Thioketones dipolarophile

Thermolysis of 16e,f in either solution or gas phase (150-350 °C) gave deuteriated ethylenes (i.e. 40e from 16e and 41f from 16f) with about 95% retention of stereochemis-try ". Similarly, pyrolysis of the stereoisomeric 2,3-diphenylthiirane oxides 16g,h proceeded smoothly to yield stilbenes and sulfur monoxide in more than 70% yield . The extrusion of SO from the trans-isomer proceeds almost stereospecifically, while that from the cis-isomer occurs with complete loss of stereochemistry. This indicates the intervention of a stepwise mechanism, and not a symmetry-allowed nonlinear chelatropic reaction . Based on the fact that all attempts to trap the intermediate with 1,3-dipolarophiles were in vain, whereas a 1 1 adduct was obtained in good yield (about 60%) with the carbon radical scavenger di-p-anisyl thioketone, a mechanistic scheme as depicted in equation 10 has been proposed . Although the radical intermediates are capable of internal rotation about the carbon-carbon bond, for the 2,3-diphenyl case (i.e. 16g,h), the rotation would be... 

Heteroatomic dipolarophiles are competent in the dipolar cycloaddition of nitronates. The in situ generated thioaldehydes and thioketones react with sUyl nitronate 120 to afford the 1,4,2-oxathiazolidine in good yield (Table 2.36) (113-116). 

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). 

The thiocarbonyl group is a highly reactive dipolarophile and in general this group dominates the reactivity of nonenolisable exocyclic thioketones as illustrated for the systems shown 5-methylene-2-thioxo-l,3-thiazolinin-4-one (260) (161), pyrimidone-2- and -4-thiones (261, 262) (134), pyrazolo[l,5,4-e/][l,5]benzodi-azepin-6-thione (263) (162). 2-Thiono-4-imidazolidinone (264) also gave a C=S cycloadduct as expected but, in the case of the analogue 265 with an additional exocyclic methylene group, the latter proved to be more reactive (163). 

Examples of 1,3-dipolar cycloadditions of nitrile sulfides (124) onto thioketones have been reported272 (equation 133). 124 were generated by thermal decomposition of 1,3,4-oxathiazol-2-ones (123) which, in turn, may be prepared bearing a wide variety of substituents R1. Thermolyses were carried out in the presence of the dipolarophile which traps the transient nitrile sulfide, with the formation of 5//-l,4,2-dithiazoles 125. Regioi-someric 1,2,3-dithiazole products were not observed. 

It was mentioned earlier that thiocarbonyl thiolates reacted with thioketones forming 1,2,4-trithiolates <1987JA902>. Aromatic thioketones (e.g., thiobenzophenone) are super-dipolarophiles and at 80 °C in a three-reagent mixture with phenyl azide and cyclobutanethiones they form spiranic compounds with X = CO, CS, or CH2 (Equation 21) <1995HCA1298>. An X-ray study of the compound with Ar = 4-MeOC6H4 confirmed the molecular stmcture. 

Other dipolarophiles have been tested leading to pyrrolidines (from vinyl sulfones),219 oxazolidines (from ketones) and thiazolidine (from a thioketone) in moderate to good yields. Noteworthy is the isolation of two adducts from ethoxycrotonaldehyde a pyrrolidine carbaldehyde implying cycloaddition onto the ethylenic double bond and an oxazolidine resulting from the cycloaddition on the carbonyl moiety of the dipolarophile.219 438... 

Thioketones are active dipolarophiles kinetic studies reveal the great superiority of C=S bonds over C=C... 

The exploration of novel preparative routes commands much attention in isothiazole chemistry. Especially interesting are the reactions of 3-phenyl-l,2,4-oxathiazol-5-one with acetylenic esters which afford isothiazoles in high yield (72, 7). The reaction is envisaged as a 1,3-dipolar addition of benzonitrile 7V-sulphide, produced as a transient intermediate, to the dipolarophilic dimethyl acetylenedicarboxylate or propiolic ester. Isothiazoles are also produced by photoisomerization of thiazoles (72, 19). Nitrenes may be implicated in the thermal decomposition of 2-azidoaryl thioketones into benzoisothiazoles (72, 51). 

The formation of 1,3-oxathiolane with chloral and 1,3-dithio-lanes with cycloaliphatic thioketones occurs regioselectively to yield the sterically less hindered products. On the other hand, aromatic thioketones, e.g., thiobenzophenone or 9/ fluorene-9-thione, intercept 8 to give comparable amounts of both regio-isomeric adducts. Usually, stereoisomeric dipolarophiles such as fumaronitrile and maleonitrile as well as dimethyl fumarate and maleate form 18 in a stereoselective manner. However, in the case of extremely electron-poor dipolarophiles, e.g., dimethyl 1,2-dicyanofumarate or ( )-l,2-bis(trifluoromethyl)ethylene-l,2-dicarbonitrile, non-stereospecific formations of the corresponding tetrahydrothiophenes are described. i- s This result is interpreted in terms of a stepwise reaction mechanism with a zwitterion as the key intermediate. Alternatively, this intermediate can cyclize to form seven-membered ketenimines of type 20. With R = Cp3, this product can be isolated in a crystalline form, whereas in the case of R = CN, stable lactam 21 is obtained only after addition of water (eq 10). 

Relatively few papers have appeared concerning heterocycles which fall into this category, and only a small number of them merit discussion. Nitrile sulphides can be generated by thermal decarboxylation of l,3,4-oxathiazol-2-ones, and if this is done in the presence of dipolarophiles new heterocycles are formed. Reactions of this type are known to occur with alkenes, alkynes, and nitriles, and they have now been shown to occur with activated aldehydes and ketones. This provides a new route to 1,3,4-oxathiazolines (312) which were previously rather inaccessible. Silylated thioketones (313) are unstable but may be prepared and reacted in situ to provide routes to a variety of new heterocycles, depending upon the dipolar species used. ... 

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