1.2.4- Triazole carbenes, reactions

The most important chemistry of azidoazoles is the fragmentation of derived nitrenes of which the prototypes are (616 — 617) and (618 — 619). Thus, 5-azido-l,4-diphenyltriazole (620) evolves nitrogen at 50°C (70JOC2215). 4-Azido-pyrazoles and-1,2,3-triazoles (621) undergo fragmentation with formation of unsaturated nitriles (8lAHC(28)23i) cf corresponding carbene reactions (Section 3.4.3.4.6). 

By contrast, 1,2,4-triazole carbene 354 displays electrophilic character. Thus, it reacts with alcohols and amines producing triazoline derivatives 355 in quantitative yields. Oxygen or sulfur gives triazolinone and triazolinethione derivatives 356 (similar reaction with tellurium is known for imidazol-2-ylidenes). Reactions of 354 with dimethyl maleate or dimethyl fumarate lead to compounds 357, probably via ring opening of a cyclopropane intermediate with subsequent 1,2-hydrogen shift. 

S.2.2.3 MCRs Involving Triazol-5-ylidenes as Key Components MCRs involving triazol-5-ylidenes V are more difficult as a result of the diminished nucleophiUcity of these carbenes compared with previously described thia-zol-2-ylidenes II and imidazol-2-yUdenes ID. However, the importance of triazole moieties in relevant organic compounds has encouraged the use of triazole carbenes as key components in MCRs. To this aim, the reaction of triazol-5-ylidene V, DMAD, and different aromatic aldehydes provided fully substituted furanone derivatives 25 [21]... 

Under presented conditions (triazolium bromide XI and DBU in CHjCy, the reaction proceeds by a cascade reaction (i) first, amidation (aza-benzoin condensation between enal and nitrosoarene, as outlined in Scheme 5.33) produces A-hydroxyacrylamide 51, and (ii) second, in the presence of base such as DBU or triazole carbene [41], oxo-Michael addition of 51 to enones would afford products 52 (Scheme 5.35). 

Reaction of the keto ylide (588) with cyanazide (589) provided a convenient route to the 1,2,3-triazole-l-carbonitrile (590). On heating, (590) lost N2 readily to form the a-cyanoimino carbene (591) (8lAG(E)ll3). 

The triazole 76, which is more accurately portrayed as the nucleophilic carbene structure 76a, acts as a formyl anion equivalent by reaction with alkyl halides and subsequent reductive cleavage to give aldehydes as shown (75TL1889). The benzoin reaction may be considered as resulting in the net addition of a benzoyl anion to a benzaldehyde, and the chiral triazolium salt 77 has been reported to be an efficient asymmetric catalyst for this, giving the products (/ )-ArCH(OH)COAr, in up to 86% e.e. (96HCA1217). In the closely related intramolecular Stetter reaction e.e.s of up to 74% were obtained (96HCA1899). 

The intermediate produced by loss of nitrogen from a l.ff-triazole can be written as an imino-carbene, as a zwitterion, or as a diradical. Subsequent reactions of the intermediate which have been observed (Scheme 57) include (a) photochemical WoUf rearrangement (suggesting that the intermediate may have a singlet carbene structure) ... 

Scheme 32. Reaction of bicyclopropylidene (1) with the stable carbene l,3,4-triphenyl-4,5-dihydro-lH-l,2,4-triazol-5-ylidene (143) [126]...

N-Heterocyclic carbenes are an example of a family of nucleophilic catalysts [84-87]. For instance, the polymerization of p-butyrolactone was catalyzed by l,3,4-triphenyl-4,5-dihydro-l//,l,2-triazol-5-ylidene in the presence of methanol as an initiator [86]. This reaction was carried out in toluene at 80 °C. Nevertheless, an undesired elimination (Fig. 4) reaction was observed and control of the polymerization was lost. This issue was overcome by using ferf-butanol as a co-solvent, which reacts reversibly with the free carbene to form a new adduct. Owing to the decrease in the concentration of the free carbene, the elimination is disfavored and the polymerization is then under control provided that a degree of polymerization below 200 is targeted. As a rule, the reactivity of N-heterocyclic carbenes depends on their substituents. Hindered N-heterocyclic carbenes turned out to be not nucleophilic enough for the ROP of sCL. Recently, it was shown that unencumbered N-heterocyclic carbenes were more efficient catalysts [87]. 

The vapor-phase pyrolysis of 4-hydroxy-1,2,3-triazole and its iV-methyl derivative affords methan-imine and its A-methyl analog. Analysis of the reaction path by the MNDO method shows the presence of two stable or metastable isomers, (liif)-4-hydroxy-l,2,3-triazole and its ketone protomer <89NJC551>. 4-Diazo-1,2,3-triazoles (122) thermolyze or photolyze in benzene to 4//-l,2,3-tri-azolylidenes (123) which convert benzene to 4-phenyl-1,2,3-triazoles and/or isomerize to a-diazo-nitriles (124). Intermediates (124) react with benzene via a carbene to give addition, ring expansion or substitution products (Scheme 17) <82TL5115>. The similar thermolysis of diazotriazoles in substituted benzene gives complex mixtures in which all of the components are sometimes impossible to isolate and identify <90AHC(48)65>. 

In addition to the metal-oxo complexes, several examples of NHC-stabilized rhenium(V)-nitrido complexes exist, e.g., 9 and 10 (Chart 1) [28]. These adducts, which feature triazole-based ligands, were prepared via displacement of phosphine ligands. The stability of both phosphine and triazole-based carbenes in these reactions suggest the nitrido ligand is relatively unreactive. 

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). 

The mechanism of this reaction was hrst described by Breslow as early as 1958 [4], Subsequently, the natural enzyme thiamine, found in yeast, was replaced by related nucleophiles like thiazole [5,6], triazole [7] and imidazole [8], Reactions that follow this mechanism include the very important Stetter reaction (the benzoin condensation of aliphatic aldehydes), the Michael-Stetter reaction (a variant of the Stetter reaction where the aldehyde reacts with an a,P-unsaturated ketone) [1], transesteriflcations [9] or the acylation of alcohols [9,10], All four reactions are carbene catalysed nucleophilic acylation processes. 

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