Dienophiles vinyl sulfones

Based on the high dienophilicity of acyclic vinyl sulfones one should expect thiete dioxides to exhibit similar properties. Indeed, several Diels-Alder (2 +4) cycloadditions with thiete dioxide as dienophile are known. For example, 1,3-butadiene and 1,3-diphenylisobenzofuran react with 3-chloro- or 3-bromo-thiete dioxides to afford the corresponding 1 1 Diels-Alder cycloadducts255 277 (equation 105). 

Since the first demonstration of a cycloaddition reaction of a, /f-unsaturated sulfones in 1938 by Alder and coworkers85, a variety of a, /3-unsaturated sulfones have been prepared and used as dienophiles. For example, when a mixture of p-tolyl vinyl sulfone and 2,3-dimethylbutadiene in benzene is heated at 145-150 °C for 10 h in a sealed tube, crystals of the cycloadduct (134) are obtained (equation 102). Other examples of this intermolecular cycloaddition reaction are given in Table 12. 

Vinyl sulfones are reactive as dienophiles. The sulfonyl group can be removed reductively with sodium amalgam (see Section 5.6.2). In this two-step reaction sequence, the vinyl sulfone functions as an ethylene equivalent. The sulfonyl group also permits alkylation of the adduct, via the carbanion. This three-step sequence permits the vinyl sulfone to serve as the synthetic equivalent of a terminal alkene.68... 

From the same zirconocene intermediates, Huang and co-workers have prepared vinyl sulfides [24,35] and sulfones [26] through use of the appropriate quenching agents (Scheme 4.6). Treatment of vinyl zirconocenes with an equivalent of a disulfide in THF at 60 °C affords, after work-up and purification, (E)-vinyl sulfides in good isolated yields. Vinyl sulfones, which as a class are generally useful as Michael acceptors and Diels—Alder dienophiles, are obtained in about two hours upon treatment of (fc)-vinyl zirconocenes with various sulfonyl chlorides in THF at 40°C. 

Normally, isomeric mixtures are obtained with monosubstituted dienophiles, but in the case of phenyl vinyl sulfone 912, 2-phenyl-6-(phenylsulfonyl)-5,6,7,8-tetrahydro-4(3//)-quinazolinone 913 was isolated in 84% yield as a single regioisomer <2006EJO2753>. 

Other synthetic approaches via sulfones make use of the Michael addition and cycloaddition to vinyl sulfones (see [401] and [402] for reviews on vinyl sulfones as dienophiles and Michael acceptors). The... 

These are good dienophiles. and aryl vinyl sulfones have found use as equivalents of ethylene and ketene through functional modifications of their adducts. However, as the base-induced elimination of a sulfinic acid to yield an olefin occurs only with difficulty, they are not direct precursors of acetylene equivalents, unless suitably modified as in ( )-l-phenyl-sulfonyl-2-trimethylsilyl ethylene (PhS02-CH=CH-TMS). In its cycloadducts the elimination to an alkene is smoothly realized by the fluoride ion. If an alkylation step is previously carried out on the adduct, the overall process realizes an indirect addition of a terminal acetylene, as in the examples given here [533]. 

The experimental conditions indicated in the previous scheme (7 d at 160°C) reflect the general observation that substituted vinyl sulfones are only moderately reactive dienophiles. Again, the introduction of a second electron withdrawing group enhances their reactivity and extends the scope of dienes which can be used as partners. Compounds of the type ArS02CH=CHX (X = NOz, COOR, CF3 or S02Ar) have been particularly investigated. 

Vinyl sulfones in general serve as excellent dienophiles in Diels-Alder reactions,4 and we5 and others2-4 have found the resultant cyclohexene to contain very useful functionality for further manipulation. Hence the vinyl sulfone moiety can serve as a synthon for ethylene,6 terminal olefins,7 acetylene,8 and vinylsilanes9 in [4+2]-cycloadditions as well as valuable synthetic intermediates in general.10... 

Vinyl sulfones are reactive dienophiles in [4 + 2]cycloadditions to provide substituted cyclohexenes.2... 

During the past two decades, the asymmetric Diels-Alder reaction has become one of the most powerful tools in asymmetric synthesis as a result of its capacity to create up to four chiral centers in one step, often in a highly stereoselective manner. In the following sections, recent advances in this area using vinyl sulfoxide and vinyl sulfone dienophiles will be considered. It should be noted that, although beyond the scope of this review, many asymmetric Diels-Alder reactions of chiral sulfinyl-1,3-dienes have been reported.111... 

Vinyl sulfone 347 easily forms adducts like 348. The sulfone group can be reductively cleaved to give 349. As an alternative, 348 can be alkylated first then cleaved to give 350. In these cases, 348 plays the role of a synthetic equivalent to ethylene or terminal alkene dienophiles. j The importance of the utilization of 347 stems from the fact that unactivated alkenes are poor dienophiles and their reactions with even the most active dienes, such as cyclopentadiene, require drastic conditions and are generally impractical. 

Vinyl sulfones are the most versatile and widely used sulfur substituted dienophiles. They may serve as both activated ethylene and terminal alkene equivalents in highly regioselective Diels-Alder additions to classical , i.e. electron-rich, 1,3-dienes. The sulfonyl moiety facilitates the introduction of further functionality into the cycloadducts and can be easily removed by mild reduction (Scheme 16). These features have been exploited in a synthesis of the terpenoid zingiberenol (56) (Scheme 17). ... 

Recent investigations into the chemistry of vinyl sulfones have revealed that they are versatile synthetic intermediates, serving either as dienophiles or Michael acceptors. Methods for the preparation of vinyl sulfones from unactivated olefins have customarily involved the catalyzed (boron trifluoride or benzoyl peroxide) addition of PhS02X (X Cl, Br, I, or SePh), followed by elimination of HX. However, when phenylsulfonyl halides are employed, yields are variable, reactions are frequently incomplete, and the Lewis acid or free-radical catalyst employed can potentially interfere... 

DIENOPHILES Acrolein. Ethynyl p-tolyl sulfone. 3-Methylsulfonyl-2,5-dihydro-furane. 3-Nitro-2-cyclohexenone. Phenyl vinyl sulfone. 

Vinyl sulfonates were found to be reactive dienophiles in both intermolecular and intramolecular Diels-Alder reactions [33, 34]. The results of the Diels-Alder reaction of 5 with various dienes are summarized in Table 9. The reaction yields are high and the endolexo selectivities for cyclic dienes are reasonably good [40]. 

The procedure for oxidation of the sulfide to the sulfone is based on that reported earlier by Bordwell and Pitt. The synthetic utility of phenyl vinyl sulfone and sulfoxide derives not only from their ability to serve as excellent Michael acceptors toward such reagents as enolate anions and organometallics, but also as moderately reactive dienophiles in Diels-Alder reactions. " The resulting adducts, in turn, can be chemically modified so that these electron-deficient olefins serve as useful synthons for acetylene,ethylene,terminal olefins,vinylsilanes, and ketene in [4 + 2] cycloadditions. Phenyl vinyl sulfone undergoes ready cycloaddition to Danishefsky s diene in the first step of a protocol for the regiospecific y-alkylation of 2-cyclohexenones. Furthermore, the ready lithiation of phenyl... 

The use of phenyl vinyl sulfone or phenyl vinyl sulfoxide as the dienophile allows for aromatization by elimination of the sulfur substituent (Equation (152)) <89LA1275>. 

Stereochemical Control Element on the Dienophile. Pyrone sulfone 47 undergoes asymmetrical cycloaddition with a number of homochiral dienophiles at room temperature and gives modest to good diastereomeric excesses. The results, shown in Table 7, were best with benzylic vinyl ethers. This methodology was employed to synthesize (-)-methyl triacetyl-4-epishikimate and an A-ring precursor to la,25-dihydroxy vitamin Dj. ... 

Activated olefin 146 as a dienophile, prepared from phenyl vinyl sulfone and acetaldehyde in the presence of DBACO, has been tested in intermolecular... 

Pindur and Haber explored the chemistry shown in equation 2 and synthesized several new cycloadducts (Scheme 7, 6-12) from IQD 4 [52], The observed regiochemistry with unsymmetrical dienophiles (methyl acrylate, nitrosoben-zene, l,l-bis(phenylsulfonyl)ethane, methyl vinyl sulfone, and methyl vinyl ketone) was low to modest, with the major isomer as predicted by simple FMO theory. However, dienophiles acrolein, propynoates, and diethyl maleate were unreactive relative to dimerization of IQD 4. Pindur and Meyer prepared several bis(tetrahydropyrrolo[3,4- ] carbazoles) by exposing IQDs (generated as shown in equation 2) to alkane-tethered bismaleimides [53]. In two... 

The regio- and stereoselectivity of three different dienophiles in the HDA reaction with two different 7-substituted norbomadienes were investigated (Scheme 14). Both acrylonitrile (AN) and phenyl vinyl sulfone (PVS) give excellent yields of the HDA products. However, a modest drop in anti syn ratios was observed whereas the exo endo ratios decrease dramatically as the dienophile changes from MVK to AN or PVS (Table 10). 

Dienophiles, phenyl vinyl sulfone 59, and ethynyl sulfone 60 in Diels-Alder reactions can serve as potential ethene and ethyne equivalents, respectively. 

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