Thiazolium organocatalysts

Examples of nonasymmetric organocatalysts that were introduced in the 1950s include analogs of thiamine reported by Breslow in 1957 as an alternative to cyanide as a catalyst for the benzoin condensation [8]. Asymmetric versions of these thiazolium catalysts were used in organocatalytic benzoin condensations by Sheehan and Hunneman in 1966 [9]. In another important development, in 1969 the nucleophilic catalyst 4-(dimethylamino)pyridine (DMAP), which is now widely used for difficult esterifications, was reported by Steglich [10]. 

Abstract. N-Heterocyclic carbenes (NHC) have become an important class of organocatalysts and class of ligands for transition-metal catalysis. In organocat-alyzed umpolung reactions, thiazolium salt-derived NHC have been used successfully for decades. Even so, during recent years there has been an increased interest in NHC-catalyzed transformations and many new reactions have been developed. This article focuses on the use of NHC in the conjugate umpolung of ,f>-unsaturated aldehydes. 

Chiral N heterocyclic carbenes (NHCs), as Lewis basic organocatalysts, have been synthesized and applied to enantioselective organocatalytic reactions in recent years. Encouraged by Sheehan and Hunneman s first report of chiral thiazolium salts as NHC precursors for organocatalytic reactions [37], Leeper, Enders, Rovis, Glorius, Herrmann, and others have synthesized series of novel chiral NHCs with mono cyclic, bicyclic, or tricyclic backbones [38]. Recently, a series of bifunctional NHCs were synthesized and applied to aza BMH reaction of cyclopent 2 enone with... 

The recent development of polymers containing imidazolium, thiazolium and related structures as supported equivalents of ionic liquids (i.e. 148 and 149, Scheme 10.23) is an interesting development of this field [356-361], The corresponding salts containing basic counter-anions can act as basic catalysts but can also be transformed, depending on the exact structure, into N-heterocydic car-benes that can act as nucleophilic organocatalysts [362]. As an example, resins 148... 

In this context, the first attempts to employ chiral iV-heterocyclic carbenes as organocatalysts in an enantioselective reaction were carried out in the context of the benzoin condensation, which combines two molecules of an aldehyde (usually an aromatic one). The first pioneering examples were developed by Sheehan and coworkers, which were followed by several authors, highlighting the report by Enders in 2002, in which, for the first time, a highly enantioselective A -heterocyclic carbene-catalyzed benzoin condensation was reported (Scheme 6.2). As can be seen in this scheme, the general principle applied to the design of these catalysts relied on a thiazolium central unit as the precursor of... 

In 2001, Tills et al. used thiazolium chloride 620 as a carbene precursor in a diastereoselective intermolecular Stetter reaction 518) between the chiral donor 621 and aldehyde 622. The 1,4-diketone 623 thus obtained was then used successfully to access roseophilin (624) (Scheme 128) 517). The promising cytotoxicity of roseophilin (624), a macrocyclic pigment isolated from Streptomyces griseoviridis 524), has attracted considerable attention resulting in a number of partial and total syntheses of this alkaloid (525), and this example demonstrates nicely how (even achiral) organocatalysts can play an important role in obtaining a complex namral product. 

The use of chiral carbenes as asymmetric organocatalysts has attracted the interest of more and more research groups over the last years [88, 100]. Noteworthy, the use of chiral heterocyclic carbenes for asymmetric benzoin condensations dates back to 1966 when Sheehan et al. used the thia-zolium salt 206 to obtain benzoin 207 with an optical purity of around 20% [101] (Scheme 6.34A), and other groups introduced more powerful chiral thiazolium catalysts later... 

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