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

Abstract

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.

Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates

“…Extensive research has shown that chiral NHCs are a class of privileged chiral ligands for transition-metal catalysis 3,4 and that they are versatile chiral organocatalysts 5,6 that can generate one enantiomer preferentially in numerous organic transformations 7,8 . NHCs can catalyse chemical bond synthesis because of several unique chemical characteristics: they are strong s-donors 1 and good Brønsted bases, and they have moderate p-acidity 9 .…”

Synthesis and properties of heteroaromatic carbenes of the imidazole and triazole series and their fused analogues

“…As a result of the syntheses of individual carbenes (Bertrand, Arduengo et al) new catalysts became available. 21,23,24,26,[28][29][30] It became possible to use the pure carbenes as catalysts and to prepare pure complex compounds for catalysis using individual carbenes.…”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20] One of the major focuses of carbene applications has been the catalysis of organic reactions. [21][22][23][24][25][26][27][28][29][30] The connection between individual carbene structure and function has been reported in many publications. However, there remains a considerable problem in that the leading structures in any particular area have not yet been well identified.…”

Benzene construction via organocatalytic formal [3+3] cycloaddition reaction

“…1d). Our approach uses enals readily prepared in three steps and unsaturated ketones as the starting material and N-heterocyclic carbene (NHC) as the organic catalyst [12][13][14][15][16][17][18][19][20][21][22][23][24] . It is a single-step reaction that affords tetra-substituted benzenes (2,4,6-trisubstituted benzoate and its analogues) with high yield.…”