Unsaturated selenoxides, oxidation

Selenoxides are even more reactive than sulfoxides toward (3-elimination. In fact, many selenoxides react spontaneously when generated at room temperature. Synthetic procedures based on selenoxide eliminations usually involve synthesis of the corresponding selenide followed by oxidation and in situ elimination. We have already discussed examples of these procedures in Section 4.3.2, where the conversion of ketones and esters to their a, (3-unsaturated derivatives is considered. Selenides can... 

Many examples of natural furans are recorded as having been prepared from five-membered heterocycles such as 2(5H)-furanones (butenolides), which are reduced to furans with diisobutylaluminum hydride. The facile elimination of selenoxides derived from a-phenylseleneyl-y-lactones with formation of endocyclic a,/3-unsaturated butenolides is reported (75JOC542) as a useful route to 2,4- and 2,3,4-substituted furans via their corresponding butenolides. The mixture of dihydrofurans obtained from the tosylhydrazone of tetrahydro-2-furanone (Scheme 88) was oxidized to furans by 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (66CJC1083). 

In another simple procedure, deprotonation of methoxy bis(trimethylsilyl)methane with butyl lithium and addition of the resulting anion to aldehydes induces Peterson elimination (Scheme 27). The product methyl enol ethers could be hydrolysed to the parent acyl silanes with hydrochloric acid-THF or could be treated with electrophiles such as M-halosuccinimides to give a-haloacyl silanes105. Alternatively, treatment with phenyl selenenyl chloride, oxidation at selenium and selenoxide elimination afforded a,/3-unsaturated acyl silanes. 

Certain alkylaryl selenides can be prepared by the electrophilic selenylation of eno-lates (Figure 4.12 also see Table 10.4). With a subsequent H2Oz oxidation to produce the selenoxide followed by the elimination of Ph—Se—OH, one proceeds in a total of two synthetic steps from a carbonyl or carboxyl compound to its a,/3-unsaturated analogue. 

Another example of alkene synthesis by the pyrolysis of selenoxide is given in Scheme 4.14. The enolate derived from 4.18 reacts with either PhSeBr or PhSeSePh to form selenide 4.19. Oxidation of 4.19 gives selenoxide 4.20, which undergoes sy -elimination to give a,P Unsaturated carbonyl compound 4.21. 

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). 

The selenosulfonates (26) comprise another class of selenenyl pseudohalides. They are stable, crystalline compounds available from the reaction of selenenyl halides with sulftnate salts (Scheme 10) or more conveniently from the oxidation of either sulfonohydrazides (ArS02NHNH2) or sulftnic acids (ArS02H) with benzeneseleninic acid (27) (equations 21 and 22). Selenosulfonates add to alkenes via an electrophilic mechanism catalyzed by boron trifluoride etherate, or via a radical mechanism initiated thermally or photolytically. The two reaction modes produce complementary regioselectivity, but only the electrophilic processes are stereospecific (anti). Similar radical additions to acetylenes and allenes have been reported, with the regio- and stereochemistry as shown in Scheme 11. When these selenosulfonation reactions are used in conjunction with subsequent selenoxide eliminations or [2,3] sigmatropic rearrangements, they provide access to a variety of unsaturated sulfone products. 

Among the available methods for introducing an unsaturated carbon-carbon bond into organic molecules, selenoxide elimination reaction has been shown to be quite useful because of its simple procedure and its characteristic regioselec-tivity. Jones et al., who discovered the first selenoxide elimination, proposed an intramolecular mechanism entailing a five-membered ring structure to explain its syn nature [11]. This proposition was shown to be correct by Sharpless et al. who applied the method that was utilized by Cram to determine the stereochemistry of elimination in amine oxides [12]. Thus, the oxidation of erythro-selenide afforded only Z-olefin and that of f/zreo-selenide gave only -olefin (Scheme 4). 

Phenylselenyl chloride, C HjSeCI, and phenylselenyl bromide, C Hs eBr, in connection with oxidizing agents such as hydrogen peroxide or sodium periodate, are used for the conversion of aldehydes, ketones, and esters into their a,p-unsaturated analogues. The key intermediate is alkyl phenyl selenoxide, which decomposes via a five-membered transition state [167] (equation 27). 

Selenoxides are useful intermediates in the preparation of a,3-unsat-urated carbonyl compounds and esters. The treatment of aldehydes, ketones, or esters with benzeneselenyl chloride, C6H5SeCl, followed by the oxidation of the selenides to selenoxides by hydrogen peroxide, peroxy acids, or sodium periodate, gives a,3-unsaturated aldehydes, ketones, or esters. Thus, dehydrogenation with the formation of a carbon-carbon double bond is accomplished under very mild conditions [167, 169] (equation 593). 

This reaction allows the synthesis of (i) p,p -dienols by oxidation of p-hydroxy-y-alkenyl sel-enides or more conveniently from a-lithioalkyl selenoxides and enones (Scheme 136 and 166) (ii) p,5-dienols from l-lithio-3-alkenyl phenyl selenoxides and carbonyl compounds (Scheme 177) and (iii) 2-(r-hydroxyalkyl)-1,3-butadienes from 1-methylselenocyclobutyllithium and carbonyl compounds (Scheme 178). a,p-Unsaturated alcohols bearing a methylselenoxy or a phenylselenoxy group at the a-position do not lead on thermolysis to propargyl alcohols however, those be ng a (trifluoro-methylphenyl)selenoxy moiety at the a-position are valuable precursors of such con unds (Scheme 179). ... 

Selenoxide elimination occurs under relatively mild conditions in comparison to the elimination reactions described above. Selenoxides undergo spontaneous yn-elimi-nation at room temperature or below and thus have been used for the preparation of a variety of unsaturated compounds. The selenide precursors can be obtained by displacement of halides or sulfonate esters with PhSeNa. Oxidation of the selenides with hydrogen peroxide or tert-huiyX hydroperoxide, sodium periodate, or peroxycar-boxylic acids furnishes the corresponding selenoxides. Their eliminations usually favor formation of the less substituted olefin in the absence of heteroatom substituents or delocalizing groups. Since selenium compounds are toxic, they should be handled with care. 

Selenoxide elimination is now widely used for the synthesis of a,p-unsaturated carbonyl compounds, allyl alcohols and terminal alkenes since it proceeds under milder conditions than those required for sulfoxide or any of the other eliminations discussed in this chapter. The selenoxides are usually generated by oxidation of the parent selenide using hydrogen peroxide, sodium periodide, a peroxy acid or ozone, and are not usually isolated, the selenoxide fragmenting in situ. The other product of the elimination, the selenenic acid, needs to be removed from the reaction mixture as efficiently as possible. It can disproportionate with any remaining selenoxide to form the conesponding selenide and seleninic acid, or undergo electrophilic addition to the alkene to form a -hydroxy selenide, as shown in... 

Masamune has also completed a synthesis of tylonide hemiacetal (291) based on the creative use of enantioselective aldol condensations, as shown in Scheme 2.26. The aldol condensation of 328, derived from (/f)-hexahydromandelic acid and prop anal, was found to be >100 1 diastereoselective, affording the 2,3 syn compound 329 in 97% yield. Transformation to the p,7-unsaturated ester 330 occurred via selenoxide elimination and periodate cleavage followed by esterification. Formation of the silyl ether, reduction, and protection of the ester followed by ozonolysis of the terminal olefin gave the diol-protected aldehyde 331. The C-11 to C-15 segment 332 was then completed via chain elongation and a subsequent reduction-oxidation sequence in 34% overall yield from 330. 

An a, jS-unsaturated carbonyl compound can be prepared by a reaction known as a selenenylation-oxidation reaction. A selenoxide is formed as an intermediate. Propose a mechanism for the reaction. 

Chiral allenyl sulfones. The oxidation of )8-arylselenenyl )3,y-unsaturated sul-fones is accompanied by in situ selenoxide elimination. 

Several oxidants can be used for oxidation to the selenoxides. Reich considers hydrogen peroxide the oxidant of choice under aqueous conditions this oxidation can be carried out directly without isolation of the selenide. The oxidation can also be carried out in a two-phase system (H2O-CH2CI2) in this case addition of pyridine as buffer is usually advantageous. Ozonization in CH2CI2 is useful where the presence of water is undesirable. m-Chloroperbenzoic acid has been used to some extent in the case of unsaturated substrates, since selenoxides are formed more readily than epoxides. Reich considers sodium metaperiodate the reagent of last resort because of expense and necessity for an aqueous methanoUc medium. 

The treatment of a,p-unsaturated ketones with organocopper reagents provides another method to access specific enolates of unsymmetrical ketones. Lithium dialkylcuprates (see Section 1.2.1) are used most commonly and the resulting enolate species can be trapped with different electrophiles to give a,p-dialkylated ketones (1.27). Some problems with this approach include the potential for the intermediate enolate to isomerize and the formation of mixtures of stereoisomers of the dialkylated product. The intermediate enolate can be trapped as the silyl enol ether and then regenerated under conditions suitable for the subsequent alkylation. Reaction of the enolate with phenylselenyl bromide gives the a-phenylseleno-ketone 12, from which the p-alkyl-a,p-unsaturated ketone can be obtained by oxidation and selenoxide elimination (1.28). 

The transformation of carbonyl compounds to a,p-unsaturated carbonyl compounds can be achieved by selenoxide elimination. In fact, this method is superior to the sulfoxide elimination, because of the milder conditions employed and the direct formation of the unsaturated product, without isolation of the selenoxide. Thus, oxidation of the seleitide 25 at 0 °C gave the a-methylene lactone 26, a structural unit found in cytotoxic sesquiterpenes (2.27). The requirement for a syn elimination pathway forces the reaction to proceed to give only the product 26 and none of the regioisomeric a,3-unsaturated lactone 28. However, the lactone 28 is the major product from oxidation of the selenide 27, illustrating the importance of the stereochemistry of the selenide, derived from the order of addition of the phenylselenyl and methyl groups, in determining the regiochemical outcome. 

Conversion of ketones into a,(3-unsaturated ketones has been effected by bromination-dehydrobromination, although a better method involves a-phenyl-seleno ketones as intermediates. These are normally obtained by reaction of the enolate of the ketone with a phenylselenyl halide or diphenyl diselenide at low temperature. Oxidation with hydrogen peroxide, sodium periodate or other oxidant gives the selenoxide which immediately undergoes syn p-elimination to form the a, -unsaturated ketone. The process is tolerant of many functional groups, such as... 

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