Sulfenamide oxidation

Scheme 13.8 Synthesis of carbonic anhydrase inhibitors via sulfenamide oxidation.

In the absence of zinc oxide, cross-linking proceeds through an accelerator polysulfide. With TBSI (14) and other sulfenamides, the accelerator decomposes upon heating during the induction period (before cross-linking) as shown in Figure 2 (13). 

In Scheme 36 the preparation of a 6-suIfeniminopenicillanate was shown. This could be converted directly to the 6a-methoxypenicillanate as shown in Scheme 44. Alternately, the 6-sulfenimino derivative may be generated from the 6/3-sulfenamide by Mn02 oxidation, followed by introduction of the 6a-methoxy group with LiOMe (79CPB2718). 

Six categories of 7V-hetero atom derivatives are considered N-M (M = boron, copper), N-N (e.g., N-nitro, A-nitroso), N-oxides (used to protect teriary amines), N-P (e.g., phosphinamides, phosphonamides), N-SiR3 (R = CH3), and N-S (e.g., sulfonamides, sulfenamides). 

Sulfenamides arc usually oxidized to sulfonamides tns(tnfluorotnetliane-sulfenyl) and bis(tnfluoromethanesulfenyl)arnineare converted to the corresponding sulfonamides by sodium hypochlorite at 20 tor 3 h m 61 and 92% yield, respecbvely [111] Oxidation of pentafluorobenzenesulfendimde by manganese dioxide yields a sulfinamide intermediate that can be trapped [772] (equabon 102)... 

In the key step, oxidation with permanganate in acetone leads from the sulfenamide to the sulfonamide. There is thus obtained ethoxysolamide (73). ... 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

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]. 

Sulfenamides. Sulfenamides (4) are often produced by oxidizing an equimolar mixture of MBT and an aliphatic amine. Alternatively, the TV-chl oroamine can react with the sodium salt of MBT. One sulfenamide, OTOS (J), uses a thiocarbamyl functionality in place of the benzothiazole group. 

The above sulfenamide derivative (9.88 g, 26.7 mmol) in CH2C12 (50 mL) was oxidized with a soln of MCPBA (5.41 g, 26.7 mmol) in CH2C12 (50 mL) at 0°C for 40 min then the soln was washed with 5% NaHC03. The organic layer was separated, dried, and the solvent removed to give an oil (7.438 g, 73%). The sulfinamide diastereoisomers were separated by column chromatography (silica gel, EtOAc/light petroleum ether 1 1). 

Early reports of an Movl-Cys complex have been shown to be erroneous because redox occurs to give the Mov complex [Mo2 03 (CysO)4]4 and cystine further electrochemical reduction to Mom is also possible. Oxidation of Cys coordinated to Co111 can give a sulfinic acid or a sulfenamide, according to the reagents and conditions used. 

In the case of the oxidation of methyl alkyl sulfides, enantioselectivity remains in the range of 50-60% ee (Table 6C.2). Disufides R-S-S-R, sulfenamides R-S-NR 2, and sulfenates R-S-O-R were oxidized to the corresponding chiral thiosulfinates, sulfinamides, and sulfinates, respectively (<52% ee, Table 6C.3) [21]. 

The hydrolysis of a series of spiro-/4-sulfanes such as (330)-(332) leads to sulfoxides in dioxane-water solutions. A mechanism involving slow nucleophilic attack of water on the positively polarized sulfur atom and simultaneous 0—H and S—N bond cleavage is proposed.298 The photo-oxidation of the sulfenamides (333 R = Me, Et, Ph, Bn, etc.) has been reported.299... 

Fu X, Mueller DM, Heinecke JW (2002) Generation of Intramolecular and Intermolecular Sulfenamides, Sulfinamides, and Sulfonamides by Hypochlorous Acid A Potential Pathway for Oxidative Cross-Linking of Low-Density Lipoprotein by Myeloperoxidase. Biochemistry 41 1293... 

Their synthesis can also be carried out as a two-phase electrolysis, using ammonium salts 326). Sulfenamides can be produced by oxidizing tetraalkylthiuram disulfides in the presence of amines 321 ... 

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