Hydroxy-selenides, from

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 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). 

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. 

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... 

P-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 P-hydroxy selenides. ... 

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 presence of the soft selenium atom and the hard oxygen however, make, the reaction of p-hydroxy selenides site selective. These have in fact been transformed selectively to vinylselenides 7) or olefins4-9,11 12), by selective activation of the hydroxy group, inter alia, with thionyl chloride alone or with thionyl, mesyl and phosphoryl chloride, trifluoracetic anhydride, phosphorus triiodide or diphosphorus tetraiodide in the presence of triethyl amine (Schemes 8Ab 8Bb). The formation of olefins from p-hydroxyselenides is regio- and stereoselective and occurs by formal removal of the hydroxyl and selenenyl moiety in an anti fashion. 

A stereoreversed cyclobutanone formation was realized starting from oxaspiropentanes by using the selenoxide function as a leaving group. Treating oxaspiropentanes 94 with sodium benzeneselenolate in ethanol affords j8-hydroxy selenides 95 which, on oxidation with 3-chloro-peroxybenzoic acid at — 78 to — 30 °C, led directly to the corresponding cyclobutanones 96 (Table 3). The stereochemistry in this reaction is opposite to that normally observed in the acid-catalyzed rearrangement of oxaspiropentanes. 

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. 

Sion of j3-hydroxy selenides (1) into olefins. The starting materials are generally prepared from alkyl phenyl selenides, readily available by reaction of tosylatcs. 

Alkenes can also be obtained by elimination of p-hydroxy selenides, under the action of methanesulfonyl chloride, thionyl chloride or other acidic conditions. The reaction is stereospecific, proceeding by anti elimination, by way of the epise-lenonium ion, e.g. 29 (2.28). High yields of di-, tri- or tetrasubstituted alkenes can be obtained and the reaction provides an alternative to the Wittig reaction when the phosphonium salt cannot be readily obtained. The p-hydroxy selenides can be prepared by a number of methods, for example from a-seleno aldehydes or ketones by reduction or reaction with a Grignard reagent, or from a-lithio selenides by... 

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). ... 

Acylamino- from 2-hydroxy-selenides and nitriles OH - NHCOR... 

Full experimental details are available for the sequence PhSeCHjLi + ketone or aldehyde -+ ff-hydroxy-selenide - olefin. The action of BuLi on (30) generates (31), and the vinyl carbanion (32) is available in the same way from (33). ... 

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. 

It is well known that a-seleno-alkyl-lithiums can be used for the formation of epoxides from ketones, but they are also valuable building blocks for the synthesis of higher homologues namely oxetans and tetrahydrofurans. The reactions proceed in a step-wise fashion via hydroxy-selenides (42), which are cyclized by reaction with bromine (Scheme 4). 

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