Sulfoxides 4+2 cycloadditions

For references see Williams, R. V. Lin, X. New ketene equivalents for the Diels-Alder reaction. Vinyl sulfoxide cycloaddition. /. Chem. Soc., Chem. Commun. 1989, 1872-1873. Ruden, R. Bonjouklian, R. Cycloaddition of vinyl triphenyl-phosphonium bromide. New synthesis of cyclic phosphonium salts. Tetmhedron Lett. 1974, 15, 2095-2098. Ranganathan, S. Ranganathan, D. Mehrotra, A. K. Nitroethylene as a versatile ketene equivalent. Novel one-step preparation of prostaglandin intermediates by reduction and abnormal Nef reaction. J. Am. Chem. Soc. 1974, 96, 5261-5262. Kozikowski, A. P. Floyd, W. S. Kuniak, M. P. 1,3-Diethoxycarbonylallene an active dienophile and ethoxycar-bonylketene equivalent in the synthesis of antibiotic C-nucleosides. J. Chem. Soc., Chem. Commun. 1977, 582-583. 

As formal a, /i-unsaturated sulfones and sulfoxides, respectively, both thiirene dioxides (19) and thiirene oxides (18) should be capable, in principle, of undergoing cycloaddition reactions with either electron-rich olefins or serving as electrophilic dipolarophiles in 2 + 3 cycloadditions. The ultimate products in such cycloadditions are expected to be a consequence of rearrangements of the initially formed cycloadducts, and/or loss of sulfur dioxide (or sulfur monoxide) following the cycloaddition step, depending on the particular reaction conditions. The relative ease of the cycloaddition should provide some indication concerning the extent of the aromaticity in these systems2. 

Two attractive routes to thiolene oxide and dioxide are the diene-SO104 and diene-S02298 cycloadditions, respectively. These cycloadditions are highly stereoselective at both carbons of the diene systems and at sulfur (see equation 62 for specifics) which, in the case of sulfoxide formation, proceed via attack of triplet SO on the diene. Equation 112 shows an example of such a cycloaddition104. The overall yields are significantly improved by running the cycloadditions in the absence of oxygen and by the use of excess diene. 

Since sulfoxides and sulfones are versatile synthetic intermediates, and since in both the thiolene oxide and dioxides the reverse dethionylation114 ( — SO), and cheletropic extrusion of sulfur dioxide296, respectively, readily take place thermally, these cycloadditions are expected to find a useful place in organic synthesis. It should be kept in mind, however, that the retrograde SO-diene reaction and interconversion of the thiolene oxides compete effectively against SO extrusion on heating, and that diene isomerization accompanies the forward reaction (SO + diene). 

Crystallization to obtain the major diastereomer in pure form is possible in some cases. These hydrogen-bonded vinylic sulfoxides undergo asymmetric 2 + 4-cycloaddition reactions with 1,3-cyclopentadiene (see p. 845). 

The enantiomerically pure, doubly activated a, /j-olefinic sulfoxides 46-5095 98 undergo highly diastereoselective Diels-Alder cycloadditions with cyclopentadiene, and pyridyl vinylic sulfoxide 5199 reacts diastereoselectively with furan. It is noteworthy that olefins singly-activated by only a sulfinyl group are not effective partners in Diels-Alder cycloadditions, as we have found after many attempts and as has been reported recently98. 

Racemic pyrone sulfoxide 52 undergoes a diastereoselective inverse-electron-demand 2 + 4-cycloaddition with 1,1-dimethoxyethylene to afford adduct 53 in > 95% yield (equation 49)100 this is the first example of an asymmetric Diels-Alder cycloaddition using a sulfinyldiene as an electron-deficient enophile101. 

Cycloaddition of nitrones and of nitrile oxides to a, /J-ethylenic sulfoxides have been recorded102. 

Enantiomers (M)- and (P)-helicenebisquinones [32] 93 have been synthesized by high pressure Diels-Alder reaction of homochiral (+)-(2-p-tolylsulfo-nyl)-l,4-benzoquinone (94) in excess with dienes 95 and 96 prepared from the common precursor 97 (Scheme 5.9). The approach is based on the tandem [4 + 2] cycloaddition/pyrolitic sulfoxide elimination as a general one-pot strategy to enantiomerically enriched polycyclic dihydroquinones. Whereas the formation of (M)-helicene is explained by the endo approach of the arylethene toward the less encumbered face of the quinone, the formation of its enantiomeric (P)-form can be the result of an unfavourable interaction between the OMe group of approaching arylethene and the sulfinyl oxygen of 94. 

Heating of bis(trimethylsilylmethyl)sulfoxide 1166 generates HMDSO 7 and, via 1167, the reactive intermediate thioformaldehyde-S-methyhde 1168, which can be trapped in situ, e.g. by N-methylmaleimide, to give 81% of the l,3-dipolar cycloaddition product 1169 [14] (Scheme 8.3). Further analogous 1,3-dipolar cycloadditions with acetylenes are discussed elsewhere [15]. 

To control the stereochemistry of 1,3-dipolar cycloaddition reactions, chiral auxiliaries are introduced into either the dipole-part or dipolarophile. A recent monograph covers this topic extensively 70 therefore, only typical examples are presented here. Alkenes employed in asymmetric 1,3-cycloaddition can be divided into three main groups (1) chiral allylic alcohols, (2) chiral amines, and (3) chiral vinyl sulfoxides or vinylphosphine oxides.63c... 

Pummerer-type dehydration of the sulfoxide 408 using acetic anhydride results in efficient formation of the 1,3-dipolar compound 409 which is able to undergo cycloaddition with dienophiles to generate tricyclic compounds such as 410 in good yield (Scheme 31) <2000T10011>. 

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