Enol sulfonates oxidation

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

The 2,2 -bis(phenylthiomethyl) dispiroketal (dispoke) derivative is cleaved by oxidation to the sulfone, followed by treatment with LiN(TMS)2. The related bromo and iodo derivatives are cleaved reductively with LDBB (lithium 4,4 -di- -butylbiphenylide) or by elimination with the P4- -butylphosphazene base and acid hydrolysis of the enol ether. The 2,2-diphenyl dispiroketal is cleaved with FeCl3 (CH2CI2, rt, overnight)." The dimethyl dispiroketal is cleaved with TFA, and the allyl derivative is cleaved by ozonolysis followed by elimination. ... 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

The procedure for oxidation of the sulfide to the sulfone is based on that reported earlier by Bordwell and Pitt. The synthetic utility of phenyl vinyl sulfone and sulfoxide derives not only from their ability to serve as excellent Michael acceptors toward such reagents as enolate anions and... 

Carbon nucleophiles which do not readily trigger the rearrangement of epoxides include lithiated dithianes [295, 304], lithiated sulfones [238], lithiated diarylphos-phine oxides [240, 305], lithium enolates [306], and allylic organolithium or organo-magnesium compounds [298, 307-310] (Scheme4.67). 

In the course of these investigations Hoffmann and his group have also developed novel entries to f-butyl 2-methylene-3-oxoalkanoates 2-109a and 2-methylene-3-oxo-sulfones 2-109b by oxidation of 2-108a and 2-108b, respectively obtained by reaction of the aldehydes 2-106 and acrylate 2-107 a or phenyl vinyl sulfone 2-107 b. The cycloadditions of these oxabutadienes to enol ethers and alkenes proceeded in the expected way (Fig. 2-29) [133]. 

Nitrogen heterocycles such as azirines and aziridines are also used effectively as building blocks for the synthesis of a,a-disubstituted amino acids. The aziridine derivative 33 is prepared in optically pure form by addition of the lithium enolate 32 to the chiral sulfinimide 31 (Scheme 7) [42]. After oxidation of the sulfoxide to the sulfone and subsequent hydration, the a-methylated phenylalanine derivative 34 is obtained in good overall yield. 

Aryl and vinyl sulfonate esters are reactive toward oxidative addition, and the perfluoroaUcyl versions are useful substrates in the Heck reaction. Conditions can be mild, comparable to those for vinyl iodide reactions. The enol (vinyl) triflates are particularly attractive, since they are prepared directly from the corresponding ketone (equation 21). ... 

Selenenyl halides are relatively stable, though moisture sensitive, compounds that are generally prepared by the reactions shown in Scheme 7 and behave as electrophihc selenium species. " They react with ketones and aldehydes via their enols or enolates to afford a-seleno derivatives (e.g. (17) in equation 11). Similar a-selenenylations of /3-dicarbonyl compounds, esters, and lactones can be performed, although the latter two types of compounds require prior formation of their enolates. Moreover, the a-selenenylation of anions stabilized by nitrile, nifro, sulfone, or various types of phosphorus substituents has also been reported (equation 12). In many such cases, the selenenylation step is followed by oxidation to the selenoxide and spontaneous syn elimination to provide a convenient method for the preparation of the corresponding a ,/3-unsaturated compound (e.g. 18 in equation 11). Enones react with benzeneselenenyl chloride (PhSeCl) and pyridine to afford a-phenylselenoenones (equation 13). 

Sammes and cowoikers devised a promising solution to the synthesis of substituted P-silyl sulfones, which has been exploited in a new approach to the antibiotic bicyclomycin (Scheme 44). In their approach the P-silyl sulfone (125) was prepared by conjugate addition of the lithium enolate of the mono-imino ether derivative (123) of a dioxopiperazine to the unsaturated P-silyl sulfone (124). After oxidative cyclization to the bicyclic system (126), the latent alkene functionality was unleashed in 89% yield on treatment with TBAF in THF at room temperature to give the basic skeleton of bicyclomycin. 

The mechanism of oxygen transfer from oxaziridines to nucleophiles is believed to involve an Sn2 type reaction and this assumption is supported by theoretical and experimental studies. When sulfides are oxidized to the corresponding sulfoxides and sulfones, the molecular recognition is steric in origin, and it is determined by the substituents on both the substrate and the oxaziridine. For the oxidation of enolates, the molecular recognition is explained with an Sn2 mechanism as well as by an open (non-chelated) transition state where the nonbonded interactions are minimized. The mechanism of oxygen transfer to an enolate to form the corresponding acyloin is shown below. ... 

This chapter is devoted exclusively to the alkylation of the above mentioned organometallic reagents with alkyl halides, epoxides and oxetanes. It includes a large variety of organosulfur- and organoselen-ium-stabilized carbanions derived from saturated and unsaturated sulfides, selenides, sulfoxides, selen-oxides and sulfones as well as those carbanions bearing another heteroatomic moiety. The chapter excludes, however, those organometallics which can be viewed as a-thio and a-seleno enolates. 

Oxidative desulfonation is achieved by reaction of a sulfonyl carbanion with a source of electrophilic oxygen. One useful reagent is MoOPH, a well-known oxidant for enolates which will convert a sulfone (183), as the sulfonyl carbanion, directly to the ketone (184) (Scheme 74). 

---