Lorenzo Testaferri

Preparation of a new chiral non-racemic sulfur-containing diselenide and applications in asymmetric synthesis.

The synthesis of the new chiral non-racemic sulfur-containing diselenide, di-2-methoxy-6-[(1S)-1-(methylthio)ethyl]phenyl diselenide, is described. When treated with ammonium persulfate this diselenide is transformed into the corresponding selenenyl sulfate, which acts as a strong electrophilic reagent and adds to alkenes, in the presence of methanol or water, to afford the products of selenomethoxylation or selenohydroxylation, respectively, with excellent diastereoselectivities. Starting from alkenes containing internal nucleophiles, asymmetric cyclofunctionalization reactions also resulted in good chemical yields, complete regioselectivities, and high diastereoselectivities. This sulfur-containing diselenide can also be used in catalytic amounts to promote one-pot selenenylation-deselenenylation processes, from which several types of products can be obtained in high yield and with good enantiomeric excess.

New nitrogen containing chiral diselenides: synthesis and asymmetric addition reactions to olefins

Abstract A simple synthesis of two new nitrogen containing diselenides, 7 and 8 , is described. These compounds were employed as starting materials to effect the asymmetric methoxyselenenylation, the hydroxyselenenylation as well as the cyclofunctionalization of olefins. Starting from 7 all these addition processes occurred with good facial selectivity. Poor results were however obtained with 8 . One-pot selenenylation–elimination sequences using catalytic amounts of the diselenide 7 have also been investigated.

Alkynyl phenyl selenides as convenient precursors for the synthesis of stereodefined trisubstituted alkenes

Abstract The addition of p-toluensulfonic acid to alkynyl phenyl selenides is regio- and stereospecific and affords (Z)-α-(phenylseleno)vinyl p-toluensulfonates in good yield. α-(Phenylseleno)vinyl halides are obtained from the reactions of these compounds with magnesium halides. The reactions of (Z)-α-(phenylseleno)vinyl p-toluensulfonates with cyanocuprates afford the corresponding trisubstituted alkenes in which the tosyl group has been selectively substituted by an aryl or an alkyl group with retention of configuration. Finally, the cross coupling reaction of these vinyl selenides with methylmagnesium bromide, in the presence of a nickel catalyst, occurs with retention of configuration and affords the selenium free trisubstituted alkenes.

The reaction of diphenyl diselenide with peroxydisulphate ions in methanol a convenient procedure to effect the methoxyselenenylation of alkenes

Abstract Methoxyselenenylation of several alkenes was effected, in one step, by oxidation of diphenyl diselenide with ammonium peroxydisulphate in methanol.

The reactions of some halogenated pyridines with methoxide and methanethiolate ions in dimethylformamide

Abstract The reactions of 2,6- and 2,5-dibromopyridines and of 2,3- and 3,5-dichloropyridines with sodium isopropanethiolate and methanethiolate afforded the products of mono- or of bis-substitution depending on the experimental conditions. The same pyridines reacted with sodium methoxide to give good yields of the mono-substituted products; bis-substitution occurred easily only in the case of the 2,6-dibromo- and of the 3,5-dichloropyridine. The syntheses of some methoxy thiomethoxypyridine, starting from the halogeno methoxypyridines or from the halogeno thiomethoxypyhdines are also described. The bis-(alkylthio)pyridines can be fragmented by sodium in HMPA to give the bis(mercapto)pyridines.

Efficient asymmetric selenomethoxylation and selenohydroxylation of alkenes with a new sulfur containing chiral diselenide

The synthesis of a new chiral non-racemic sulfur containing diselenide is described. The electrophilic selenium reagent, produced from this diselenide by treatment with bromine and silver triflate, has been used to effect the selenomethoxylation and the selenohydroxylation of alkenes. These addition reactions occurred with good chemical yield and with high diastereoselectivities.

Synthesis of enantiopure 1,4-dioxanes, morpholines, and piperazines from the reaction of chiral 1,2-diols, amino alcohols, and diamines with vinyl selenones.

The reactions of readily available vinyl selenones with enantiopure 1,2-diols, N-protected-1,2-aminoalcohols, and diamines gave substituted enantiopure 1,4-dioxanes, morpholines, and piperazines, respectively, in good to excellent yields. The same procedure was extended to the synthesis of thiomorpholine, benzodiazepine, and benzoxazepine. The reactions proceeded in one pot, in the presence of base, through a simple and novel application of the Michael-initiated, ring-closure (MIRC) reactions. The formed heterocycles constitute a framework that is observed in a large number of pharmaceutical compounds.

A convenient synthesis of aromatic thiols from unactivated aryl halides

Abstract Aromatic thiols are obtained in good yields from unactivated aryl halides and excess MeSNa in HMPA.

A Highly Enantioselective One‐Pot Synthesis of Spirolactones by an Organocatalyzed Michael Addition/Cyclization Sequence

Spirocyclic compounds are attractive targets in organic synthesis because of their broad distribution in biologically active natural products and pharmaceuticals, as well as their increasing use in a range of important chemical and technological processes, such as asymmetric synthesis and organic optoelectronics. On this basis the development of novel methods for the construction of spirocyclic frameworks is of considerable importance, particularly when these methods give rise to the enantioselective formation of an all-carbon quaternary stereocenter, which itself is considered to be a challenging transformation. 4] Over the past decade, extensive work on organocatalyzed asymmetric conjugated additions of trisubstituted carbon nucleophiles to electron-deficient alkenes demonstrated that these reactions represent an attractive solution to the problem of selectively generating quaternary stereocenters. Recently several organocatalytic cascade processes involving Michael additions have been successfully applied to the synthesis of spirocyclic compounds. These methods, are based on Michael or Michael/ aldol-type sequences and provide access to spiro-oxindoles, spirobenzofuranones, or spiro-3,4-dihydropyrans with high stereocontrol. The use of novel substrate combinations and the development of new cascade or one-pot reactions are significant advances in this field, thus making the asymmetric assembly of structurally diverse spirocyclic compounds possible from simple and readily available precursors. In this field and in continuation of our efforts to expand the scope of privileged organocatalysts in the field of selenium chemistry, 7] we herein report the first highly enantioselective synthesis of spirolactones starting from racemic cyclic bketoesters and the vinyl selenone catalyzed by bifunctional cinchona-alkaloid-derived catalysts. The operationally simple, one-pot Michael addition/cyclization sequence is based on the peculiar properties of the phenylselenonyl substituent, which plays a dual role as an electron-withdrawing group, during the addition step, and as a leaving group, during the cyclization by intramolecular nucleophilic substitution. Initial studies were performed with an excess of the tertbutyl b-ketoester 1a and the easily available vinyl selenone 2 in toluene in the presence of a catalytic amount of anhydrous Na2CO3 (Scheme 1).

New synthesis of vinyl selenides nucleophilic substitutions of unactivated vinyl halides by selenide anions

Abstract Alkyl and aryl selenide anions react with unactivated vinyl halides, in dipolar aprotic solvents, to give alkyl or aryl vinyl selenides in good yields. These reactions are stereospecific and occur with retention of configuration.