Gem-Disulfides

The reaction of thioacetals with two equivalents of peroxy acids generally affords epimeric gem-disulfoxides, the ratio of epimers being subject to kinetic and/or equilibrium control (70). However, Poje, Sikirica, Vickovic, and Bruvo (71) have reported the first example of a stereospecific oxidation in the gem-disulfide series. They found that 2,2-bis(methylthio)-l,3-diphe-nylpropane is smoothly oxidized to the corresponding meso-disulfoxide with m-chloroperbenzoic acid. The study of conformational properties in solution by nmr indicated that the meso-disulfoxide exists in conformation 119 which... 

Pot-pourri 323 is the same as that found in the solid state by X-ray analysis. The above authors have suggested that the configuration and conformation of meso-disulfoxide 119 is the result of a stereospecific oxidation of conformation 118 of the gem-disulfide. They have further suggested that this particular stereochemical course cannot be explained by steric effects it must have an electronic origin. 

Reduction of the vinylic gem-disulfide (XIV) in the presence of CO2 yields the carboxylated compound (XV) [130] described as an addition-elimination ECEC reaction. 

Another example for gem-functionalization is demonstrated in the reaction with disulfides. The tandem sulfenylation and carbonylation to 1-alkylthiocy-clopropanecarbothioates 168 are realized, indicating that disulfides can serve both as nucleophiles and electrophiles [81], (Scheme 63)... 

Figure 16.5 A catch-and-release ICAT design incorporates a gem-methyl group and an isopropyl group on either side of a disulfide bond within its spacer arm. The hindered disulfide permits the use of standard reducing gel electrophoresis conditions using DTT without reduction. After purification on a (strept)avidin affinity column, however, the disulfide group can be cleaved with TCEP, which provides recovery of the labeled peptides prior to mass spec separation.

The l3C chemical shifts of methyl derivatives with sulfur substituents [e.g., SH, -S, -SCH3, -SSCH3, -SSSCHj, -S(0)CH3, -S02CH3, -S(CH3)2+, -SC(0)CH3, -SC(S)CH3, and -SC(S)SCH3] (130,131) and of vicinal and gem-inal bis-sulfides (290) have been reported. Freeman and co-workers have published similar studies on thiols, sulfides, disulfides, and sulfinic and sulfonic acid derivatives (131,132,433) and Tseng and Bowler (434), on thiocarbamates, their S-oxides and S,5-dioxides [R-X-C(0)-NR 2 with X = S, SO, S02]. 

Active methylene compounds with carbon disulfide and base form reactive salts which undergo [3 +1] additions to a variety of alkylating agents, even gem-dihaloethylenes (Scheme 29) (77CC207, 80S907). The salts can be oxidized to symmetrical desaurin derivatives (Scheme 30) (62CB2861). 

The reaction of carbon disulfide with a-functional phosphonates [(Rl0)2P(0)CH2X] in the presence of bases gives di-thiolates which, on treatment with gem-dihalides (R2CHBr2), yield (46) (94MI409). 1,3-Dithietanes (47) on reaction with hydrazides (RCONHNH2) yield the 1,3,4-oxadiazoles (48) (94H185,... 

Gem-dibromocyclopropanes can be converted into synthetically useful cyclopropanone equivalents by a process consisting of lithium-halogen exchange followed by reaction of lithiocyclopropane (113) with dimethyl disulfide (Scheme 43) . The resulting bromo-methylthio derivative (114) undergoes a variety of substitution reactions. Methanolysis gives S,0-dimethylketal (115) which can be converted into l,l bis(methyl-thio)cyclopropane (116) with methyl mercaptan in trifluoroacetic acid. Reaction of 114 with other nucleophiles provides the derivatives shown in Scheme 44 . The sulfur-... 

The process scheme (Fig. 12.7-7) starts from the N-protected dipeptide dimer [l-lys-L-homocys]2 disulfide which, after reduction of the S - S bond, is oxidized enzymatically to N-Cbz-L-homo-cys-L-lys-e-aldehyde. Under acidic conditions, the aldehyde group is present as a gem-diol, attacks the a-N and closes the ring to the aminol. After nucleophilic attack of the S - H group, the hydroxyl group acts as a leaving group and affords closure of the 1,3-thiazepine ring. 

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