Phenyl selenides, oxidation with

Formation of CK-configurated cyclobutanones has also been observed with 2-methylcyclopen-tanone and 2-methylcyclohexanone/8 However, stereoreversed eyclobutanone formation can be achieved by opening the intermediate oxaspiropentane with sodium phenyl selenide, oxidation of the resulting / -hydroxy selenide with 3-chloroperoxybenzoic acid and subsequent rearrangement in the presence of pyridine/18 Thus, from one oxaspiropentane 8, either stereoisomeric eyclobutanone cis- or lrans-9 was produced. The stereoreversed eyclobutanone formation proceeds from a stereohomogenous / -hydroxy selenoxide and is thought to be conformationally controlled. 

The 7 a-bromo steroid (9) can also be treated with sodium phenyl selenolate (41). The resultant 7 P-phenyl selenide (13) can be oxidized and the corresponding phenyl selenoxide elirninated to form the 7-dehydtocholesteryl ester (11). 

Diphenyl diselenide has been prepared by disproportionation of phenyl selenocyanate in the presence of potassium hydroxide" or ammonia/ and by air oxidation of benzeneselenol. The preparation of benzeneselenol is described in an earlier volume in this series/ In the present procedure phenylselenomagnesium bromide formed from phenylmagnesium bromide and selenium is oxidized directly to diphenyl diselenide with bromine/ Thus the liberation of the malodorous and toxic hydrogen selenide and benzeneselenol is avoided. Benzeneselenenyl chloride has been prepared by thermal elimination of ethyl chloride from ethyl phenyl selenide di-chloride/ by thermal elimination of chlorine from phenylselenium trichloride," and by chlorinolysis of diphenyl diselenide with either sulfuryl chloride " or chlorine. " ... 

This regioselectivity is practically not influenced by the nature of subsituent R. 3,5-Disubstituted isoxazolines are the sole or main products in [3 + 2] cycloaddition reactions of nitrile oxides with various monosubstituted ethylenes such as allylbenzene (99), methyl acrylate (105), acrylonitrile (105, 168), vinyl acetate (168) and diethyl vinylphosphonate (169). This is also the case for phenyl vinyl selenide (170), though subsequent oxidation—elimination leads to 3-substituted isoxazoles in a one-pot, two-step transformation. 1,1-Disubstituted ethylenes such as 2-methylene-1 -phenyl-1,3-butanedione, 2-methylene-1,3-diphenyl- 1,3-propa-nedione, 2-methylene-3-oxo-3-phenylpropanoates (171), 2-methylene-1,3-dichlo-ropropane, 2-methylenepropane-l,3-diol (172) and l,l-bis(diethoxyphosphoryl) ethylene (173) give the corresponding 3-R-5,5-disubstituted 4,5-dihydrooxazoles. 

Optically active phenyl-t-butylphosphine oxide with the same sign of rotation has been prepared by the reaction of Raney nickel with the (+)-selenide (107) and the (+)-sulphide (108),82 which suggests that the latter compounds have the same sign of rotation for the same absolute configuration. The absolute configuration of (—)-phenyl-t-butylphosphine oxide was apparently established by conversion into (—)-methylphenyl-t-butylphosphine oxide, but no details have been given. 

Synthesis of alkenes. Terminal alkenes are formed in good yield by oxidation of primary alkyl 2-pyridyl selenides with a slight excess of H202 (equation I). The same reaction with primary alkyl phenyl selenides proceeds in much lower yield. 

Another example of oligomer preparation by C-C bond formation is outlined in Figure 16.30. In this synthesis, nitroalkyl phenyl selenides are converted into nitrile oxides in the presence of support-bound terminal alkenes, forming isoxazolines. Oxidative elimination of the selenide yields a new alkene, which can then be subjected to further 1,3-dipolar cycloaddition with a new nitrile oxide. Although this synthesis is short and easy to perform, the cycloadditions proceed with low diastereoselectivity... 

Alkenes from organomercurials.1 Photoinitiated reaction of diphenyl diselenide with the organomercurial 1 provides a mixture of the corresponding a- and P-phenyl selenides, which undergo oxidative elimination to 2. The reaction provides a key step in a total synthesis of K-76 (3), which counteracts the inflammatory... 

Diphenyl diselenide, (CeH5)2Se2, is formed as a by-product in the preparation of phenyl selenide when magnesium phenyl bromide in ether solution reacts with selenium.5 A 2 per cent, yield is obtained when benzene, aluminium and selenium bromides react in dilute carbon disulphide solution. The product melts at 62° C.6 The corresponding oxide is an oil, B.pt. 230° C. at 65 mm.,7 and the sulphide, (C6H5)2Se2S, M.pt. 55° C., is obtained from sulphur chloride and phenyl selenide in carbon disulphide solution.8... 

Alternatively, the ambident oi-hetero substituted allyl anions have been utilized as homoenolate equivalents. For example, in the presence of HMPA, allyl phenyl sulfides (251),192 allyl phenyl sulfones (252)192b c and allyl phenyl selenides (253)192d e add to a,(3-enones in a l,4(0)-mode, while allyl phenyl sulfoxides (254) and allyl phosphine oxides (255) afford 1 A j-addition exclusively, irrespective of solvent used.193 Hua has shown that additions of either chiral sulfoxide (254 R1 = R2 = R3 = R4 = H, R5 = p-tolyl) or allyl oxazaphospholidine oxide (256) occur with excellent enantioselectivity (>95% ee).194 Similarly, Ahlbrecht reports that the a-azaallyl (257) adds exclusively in a 1 A j-mode to acceptor (59) to afford 1,5-diketones (Scheme 86).195... 

Asymmetric [2,3]sigmatropic rearrangements can proceed via optically active selenoxides. It has been shown that the Davis oxidant 158 can be used for the oxidation of selenides such as 172. The reaction product, after oxidation and rearrangement, is the allylic alcohol 173 formed with 35% ee (Scheme 50).279,282 Also Sharpless conditions (Ti(/ -PrO)4, (+)-DIPT, /-BuOOH) have been applied to this reaction and the product has been obtained in 69% ee. When, however, the phenyl selenide moiety in 172 is replaced with an or/ < -nitrophenyl selenide, the selectivity is increased to 92% ee in the allylic alcohol 173 using Sharpless conditions.296 Other selenides such as 2 -pyridyl or ferrocenyl selenides gave much lower selectivities. 

RSeCJIi — ROCHi. Oxidation of an alkyl phenyl selenide with m-chloroperben-zoic acid (2-5 equiv.) in methanol affords the corresponding alkyl methyl ethers in high yield. Oxidation of selenides with a vicinal phenyl group is accompanied by rearrangement of the phenyl group. vtc-Methoxy selenides derived from cycloalkenes are oxidized under these conditions to dimethyl acetals of ring-contracted aldehydes. 

Another interesting sequence is the amidoselenenation of alkenes for the synthesis of allylic amides. The seleniranium ion is trapped by a nitrile group which is first converted to an iminium chloride and then hydrolyzed to the amide (similar to the Ritter amide synthesis). Several differing nitriles (e.g. methyl to phenyl) have been utilized and all provide good yields of amides. The stereochemistry of addition is always trans but mixtures of regioisomers occur with terminal and unsymmetrically substituted oleflns (equation 24). The -seleno amide is easily converted to the allylic amide by oxidation of the phenyl selenide using the standard conditions. ... 

Oxidation of alkyl phenyl selenides with excess MCPBA in alcohols results in a facile substitution of a selenone moiety by an alkoxy group (Scheme The intermediate addition compound (47) be-... 

Until quite recently the isolation of optically active seienoxides has been limited to those contained in steroids (isolated as diastereoisomeis). < The difficulty in obtaining these compounds was attributed to the racemization through the achiral hydrated intermediates. Simple optically active sel enoxides (S-11% ee) were first prepared by kinetic resolution. Direct oxidation of selenides to seienoxides 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% 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), 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) 27 gjyj selenides (ee 1-28%) using... 

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... 

Disubstituted alkenes. Under controlled conditions to prevent a-deprotonation or C—Se cleavage (DME or ether, 0°) alkyllithium reagents (with the exception of methyllithium) add to phenyl vinyl selenide to give a-lithioalkyl phenyl selenides (2), which can be trapped with electrophiles to give 3. On oxidation, these products form alkenes (4) by elimination of benzeneselenenic acid. The reagent thus functions as CH=CH. 

Epoxide opening by benzeneselenolate anion gave the rphenyl selenide with high regioselectivity (Table 8, entry 4)22. Oxidation and rearrangement yielded (+)- ra/t. -2-cyclohexene-1,4-diol. A similar approach was the key step in the synthesis of a ( + )-chorismate-prephenate analog (Table 8, entry 5)24. 

The first example of the use of the catalytic one-pot procedure described above, in which the deselenenylation occurs with substitution, is represented by the conversion of vinyl halides into a-alkoxy acetals [116]. This is illustrated in Scheme 38 in the case of -bromostyrene 235. The regioselective methoxy-selenenylation affords the a-bromo selenide 236, which undergoes a rapid solvolysis, through a selenium-stabilized carbocation to produce the selenide 237. Oxidation of this alkyl phenyl selenide with ammonium persulfate produces an oxygen stabilized carbocation, which affords the final product 238, and, at the same time, regenerates the selenenylating agent. 

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... 

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. 

Like sulfides, selenides can be oxidized to the corresponding oxides, selenoxides, or to selenones. Oxidation to selenoxides is much faster and, with some oxidants, final. Reaction conditions are specified in equation 592 for the oxidation of methyl phenyl selenide [325, 711, 773, 1034]. 

Diphenyl selenide is oxidized with peroxyacetic acid at room temperature to diphenyl selenoxide hydrate, C6H5Se(OH)2, in 43% yield after 2 h [1198]. Benzyl phenyl selenide is oxidized to benzyl phenyl selenoxide by sodium periodate in aqueous methanol at 0 °C in 95% yield and by iodobenzene dichloride in aqueous pyridine at -40 °C in 85% yield [773]. 

On p-hydroxyalkyl phenyl selenides, die oxidation-elimination is best achieved with an excess of 30% aqueous hydrogen peroxide according to die original description of Sharpless (Scheme 174, c and d). Although l-(l -hycyclohexyl phenyl selenide p uces under these conditions a hydroperoxide (Scheme 174, a), the sired elimination reaction has been successfully achieved with sodium periodate in ethanol (Scheme 174, b). 

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