Francis Outurquin

Synthesis of azetidines by electrophilic selenium-induced cyclization of homoallylic benzylamines

Abstract Homoallyl benzylamines, prepared by allylation of the corresponding N-benzylimines, have been subjected to a selenium-induced cyclization under various conditions. At room temperature, the 4-exo and the 5-endo modes are competitive. In acctonitrile, the azetidine has been isolated as the major cyclization product, especially for homoallylamines derived from ketimines. With an excess of selenium reagent, 3-halopyrrolidines have been obtained.

Stereocontrolled Synthesis of 1,2‐Dialkyl‐4‐halopyrrolidines through PhSeX‐Induced Cyclization of Secondary Homoallylamines

The selenium-induced cyclization of α-alkyl or α,α-dialkyl-homoallyl-benzylamines 1 by use of PhSeX (X = Cl, Br, I; 1.5 equiv.) provided a mixture of (phenylselanylmethyl)azetidines 2 and (phenylselanyl)pyrrolidines 3.1 When an excess of PhSeX (X = Cl, Br) was used, 4-halopyrrolidines 4 (X = Cl) or 5 (X = Br) were formed and isolated in very good yields. Mono- or dialkyl 4-halopyrrolidines 4 and 5 could also be obtained stereospecifically by SO2Cl2 or Br2 treatment of 4-(phenylselanylmethyl)azetidines 2, by way of the intermediate (halomethyl)azetidines 14 (X = Cl) or 15 (X = Br). When starting from 4-(phenylselanyl)pyrrolidines 3, monoalkylated 4-halopyrrolidines 4 or 5 could be obtained stereospecifically after decomposition of the unstable dihaloselenuranes 16 and 17. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Stereospecific synthesis of 2,3-disubstituted aziridines from β-alkylamino phenylselenides

Reduction of α-phenylselanyl imines derived from β-phenylselanyl α-oxoesters or PhSeCl assisted nucleophilic addition of primary amines to α,β-unsaturated esters have led to β-alkylamino phenylselenides 4, 5, 12 and 13 which were cyclised into aziridines 8, 9 and 14 after selenium activation. threo-Amino selenides led stereospecifically to cis-2,3-disubstituted aziridines. Depending on the structure, non-functionalised amino selenides 19–20 were also cyclised into aziridines 21–22.

Enantioselective α-selenenylation of 2-phenylpropanal

Abstract The parameters (media, temperature, structures of the reactants) relative to the enantioselective α-selenenylation of 2-phenylpropanal with chiral areneselenenamides have been studied. Enantiomeric excesses as high as 60 % have been observed. Recrystallization yielded an α-seleno-aldehyde in an optically pure form.

Synthesis of α-halo β,γ-unsaturated esters from γ-phenylseleno α,β-unsaturated esters

Abstract γ-Phenylseleno α,β-unsaturated esters, prepared from α-phenylseleno aldehydes by Horner-Emmons reaction and treated with bromine or sulfuryl chloride, form adducts whose decomposition leads to α-halo β,γ-unsaturated esters in fair to good yields.

Synthesis of Azetidine and Pyrrolidine Derivatives through Selenium-Induced Cyclization of Secondary Homoallylamines − A77Se NMR Study

Treatment of α-alkyl and α,α-dialkyl homoallylic amines 1 with PhSeX (X = Cl, Br, I), in CH3CN containing sodium carbonate produced mixtures of azetidines 2 and pyrrolidines 3. The cyclization also occurred in the absence of Na2CO3, and the corresponding azetidinium and pyrrolidinium salts 2(HX) and 3(HX) were formed in CDCl3 or CH3CN. The crude reaction mixtures were analysed by 77Se NMR. Each product − 2, 3, 2(HX), and 3(HX) − was characterized by its 77Se chemical shift, and the product ratios were determined for each reaction. The ratios of azetidine 2 to pyrrolidine 3 increased not only according to the steric hindrance around the α-carbon, but also with the nature of the counterion X− (PhSeCl < PhSeBr < PhSeI). Use of PhSeI and amines 1g to 1k (R1, R2 ≠H), produced only the azetidinium salts 2(HI), allowing the isolation of the corresponding azetidines 2, albeit in poor yield. Some reactions were monitored by 77Se NMR at the beginning of the addition−cyclization process. No intermediates were observed when PhSeI was used, but the thermodynamic addition products 5(Br), 5(HBr), and some dibromoselenuranes 8 were detected. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Preparation and Oxidation of α-Phenylselanyl Esters

Abstract Alkylation and selenenylation of selenium-stabilized ester enolates have allowed the preparation of α-phenylselanyl esters 5 , 7 , 8 and of α,α-bis(phenylselanyl)esters 6 , respectively. The competitive selenophilic reaction, leading to an allylic phenylselenide 9 , was avoided in the presence of HMPA. α-phenylselanyl α,β-unsaturated esters 15 were prepared by oxidation of compounds 6 and dehydrohalogenation of β-chloroesters 17 . Some other transformations: oxidation, transesterification and Grignard reaction were also studied. H 2 O 2 oxidation of Z -esters 15 has led to stable E -α-seleninyl esters 20 .

Synthesis and reactivity of β-phenylselanyl α-oxoesters

β-Phenylselanyl α-oxoesters 2 were prepared by N-phenylselanyl morpholme treatment of α-oxoesters 1, oxidized into β-unsaturated α-oxoesters 5 and subjected to the Wittig-Horner olefination. The diethyl (l-phenylselanylalkyl)maleates 6 have led, after [2,3]sigmatropic rearrangement of the corresponding selenoxides, to the diethyl 3-alkylidene-2-hydroxysuccinates 7. The 2-(t-butoxycarbonylamino)-3-alkylidenesuccinates 8 were prepared in a similar way. The decomposition of halo-adducts derived from compounds 6 has allowed the synthesis of the diethyl 3-alkylidene-2-halosuccinates 9 and 10.

Acid catalyzed α-alkylation of β-Aminothiophenes using aldehydes and selenophenol synthesis of bis(3-amino-2-thienyl)methane derivatives

Abstract The acid-catalyzed reaction between β-aminothiophenes and aldehydes, in the presence of selenophenol, leads to α-alkyl β-aminothiophenes. The reduction step is not observed with thiophenol. Without selenol, a second alkylation reaction occurs and bis(3-amino-2-thienyl)methane derivatives are isolated.

Reactivity of α-arylseleno-aldehydes towards halogens and benzeneselenenyl chloride

Abstract Chlorination of α-seleno-aldehydes bearing an α-hydrogen gives selenium dichlorides which decompose into α-chloro α-seleno-aldehydes and α-chloroenal. Bromination, in all cases, and chlorination for the other α-seleno-aldehydes lead to the α-halogenoaldehydes.