Cristina Tomassini

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.

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.

Asymmetric synthesis of thioamido selenides. A simple synthetic route to enantiopure thiazolines

The mixtures of two enantiomerically pure diastereoisomeric amido selenides, obtained from the reactions of alkenes with camphorselenyl sulfate in a mixture of water and a nitrile, were treated with Lawessons reagent to afford a mixture of the two corresponding thioamido derivatives. The two diastereoisomeric thioamido selenides could be easily separated by flash chromatography. The thioamido selenides, after activation with PhSeCl, underwent deselenylation by a stereospecific intramolecular substitution. Thus both enantiomeric thiazolines could be obtained in enantiomerically pure form.

Asymmetric Amidoselenenylation of Alkenes Promoted by Camphorselenenyl Sulfate: A Useful Synthetic Route to Enantiopure Oxazolines

Camphorselenenyl sulfate is an efficient chiral, nonracemic electrophilic reagent which can be produced from the easily available camphor diselenide by treatment with ammonium persulfate. This electrophilic selenium reagent reacts with alkenes, at room temperature in acetonitrile, in the presence of water and trifluoromethanesulfonic acid to afford the amidoselenenylation products with moderate facial selectivity. However, the two diastereomeric addition products can be easily separated. After activation of the selenium moiety with phenylselenenyl triflate or with SO2Cl2, these products are deselenenylated stereospecifically by intramolecular substitution and afford enantiomerically pure oxazolines.

Diastereo and Enantioselective Synthesis of 1,2-Diols Promoted by Electrophilic Selenium Reagents

Here we report the first example in which the phenylseleno group is directly substituted by a hydroxy function. The reaction is promoted by the PhSeOSO 3 H generated “in situ” by oxidation of (PhSe) 2 with (NH 4 ) 2 S 2 O 8 at reflux in a 3:1 mixture of MeCN-H 2 O. Interestingly the reaction can be performed in “one pot” using a catalytic amount of diselenide affording the corresponding diols ( 5 and 6 ) with good yield and good level of diastereo- and enantioselectivity.

Electrophilic 2-Thienylselenenylation of Thiophene. Preparation of Oligo(seleno-2,5-thienylenes)

Abstract The substitution reactions of thiophene and 2-methylthiophene with the electrophilic selenenylating agent produced from the 2,2′-dithienyl diselenide by oxidation with iodobenzene diacetate involve only the α-positions and give rise to the formation of oligo(seleno-2,5-thienylenes). Products deriving from the attack at the α-positions of thiophene and 2-methylthiophene were also observed starting from the 5,5′-dimethyl-2,2′-dithienyl diselenide. The same electrophilic reagents reacted with furan and 2-methylfuran to afford a mixture of the mono- and di-substituted compounds.

Asymmetric Syntheses Promoted by Organoselenium Reagents

Using chiral nonracemic electrophilic-organoselenium-reagents-asymmetric alkoxy-, hydroxy-, azido- and amido-selenenylation of alkenes were effected with high diastereoselectivity. These reagents have also been employed in catalytic amounts to promote one-pot selenenylation-deselenenylation processes. The asymmetric cyclization of properly substituted alkenes diastereoselectively afforded lactons, tetrahydrofurans oxazolines, thiazolines, pyrrolidines, isoxazolidines, 1,2-oxazines, and cyclic nitrones. Enantiopure dioxane, morpholine, tetrahydrofuran, oxazolidin-2-one and aziridine derivatives were prepared from alkenes, PhSeX, and optically active nucleophiles or substrates.

Kinetic Resolution of Allylic Alcohols Promoted by Electrophilic Selenium Reagents

Abstract The first example of a kinetic resolution process promoted by an electrophilic selenium reagent is reported. Racemic allylic alcohols react with half equivalents of a selenenylating agent in methanol leading to the regiospecific formation of the corresponding addition products with a very high level of facial selectivity (98% de). The unreacted alcohol can be recovered in a optically enriched form (92% ee).

Organic Diselenides: Versatile Reagents, Precursors, and Intriguing Biologically Active Compounds

In this account, we describe how some organic diselenides were successfully used in the past as reagents for asymmetric stereoselective synthesis and more recently as precursors of catalysts and reagents applied in new green protocols. A biomimetic approach offered the possibility to perform oxidative reactions using hydrogen peroxide as oxidant and water as medium affording the desired products in excellent yields under mild conditions. The umpolung of the selenium atom gave novel nucleophilic reagents having a strongly accelerated reaction rate in on water conditions. Finally, the use of diselenides to exploit specific biological activities is described here as seminal examples of a promising field of research currently under investigation in our group.