N-Heterocyclic carbene (NHC) catalyzed transformations have emerged as powerful tactics for the construction of complex molecules. Since Stetter’s report in 1975 of the total synthesis of cis-jasmon and dihydrojasmon by using carbene catalysis, the use of NHCs in total synthesis has grown rapidly, particularly over the last decade. This renaissance is undoubtedly due to the recent developments in NHC-catalyzed reactions, including new benzoin, Stetter, homoenolate, and aroylation processes. These transformations employ typical as well as Umpolung types of bond disconnections and have served as the key step in several new total syntheses. This Minireview highlights these reports and captures the excitement and emerging synthetic utility of carbene catalysis in total synthesis.

A Continuum of Progress: Applications of N-Hetereocyclic Carbene Catalysis in Total Synthesis

Katalytische Umwandlungen mit N-heterocyclischen Carbenen (NHCs) haben sich als effiziente Ansatze zum Aufbau komplexer Molekule erwiesen. Seit der Veroffentlichung von Stetter 1975 zur Totalsynthese von cis-Jasmon und Dihydrojasmon durch Carbenkatalyse hat sich die Anwendung von NHCs in der Totalsynthese, insbesondere in den letzten zehn Jahren, schnell verbreitet. Dieser Aufschwung ist zweifellos die Folge neuerer Entwicklungen bei NHC-katalysierten Reaktionen, einschlieslich der neuen Benzoin-, Stetter-, Homoenolat- und Aroylierungsprozesse. Die Umwandlungen ermoglichen ebenso typische wie auf Umpolung beruhende Bindungsbildungen und sind bereits als Schlusselschritte in mehreren neuen Totalsynthesen aufgetreten. Dieser Kurzaufsatz beschreibt diese neuen Arbeiten und zeigt die verstarkten Einsatzmoglichkeiten der Carbenkatalyse in der Totalsynthese auf.

Anwendungen der Katalyse mit N‐heterocyclischen Carbenen in Totalsynthesen

Copper-catalyzed ortho-acylation of phenols with aryl aldehydes and its application in one-step preparation of xanthones.

Biologically significant clavilactones A, B, and the previously proposed D have been synthesized through iron-catalyzed carbonylation–peroxidation of a 1,5-diene. Three steps from aldehydes, alkenes, and tert-butylhydroperoxide build up α,β-epoxy-γ-butyrolactone skeleton as a key building block for synthesis of clavilactone family and its derivatives. Based on our results, the structure of the proposed clavilactone D is not correct and requires revision.

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Total synthesis of (±)-clavilactones A, B, and proposed D through iron-catalyzed carbonylation-peroxidation of olefin.

Thiazolium-functionalized polystyrene monolithic microreactors for continuous-flow umpolung catalysis

The total synthesis of atroviridin has been accomplished by a linear route involving the N-heterocyclic carbene (NHC)-catalyzed aroylation of the fluorobenzene derivative, Claisen cyclization of the O-propargylated benzophenones, and intramolecular 1,4-addition of the quinone intermediates. The result provides a viable route to xanthone natural products.

Masayo Kamiya

Papers

Xanthone natural products via N-heterocyclic carbene catalysis: total synthesis of atroviridin.