3-Sulfolenes substituted

Several methods for sulfolene substitution have been devised which utilize bromo groups to introduce other substituents into the sulfolene ring. 

The Diels-Alder reaction is usually reversible and has been used to protect double bonds. A convenient substitute for butadiene in the Diels-Alder reaction is the compound 3-sulfolene since the latter is a solid that is easy to handle while the former is gas. " Butadiene is generated in situ by a reverse Diels-Alder reaction (see 17-20). 

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). 

Takayama et al. [547] have shown that 3-sulfolene can be directly alkylated at the 2 and 5 positions. The 2-substituted 3-sulfolenes (4) were obtained in a fair yield when the labile sulfolene a-carbanion was generated by LHMDS in a THF-HMPA solution at -78°C in the presence of an alkyl iodide. fran -2,5-Dialkyl-3-sulfolenes (5) were similarly... 

Few examples of functionalization on the benzene ring of benzisothiazole have been reported (see Section 4.05.7.2). Studies on the reactivity of unsaturated chains in cycloaddition reactions have been reported (see Section 4.05.7.3). The high reactivity of 4-vinylisothiazolin-3-one A-oxides in Diels-Alder cycloadditions, both as diene and dienophile, is illustrated by their tendency to dimerize. 5-Vinylisothiazole A,A-dioxides react at the vinyl function with different 1,3-dipoles. Isothiazolo-3-sulfolenes 265 give an o-quinodimethane which can be trapped with a dienophile. Different isothiazole derivatives substituted with a carbon chain functionalized with heteroatoms have been prepared as ligands for the formation of complexes. 3-Oxocamphorsulfonimide reacts with the anion of alkynes and several studies on the reactivity of the products with electrophiles are reported. 

The alkylation of 2-alkyl-substituted sulfolenes takes place with complete regio- and high stereo-selectivity to yield approximately 60% of rra/ -2,5-disubstituted 3-sulfolenes. When 1,4-diiodobutane and 1,3-diiodopropane are used instead, one-pot dialkylation occurs at the 2-position in the first case and leads to a spiro sulfolene, whereas 2,3-dialkylation proceeds in the second case leading to a fused bicy-clic product. Interestingly 2,S-dialkylation has been achieved, from 3-bromo(bromomethylpropene), thus allowing the synthesis of bicyclo[3.2.1]sulfones. ... 

Sulfolenes are valuable precursors of 1,3-dienes. Thermolytic desulfonylations of 2,S-disubstituted derivatives lead exclusively to ( ,Z)-dienes in agreement with the symmetry rules. The stereoselectivity of the reaction is dramatically changed however by carrying out the reaction in a protic solvent and in the presence of a base (which probably isomerizes the trans sulfolene to the cis isomer), since ( , )-dienes are now obtained exclusively and contrary to the symmetry rules. a-Metallo sulfolenes may be viewed therefore as masked 1,3-dienyl anion equivalents ( C =>C—C =C—R). The above mentioned set of reactions has been used for the regioselective syntheses of 6- and 16-alkyl-substituted vitamin D3 analogs, as well as rrani-3-ocimene and oi-famesene. ... 

Exposure of 3-sulfolenes to BuLi and then A(-chlorosuccinimide accomplishes the synthesis of substituted 1,3-butadiene-1-sulfonyl chlorides. ... 

Chloro-4-fluorothiophene-1,1-dioxide 234, a new synthetically useful fluoro-diene was prepared from commercially available 3-sulfolene. This compound reacts with different types of dienophiles acetylenes, alkenes, furans quinine, and antracene giving the 3-fluoro-4-chloro-substituted arenes or cyclic chlorofluorodienes. " ... 

The cheletropic extrusion of SO2 from heterocyclic sulfones is now the most widely used and flexible route to the r)-quinodimethanes. The sulfones are stable, easily handled and readily synthesised. The ease of this thermal elimination depends on the bond order of the sulfolene 3,4-bond. It is normally in the range 150-200 C for a typical aromatic heterocyclic fused system but can be much higher for 2,3-naphtho fused and other systems, e.g. 11, where this bond order is reduced by bond fixation. The extrusion temperature for the 2-substituted pyrazoles 29 is significantly higher than for the 1-substituted isomers 30 and, in contrast to the... 

Side-chain functionalization of substituted 3-sulfolenes has given a variety of important intermediates <890PP259>. Some examples are given in Scheme 64. 

Appropriately substituted tetrahydrothiophenes have been used as starting materials for 3-sul-folenes which are fused to other heterocycles. As mentioned in the previous section, these are convenient precursors for ort/io-bismethylene heterocycles. Thus the masked / -ketoaldehyde (361) with hydrazine hydrate followed by acid treatment, gave the bicyclic compound (362), which could be oxidized by MCPBA to the 3-sulfolene (363) (Scheme 75) <93JOC493>. Similarly, treatment of the ketoaldehyde derived from (361) with hydroxylamine gave the isoxazole (364) which could be... 

Chou and co-workers ° investigated 4,6-dihydro-2-substimted-thieno[3,4-d] oxazole 5,5-dioxides 758 both experimentally and theoretically. The authors were initially disappointed to find that 4-bromo-3-sulfolanone 757 did not react with formamide or acetamide to yield 754 or 758 (R = CH3) (Scheme 1.208). This synthetic approach had been successful for preparing 2-substituted thiazolo-3-sulfolenes 759. ... 

Cheletropic Cycloadditions. If an atom can both donate an electron pair and accept an electron pair to move to a higher covalency, it can act as a dienophile to a diene. Such is the case with the sulfur atom in sulfur dioxide and with phosphoms in tricovalent halides. This type of cycloaddition is called cheletropic, and results in the formation of 5-membered rings. The reaction of butadiene with SO2 is particularly important it is conducted on a commercial scale to produce the cyclic sulfone 5.18 (called sulfolene). Its hydrogenation product 5.19 (sulfolane) is widely used as a nonaqueous highly polar solvent. Substituted dienes also participate in the cycloaddition. Here, the sulfur can donate its electron pair while accepting an electron pair to form a new carbon-sulfur bond. 

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