Huisgen ylide

Over the past two decades, important contributions to the chemistry of thiocarbonyl ylides were made by Huisgen et al. (27). By carrying out the reaction of thiobenzophenone with diazomethane at low temperature, formation of 2,5-dihydro-l,3,4-thiadiazole (15) with subsequent elimination of N2 was established as the route to the reactive thiobenzophenone (S)-methylide (16) (17,28). In the absence of intercepting reagents, 16 undergoes electrocyclization to give 17 or head-to-head dimerization to yield 1,4-dithiane 18 (Scheme 5.3). 

Based on a series of kinetic studies, Huisgen et al. (91-93) established that thiocarbonyl compounds, especially aromatic thioketones, function as very active dipolarophiles (superdipolarophiles) toward thiocarbonyl ylides. In fact, the trapping reaction of thiocarbonyl ylides with thiocarbonyl compounds represents an excellent method for the preparation of 1,3-dithiolanes. 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

Thiocarbonyl ylides are the 1,3-dipoles with the highest ir-MO energies.28,29 Huisgen described the cycloadditions of 2,2,4,4-tetramethyl-l-oxocyclobutane-3-thione S-methylide (10) and of adamantane-thione S-methylide (11) to dimethyl 2,3-dicyanofumarate which proceed in a nonstereospecific manner (Scheme 4).27 The presence of four electron-attracting substituents in the dipolarophile significantly lowers the MO energy of the ethylenic dipolarophile. Thus, in this particular case, the pair of reactants ful-... 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

Oxazoles of various substitution patterns are well known heterocycles for which a number of methods of synthesis have been reported.129 Acyl carbenes or functionally equivalent species have been found to undergo cyclization with nitriles to give oxazoles in high yield via nitrile ylide intermediates.130,131 This reaction can be induced to occur under thermal, photolytic, or catalytic conditions.129,132,133 Huisgen and coworkers were the first to study this process in some detail.132 Thermolysis (or copper catalysis) of a mixture of ethyl diazoacetate and benzonitrile resulted in the formation of oxazole 254. The isolation of this product is... 

As early as 1967, Huisgen and coworkers [37] had shown that, upon photolysis, certain aziridines of type 96 undergo C—C bond fragmentation stereospecifkally to produce octet-stabilized azomethine ylides which, on cycloaddition with electron-deficient dipolarophiles, produce pyrrolidine ring systems (Scheme 8.29). 

Markowski, V. and Huisgen, R. (1976) Disrotatory photoconversion of cis,trans isomeric oxiranes to carbonyl ylides. Tetrahedron Letters, 17, 4643-4646. 

Huisgen, R., Scheer, W., and Huber, H. (1967) Stereospecific conversion of cis-trans isomeric aziridines to open-chain azomethine ylides. Journal of the American Chemical Society, 89, 1753-1755. 

Huisgen and co-workers reported, in three papers (02T507, 02T4185 and 02HCA1523> the conversion of various 1,3,4-thiadiazolines 86 into thiocarbonyl ylides 87 via extrusion of N2. They then described cycloaddition reactions of these ylides 87 with various a,P-unsaturated esters and nitriles and postulated reaction mechanisms for the regioselectivity and stereochemistries observed in the transformations. 

This structure was also proposed by Huisgen et al. From a very strained molecule, strikingly stable ylides can be produced photolytically or thermally (Eq. 

According to Huisgen [26] the reaction proceeds via ylide formation followed by a Stevens-type rearrangement. This was disputed by Franzen and Fikentscher [27] who found, using CH2, that EtOPr from EtOEt was labelled in the 7-position rather than the a-position expected from an ylide rearrangement. 

Huisgen and his co-workers190 have recently reported that the addition of aromatic nitrile ylides to carbonyl compounds results in the formation of A3-oxazolines, which are easily oxidizable to oxazoles. Typically, benzonitrile 4-nitrobenzylide (131, Ar = p-OsNC6H4), generated from the imidoyl chloride (130) by 1,3-elimination of hydrogen chloride with triethylamine, reacts smoothly with benzaldehyde to give a pair of... 

This investigation opened the way to further two-step cycloadditions of the thiocarbonyl ylide 6.23 with other electrophilic alkenes, e.g., with l,2-dicyano-l,2-bis(trifluoromethyl)ethene (Huisgen et al., 1989). Both the latter dipolarophile and tetracyanoethene demonstrated that, besides the 1,3-dipolar addition product 6.28, the cyclic ketene imine 6.29 is formed in a reversible 1,7-ring closure (6-18, Huisgen et al., 1986b, 1989). 

Huisgen s experimental evaluation of the thiocarbonyl ylide cycloadditions allows an understanding of the dichotomy of answers to the question concerted or two-... 

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