Acetal phenylselenyl

Synthesis of 31 by Method I (107,108) and its conversion to the related anti and syn diol epoxide derivatives (32,33) has been reported (108). The isomeric trans-1,lOb-dihydrodiot 37) and the corresponding anti and syn diol epoxide isomers (38,39) have also been prepared (108) (Figure 19). Synthesis of 37 from 2,3-dihydro-fluoranthene (109) could not be accomplished by Prevost oxidation. An alternative route involving conversion of 2,3-dihydrofluoranthene to the i8-tetrahydrodiol (3-J) with OsO followed by dehydration, silylation, and oxidation with peracid gave the Ot-hydroxyketone 35. The trimethylsilyl ether derivative of the latter underwent stereoselective phenylselenylation to yield 36. Reduction of 3 with LiAlH, followed by oxidative elimination of the selenide function afforded 3J. Epoxidation of 37 with t-BuOOH/VO(acac) and de-silylation gave 38, while epoxidation of the acetate of JJ and deacetylation furnished 39. 

Bromination of norperistylane-5,ll-dione (835) gives rapidly and quantitatively the Cj -symmetric dibromide 836a. Similarly, reaction with phenylselenyl chloride delivers 836b . Decomposition of the bis(selenoxide) in glacial acetic acid led to diketo diacetate 837. This product enters into twofold exchange reactions with representative nucleophiles. 

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). 

The total synthesis of ( + )-Erysotramidine (2) has been described by Ito et al. (137) starting from the amide (174) (Scheme 39). After O-mesylation to 177, base-catalyzed reaction gave the cyclopropane derivative (178) which with zinc in acetic acid was reduced to 179, which was identical to the product (135) of O-methylation of 172. Conversion of 178 to the thioketal (180) was followed by reaction with phenylselenyl chloride. A mixture of two compounds, 181 and 182, was produced the former could be transformed quantitatively to the latter. Finally, treatment of 182 with silver nitrate in methanol gave 183, which was then desulfurized to yield erysotramidine (2). 

Carbocyclic compounds can be formed by the nucleophilic intramolecular capture of a seleniranium intermediate of an olefinic bond. The carbonium ion which is formed as intermediate can react with another nucleophile or with the solvent. The first examples of these carbocyclization reactions were observed with dienes. Clive [105] reported that the reaction of the diene 203 with phenyl-selenyl chloride in acetic acid afforded the intermediate 204 which reacted with the solvent to give the bicyclic compound 205 (Scheme 31). Carbocyclization reactions were efficiently promoted by phenylselenyl iodide produced by diphenyl diselenide and iodine. As indicated in Scheme 31,Toshimitsu reported that the reaction of 1,5-hexadiene 206, in acetonitrile and water, afforded the acetamido cyclohexane derivative 209, derived from the cyclization of the seleniranium intermediate 207 followed by the reaction of the carbocation 208 with acetonitrile [106]. In several cases, carbocyclization reactions can be more conveniently effected by independently generating the seleniranium intermediates. A simple procedure consists of the reaction of trifluoromethane-sulfonic acid with j9-hydroxyselenides, which can be easily obtained from the... 

Scheme 38. Phenylselenyl Sulfate Catalyzed One-Pot Conversions of Vinyl Halides into Alkoxy Acetals and of Styrene Derivatives into 1,1- and 1,2-Dialkoxy Alkanes...

Orthoesters react with hydrocyanic acid, catalyzed by ZnCh, to give 2,2-dialkoxycarbonitriles (424 equation 201)." These nitriles can also be obtained by treatment of orthoesters with acyl cyanides" or trimethylsilyl cyanide in the presence of Lewis acids (BF3, SnCh)." Cyanoselenation of ketene 0,0-acetals affords the nitriles (425 Scheme 77)," " from which other compounds of this type can be prepared, e.g. (426) and (427), by splitting off the phenylselenyl group. The acetonitrile derivative (428 equation 202) is a byproduct (23%) in the photochemical cycloaddition of ketene diethylacetal to 6-cyanouracil." ... 

The intermediate 591a was also used in a synthesis of tabersonine. Alkylation of 591a by Z-l,3-di-iodopropene followed by elimination of the phenylselenyl group gave a ring C diene 594, which was cyclized by a reductive Heck reaction with palladium acetate, sodium formate, triphenyl-phosphine, and base, with formation of tabersonine (78) in 43% yield (Scheme 77) (346). 

The [3,3] siginatropic shift itself proceeds with high stereoselectivity. Mixed ketene acetals can also be generated from vinyl ethers and allylic alcohols in the presence of phenylselenyl bromide157. 

The electrophilic addition of arylbis(arylthio)sulfonium salts to glycals in the presence of alcohols, directly provide 2-thio-(5-glycosides with good stereoselectivity [162]. Stereoselective syntheses of [5-glycosides were also obtained from the reaction of 1,2-trans acetoxysele-nides, prepared by treatment of glycals with phenylselenyl chloride and silver acetate, in the presence of trimethylsilyl triflate [163]. Combined application of this method and the trichlo-roacetimidate method (see section 3.3) was suggested for the synthesis of functionalized precursors of the olivomycin C-D-E trisaccharide [164] (Scheme 34). 

Michael addition of lithium thiophenolate to the enaminone 697 followed by treatment with mercuric acetate gives the hydroxy lactone 698. N-Methylation followed by base treatment and phenylselenyl chloride provides the azocinone derivative 699, which has been elaborated on to the alkaloid Otonecine 700, Scheme 194 (83TL5731). 

Ando and coworkers have developed a synthesis of (+)-tuberiferin (11a) from tetrahydrosantonin 3b [10] (Scheme 2). These authors noticed that the Of-methylene-/-lactone moiety was stable under acidic and mild basic conditions and also to bromination by phenyltrimethylammonium perbromide (PTAB), and so the introduction of this moiety was carried out at an early stage of the synthesis. This approach was shown to be more efficient than other previous routes, in which the introduction of the a-methylene-/-lactone was left to the final stage. Thus, after acetalization of the C(3) carbonyl group of 3b the C(11)-C(13) methylene group was formed by the Grieco method, which involves phenylselenylation to give... 

The epimeric mixture of 16-ethoxycarbonylmethyl-17-oxo-compounds (45) was prepared from the jS-keto-thiolesters (44) by successive alkylation with bromoacetic ester and treatment with Raney nickel. The epimeric 16-phenyl-selenylandrostenones (46) were prepared via LDA-PhSeCl reaction of the 17-oxo-compound appropriately protected at C-3. Similar reaction of a 20-oxopregnane gave the 21-phenylselenyl derivative (47), and the preparation of the 17a-phenylselenyl analogue involved the reaction of the A -enol acetate... 

Compounds 25 and 26 were used as the key reactants in the synthesis of the branched maimononaose 27, the acetal ring system of the former disarming the phenylselenyl group to allow specific reaction of 26 as glycosylating agent. 

To a solution of 70 mg (l/f,l 5, 85, 9R)-l -((l-phenylmethoxy)hexane)-l,2,8-tetra-hydro-8-phenylselenyl-2-oxaindolizine-3,7-dione (0.140 mmol) and 103 mg 1-methoxy-1-trimethylsiloxyethene (0.704 mmol) in 15 mL CH2CI2 at —18°C was added dropwise 22 mg boron trifluoride etherate (0.154 mmol). The reaction mixture was allowed to stir at -78°C for 30 min and then quenched with saturated aqueous NaHCOs. The organic layer was separated and concentrated under reduced pressure. The crude residue was redissolved in 7 mL THF, and then 1 mL H2O followed by 2 drops 5% HCl were added. After 1 h, the reaction mixture was diluted with water and extracted with EtOAc. The combined organic extracts were dried over MgS04 and concentrated under reduced pressure. The residue was purified by silica gel radial PLC (20% EtOAc/hexanes) to give 79 mg (l/f,l 5, 5/f,85, 95)-l-((l -phenylmethoxy)hexane)-8-phenylselenyl-l,2,5,6,6a,8-hexahydro-2-oxaindolizine-3,5-dione acetic acid methyl ester as a clear oil, which was an inseparable mixture of diastereomers. 

Phenylselenyl halides, phenylselenyl trifluoroacetate, and phenylselenyl acetate add to alkenes ... 

Phenylselenyl bromide is an alternative reagent for allylic oxidation of alkenes. Addition takes place, and reaction of the adduct with acetic acid, followed by oxidation, generates the allylic acetate. 

Holmes has also reported an interesting route to synthesise ketene a 0-acetals starting with phenylselenyl acetal 286. In the example, transacetalization of 285 with aminoalcohol derivative 284 results phenylselenyl A, 0-acetal 286. Selenoxide formation and syn-elimination... 

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