Sulfide, dimethyl oxidative cleavage

PV2M010O40 has usually been used in the acid form. H5PV2M010O40 catalyzes aerobic oxidative cleavage of cycloalkanes, 1-phenylalkanes, and ketones. For example, the oxidation of 2,4-dimethyl cyclopentanone and 2-methylcyclo-hexanone gives 5-oxo-3-methylhexanoic acid and 6-oxoheptanoic acid, respectively, in yields higher than 90% [285, 286). Bromination of arenes with HBr [287), oxidative dehydrogenation of cyclohexadiene [288, 289) and a-terpinene [290), oxidation of 2,4-dimethylphenol [291) and sulfides [292) are other examples. 

These amines can be deprotected under reduction conditions (Pd-C/R0H/HC02NH4 or Na/NH3). The allyl amines can be deprotected by oxidative cleavage with ozone (dimethyl-sulfide work up) or with KMn04 in acetone. 

Oxidative cleavage of N,N-dimethylhydrazones. This reaction can be conducted by photosensitized oxygenation followed by reduction (dimethyl sulfide) and hydrolysis. Yields of carhonyl compounds are in the range 50-85%. The mechanism is considered to involve an ene-type reaction (equation I). ... 

Ozone dimethyl sulfide Aldehydes from ethylene derivatives hy oxidative cleavage... 

Ozonolysis (Sections 8.16B and 8.19) The oxidative cleavage of a multiple bond using O3 (ozone). The reaction leads to the formation of a cychc compound called an ozonide, which is then reduced to carbonyl compounds by treatment with dimethyl sulfide (M02S) or zinc and acetic acid. 

For any alkene, hydrogen peroxide may be used as the oxidizing agent and either dimethyl sulfide or zinc and acetic acid may be used as the reducing agent (see Chapter 18, Section 18.4.3). Ozonolysis of a cyclic alkene leads to oxidative cleavage to a diketone, a dialdehyde, a keto-aldehyde, a keto acid, or a dicarboxylic acid. When 1,3-dimethylcyclopentene (67) is treated with ozone and then with zinc and acetic acid, oxidative cleavage leads to keto-aldehyde 68 (2-ethyl-5-oxooctanal). 

The second method of preparation that we studied is the oxidative cleavage of carbon-carbon double bonds—ozonolysis (Section 12-12). Exposure to ozone followed by treatment with a mild reducing agent, such as zinc metal or dimethyl sulfide, cleaves alkenes to give aldehydes and ketones. 

For moderate pH values, perhaps between 2 and 12, the reaction coordinate leading to oxidation of dimethyl sulfide by H2O2 involves 0-0 bond cleavage with the formation of the S—O bond. Under these conditions, water molecules can stabilize the transition complex via specific interactions including formation of hydrogen bonds with H2O2. 

Thermal Stability. Dimethyl sulfoxide decomposes slowly at 189°C to a mixture of products that includes methanetliiol. formaldehyde, water, bis(methyhhio)methane, dimethyl disulfide, dimethyl sulfone, and dimethyl sulfide. The decomposition is accelerated by acids, glycols, or amides. Sulfoxides undergo oxidation, reduction, carbonsulfide cleavage, and Pttmmerer reactions. 

The most common procedure is ozonolysis at -78 °C (P.S. Bailey, 1978) in methanol or methylene chloride in the presence of dimethyl sulfide or pyridine, which reduce the intermediate ozonides to aldehydes. Unsubstituted cydohexene derivatives give 1,6-dialdehydes, enol ethers or esters yield carboxylic acid derivatives. Oxygen-substituted C—C bonds in cyclohexene derivatives, which may also be obtained by Birch reduction of alkoxyarenes (see p. 103f.), are often more rapidly oxidized than non-substituted bonds (E.J. Corey, 1968 D G. Stork, 1968 A,B). Catechol derivatives may also be directly cleaved to afford conjugated hexa-dienedioic acid derivatives (R.B. Woodward, 1963). Highly regioselective cleavage of the more electron-rich double bond is achieved in the ozonization of dienes (W. KnOll, 1975). 

Both permanganate and ozonolysis break the carbon-carbon double bond and replace it with carbonyl (C=0) groups. In the permanganate cleavage, any aldehyde products are further oxidized to carboxylic acids. In the ozonolysis-reduction procedure, the aldehyde products are generated in the dimethyl sulfide reduction step (and not in the presence of ozone), and they are not oxidized. 

Taking advantage of the experience gained with ammonium iodide/TFA for reduction of Met(O) residues, a new resin-cleavage-deprotection cocktail has been used that consists of TFA (81%), phenol (5%), thioanisole (5%), ethane-1,2-dithiol (2.5%), water (3%), dimethyl sulfide (2%), and ammonium iodide (1.5% w/w).P It was found to prevent oxidation of Met residues in the acid cleavage step that was observed to occur in considerable extents with other deprotection cocktails. 

Ozonides are rarely isolated [75, 76, 77, 78, 79], These substances tend to decompose, sometimes violently, on heating and must, therefore, be handled with utmost safety precautions (safety goggles or face shield, protective shield, and work in the hood). In most instances, ozonides are worked up in the same solutions in which they have been prepared. Depending on the desired final products, ozonide cleavage is done by reductive or oxidative methods. Reductions of ozonides to aldehydes are performed by catalytic hydrogenation over palladium on carbon or other supports [80, 81, 82, S3], platinum oxide [84], or Raney nickel [S5] and often by reduction with zinc in acetic acid [72, 81, 86, 87], Other reducing agents are tri-phenylphosphine [SS], trimethyl phosphite [89], dimethyl sulfide (DMS) [90, 91, 92], and sodium iodide [93], Lithium aluminum hydride [94, 95] and sodium borohydride [95, 96] convert ozonides into alcohols. 

Fig. 8.3 Ozonolysis allows the cleavage of alkene double bonds. According to the Criegee mechanism the primary ozonide (POZ) is rapidly transformed into the more stable secondary ozonide (SOZ). Depending on the work-up, different products may be isolated. Oxidative work-up with hydrogen peroxide leads to carboxylic acids/ketones, while reductive work-up with either dimethyl sulfide or sodium borohydride gives aldehydes/ketones or alcohols, respectively...

---