Sulfoxides sulfenic acid elimination

Sulfoxides containing P-hydiogen atoms, eg, di-Abutylsulfoxide [2211 -92-9] react with strongly basic systems, eg, potassium /-butoxide, in DMSO by sulfenic acid elimination to produce olefins (eq.l2) (44) ... 

The thermolysis of acyclic- and/or six- and larger ring sulfoxides to yield olefins and sulfenic acids is well documented . The formation of allylic sulfenic acids and thiosulfinates in the thermolysis of thiirane oxides containing hydrogen on the a-carbon of the ring substituent (which is syn to the S—O bond) has been discussed previously in terms of /i-elimination of hydrogen, which is facilitated by relief of strain in the three-membered ring (Section llI.C.l). 

A range of other sulfur(IV) and (VI) derivatives formally obtained by the oxidation of thioglycosides have been prepared, but they are apparently not employed to date in O-glycosylation reactions. These include glycosyl sulfenamides and sulfonamides, as well as sulfinates and sulfonates [289]. S-Glycosyl sulfenic acids have been prepared as transients by the syn-elimination of S-(2-cyanoethyl) glycosyl sulfoxides [311]. 

In recent years, besides the thermolysis of sulfoxides, several other E,-type eliminations have been discovered that also result in the generation of sulfenic acids. Block (1972a) showed that alkyl thiolsulfinates rather easily undergo thermolysis in the manner shown in (7) to generate sulfenic acids. These could... 

Taking advantage of a tandem sulfoxide elimination-sulfenic acid addition approach to cyclic sulfoxides <1977J(P1)1574>, the synthesis of a number of novel 1,4-oxathiane oxides 229 and 230 based on the intramolecular addition of sulfenic acids to alkenes or alkynes tethered through an ether linkage has been reported (Equation 38) <20050BC404>. 

On treatment with weak base, 1,3-oxathiolane sulfoxide (80) was shown to undergo a reversible intramolecular ene reaction to sulfenic acid (81). Using stronger base, it was found that this pericyclic reaction cannot compete with elimination to enone (82), which then oxidizes or dimerizes to the observed products (83) and (84). The diastere-omeric sulfoxide (79) was found to undergo retro-ene elimination then dimerization to (85) or to (83) and (84) with even a weak base.85... 

The authors suggested a stepwise mechanism in which precomplexation of the sulfoxide to the lithium azaenolate would take place, thus allowing conjugate addition to follow. This notion was based on Posner s and Paquette s earlier work on conjugate additions of nucleophiles to 57. As before, thermal elimination of toluene sulfenic acid led to the conjugated products (not shown) in 92-93% yields for R2 = methyl.30 However, for R2 = H thermal elimination of arylsulfenic acid did not afford any dihydropyrrole product but rather led to the formation of pyrroles. Treating 58 or 59 with Raney nickel at low temperature led to the rapid formation of 60 and 61, respectively, in 82-86% yield. 

It is remarkable that elimination of sulfenic acid was not observed during the formation of unsaturated sulfinyl dithioesters. These results are now being extended to enantiopure starting materials, with diacetone glucose as a chiral source of the starting sulfoxides [203]. 

An interesting disulfide cleavage is performed with 7,7/-dithio-bis[l,3,6-trimethyllumazine] (276) in basic medium yielding the relatively stable silver 7-sulfenate (277) and thiol (278) (Scheme 44). The free 1,3-dimethyllumazine-7-sulfenic acid (279) has been prepared from 7-isopropylthio and 7-[2-(4-nitrophenyl)ethylthio]-l,3-dimethyllumazine first by oxidation to the corresponding sulfoxides (282, 283) then by a modified Cope elimination and dbu treatment, respectively (Scheme 44). 

In garlic, a simple sulfoxide elimination creates an unstable sulfenic acid. When we looked at sulfoxide eliminations before, we ignored the fate of the unstable sulfenic acid, but here it is important. It dimerizes with the formation of an S-S bond and the breaking of a weaker S-O bond. 

In onions, things start much the same way but the initial amino acid is not quite the same. The skeleton is the same as that of the garlic compound but the double bond is conjugated with the sulfoxide. Elimination and dimerization of the sulfenic acid produce an isomeric thiosulfinate. 

Early investigations by Davis and co-workers demonstrated that arylsulfinimines 39 undergo thermo-elimination to produce sulfenic acids 99, key intermediates in biological transformations, when heated for 24 h at 77-110 °C. These thermolyti-cally generated sulfenic acids can be trapped as silyl sulfenates 101 or vinyl sulfoxides 103.67-69... 

The sulfenic acids usually generated in this way are very unstable and react instantaneously with alkenes present in the reaction medium to form sulfoxides88,89. A number of reversible intramolecular cyclic eliminations of sulfenic acids from cyclic sulfoxides have been reported, for example, thiepane 1-oxide decomposes at 140 C with a half-life of ca. 28 hours to give cis-2-methyTtetrahydro-2//-thiopyran l-oxide (1), which is stable under these conditions for 6 days90. 

The addition of an allyl alcohol to racemic allenyl sulfoxides results in vinyl ethers with the sulfinyl moiety at C-1 that undergo sigmatropic rearrangements upon distillation to produce 2,4-dienones after ehmination of sulfenic acid. In one example, an isomeric vinyl ether was obtained with a sulfinyl methyl substituent at C-2 that gave rise to a sulfinyl enone upon rearrangement [138]. In related work, the addition-elimination of an allyl alkoxide to a functionalized vinyl sulfoxide results in a sulfinyl enol ether that rearranges with loss of sulfenic acid to the unsaturated ester [139-141] (Scheme 21). 

Vinyl sulfoxides mostly require a second electron-withdrawing groiq) to increase their dienophilic character. Thus vinyl sulfoxides bearing a carbonyl moiety at Cp undergo carbonyl-directed diene addition followed by a spontaneous elimination of sulfenic acid, as applied to a synthesis of disodium pre-phenate (74) (Scheme 21). ... 

The iS-oxide 400 undergoes ring-opening, presumably to the sulfenic acid 401, which cyclizes to five-membered products. The intermediate may be trapped by reaction with trimethylsilyl chloride it reacts with norbornene to give bis-norbornyl sulfoxide, probably via an elimination of 2,4-dimethyl-l,4-pentadien-3-one from an initial adduct. 

The stereochemistry of trisubstituted alkene formation was demonstrated by Kingsbury and Cram who found that the ctyr/iro-sulfoxide (37) gave mainly the ( )-alkene (38 equation 19) with the (Z)-alkene (40 equation 20) being the major product from thermolysis of the r/treo-sulfoxide (39). The rate and stereochemistry of elimination was found to be independent of solvent, and so the concerted syn elimination mechanism outlined in equation (21) was proposed. The variation of the -deuterium isotope effect with temperature is consistent with a linear hydrogen transfer, and the elimination has been found to be reversible, with sulfenic acids being trapped both inter- and intra-molecularly by addition to alkenes to give sulfoxides (Schemes 2 and... 

The temperatures required for sulfoxide elimination depend upon the stability of the alkene being formed, with temperatures in the range 50-110 °C commonly used for conjugated alkenes. Phenyl sulfoxides fragment faster than the analogous methyl sulfoxides. reaction has also been used for the generation of sulfenic acids and this will be briefly discussed in Section 5.3.3.3.3. 

Sulfenic acids also react with alkynes, and (r-butylsulfinyl)alkynes (85) eliminate 2-methylpropene on thermolysis to give the ( )-alkenyl sulfoxides (87) stereoselectively via cyclization of the intermediate sulfenic acids (86 Scheme 20)7 The stereochemistry of the adduct (87) is established by the mechanism of sulfenic acid addition. For the intermolecular trapping of sulfenic acids by alkynes, generation of the sulfenic acids by thermolysis of the corresponding 3-sulfinylpropionitrile (88 equation 35) is the preferred route. Sterically hindered sulfenic acids have also been generated by flash vacuum pyrolysis of sulfoxides and trapped intermolecularly by alkynes. ... 

The oxidation of allylic sulfides with equivalent amounts of, for example, peroxyacids or sodium per-iodide leads to allylic sulfoxides. These sulfoxides do not usually eliminate sulfenic acid to provide... 

Sulfenic acids (45) are generally quite unstable they easily dimerise and eliminate water to form thiol sulfinates (46) (Scheme 28). Several sulfenic acids have, however, been isolated and many of these are stabilised by hydrogen bonding to a carbonyl or amino group. The first sulfenic acid to be isolated was the anthraquinone derivative (47) in 1912. Sulfenic acids have been postulated as transient intermediates in many chemical and biochemical processes, e.g. the oxidation of thiol groups in proteins and the thermolysis of sulfoxides, including the acid-catalysed rearrangement of penicillin sulfoxides (48) to cephalosporins (49) (Scheme 29)... 

Sulfoxides on prolonged heating in the presence of strong bases eliminate sulfenic acids which can be trapped by the addition of activated alkenic compounds, e.g. ethyl acrylate (see Chapter 4, p. 53). Some examples are shown in Scheme 19. The thermolysis involves a -elimination as shown for the reaction of the diastereoisomeric 1,2-diphenylpropyl phenyl sulfoxide (32) to give >l,2-diphenylpropene (33) (Scheme 19). 

When (6), prepared from (1) and the anion of ethyl phenyl sulfoxide, is heated with (4), the cyclized product (7) is obtained in 35% yield. Probably benzene-sulfenic acid, produced by elimination of (6), serves as an acid catalyst for cyclization of (5) to (7). 

Pyrolysis of sulfoxides provides a convenient method for introducing unsaturation at the position a- to carbonyl compounds. Formation of the enolate and reaction with dimethyl (or diphenyl) disulfide gives the a-methylthio (or phenylthio) derivative. Oxidation with a suitable oxidant, such as mCPBA or NaI04, gives the sulfoxide, which eliminates sulfenic acid on heating to give the a,(3-unsaturated carbonyl compound. For example, the methyl ester of a pheromone of queen honey bees was synthesized from methyl 9-oxodecanoate after initial protection of the ketone as the acetal (2.24). The -isomer usually predominates in reactions... 

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