Alkyl sulfenyl ester

The suggestion has been made that the entire system is a reversible one up to the point of Hg mercaptide formation. The equilibrium would be very far on the left for the first reaction, being drawn over by the two succeeding ones. The first reaction is at least formally a hydrolysis followed by a dismutation of the extremely unstable and as yet totally unknown aliphatic sulfenic acid or sulfenate ion. It is perhaps of interest to note that from Table I it is possible to estimate that the dialkyl sulfoxide, which is isomeric with an alkyl sulfenyl ester, is unstable to the dismutation reaction by about 30 Kcal. 

A variation effects alkylation and transposition of the carbonyl group. For example, methyllithium adds to the sulfenylated ester (12) to give (13). Dehydration, isomerization, and hydrolysis leads to (16). ... 

The amino group can be protected by forming its sulfonyl [such as arylsulfonyl or 2-(trimethylsilyl) ethyl sulfonyl], sulfenyl and silyl derivatives. The 2- or 4-nitrophenylsul-fonamide derivatives of amino acids are useful substrates for mono-N-alkylation using only cesium carbonate (CS2CO3) as the base. The sulfonamide group can be removed in 1.89 by potassium phenyl thiolate (PhSH and K2CO3) in acetonitrile to give the N-alkylated a-amino esters 1.90 and the reaction occurs without racemization. 

A variety of sulfur compounds are converted directly to sulfonyl halides by the action of bromine or chlorine water. The list includes mer-captans, sulfides, disulfides, thiol esters, thiocyanates, alkyl xanthates, and S-alkylthiouronium salts. Chlorination of the thiouronium salts sometimes leads to highly explosive products. Most of the reactions occur at low temperatures and give excellent yields of sulfonyl chlorides. The corresponding bromides are formed in somewhat lower yields (36-67%). Under anhydrous conditions halogenation of disulfides gives sulfenyl halides, viz., RSSR + Xj — 2RSX. 

An illustration of this approach may be seen in the studies on streptococcal proteinase (Liu 1967). The activity of this enzyme is dependent upon the presence of a free sulfhydryl group. The active form of the enzyme was first converted to the inactive S-sulfenyl-sulfonate derivative. Treatment of this derivative with a chemically-reactive substrate "analogue, a-N-bromoacetylarginine methyl ester, resulted in the alkylation of a single histidine residue. The sulfhydryl group of the modified enzyme was regenerated by reduction, however, this did not restore enzymatic activity, thus providing presumptive evidence for the involvement of both a cysteinyl and a histidyl residue in the active site of this enzyme. 

The intermediate a-sulfenyl carbonyl compounds may be alkylated prior to oxidative elimination. Phe-nylsulfenylation of the cw-fused butyrolactone (61), followed by methylation and oxidative elimination, gave the a-methylenebutyroiactone (62) because endocyclic elimination is stericaliy inhibited (Scheme 6). For the tran -fused butyrolactone (63), the alkylation was carried out first to ensure exocyclic elimination (Scheme 1). The intermediate a-sulfinylcarbonyl compounds may also be modified before elimination, the alkylation of keto sulfoxides (64) providing a useful synthesis of a,p-unsaturated -y-keto esters (65 Scheme In some cases the use of an excess of strong base provides a dimetaliated... 

More conveniently, 2-(methylthio)alkanoic esters are prepared from 2-acetylalkanoates (eq 2)] MeSSMe cannot replace MeSS02Me as the sulfenylating agent in this transformation. Advantages of these methods over others such as sulfenylation of an alkanoic acid and its ester or alkylation of (methylthio)acetic acid are (1) simplicity of the procedure (2) efficiency and convenience of using inexpensive base (EtONa) and EtOH as solvent with high product yields and (3) no bissulfenylation. Moreover, the latter... 

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