Sulfene, reaction with enamines

Only a few papers on the formation of compounds with small rings have been published. One example is the [2 + 2]-cycloaddition of electron-rich enamines to Schiff bases under high pressure (1.4 GPa) (87JOC365). The reaction leads to substituted azetidines (1). Four-membered ring heterocycles, thietane derivatives (4), are formed by interaction of sulfene (2) with enamines (3) (86CB257 93JOC3429). 

The aromatic sulfonyl chlorides which have no a-hydrogen and thus cannot form sulfenes give acylic sulfones. Thus 1-piperidinopropene on reaction with benzene sulfonyl chloride (9J) gave 2-benzenesulfonyl-l-piperidinopropene (153). Similarly the enamine (28) reacts with p-toluene-sulfonyl chloride to give the 2-p-toluenesulfonylcyclohexanone (154) on hydrolysis (/OS). 

The reaction of enamines with ketene (146) and sulfene (147) are presumed to proceed by a two-step process involving an iminium intermediate such as 99. In fact, reaction with all electrophilic olefins such as acrylonitrile and related reagents could be thought of as going through an iminium intermediate similar to 99. Another example is given by addition to an enamine... 

This is illustrated by the reaction of enamine, 113 with sulfene to produce adduct 114 in an 80 % yield (146). The product 114 was also observed in an 18% yield from the reaction of diazomethane, sulfur dioxide, and enamine 113 (153). It was demonstrated that this cyclization reaction must involve sulfene adding to the enamine directly and not acylation of the enamine by... 

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). 

Vinyl ethers undergo many cycloaddition reactions similar to those which take place with enamines. In general, however, these cycloaddition reactions with vinyl ethers take place less readily than those with enamines. These reactions include cycloaddition of vinyl ethers with ketene (200-205), phenyl isocyanate (206), sulfene (207,208), methyl acrylate (209), diethyl acetylenedicarboxylate (210), and diphenylnitrilimine (183). 

The preparation and investigation of the thietane oxide system (5a) is largely associated with stereochemical and conformational studies . The investigation of the thietane dioxides (5b) is substantially related to the chemistry of sulfenes , the [2 -I- 2] cycloaddition of which with enamines is probably the method of choice for the synthesis of 5b . The study of the thiete dioxide system (6) evolved, at least in part, from the recognition that the unstable thiete system 183 can be uniquely stabilized when the sulfur in the system is transformed into the corresponding sulfone , and that the thiete dioxide system is very useful in cycloadditions and thermolytic reactions. The main interest in the dithietane oxides and dioxides (7) appears to lie in the synthetic challenge associated with their preparation, as well as in their unique structural features and chemical behavior under thermolytic conditions . ... 

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... 

One of the most widely applied cycloaddition techniques for the preparation of thietanes is the reaction of sulfenes with enamines. The stereochemistry of these reactions has been extensively investigated by Truce and Rach. Whether the mechanism is a two-step or a concerted process, both in accordance with the stereoselective formation of the cis form in Scheme 1, is still unresolved. The special orientation of the 1,4-dipolar intermediate 64, in which the charged phenyl and dimethylamino moieties are in proximity, enforces the cis geometry of the resulting thietane dioxide. In the concerted mode of reaction, formation of the orthogonal oriented unsaturated system, 65 should also yield the cis cycloadduct. 

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. 

Tris(organoamino)boranes have been utilized to prepare, in reasonable yields,4,5 mono- and dihalo(organoamino)boranes which are often difficult to obtain by direct amination of the boron trihalides. Carboxylic acids, 1,3-diketones, ketones, and /3-ketoesters have been converted into carboxamides, enamino-ketones, enamines, and j -enamino-amides, respectively, by reaction with an appropriate tris(organoamino)borane under very mild conditions.6 Sulfenamides (R2NSC6H5) have also been prepared in high yield from selected tris(organoamino)boranes and sulfenic esters under relatively mild conditions.7... 

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 . ... 

AAAcylimines, e.g., 4, are the most widely recognized and the most extensively investigated hetero-2-azadiene system capable of participation in Diels-Alder reactions, and comprehensive reviews have been published.7,71 In general, substituents X and Y are strongly electron-withdrawing groups and consequently the AAacylimines participate as electron-deficient partners in cycloaddition reactions with electron-rich dienophiles. Diels-Alder reactions of electron-deficient /V-acylimines with vinyl ethers, enamines, olefins, sulfenes, acetylenes, and the carbon-carbon or carbon-oxygen double bond of ketenes have been detailed.57 71 This 47t participation of electron-deficient AAacylimines does complement the ability of many simple AAacylimines to behave as 2ir dienophile components in Diels-Alder reactions with typical electron-rich dienes.6... 

The cycloaddition reaction of sulfenes to numerous electron-rich alkenes is a general reaction. In this respect sulfenes are very similar to ketenes. An example is the reaction of sulfenes with enamines to give aminothietane sulfones 8. 

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. 

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. 

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. ... 

The reaction of methanesulfonyl chloride with cyclohexanone enamine in the presence of a proton acceptor produced a four-membered cyclic aminosulfone (equation 64). Stork and Borowitz36 suggested sulfene formation as the first step of this reaction. 

Opitz1 has pointed out that if the sulfene-enamine reaction is concerted it should be stereospecific, and if it is stepwise then stereospecificity would be observed only if the intermediate is very short-lived. The reaction of sulfene with trans-N-( 1-propenyl)-morpholine gave one product but the ds-enamine gave both stereoisomers. No definite conclusion can be drawn from these results, however, as cis-trans isomerization of enamines prior to sulfene addition cannot be ruled out1. 

Paquette72 has described experiments designed to assess the stereoselectivity of the sulfene-enamine reaction. He found that sulfenes reacted stereoselectively with bicyclic enamines giving a single product, where the sulfene attacks the bicyclic enamine from exo side in most of the cases. Stephen and Marcus190 further supported this result when they... 

---