Sulfoxides, vinyl Diels-Alder reaction

The use of phenyl vinyl sulfoxide as an acetylenic synthon in Diels-Alder reactions was reported in 1978 [525]. By heating phenyl vinyl sulfoxide with anthracene in chlorobenzene at 130°C for 120h, dibenzobarrelene was obtained in an 83% yield through elimination of phcnylsulfinic acid (see Section 3.1) from the primary cycloadduct. 

New possibilities were reported by Kagan [529], who observed that vinyl sulfoxides could be activated for the Diels-Alder reaction by alkylation into vinyl sulfonium salts. A number of cycloadditions of these salts occurred then under mild conditions and with high stereoselectivities. The results could be particularly striking, as in the case of the low-temperature (-78°C) reaction of ethoxy p-tolyl vinyl sulfonium tetrafluoroborate (2) with cyclopentadiene. Only the endo isomer (3) was formed with a de. higher than 99%. and isolated in a 62% yield after transformation of the sulfonium adduct into a sulfoxide (with inversion at sulfur) by sodium hydroxide. 

Sulfinyl dienes and vinyl sulfoxides have rarely been used in asymmetric hete-ro-Diels-Alder reactions [145]. The first example was reported in 1992 and describes an intramolecular cycloaddition using a heterodiene bearing a chiral sulfinyl group [146a]. In this paper, the conversion of a-p-tolylsulfinyl a,ft-unsaturated ketone 176 (prepared by Knoevenagel reaction of 3-methylcitronellal and (S)-p-toluenesulfinylacetone) into the hetero-Diels-Alder adducts 177... 

Di-r-butylbenzenes.1 This reagent undergoes a Diels-Alder reaction with phenyl vinyl sulfoxide, an acetylene equivalent (8,399), with loss of benzenesulfenic acid to give o-di-f-butylbenzene in 77% yield. 

An unusual nickel-catalyzed [2+2+2] homo-Diels-Alder reaction of norbomadiene (140) with (S)-(-)-p-tolyl vinyl sulfoxide (141), which yielded deltacyclane (142), has been reported (Scheme 38).85 A high degree of stereoselectivity was observed, with mainly the exo-product being formed. 

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 Diels-Alder reactions of a variety of acyclic chiral vinyl sulfoxide dienophiles, bearing additional electron-withdrawing groups at the double bond, have been investigated (Fig. 6). The asymmetric Diels-Alder reaction of enantiopure (5)-benzyl 2-p-tolylsulfinylacrylate (167) with furan, under high pressure, afforded mainly a 2 1 mixture of endo adducts. These were then stereoselectively transformed into (+)-shikimic acid and (+)-5-epi -shikimic acid.101 However, the poor control of the endo/exo selectivity and the low reactivity were the two main problems restricting the general synthetic usefulness of such a-sulfinylacrylate dienophiles. 

Thus, the results of this comparative study clearly indicated that (1) the 7t-facial selectivity of the Diels-Alder reactions of vinyl sulfoxides must be explained by assuming a steric approach control of the diene on the less hindered face of the dienophile (that supporting the lone pair at sulfur), taking into account the relative reactivity of the retainers around the C-S bond, in addition to their populations (2) both the endo and the 7i-facial selectivities of the cycloadditions of vinylsulfox-ides with acyclic dienes are substantially higher than with cyclic ones. 

Carmen Carreno and co-workers have investigated Diels-Alder reactions of a wide variety of benzoquinone-based chiral vinyl sulfoxide dienophiles (Fig. 9). 

Ketene equivalents have found widespread use as partners in Diels-Alder reactions for the construction of cyclic, fused, and bridged unsaturated ketones. However, ketene equivalents based on simple vinyl sulfoxides are poor dienophiles and show low levels of diastereocontrol. Recently, Aggarwal and colleagues reported that (l/ ,3/ )-2-methylene-l,3-dithiolane 1,3-dioxide (187) was a highly reactive and highly selective chiral ketene equivalent.116 Diels-Alder cycloaddition of this... 

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... 

The vinyl sulfoxides have a variety of synthetic uses, including their ability to serve as Michael acceptors393 towards enolate anions and organometallics, and as moderately active dienophilies in Diels-Alder reactions.394... 

The chirality at sulfur also confers to (Z)-3-carbonylmenthoxy vinyl sulfoxides a useful topological bias which will be discussed in context with asymmetric Diels-Alder reactions (Section 4.1.6.2.1 (vi)). 

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). 

Vinylic sulfoxides have also been used in asymmetric Diels-Alder reaction.A very high dia-stereoselectivity was observed with optically active sulfmylacrylates. One example is given in Scheme 44. 

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. 

Paquette first demonstrated the reactivity of phenyl vinyl sulfoxide (36) in Diels-Alder reactions [22,23]. We used the vinyl sulfoxide as a two-carbon synthon in the syntheses of alkaloids and heterocycles. 

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