Pfitzner—Moffatt oxidation

DMSO (xs) / solvent acid (catalytic) acid pyr-HCI, pyr-TFA, CI2CCO2H, H3PO4 r3 = /-Pr, Chx 

The mechanism of the P-M oxidation consists of three distinct steps 1) activation of the DMSO by a protonated dialkyl carbodiimide 2) activation of the alcohol substrate and the formation of the key alkoxysulfonium ylide intermediate and 3) the intramolecular decomposition of the alkoxysulfonium ylide to afford the product ketone or aldehyde and the dialkyl urea by-product (established by isotopic labeling studies). The alkoxysulfonium ylide is a common intermediate in all other oxidations using activated DMSO. 

The first total synthesis of the nucleoside antibiotic herbicidin B was accomplished in the laboratory of A. Matsuda. The key step was a novel aldol-type C-glycosidation reaction promoted by Sml2 between a 1-phenylthio-2-ulose derivative and a 1- 3-D-xylosyladenine-5 -aldehyde derivative. During the preparation of the phenylthio sugar subunit, the Moffatt oxidation was applied to convert the primary alcohol to the corresponding aldehyde, which was immediately oxidized with PDC in DMF/MeOH to the methyl ester. The reaction conditions were completely compatible with the silyl protecting group as well as the thioacetal functionality. 

The Moffatt oxidation was utilized in the endgame of the total synthesis of (+)-paspalicine by A.B. Smith et al. The advanced intermediate hexacyclic homoallylic alcohol was subjected to the Moffatt oxidation conditions using pyridinium trifluoroacetate as the acid catalyst. Under these conditions, the desired p,y-unsaturated ketone and the rearranged a,p-unsaturated ketone (paspalicine) were formed in a 5 1 ratio. The final step was the Rh-catalyzed isomerization of the p,y-unsaturated ketone to the natural product. 

DCC (1.2 equiv), DMSO, benzene pyridine (4 equiv) pyridine-TFA (2 equiv) 

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Oxidation of alcohols using DCC and DMSO, also known as Pfitzner-Moffatt oxidation . 

All of the usual chromium-based oxidation reagents that have been used for the oxidation of cyclobutanols to cyclobutanones, for example, chromium(VI) oxide (Jones reagent),302 pyri-dinium chlorochromate,304 pyridinium dichromate,307 and chromium(YI) oxide/pyridine (Collins),303 are reported to do so without any serious problems. Alternatively, tetrapropylam-monium perruthenate in the presence of A-methylmorpholine A -oxide. oxalyl chloride in the presence of triethylamine in dimethyl sulfoxide (Swern),158,309,310 or phenyl dichlorophos-phate in the presence of triethylamine and dimethyl sulfoxide in dichloromethane (Pfitzner-Moffatt),308 can be used. The Pfitzner-Moffatt oxidation procedure is found to be more convenient than the Swern oxidation procedure, especially with respect to the strict temperature control that is necessary to achieve good yields in the latter, e.g. oxidation of 1 to give 2.308... 

With DMSO. provides a mild oxidizing agent (Pfitzner-Moffatt Oxidation). The reagent has been useful in forming the peptide linkage from amino acids. 

Pfitzner-Moffatt oxidation or Dess-Martin periodinane 70-72%... 

Pfitzner-Moffatt Oxidation (Carbodiimide-Mediated Moffatt Oxidation)... 

In variance with other oxidants, such as the chromium-based ones, no carbon-carbon bond breakage is observed in the Pfitzner-Moffatt oxidation of this 1,2-diol. 

The Pfitzner Moffatt oxidation is performed in the presence of a carbo-diimide that is transformed into a form of activated DMSO . As both the carbodiimide and the activated DMSO are strong electrophiles, it would seem reasonable to expect that nucleophilic sites in a molecule would interfere with the oxidation. Nevertheless, Pfitzner-Moffatt oxidations very often can be carried out in the presence of thiols,14b amines40 and amides.23c,d... 

Carboxylic acids react under Pfitzner-Moffatt conditions, resulting in the formation of methylthiomethyl esters and /V-acylureas.41 Nevertheless, although the authors are not aware of any report involving the selective oxidation of alcohols in the presence of a carboxylic acid, such outcome would be likely with carboxylic acids with little nucleophilicity, as standard Pfitzner-Moffatt oxidations are performed in the presence of trifluoroacetate that is known for not to interfere. 

Quite puzzingly, thiols are reported14b to be unreactive under Pfitzner-Moffatt conditions, while this being one of the few oxidation methods for alcohols compatible with this functionality. Sulfides also resist the action of Pfitzner-Moffatt oxidations.42,43... 

In fact, the interference of amines in Pfitzner-Moffatt oxidations very often results from the trivial fact that basic sites in a molecule can quench the acidic catalyst. In such cases, the oxidations must be carried out by adding an excess of one equivalent of acidic catalyst. 

In an enantioselective synthesis of a key intermediate for the preparation of poisons from the skin of tropical frogs, a key oxidation was performed under Swern conditions with 77% yield, while PCC provided a 28% yield and Pfitzner-Moffatt oxidation 73% yield. 

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