Other Alcohol Oxidations Using Activated DMSO

Other Alcohol Oxidations Using Activated DMSO 

Almost any electrophile, able to react with DMSO, can generate an active DMSO species that can be used for the oxidation of alcohols. Dozens of such activators have been described in the literature as shown in Table 2.2. Many of these activators have been the subject of very superficial analyses and, therefore, their potential for Moffatt oxidation of alcohols is not known in detail. Some of these activators particularly 

Benzoic anhydride Bz20 Briefly mentioned by Albright268 as an efficient substitute of Ac20 

Methanesulfonic anhydride Ms20 Briefly mentioned by Swern269 and Albright,268 it delivers from good to excellent yields at —20°C 

Trifluoromethane sulfonic anhydride Tf20 Briefly mentioned by Hendrickson and Schwartzman270 

---

Other Alcohol Oxidations Using Activated DMSO... 

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 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

The activation of DMSO by electrophilic reagents such as oxallyl chloride or trifluoroacetic anhydride (TFAA) (among many others) produces an oxidant capable of oxidizing primary alcohols to aldehydes in high yields. This oxidation is called the Swern oxidation and yields the aldehyde (oxidized product) by reductive elimination of dimethylsulfide (reduced product) and proceeds under mild, slightly basic conditions. It is a second widely used and effective oxidative method for the production of aldehydes from primary alcohols. 

The Pfitzner-Moffatt oxidation utilises 1,3-dicyclohexylcarbodiimide as the DMSO activator in the presence of acid to afford oxidation of alcohols to carbonyls.2,24,25 Initial work was carried out on steroids and thymidine residues although the procedure has since been found to be applicable to a large range of alcohols. In the following example, the Pfitzner-Moffatt method was used as an alternative to the Swem reaction which had resulted in the formation of an unwanted a-chloroketone (see later).26 Other oxidation procedures were attempted (PDC, PCC, Dess-Martin periodinane) however the Pfitzner-Moffatt gave the best, albeit modest, yield. 

The versatility and efficiency of the Swem conditions means that they can also be applied to various functional groups to effect different transformations other than just oxidations of alcohols. For example, primary amides have been converted to nitriles using the Swem reagents as dehydrating agents.42 Although different activators of DMSO were tested, for example, the S03-pyridine complex and TFAA, oxalyl chloride was found to be the best based on the yield of the final product. 

C.iii. Other DMSO Oxidations. Albright and Goldman developed a reagent using DMSO and acetic anhydride that formed an active sulfoxonium complex. 12 jj (jje initial work, yohimbine was oxidized to the ketone (yohimbinone) in 85% yield, at ambient temperatures in 24 h. 2 As with DCC, DMSO initially reacts with acetic anhydride to form sulfoxonium salt 66, which then reacts with the alcohol. Acetate is the leaving... 

---