Sulfones, vinyl Diels-Alder reactions

Another total synthesis of pamamycin-607 (lb) was reported in 2001 by our own group [6] at about the same time as the Lee synthesis. Here, the approach was based on the stereoselective intramolecular Diels-Alder reaction of vinyl-sulfonates and novel methods for elaboration of the resulting sultones [13,14]. 

Oxidative desulfonylation.- Aryl sulfones are converted into ketones by oxidation of the a-carbanion (LDA) with Mo05Py-HMPT in THF at —78 in 50-97% yield. This conversion permits use of phenyl vinyl sulfone as an equivalent of kctcnc in Diels Alder reactions. 

Diels-Alder reactions.2 This vinyl sulfone has been used as an acetylene equivalent in a new synthesis of vitamin Be. Thus 1 undergoes a Diels-Alder reaction with 4-methyloxazole (2) to give a pyridoxine derivative (3) with elimination of mcthanesulfinic acid. The product is converted into the vitamin (4) in three simple steps. 

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... 

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... 

The synthesis of electron-deficient diene 285 was achieved by the Stille coupling of P-trifluoromethanesulfonyl-a,P-unsaturated sulfone (284) with a 3-stannyl-a,P-unsaturated ester (283) (Scheme 74).148 Similarly, the preparation of a diverse range of enantiomerically pure 1- and 2-sulfinyl dienes has been achieved via Stille coupling of halovinyl sulfoxides and vinyl stannanes.149,150 Enantiomerically pure 1- and 2-sulfinyl dienes have been used extensively in asymmetric Diels-Alder reactions.111... 

It was demonstrated that the use of phenyl vinyl sulfoxide or sulfone in a thermal Diels-Alder reaction was highly unsatisfactory as an alternate route. The synthesis of the neolignins galbulin, isogalbulin [82], magnoshinin, and magnosalin [83] have all been accomplished by means of a cation radical cycloaddition (Scheme 42). 

The Chiron (-)-(lOa) was obtained with very high diastereoselectivity from a-pyrone sulfone and optically active vinyl ether (Scheme 69). This lactone was later used in the asymmetric synthesis of (-)-methyltriacetyl-4-epishikimate (10b). 3-Sulfonylnitroalkenes were also shown to be reactive alkyne equivalents in Diels-Alder reactions. ... 

Metz has developed a highly diastereoselective intramolecular Diels-Alder reaction of furans with vinyl sulfonates [22]. When hydroxyfuran 10 a was esterified with vinylsulfonic acid chloride, the intermediate sulfonate spontaneously underwent cycloaddition to give sultone 11a, Eq. 9. In the same manner, (-)-llb was obtained from (i )-10b which was derived from L-valine. 

Sulfoxide, sulfinate and sulfonate are used as activators of acetylenic or vinyl units. Several a, P unsaturated synthons, namely acetylenic sulfoxide (1), vinyl sulfoxide (2), acetylenic sulfinate (3), acetylenic sulfonate (4), and l-propene-l,3-sultone (5) are developed. Their applications in Diels-Alder reactions, heterocycle and alkaloid syntheses are also investigated. For the chiral acetylenic sulfoxide, the sulfoxide moiety not only enables chemical activation of the acetylene unit, it can also induce stereochemical control at the adjacent carbon centers to achieve enantioselective synthesis. 

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]. 

Simple alkencs that do undergo the Diels-Alder reaction include conjugated carbonyl compounds, nitro compounds, nitriles, sulfones, aryl alkenes, vinyl ethers and esters, haloalkenes, and dienes. In addition to those you have seen so far, a few examples are shown in the margin. In the last example it is the isolated double bond in the right-hand ring that accepts the diene. Conjugation with the left-hand ring activates this alkene. But what exactly do we mean by activate in this sense We shall return to that question in a minute. 

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... 

Simple alkenes that do undergo the Diels-Alder reaction include conjugated carbonyl compounds, nitro compounds, nitriles, sulfones, aryl alkenes, vinyl ethers and esters, haloaUc-... 

Heteroaromatic motifs are not the only accessible products of a cycloaddition/cycloreversion strategy. Cleverly shaped six-membered dienes with an intrinsic leaving group might also act as precursors for phenyl moieties. A definitely irreversible cycloreversion tailors this route for the integration of arenes into strained scaffolds. Beaudry and co workers [12] embarked on the synthesis of the conforma-tionally chiral macrocyclic natural product cavicularin. A vinyl sulfone moiety, acting as an alkyne equivalent, underwent a Diels-Alder reaction with a neighboring... 

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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