Alkyl phenyl selenoxides

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). 

Alkyl phenyl selenoxides bearing a p-hydrogen undergo syn elimination to form olefins. 

Alkyl phenyl selenoxides bearing a P-hydrogen undergo facile syn elimination to form olefins under much milder conditions than the corresponding sulfoxides. The selenium anion formed from (PhSe)2 is an excellent nucleophile and easily opens the epoxide to give the corresponding hydroxyl selenide. This intermediate is not isolated but... 

This limitation can be overcome using the anion of alkyl phenyl selenoxides which add to ketones and rearrange in situ (equation 34).The amalgam reduction is required to remove the small amount of a-phenyl selenated ketones formed in the reaction. 

Olefin synthesis. The preparation of olefins by decomposition of alkyl phenyl selenoxides (Diphenyl diselenide, 5, 272-276) is very useful, except in the case of primary alkyl phenyl selenoxides, which usually give low yields of terminal olefins on decomposition. However, the presence of electron-withdrawing substituents on the benzene ring increases both the rate of elimination and the yield of olefins. In instances where use of diphenyl diselenide results in low yields. Sharpless and Young recommend use of o-nitrophenyl selenocyanate (1) or 4,4 -dichlorodiphenyl diselenide, both of which are converted into the corresponding ArSe Na" reagents on reduction with sodium borohydride in ethanol. 

That alkyl phenyl selenoxides decompose at or below room temperatures (10) is in keeping with the very soft nature of Se, which prefers being at low oxidation states. 

The selenoxide elimination of primary alkyl 2-pyridyl selenides to give terminal alkcnes also proceeds in higher yield than the corresponding reaction with alkyl phenyl selenides.2 Example ... 

In the former case, almost complete stereoselective oxidation to the chiral selenoxides has been accomplished quite recently. The Davis oxidant, 3,3-di-chloro-l,7,7-trimethyl-2 -(phenylsulfonyl)spirobicyclol2.2.11heptane-2,3 -oxa-ziridine, was found to be the most efficient reagent for the enantioselective oxidation of a variety of prochiral alkyl aryl selenides [81. Asymmetric oxidation was accomplished by the treatment of the selenides with 1 molar equivalent of the Davis oxidant at 0°C to afford the corresponding chiral alkyl aryl selenoxides in quantitative yields with 91-95% ee (Scheme 1). The oxidation of methyl phenyl selenide was complete within 1 min, whereas that of triiso-propyl(a bulkier alkyl) phenyl selenide required a few hours. Typical results are... 

Selenoxide elimination. The yield of alkenes from alky) phenyl selenoxides and alkyl methyl selenoxides under usual conditions (30% H2O2, O3, Oa) tends to be rather low because of formation of the original selenide. Much higher yields are obtained if the selenides are oxidized with /-butyl hydroperoxide (4 equiv.) in the presence of basic alumina (8 equiv.) in THF at 55°. No epoxida-tion is observed under these conditions. A less satisfactory method is ozonization in CH2CI2 in the presence of 1-3 equiv. of triethylamine. ... 

Propargyl phenyl selenide is a versatile multifunctional acrylate synthon, as shown in Scheme 12. The (Uanion is prepared and reacted successively with an alkylating agent (R— X) and an electrophile (E ). The oxidative rearrangement of the propargylic selenoxide (35) to an allenic selenenate (36), and thence to the a-phenylselenoenone (37), forms the keystone of this synthetic method, and ovendl yields firom propargyl phenyl selenide are in the range of 38-68%. Further elaboration of (37) is possible... 

Until quite recently the isolation of optically active selenoxides has been limited to those contained in steroids (isolated as diastereoisomers). The difficulty in obtaining these compounds was attributed to the racemization through the achiral hydrated intermediates. Simple optically active selenoxides (5-11% ee) were first prepared by kinetic resolution. Direct oxidation of selenides to selenoxides was first reported using optically active oxaziridine derivatives under anhydrous conditions, but the extent of the asymmetric induction was somewhat unsatisfactory with methyl phenyl selenide as substrate (8-9% ee). Recently much improved enantiomeric excesses (45-73%) were achieved with new oxaziridine reagents such as (70). An attempt at the asymmetric oxidation of more bulky selenides was independently carried out using Bu OCl in the presence of (-)-2-octanol (equation 55),2 but resulted in unsatisfactory enantioselectivities (ee 1%). Much better results were obtained by the oxidation of P-oxyalkyl aryl selenides (ee 18-40% equation 56) and alkyl aryl selenides (ee 1-28%) 2S using TBHP in the presence of (+)- or (-)-diisopropyl tartarate (DIPT) and titanium(IV) alkoxide. 

Thus, when cyclohexyl selenides 1, prepared from the corresponding 4-sub-stituted cyclohexanone via the selenoketals, were oxidized with various Davis and Sharpless oxidants, the chiral alkyl aryl 4-substituted cyclohexylidenemethyl ketones were obtained in excellent chemical yields with high enantiomeric excesses. Typical results are summarized in Table 4. In this asymmetric induction, of the substrate and the chiral oxidant employed were revealed to show a remarkable effect upon the enantioselectivity of the product. The use of a methyl moiety as instead of a phenyl moiety gave a higher ee value, probably due to the steric difference between the two groups bonded to the selenium atom of the substrate. The results indicate that the titanium complex of the Sharpless oxidant may promote the racemization of the chiral selenoxide intermediate by acting as a Lewis acid catalyst, whereas the racemization in the case of the Davis oxidant, which is aprotic in nature, is slow. 

Syntheses of Alkylidene cyclopropanes Via the Selenonium route The selenonium route proved to be more valuable. It has been specifically designed by us to replace the deficient selenoxide route (Scheme 38). It was expected to produce alkylidene cyclopropanes by a mechanism which mimics the selenoxide elimination step but which involves a selenonium ylide in which a carbanion has replaced the oxide. Cyclopropyl selenides are readily transformed to the corresponding selenonium salts on reaction with methyl fluorosulfonate or methyl iodide in the presence of silver tetrafluoroborate in dichloromethane at 20 °C and, as expected, methylseleno derivatives are more reactive than phenyl-seleno analogs. Alkylidene cyclopropanes are, in turn, smoothly prepared on reaction of the selenium salts at 20 °C with potassium tert-butoxide in THF (Scheme 38). Mainly alkyl cyclopropenes form at the beginning of the reaction. They then slowly rearranges, in the basic medium, to the more stable alkylidene cyclopropanes( 6 kcal/mol). In some cases the complete isomerisation requires treatment of the mixture formed in the above reaction with potassium fcrt-butoxide in THF. The reaction seems to occur via a selenonium ylide rather than via a P-elimina-tion reaction promoted by the direct attack of the /crt-butoxide anion on the P-hydrogen of the selenonium salt, since it has been shown in a separate experiment that the reaction does not occur when a diphenylselenonium salt (imable to produce the expected intermediate) is used instead of the phenyl-methyl or dimethyl selenonium analogs. It has also been found that the elimination reaction is the slow step in the process, since styrene oxide is formed if the reaction is performed in the presence of benzaldehyde which traps the ylide intermediately formed... 

Conductometric studies demonstrated that alkyl selenoxides and selenones are completely ionized bases in chlorosulfonic acid, whereas the corresponding phenyl compounds and their nitro derivatives are only weakly basic. The selenones were found to be stronger bases than the corresponding sulfones. ... 

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