Mechanism Moffatt oxidation

Scheme 8.6 Proposed mechanism for Swern-Moffatt oxidation using TFAA...

A mechanism suggested for Swern-Moffatt oxidation with TFAA is shown in Scheme 8.6. In the first step, DMSO reacts with TFAA to form cationic reactive species I, which is known to be stable only below —At higher temperatures, rearrangement of I takes place to give species II. The reaction of II with an alcohol IQ upon treatment with a base leads to formation of a major by-product, trifluoroacetic acid (TFA) ester VII. Therefore, the first step should be carried out below —50 °C. In the second step, reactive species I is allowed to react with an alcohol HI at or below —50°C to obtain intermediate IV. IV may also undergo the Pummerer rearrangement to give a methyl thiomethyl (MTM) ether VI upon treatment with a base. In the third step, IV is treated with a base (usually triethylamine) to obtain the desired carbonyl compound V and dimethyl sulfide. 

Displayed below is the mechanism for Pfitzner-Moffatt oxidation in the presence of both an acid and base. 

Dimethyl Sulfoxide and elimination by base (eq 3), a mechanism closely related to that of the Swem and Moffatt oxidations. ... 

A look at the mechanism (page 98) shows that DCC—in order to be attacked by DMSO needs to be activated by protonation. On the other hand, the reaction fails in the presence of a strong acid, such as HC1, H2SO4 or HCIO4, because these would prevent the formation of the sulfur ylide.11 Moffatt et al. found that the oxidation of testosterone (14) succeeds using mild acids with pKa inside a narrow window.14a For example, no oxidation occurs with acetic acid (pKa = 4.76) or trichloroacetic acid (pKa = 0.66), because their pKas lay outside the acidity window, while monochloroacetic acid (pKa = 2.86) leads to a slow and incomplete reaction, and dichloroacetic acid (pKa = 1.25) produces a quantitative oxidation in ten minutes. 

Moffatt, J. G. Sulfoxide-carbodiimide reactions. X. Mechanism of the oxidation reaction. J. Org. Chem. 1971, 36,1909-1913. 

Pfltzner and Moffatt report the interesting finding that an equatorial 11 a-hydroxy-steroid is oxidized readily by the DMSO-DCC combination whereas the 11 /3-epimer is inert under the same conditions. The situation is thus the reverse of that found in chromic acid oxidation (Eschenmoser). The authors offer an explanation based on a suggested mechanism for the oxidation. 

Sulfoxides (essentially DMSO) can be used for oxidation of alcohols to carbonyl compounds as in the Moffatt, Swern and related oxidations [237, 238]. These mild and useful processes proceed through an oxosulfonium salt. In the Pfitzner-Moffatt procedure the alcohol is treated with DMSO, DCC and anhydrous phosphoric acid. The proposed mechanism involves an alkylsulfonium ylide as an intermediate. 

The original Pfittner-Moffatt procedure for alcohol oxidation by activated dimethyl sulfoxide utilized dicyclohexylcarbodiimide (DCC) and a source of protons such as polyphosphoric acid or pyridinium tri-fluoroacetate. The use of strong acids such as the common mineral acids must be avoided since, although acidic conditions are initially required, the reaction must readily become basic in the later stages of the process. Mechanistically it is reasonable to suggest that the activation follows the pattern whereby initial attack of the nucleophilic sulfinyl oxygen of dimethyl sulfoxide, with the protonated carbodiimide, forms a sulfonium isourea. This is followed by displacement of dicyclohexylurea by the alcohol to form an alkoxysulfonium salt. Base treatment of this salt forms an ylide, which collapses via the proven cyclic mechanism to the carbonyl compound and dimethyl sulfide (Scheme 4). 

Claus and Yycudilik have reported the details of the dehydration reaction catalysed by phosphorus pentoxide between DMSO and aryl amines to afford iminosulphuranes in good yield. Lerch and Moffatt have reported that the DMSO-DCC oxidation reaction could be applied to iminosulphurane synthesis simply by the addition of an aryl amine to the reaction mixture rather than the usual alcohol. In both instances the mechanism probably involved displacement from sulphur by the amine of an oxy-leaving group (a pyrophosphate or a urea). The latter workers found that hydrazines could not be used in the place of the aryl amine, probably because of subsequent intramolecular eliminations by the iminosulphuranes. 

---