Bicyclic sulfur heterocycles

The formation of cyclopropane derivatives by photolysis of diazoalkanes in the presence of alkenes is believed to occur by photolytic decomposition of the diazoalkane to yield the carbene, followed by addition of this carbene to the alkene. Cycloaddition of this type has been reported in furan, dihydrofuran, and thiophene.198 Thus, photolysis of ethyl diazoacetate in thiophene yields the bicyclic sulfur heterocycle (215). Alternatively, photolysis of 3-diazo-l-methyl-oxindole (216) in cyclohexene leads to the formation of two isomers which are thought to have the spirocyclopropyl structure (217) photolysis in ethanol yields 3-ethoxy-1-methyloxindole.194... 

In an earlier study the authors proposed a [3.2.0] bicyclic sulfonium salt 8 as the reactive intermediate in the trimethylsilyl iodide mediated ring contraction of 4-methoxythiephane <1996T5989>. Enantiomerically pure thio-lane derivatives were synthesized via a ring contraction of a seven-membered sulfur heterocycle by nucleophilic transannular substitution <2000TA1389>. The thiepane derivative 15, derived from d-sorbitol, was converted into the dimesyl derivative 16 following deprotection under acidic conditions. Treatment of 16 with sodium azide in DMSO at 120°C yielded the corresponding thiolane as a mixture of two diastereoisomers, 17a and 17b, in a 5 1 ratio (see Scheme 1). 

Bis-titanocene complex 184 reacted with one equivalent of sulfur monochloride to give intermediate mono-titanocene 185 which, upon treatment with ethane-1,2-disulfenyl chloride, transformed to bicyclic sulfur-carbon heterocycle 186 (1991CB2141 Scheme 93). 

The reaction has been the subject of reviews,316,45 from which it will be seen that the reaction can be applied to synthesis of five- and six-membered oxygen-heterocycles, sulfur-heterocycles, bicyclic compounds, and compounds containing an additional heteroatom in the ring. 

Regiospecilic intramolecular cycloadditions of nitrones to sulfur-substituted dienes, with 3-sulfolene precursors, has been realized (Scheme 2.217). The stereochemical outcome of these reactions is affected by the structure of the substituent (sulfide or sulfone) in the diene and by the chain length connecting the diene and nitrone (a) and (b) (see Scheme 2.211). The bicyclic products obtained from these reactions have been converted to interesting heterocyclic compounds (709). 

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). 

Heterocycle 32, on exposure to various amines, undergoes nucleophilic attack at the ring junction carbon atom, giving either the bicyclic material 33 or the monocyclic product 34 <1999JHC161>. Interestingly, when the sulfur atom at the 3-position is in the lower oxidation state, the major product is the monocyclic product 34, with the bicyclic material being isolated in low yield (Equation 3). When S-3 is oxidized however, the bicyclic material 36 is isolated in near-quantitative yields (Equation 4). 

Current IUPAC and Chemical Abstracts nomenclature has been employed in this index with the former given preference. Substitutive nomenclature has been given preference over radicofunc-tional, additive, subtractive, conjunctive or replacement nomenclature, except where this becomes unwieldy. With many bicyclic and polycyclic compounds bearing heteroatoms, standard bicyclic or polycyclic oxa, aza, and thia replacement nomenclature has often been used. With certain functional groups, where the names are rather complex and probably not familiar to most organic chemists, such as ylides, those compounds have simply been named as sulfur, tellurium and arsonic ylides. Metal catbenes have been treated similarly. With more complex functionality and many heterocycles, the Beilstein Commander Crossfire nomenclature system has been used with certain modifications. 

Terem B (1996) Bicyclic systems with ring junction sulfur, selenium or tellurium atom. In Katritzky AR, Rees CW, Scriven EFV (eds) Comprehensive heterocyclic chemistry II. Pergamon, Oxford, chap 8.32, p 833... 

Few examples of photochemical transformations of the 10n heterocycles in this series have been reported. Notable is the conversion of thieno[2,3-c]isothiazoles (33) to thiophenes (37) by homolytic cleavage of the nitrogen-sulfur bond (Scheme 4). The enedithione (34) which arises from the initial diradical may undergo (a) cyclization via the bicyclic thiirane (35) or (b) electrocyclization to the 1,2-dithiine (36) <88H(27)2539>. Since similar rearrangements do not occur with isothiazoles, benzoisothiazoles, or the isomeric thieno[3,2-d]isothiazoles, this unique transformation is a direct consequence of the thieno[2,3-c]annelation. However, substituent effects on the efficiency of the transformation have not been explored. 

Numerous structures containing the thiocarbonyl ylide dipole are conceivable. Incorporation of the thiocarbonyl ylide dipole into a bicyclic heterocyclic system is possible by the conversion of the cyclic thione (203) into the ring-fused mesoionic system (204). The thiocarbonyl ylide dipole (205) undergoes cycloaddition with both alkenic and alkynic electron-poor dipolarophiles in refluxing benzene or xylene so that, after extrusion of hydrogen sulfide or sulfur, respectively, from the initial 1 1 cycloadducts (206) and (207), a ring-fused pyridinone is formed. The method has been used for the annelation of pyridinones to the imidazole, 1,2,4-triazole, thiazole and 1,3,4-thiadiazole systems... 

In a study related to the conformational properties of the cyclohexane-fused six-membered heterocycles, new bicyclic dithiolanes, 285-/ra r (Scheme 52) and 285-crr (not shown), were prepared along the reaction pathway, as precursors used further for the syntheses of 2-methyl substituted and unsubstituted /ra r-fused 4a,5,6,7,8,8a-hexahydro-2//,4//-1,3-benzodithiines, exemplified by structure 288-/ra ir (R=R = H) <2002JOC1910>. Thus, ditosylation of cis-Z-hydroxymethyl cyclohexanol 284, and subsequent reaction with sodium sulfide and sulfur, provided a mixture of new bicyclic products 285 and 286, albeit in very low yields, with configurational inversion at C-1. These were reduced by LiAlH4 to provide /ra r-2-mercaptomethyl cyclohexanethiol 2 l-trans. Upon acetalization or transacetalization, the desired 2SS-trans derivative was obtained. The same methodology with the precursor 2E4-trans was extended to the preparation of the r-fused bicyclic compounds 285-288. 

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