Esters, unsaturated selenoxides

Both the selenoxide and sulfoxide " reactions have been used in a method for the conversion of ketones, aldehydes, and carboxylic esters to their a, P-unsaturated derivatives (illustrated for the selenoxide). 

Unsaturated -Keto Esters, (3-Diketones, and a /3-Keto Sulfoxide Prepared by Selenoxide Elimination... 

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... 

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). 

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). 

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. 

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. 

Most of the published syntheses of necine bases have been directed towards fully saturated pyrrolizidine derivatives. Robins and Sakdarat have developed a method for the conversion of saturated pyrrolizidine esters into their 1,2-didehydro-derivatives. Thermal elimination of a phenylseleno-group was used to introduce the unsaturation, and ( )-supinidine (17) was synthesized using this technique. The ester (5) is most conveniently prepared by the two-step stereospecific route of Pizzorno and Albonico. Phenylselenenylation of the lithium enolate derived from the ester (5) gave the phenylseleno-ester (15), which was reduced to the corresponding alcohol (16) (Scheme 5). syn-Elimination of the selenoxide derived from (16) gave ( )-supinidine (17). Each step proceeded in about 60% yield. None of the isomeric 1,8-didehydro-base was detected. 

Selenoxides are even more reactive than amine oxides toward p 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 4.7, where the conversion of ketones and esters to their a,j5-unsaturated derivatives was considered. Selenides can also be prepared by electrophilic addition of selenenyl halides and related compounds to alkenes (see Section 4.5). Selenide anions are powerfiil nucleophiles that can displace halides or tosylates and open epoxides. Selenide substituents stabilize an adjacent carbanion so that a-selenenyl carbanions can be prepared. One versatile procedure involves conversion of a ketone to a bis-selenoketal which can then be cleaved by w-butyllithium. " The carbanions in turn add to ketones to give jS-hydroxyselenides. Elimination gives an allylic alcohol. 

Kocienski et al 88) generated the P-allenic ester (23) by a modified Claisen rearrangement of ynol (6) (Scheme 5). After chain extension to a y-allenic ester, the E a, P-unsaturation was introduced by selenoxide elimination. 

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