Benzoin reactions, carbene catalysis

Enders D, Niemeier O, Balensiefer T (2006c) Asymmetric intramolecular cros-sed-benzoin reactions by N-heterocyclic carbene catalysis. Angew Chem Int Ed Engl 45 1463... 

Enders D, Kallfass U (2002) An efficient nucleophilic carbene catalyst for the asymmetric benzoin condensation. Angew Chem Int Ed 41 1743-1745 Enders D, Niemeier O (2004) Thiazol-2-ylidene catalysis in intramolecular crossed aldehyde-ketone benzoin reactions. Synlett 2004 2111-2114 Enders D, Niemeier O, Balensiefer T (2006) Asymmetric intramolecular crossed-benzoin reactions by N-heterocyclic carbene catalysis. Angew Chem Int Ed 45 1463-1467... 

With respect to the application of asymmetric carbene catalysis as a tool for enantioselective synthesis, the last decade s major success is based on substantial improvements in catalyst development. Early reports dealt with implementing chirality in thiazolium scaffolds (Sheehan and Hunneman 1966 Sheehan and Hara 1974 Dvorak and Rawal 1998), but their catalytic performance suffered from either low yields or low ee-values. In this regard, the investigation of triazole heterocycles as an alternative core structure (Enders et al. 1995) has played a crucial role to provide heterazolium precatalysts improving both asymmetric benzoin and Stetter reactions. An intramolecular Stetter reaction yielding chromanones upon cyclization of salicylaldehyde-derived substrates is commonly used as a benchmark reaction to compare catalyst efficiency (Scheme 1 Ciganek 1995 Enders et al. 1996 Kerr et al. 2002 Kerr and Rovis 2004). 

In 2012, Melchiorre et al. reported a novel stereoselective access to chiral frans-fused tetracyclic indole-based products having four stereogenic centres on the basis of a multicatalytic tandem Diels-Alder-benzoin reaction involving JV-Boc protected 3-(2-methyl-indol-3-yl)acrylaldehyde derivative and fra s-l,2-dibenzoylethylene derivative as substrates." As shown in Scheme 2.32, the process was successively induced by chiral diphenylproli-nol trimethylsilyl ether in the presence of bullgr 2,4,6-trimethylbenzoic acid (TMBA) as co-catalyst for the Diels-Alder reaction (trienamine catalysis), and an AT-heterocyclic carbene for the following cross-benzoin condensation... 

Carbene Catalysis Beyond the Benzoin and Stetter Reactions... 

N-heterocyclic carbene catalysis has become one of the major categories in orga-nocatalysis. Azolium salts are ready deprotonated by weak bases to generate a carbene, which then adds to an aldehyde to form an acyl anion equivalent, generally called the Breslow intermediate. The reactive acyl anion attacks an electrophile to promote the various transformations such as benzoin, Stetter, and redox reactions [107]. Recently, an interesting approach for NHC-catalyzed generation of an enol/enolate intermediate was reported. Enantio-enriched (i-amino acid derivatives (217) are formed by the reaction between the a-aryloxyaldehyde 214 and N-tosyl-imines (215) in the presence of phenyalanine-derived azoUum salt 216 as a pre-catalyst and aryl phenoxide as a base (Scheme 28.28) [108]. 

As well as the traditional benzoin and Stetter reactions, some new synthetic transformations were disclosed via carbene catalysis. In 2007, the Scheldt group developed an intramolecular Michael-type reaction with unsaturated substrates 56 through catalysis with chiral triazolium salt 55. The intermediates 57 were generated via a domino Michael addition/lactonization sequence, and bicyclic products 58 were afforded in satisfactory yields and with excellent enantioselectivity after... 

Abstract. Within the context of Lewis base catalysis /V-heterocyclic carbenes represent an extremely versatile class of organocatalyst that allows for a great variety of different transformations. Starting from the early investigations on benzoin, and later Stetter reactions, the mechanistic diversity of /V-hctcrocyclic carbenes, depending on their properties, has led to the development of several unprecedented catalytic reactions. This article will provide an overview of the versatile reactivity of A-heterocyclic carbenes. 

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