Cycloaddition with sulfenes

Dienamines undergo 1,4 cycloaddition with sulfenes as well as 1,2 cycloaddition. For example, l-(N,N-diethylamino)butadiene (111), when treated with sulfene (generated from methanesulfonyl chloride and triethyl-amine), produces 1,4 cycloadduct 116 in an 18 % yield and di-1,2-cycloadduct 117 in a 60 % yield (160). Cycloadduct 116 was shown not to be the precursor for 117 by treating 116 with excess sulfene and recovering the starting material unchanged (160). This reaction probably takes place by way of zwitterion 115, which can close in either a 1,4 or 3,4 manner to form cycloadducts 116 and 118, respectively. The 3,4 cycloaddition would then be followed by a 1,2 cycloaddition of a second mole of sulfene to form 117. Cycloadduct 117 must form in the 3,4 cycloaddition followed by a 1,2-cycloaddition sequence rather than the reverse sequence since sulfenes undergo cycloaddition only in the presence of an electron-rich olefinic center (159). Such a center is present as an enamine in 118, but it is not present in 119. 

Enaminoketones undergo 1,4 cycloadditions with sulfene (162a). This is illustrated by the reaction of enamine 120 with sulfene to form sulfone 121 in an 80 % yield (162,163). 

Heterocycles. Sulfene, generated by the treatment of methanesulfonyl chloride with base, undergoes [2 + 2], [3 + 2], and [4 + 2] cycloadditions to produce four-, five-, and six-membered heterocycles, respectively. Alkynyl amines and enamines both undergo [2 + 2] cycloadditions with sulfene to produce four-membered cyclic sulfones (eqs 19 and 20). 

Stable sulfenes have been isolated by treating methanesulfonyl chloride, with triethylamine or trimethylamine in acetonitrile solvent at -40°C (165,166). These stable sulfenes undergo 1,2 cycloaddition with enamines to form the expected thietanes (trimethylenesulfones). 

Simple unsaturated sulfides cannot be used in place of enamines in cycloaddition reactions with sulfines leading to thietane dioxide derivatives. " Alkyl, vinyl, and cycloalkylvinyl sulfides, which carry a C=C double bond, are considerably less nucleophilic than the enamines and thus do not partake in cycloadditions to sulfene. But when the more electrophilic methylsulfonyl sulfene is used in association with an unsaturated sulfide substituted with a strong electron donating alkylamino group, the formation of thietane dioxides 72 is successful. 

An interesting variation to cycloadditions involving sulfenes is a reaction carried out with a-amino ketoximes, by which thietane dioxides are produced. The authors suggested a two-step mechanism via the intermediate cyanoenamine 83. Higher yields were obtained when the oximes were... 

Cycloaddition of ynamines with sulfenes (generated from sulfonyl chlorides) to give thiete sulfones 132 and 133 has been reported by Truce et (Eq. 21). Acid hydrolysis yields the corresponding enols (134). Other compounds that have been prepared in this manner are 135 and 136. Sulfene... 

Sulfenes are reactive 27r-components in cycloaddition reactions and treatment of methanesulfonyl chloride with triethylamine in the presence of (CF3)2C=NCOPh gives the 1,2,5-oxathiazine (119) via a formal [4+2] cycloaddition of sulfene to the heterodiene (69IZV2059). 

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) . 

Both [2 + 2] and [4 + 2] cycloadditions have been observed in the reaction of dienamines with sulfenes. For example, reaction of cross-conjugated dienamine 202 with sulfene afforded a mixture of 203 and 204 (equation 44)111. Also, enamines of 1-tetralone (205, 206) can react as enamines or as aminodienes with phenylsulphene giving 207-209 (equation 45)112. 

In addition to 4-alkenylthiazoles 104, A-methylenethiazol-2-amine derivatives are also utilized in the Diels-Alder reactions with sulfene 112 <07JCR127>. Cycloaddition of (E)-N-benzylidene-4-phenylthiazol-2-amines 111 with sulfene 112, generated in situ from methanesulfonyl chloride in the presence of triethyl amine, provides a mixture of regioisomers 113 and 114 in moderate yields. 

Sulfenes have received little attention to date as dienophiles. These reactive species undergo [4 + 2] cycloadditions with certain dienes upon occasion, but [2 + 2] cycloadditions and electrophilic reactions are also common (c/. Scheme 25). In addition, the mode of reaction of a sulfene may depend upon its method of formation. 

The exocyclic double bond in thiete sulfone 276 may be isomerized to the endo-cyclic position by treatment with potassium hydroxide. Hydroxide ion also effects ring-opening of thiete sulfones (see Section D) so that it is not a general reagent for isomerizations of the double bond. Cycloadditions of sulfenes to... 

Thietanone 1,1-dioxide ketals and 3-aminothiete 1,1-dioxides are readily available by cycloaddition of sulfenes to ketene acetals and enamines, respectively (Section V.3.B.). Hydrolysis of these ketals " and the aminothiete sulfones (which are enamines) " " gives 3-thietanone 1,1-dioxides in fair to good yields, as exemplified by the hydrolysis of 133 and 402. Aqueous mineral acids or acidic ion-exchange resins catalyze the reaction. Cis-2-chloro-2,4,4-trimethyl-3-morpholinothietane 1,1-dioxide reacts with N sodium hydroxide to give 38% 2,2,4-trimethyl-3-thietanone 1,1-dioxide, but the trans isomer is recovered unchanged. 3-Methoxy- and 3-ethoxythiete 1,1-dioxide (enol ethers) are also hydrolyzed to 3-thietanone 1,1-dioxide. In several cases, the hydrolysis products are written as enols of the 3-thietanone sulfone. ... 

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. ... 

Phenylsulfene (98) was later shown to add to Schiff bases (123) to give a mixture of the cis-[2+2] cycloadduct (124) and the trans-[2+2] cycloadduct (125) (Scheme 76). The predominant formation of the cis-product (124) may indicate the operation of a concerted [2 + 2] cycloaddition mechanism. Sulfene (75) reacts with benzylideneanilines to give... 

The cycloaddition of sulfenes with enamines provides a good synthetic route to thiete 1, 1-dioxides (174) (see Chapter 7, p. 115) (Scheme 69).8 Thiete-1, 1-dioxides like (174) react with alkylamines by conjugate addition to yield the corresponding amino derivatives (175), and by heating in the presence of a reactive alkene, e.g. norborene (176), they form the [2+4] cycloadducts, e.g. (177) (Scheme 69). 

Transition metal complexes in synthesis of heterocycles 80KGS147. Tropone derivatives, cycloaddition reactions with sulfenes or ketenes... 

Sulfonyl imides(RN=S02), generated from alkylsulfamoyl chloride (RNHSOjCl) and triethylamine, react with enamines in the same way as sulfenes do, to give four-membered heterocycloadducts such as 210 Phenyl isocyanate undergoes [2 -t- 2] cycloaddition with enamines affording azetidinones (211) whereas azetidinothiones (212) have been obtained from the reaction of isothiocyanates with enamines without j8-hydrogens . ... 

The formation of 1,2,4-thiadiazine 1,1-dioxides occurs by the addition of carbonitriles to alkyl-sulfonamide dianions followed by carbonylation with phosgene or phenyl chloroformate (Section 6.14.9.2.3(h)), and by the [4-1-2] cycloaddition of 1,3-diaza-1,3-butadienes with sulfene (Section 6.14.9.2.2(iii)). 

Sulfines, although not so reactive as sulfenes, have the advantage of being able to participate in Diels-Alder reactions. Xanthenethione 5-oxide (314) and thiofluorenone 5-oxide (317) undergo [4 4- 2] cycloaddition with the diene equivalent, tetrachloro-o-benzoquinone (315), to form the 1,4,2-dioxathiane 5-oxides (316) and (318) (Scheme 47) <67RTC64l>. 

However, the C-4 substitution of the 1-oxabutadiene system with strong electron-donating substituents (—OR, —NR2) does serve to increase the nucleophilic character of the a,/3-unsaturated carbonyl compound to the extent that stepwise, addition-cyclization [4 + 2] cycloadditions, often in competition with [2 + 2] cycloadditions, with reactive electrophilic olefins, e.g., ketenes121-127 or sulfenes,127-130 have been observed and extensively investigated (Scheme 7-II). For early investigations, prior reviews should be consulted.5... 

One class of reaction evidently missing from this list is the reaction of sulfenes with electrophiles. Sulfene itself is strongly electrophilic and this class may be expected to be small. One class of reaction formally involving a sulfene and an electrophile is the cycloaddition with chloral and related carbonyl compounds. Evidence has been obtained for the importance of tertiary amines in this process and, as is discussed in Section V.B.5, it is unlikely that it is a simple reaction of a sulfene with an electrophile. The reaction of (trimethylsilyl)methanesulfonyl chloride with cesium fluoride in the presence of bromine... 

The first cycloaddition of sulfene to the C=N bond was reported by Staudinger and Pfenninger107, who showed that the reaction of diphenylsulfene, generated from diphenyldiazomethane and sulfur dioxide, gave a four-membered cyclic compound with benzylideneaniline (equation 118). 

The interaction of 4-alkyl-5-arylimino-l,2,3,4-thiatriazoline (69) and sulfenes (generated in situ from alkylsulfonyl chlorides and triethylamine82) produces sultams (72), possibly by way of the heteropentalenes (71) these isomerize above 60°C under the influence of acidic catalysts to 73, by a Dimroth rearrangement.77 The sultams (72) are themselves capable of acting as masked 1,3-dipoles, undergoing cycloaddition with heterocumulenes, with elimination of the sulfene moiety. Thus reaction of 72 with phenyl isocyanate produces the 1,2,4-thiadiazolidine (70), also directly accessible from 69 by Path A.83... 

Danishefsky and coworkers have used the racemic P-phenylsulfinyl-a,P-unsaturated ketone (160) as an a,P-ethynyl carbonyl synthetic equivalent and found that the phenylsulflnyl group did not compete with the carbonyl group in determining the regioselectivity of cycloaddition with the l-methoxy-3-trimethylsilyloxy-1,3-butadiene (161), now known as Danishefsky s diene [140] (Scheme 5.54). Loss of methanol and phenyl sulfenic acid from the initial cycloadduct (162) gave the aromatic product (163). 

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