synthetic methods of spirooxindoles-based derivatives are also reviewed.Expert opinion: Recent progress in the biological activity profiles of spirooxindole derivatives have demonstrated their significant position in present-day drug discovery. Furthermore, we believe that the multidirectional development of novel drugs containing this core scaffold will continue to be the research hotspot in medicinal chemistry in the future.

An overview of spirooxindole as a promising scaffold for novel drug discovery.

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.

Kooperative Katalyse mit N‐heterocyclischen Carbenen

γ-Carbon Activation through N-Heterocyclic Carbene/Brønsted Acids Cooperative Catalysis: A Highly Enantioselective Route to δ-Lactams.

Asymmetric Synthesis of Spirooxindoles via Organocascade Strategies

A homogeneous photocatalytic recyclable system for the selective radical-radical cross-coupling of N-substituted amines and indoles has been established. This system could conduct in water or acetonitrile, featuring the reuse of uranyl nitrate as the recyclable photocatalyst via a simple extraction. With this mild strategy in hand, good to excellent yields of cross-coupling products could be achieved even under the irradiation of sunlight, including 26 natural product derivatives and 16 natural product inspired re-engineered compounds. A radical-radical cross-coupling mechanism was newly proposed based on experimental evidence and reported literature. This strategy has been also applied to a gram scale synthesis to demonstrate its practical utility.

https://pubs.rsc.org/en/content/articlepdf/2023/ra/d3ra01037f

Jinxin Wang

Papers

γ-Carbon Activation through N-Heterocyclic Carbene/Brønsted Acids Cooperative Catalysis: A Highly Enantioselective Route to δ-Lactams.

Asymmetric Synthesis of Spirooxindoles via Organocascade Strategies

Uranyl nitrate as a recyclable homogeneous photocatalyst for selective cross-coupling of N-substituted amines and indoles.

Nickel/Photoredox-Catalyzed Direct Amidation of Aldehydes with Nitroarenes via Fully Catalytic Process.

γ‐Carbon Activation Through N‐Heterocyclic Carbene/Broensted Acids Cooperative Catalysis: A Highly Enantioselective Route to δ‐Lactams.