Secondary phosphites sulfoxides

Process 5, the conversion of hydroperoxides to alkoxy and hydroxyl radicals, can be interrupted by incorporation of a secondary antioxidant such as phosphites (e.g. Irgafos 168) or thioesters (e.g. Evanstab 12). These materials act as reducing agents, converting hydroperoxides to alcohols and themselves being converted to phosphates or sulfoxides, respectively (see Fig. 16). 

In the stereoselective total synthesis of ( )-14-deoxyisoamijiol by G. Majetich et al., the last step was the epimerization of the C2 secondary allylic alcohol functionality. The Mitsunobu reaction resulted only in a poor yield (30%) of the inverted product, so the well-established sulfoxide-sulfenate rearrangement was utilized. The allyic alcohol was first treated with benzenesulfenyl chloride, which afforded the thermodynamically more stable epimeric sulfenate ester via an allylic sulfoxide intermediate. The addition of trimethyl phosphite shifted the equilibrium to the right by consuming the desired epimeric sulfenate ester and produced the natural product. 

These allylic sulfoxides 41 are in equilibrium with a sulfenate ester 43 by a [2,3]-sigmatropic rearrangement 41a. It is not usually possible to detect the sulfenate ester by NMR so there must be less than about 3% of it, but it can be trapped by various nucleophiles that like to attack sulfur. These thiophiles include secondary amines, thiolate anions and, most important, phosphite esters. The reaction is carried out in a protic solvent (usually the alcohol already present in the phosphite ester) and a rearranged allylic alcohol 45 is formed. 

A new selective method of oxidizing alcohols was found by Pfitzner and Moffat.425 Treating primary or secondary alcohols with 2-5 moles of dicyclo-hexycarbodiimide (or related compounds such as diisopropylcarbodiimide) in anhydrous dimethyl sulfoxide containing 0.1-2 moles of H3P04 leads to aldehydes or ketones. The phosphoric acid can be replaced by pyridinium phosphite, cyanoacetate, hydrochloride, sulfate, or even phosphate the dimethyl sulfoxide may be diluted with 9 times its volume of an inert solvent. The reaction is carried out at 20° and sometimes gives superlative yields it is recommended particularly for steroid chemistry testosterone gives, e.g., 92% of 4-androstene-3,17-dione by this method. 

Another type of antioxidant sacrificially reacts with oxygen, probably in the form of a peroxide. This type of antioxidant is often called a secondary antioxidant. Commonly they are used in conjunction with a primary antioxidant such as a hindered phenol. They are typically phosphites, which upon reaction with oxygen become phosphates or sulfides that can react with oxygen to form sulfoxides or sulfones, depending on the degree of oxidation. The same concerns about polymer compatibility and volatility apply here also. 

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