Imines with sulfenes

Thiazetidine 1,1-dioxides (-sultams) are prepared by cyclization of appropriate precursors (e.g., Scheme 20) <1975BSF(2)807> or via [Z + Z cycloaddition of imines with sulfenes 32, generated in situ from the corresponding sulfonyl chloride and an organic base (Scheme 21) . 

On the basis of these findings, the reaction of acyl imines with methanesulfony 1 chloride-triethylamine is not expected to proceed via a sulfene intermediate as previously proposed [99]. Again, a carbanion intermediate accounts nicely for the experimental facts. The electrophihcity of the hetero-l,3-diene is exdemely high, therefore the carbanion, formed on reaction of triethylamme with methanesulfonyl chloride, should undergo nucleophilic attack at C-4 of the hetero-1,3-diene faster than sulfene formabon by chloride elimination. 

Highly reactive dipoles like azomethine imines (135) form [3 + 2] cycloadducts (136) with sulfenes (Scheme 81). 

Highly reactive dipoles, such as azomethine imines, react with sulfenes in the presence of triethylamine to produce the [3 + 2] cycloadducts in good yields (equation 144) the reaction is evidently general228. 

Also, azomethine imines 28 react with sulfenes, generated from the corresponding sul-fonyl chlorides and triethylamine, to give 1,2,3-thiadiazolidines 29" . 

Alkylidene sulfenes (75), generally prepared by the dehydrohalogenation of alkylsulfonyl chlorides, add readily to electron-rich multiple bonds. For example, with enamines, the thietane dioxide (e.g., 76) is formed diazoalkanes yield thiirane dioxides (episulfones) and imines (Schiff bases) afford 1,2-thiazetidine 1,1-dioxides. There are available numerous reviews of sulfenes, including cycloaddition reactions.102... 

Sulfonyl chlorides possessing an a-hydrogen undergo elimination of hydrogen chloride when treated with bases to yield sulfenes. Like ketenes, sulfenes can undergo [2 + 2] cycloaddition to support-bound imines to yield p-sultams (Entry 5, Table 15.2). 

Cycloaddition of sulfenes to Schiff bases (e.g., 434) and carbodiimides yields 1,2-thiazetidine 1,1-dioxides and 3-imino derivatives. A concerted mechanism was suggested. An earlier report of the cycloaddition of a sulfene to a Schiff base lacked proof for the structure of the adduct. Best yields are obtained with two equivalents of imine. The cis isomers can be converted to trans by treatment with triethylamine. ... 

This transformation presumably proceeds with initial formation of allylic sulfilimine 55, which rearranges via an envelope-like transition state to sulfenamide 56 (cf. Scheme 1-XIU). Interestingly, NMR analysis showed that this [2,3]-sigmatropic rearrangement lies totally on the side of this sulfenamide, unlike the allylic suUbxide-sulfenate ester system, which lies predominantly to the side of the sulfoxide. Similarly, C-3 epimeric dihydrothiazine imine 58 can be converted by an identical pathway to E-erythrp vicinal diamine 59 in an efficient and totally stereoselective manner [Eq. (28)]. 

Acyl sulfenes, like all sulfenes, prefer to participate as 2it components of [2 + 2] or [4 + 2] cycloadditions (Chapter 5). Nonetheless, a range of [4 + 2] cycloaddition reactions of acyl sulfenes have been described46,47 (Scheme 8-XII), including their 4n- participation in dimerization reactions46-48 and reactions with imines,49 carbodiimides,50 ketenimines,51 1-azirines,52 vinyl ethers,53 and ketenes.47 The reactions often provide mixtures of [4 + 2] and [2 + 2] cycloadducts, and the observed course of the reaction usually depends on the reaction conditions. Consequently, many of the observed [4 + 2] cycloadditions of acyl sulfenes proceed by a stepwise, polar addition-cyclization reaction. 

Heteroatom Oxidation Drugs and other chemicals that contain heteroatoms (mostly N and S) with hydrogen attached form the corresponding hydroxylamines and sulfenic acids. This oxidation is most commonly observed when the heteroatom is eonnected to an aromatic ring. Tertiary amines or heteroaromatic amines and sulfur ethers form N-oxides and sulfoxides, respectively, whereas imines ean form oximes or nitrones. 

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