3-Sulfolene selectivity

Sulfolene (2) is the next most commercially important sulfone after sulfolane. Besides its precursor role in sulfolane manufacture, 3-sulfolene is an intermediate in the synthesis of sulfolanyl ethers, which are used as hydrauHc fluid additives (see Hydraulic fluids). 3-Sulfolene or its derivatives also have been used in cosmetics (qv) and slimicides. Selected physical properties of 3-sulfolene are Hsted in Table 3. 

Sulfur dioxide acts as a dienophile ia the Diels-Alder reaction with many dienes (253,254) and this reaction is conducted on a commercial scale with butadiene. The initial adduct, sulfolene [77-79-2] is hydrogenated to a solvent, sulfolane [126-33-0] which is useful for selective extraction of aromatic hydrocarbons from... 

EyZy or (E,E)-1>3-Dienes. Dialkylation of 3-sulfolene results selectively in trans-2,5-dialkyl derivatives (1) in 50-70% yield. The products are converted into (E,Z)-1,3-dienes (2) on thermal or reductive desulfonylation. In the presence of base, trans-1 isomerizes to ci s-1, which undergoes thermal desulfonylation to (E,E)-1,3-dienes (2).1... 

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. ... 

The main part of this chapter is split into four sections, each of which highlights a particular aspect of the chemistry of sulfolenes which is important to those contemplating the use of sulfolene intermediates in organic synthesis. In the first section we describe some important methods for construction of particular sulfolene nuclei in the second section we review methods for installing substituents selectively into various sulfolene rings in the third section we consider the selective formation of dienes from sulfolenes and finally we use examples to illustrate how dienes generated from sulfolene intermediates have been incorporated in Diels-Alder based synthetic routes. 

On further alkylation, 2-substituted-3-sulfolenes delivered tran5-2,5-disubstituted 3-sulfolenes (72) in moderate to high yield with -90% stereoselectivity and 100% regioselectivity. A selection of the results is shown in Scheme 6.20, Table 6.5. 

When the reaction product from the ethylation of 3-sulfolene was analysed carefully, small amounts ( 10% yield) of 2,5-diethylated sulfolenes were also identified, but no 2,2-diethylated material was detected. The regioselectivity of direct alkylation of 2- and 3-substituted 3-sulfolenes was therefore investigated. Under the conditions already outlined, 2-ethyl-3-sulfolene (79) was ethylated in the 5-position with high regioselectivity. The trans stereoisomer was the major product, but the selectivity was low, and 2-sulfolene products were again also produced as the result of double-bond isomerization (Scheme 6.23). 

The presence of a phenyl group at the 3-position of the sulfolene nucleus stabilizes an anion at C-5, and thus alkylation occurs selectively in that position. The selectivity is slightly reduced when the phenyl ring carries an electron donating methoxy substituent. The disubstituted compounds (91), obtained after alkylation, could then be selectively alkylated in the 2-position. 

A comparison of the effect of different substituents in the 3-position of 3-sulfolenes upon deprotonation/alkylation was carried out [107]. The in situ alkylation conditions (LiHMDS/THF/HMPA) were also compared with the 2-step (BuLi/THF/HMPA) procedure. When the 3-substituent was an alkyl group, the reactions were generally high-yielding, with high selectivity for 2-substitution, and the 2-step procedure was generally more efficient. Considerable polymerization of the 3-halogenated sulfolenes always occurred and this was ascribed to destabilization of the adjacent carbanion. However, 2-alkylated sulfolenes were isolated in low yield, as the only products, and the in situ procedure was more efficient in these cases. 

It was no surprise that deprotonation of 3-carbomethoxy-3-sulfolene (103g) occurred at the 5-position, since the anion formed at this position can be stabilized by the ester group, but it is interesting that alkylation occurred at the 3-position. A selection of the results is presented in Scheme 6.32, Table 6.14. 

Other methods for the selective preparation of thiophenyl derivatives have eiIso been described [20]. 2-Alkyl-3-sulfolenes were converted to 3-thiophenyl derivatives (135) by treatment with phenylsulphenyl chloride in the presence of Et3N, and 3-thiophenylsulfolenes were alkylated selectively via their lithium anions, providing (136a-d) (Scheme 6.40). 

An example of the stereoselective formation of ( )-dienes was the synthesis of a red bullworm moth pheromone (160). Sulfolene (159) was available from 3-sulfolene by selective alkylation, and on heating gave diene (160) as a single isomer [116,117] (Scheme 6.51). 

From the examples above, it appears that 2,3-substituted sulfolenes with a methyl group as the 3-substituent open in a highly selective manner to provide the diene with the two substituents cis to one another, but this is not always the case with other 3-substituents. 

As illustrated in the previous sections, a variety of methods has been developed for selective functionalization of the sulfolene nucleus. Sulfolenes are also readily... 

Over recent years a diverse range of methods has been developed for preparing selectively functionalized 3-sulfolenes. The use of such compounds as diene precursors for intermolecular and intramolecular Diels-Alder reactions has also been explored extensively. Thus, it is now possible to prepare and utilize substituted sulfolene intermediates in efficient strategies for the synthesis of complex organic molecules. There is, however, scope for more research into the basic principles underlying the preparation and reactions of substituted sulfolenes. 

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