Selenides, 3-hydroxy

The stereoselective formation of /3-hydroxy selenides has also been reported 36 in the reaction of alkenes with, V-(phenylseleno)phthalimide or the succinimide derivative in aqueous acetonitrile or dichloromethane. The use of phenylselenenyl chloride under these conditions gives similar results (Table 5)37. 

Hydroxy selenides prepared by the reaction of epoxides with selenophenol and methanol are converted to alkenes upon treatment with thionyl chloride/triethylamine in methylene chloride (equations 33... 

Procedures which utilize selenides are similar, but a-lithio selenides are not generally preparable via simple deprotonation chemistry, due to facile selenium-lithium exchange. - Selenium-stabilized anions are available, however, by transmetalladon reactions of selenium acetals and add readily to carbonyl compounds. The use of branched selenium-stabilized anions has been shown to result exclusively in 1,2-addidon to unhindered cyclohexenones, in contrast to the analogous sulfur ylides. The resulting 3-hydroxy selenides undergo elimination by treatment with base after activation by alkylation or oxidation (Scheme 10). An alternative method of activating either p-hydroxy selenides or sulfides toward elimination involves treatment of a chloroform solution of the adduct with thallium ethoxide (Scheme 11). A mechanism involving the intermediacy of a selenium ylide is proposed. 

Alkenes from / -oxygenated selenides,4 /3-Phenylseleno lactones, ethers, and alcohols are converted into alkenes on treatment with ClSi(CH3)3 and Nal in C H ( N. Hydriodic acid (formed by inadvertant hydrolysis) may play a role this acid can effect this reaction, but in lower yield. This elimination thus reverses cyclo-l inctionalizations induced by C6H5SeX cf Na-NH3, 9, 26), and in addition provides a stereospecific route to alkenes by way of /3-hydroxy selenides. 

The unusual reactivity of selenoboranes towards epoxides gives new selective routes to /3-hydroxy-selenides and allyl alcohols.Thus, 1,2-epoxyoctane with B(SeMe)3 at 0°C for 0.7 h, followed by aqueous NaHCOa, gave (164) (81%) whereas the same reaction with styrene oxide gave (165) (63%) as the major product. For trisubstituted oxirans, however, the products were allylic alcohols, e.g. (167) (76%) from (166) on treatment with B(SePh)3 at 20 °C for 1.5 h. 

The Z-a, 3-unsaturated ester 2 is formed from the syn 3-hydroxy selenide by an anti elimination. 0-Mesylation and loss of the leaving group generates the cis episelenonium ion and hence the Z-alkene 2 (see Scheme 2.28). The syn 3-hydroxy selenide is formed by an aldol reaction of the Z-titanium enolate via a chair-shaped transition state (see Section 1.1.3). See S. Nakamura, T. Hayakawa, T. Nishi, Y. Watanabe andT. Torn, Tetrahedron, 57 (2001), 6703. 

Athene synthesh. The reaction of )3-hydroxy selenides with this reagent results in formation of alkenes. This reagent is superior to p-TsOH, HCIO4, or TFAA-triethylamine, which have been used previously. The complete synthesis of alkenes from two ketones is formulated in equation (I). ... 

Hydroxy selenides are conveniently prepared from epoxides by treatment with sodium phenylse-lenide (Scheme 32) and by the addition of benzeneselenenic acid and its derivatives to alkenes (Scheme 33), - - although in some cases these reactions are not regioselective. Useful phenylseleno -etherification and -lactonization reactions have been developed which can be regioselective (equation 42 and Schemes 34 and 35). -" "" Selenide- and selenoxide-stabilized carbanions have been used in addition reactions with aldehydes and ketones, -" and the reduction of a-seleno ketones also provides a route to 3-hydroxy selenides. ... 

Reich has now described the ready preparation of a-lithio-selenides and -selenoxides, which smoothly condense with aldehydes and ketones. The resultant /3-hydroxy-selenides and -selenoxides can be reductively eliminated under very mild conditions to give tetrasubstituted olefins, which are not readily available from the Wittig reaction. The /3-hydroxyselenides can be converted into olefins under milder conditions than their sulphur equivalents, using methane-sulphonyl chloride in triethylamine. 

Oxidation of -hydroxy selenides.s p-Hydroxy selenides (1), obtained by reaction of a dialkyl ketone with phenylselenenylrnethyllithium, are oxidized by... 

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. 

Spiro compounds.1 Diphenyl diselenoketals (6, 361-362) on transmetallation react with aldehydes to form hydroxy selenides. On treatment with (C6H5)3SnH and AIBN, these products undergo radical cyclization to spiro compounds. Example ... 

Hydroxylamines and derivatives Borane-Tetrahydrofuran, 42 Dimethylphenylsilane, 123 Hydroxy nitriles (see also Cyanohydrins) Nickel, 197 Hydroxy selenides... 

Selenides (see also Hydroxy selenides, Ketones-a-Substituted ketones)... 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

In the presence of /9-cyclodextrin, that binds to the R group of substituted epoxides, benzeneselenol reacts regio- and stereo-specifically to give an 80% yield of the j3-hydroxy selenide.42 Because the selenol only attacks the least substituted carbon with inversion of configuration, the reaction must occur by an SN2 mechanism. 

Cyclic ethers from dienes, The reagent 1 reacts with 1,5-cyclooctadiene in CH2CI2 at 25° to give 2 in 90% yield. Presumably the first step is addition of 1 to one double bond to form a jS-hydroxy selenide, which undergoes further reaction with 1 to form the cyclic ether 2. The product can be converted to 3 or to 4 by oxidation or reduction. 

Oxyselenation ofalkeues, - Treatment of olefins with 1 or 2, water, and an acid catalyst (e.g., p-TsOH) in CH2CI2 affords j3-hydroxy selenides in excellent yield. Unsaturated carboxylic acids, phenols, alcohols, thioacetates, and urethanes react with 1 or 2 and an acid catalyst ( —78- 25°) to afford products of oxidative cyclization. These reagents are superior to benzeneselenenyl halides for selenium-induced ring closures. This reaction is also useful for synthesis of 14- and 16-membered lactones. Benzeneselenenyl halides and benzeneselenenic acid do not promote macrolide formation under similar conditions. 

Phenylselenomethyl ketones. The reagent reacts with Grignard reagents to form /8 -hydroxy selenides (2), generally in 80-90% yield. Oxidation of the selenides to the desired phenylselenomethyl ketones (3) proved to be more difficult than anticipated. In the case of saturated alcohols, the Corey-Kim reagent (4, 87-90) is satisfactory. Allylic alcohols are best oxidized with DDQ. 

Nitroselenenylation of alkenes141-149 is performed in a mixture of acetonitrile/tetrahydro-furan (compared to the nitromercuration reaction, this allows application to alkenes that may be insoluble in water) by the addition of phenylselenenyl halides, mercury(ii) chloride, and silver nitrite. Mercury chloride is necessary to significantly or completely suppress the formation of -hydroxy selenides due to the ambident character of the nitrite anion. 

The formation of -hydroxy selenides through reaction of a selenium-stabilized carbanion with a carbonyl compound has been extensively used, in particular for the synthesis of natural products [1 - 4, 33]. The most recent... 

Diphenyl diselenide has been used to convert alkenes into 2-acetoxy, 2-methoxy, and 2-hydroxy selenides by indirect oxidation in MeCN-H20, MeOH, and HOAc, respectively, in the presence of Et4NX(X = Cl, Br, I) as supporting electrolytes [57]. High regio-selectivities (Markownikoff-type adduct) are observed, and best current efficiency is obtained for X = Cl or Br. Examples are shown in Eq. (26). 

Epoxides can also be prepared from a variety of 3-functionalized alcohols such as p-hydroxy sulfoxides," p-hydroxysulfonium salts," P-hydroxy selenides" and vicinal diols. In the use of unsymmetri-... 

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... 

The semipinacolic rearrangements of 2-hydroxy selenides are closely related to those of 2-hydroxy sulfides, but they have not been studied as extensively, and the use of selenium does not seem to offer any advantages over sulfur. The rearrangement has been applied mainly to the ring expansion of cyclic ketones via the addition of a-selenoalkyl anions. 

Dichlorocarbene (generated in situ), is generally used to induce migration, but silver tetrafluoroborate has also been used, as in the preparation of cuparenone (23 equation 32). Rearrangement occurs only if the selenyl moiety is attached to a fully substituted carbon. For example, the hydroxy selenide (26) does not rearrange but instead yields the epoxide (27 equation 33). ... 

Hydroxy selenides undergo elimination to alkenes when treated with an excess of methanesulfonyl chloride, but elimination is not an important side reaction in rearrangement reactions. ... 

Cleavage of epoxides.1 Tris(phenylseleno)borane and tris(methylseleno)borane2 react rapidly with terminal and a./l-disubstituted epoxides to give -hydroxy selenides, or in some cases alkenes. In the latter case, there are marked differences between the cis- and trans-epoxides the latter react very slowly to give mainly trans-alkenes. 

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