Silvia Sternativo

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).

A sulfur-containing diselenide as an efficient chiral reagent in asymmetric selenocyclization reactions

Abstract Treatment of the di-2-[(1 S )-1-(methylthio)ethyl]phenyl diselenide with bromine and silver triflate afforded the corresponding selenyl triflate which was used in situ as a strongly electrophilic selenium reagent to effect the asymmetric synthesis of oxygen- or nitrogen-containing heterocycles. Cyclic ethers, lactones, lactams or N -protected pyrrolidines have been prepared in good yield with complete regioselectivity and high diastereoselectivity.

Optically active isoxazolidines and 1,3-amino alcohols by asymmetric selenocyclization reactions of O-allyl oximes

Abstract The selenyl triflate generated from the reaction of di-2-[(1 S )-1-(methylthio)ethyl]phenyl diselenide with silver triflate reacts with various substituted O -allyl oximes to promote ring closure, which affords optically active isoxazolidines in high yields and with good diastereoselectivity (up to 93:7). Enantiomerically enriched 1,3-amino alcohols can be easily obtained by N  O bond cleavage of these heterocycles, which was readily effected by treatment with zinc in aqueous acetic acid.

Synthesis of enantiomerically pure 1,4-dioxanes from alkenes promoted by organoselenium reagents

Abstract An alkene can be converted into two enantiomerically pure diastereomeric selenoethers through a regio- and stereospecific anti addition reaction mediated by N -(phenylseleno)phthalimide in the presence of an enantiomerically pure 1,2-diol. This alkoxyselenylation reaction can be employed as the key step to allow the synthesis of several isomeric tetrasubstituted 1,4-dioxanes in enantiomerically pure form.

Selenium-promoted synthesis of enantiomerically pure substituted morpholines starting from alkenes and chiral aminoalcohols

Abstract Enantiomerically pure 2,3,5-trisubstituted morpholines with two newly created stereocenters have been prepared by a short synthetic sequence having as the key step the selenium-promoted addition of ( R )-phenylglycinol to a substituted alkene.

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.

Direct chromatographic enantioresolution of fully constrained β-amino acids: exploring the use of high-molecular weight chiral selectors

To the best of our knowledge enantioselective chromatographic protocols on β-amino acids with polysaccharide-based chiral stationary phases (CSPs) have not yet appeared in the literature. Therefore, the primary objective of this work was the development of chromatographic methods based on the use of an amylose derivative CSP (Lux Amylose-2), enabling the direct normal-phase (NP) enantioresolution of four fully constrained β-amino acids. Also, the results obtained with the glycopeptide-type Chirobiotic T column employed in the usual polar-ionic (PI) mode of elution are compared with those achieved with the polysaccharide-based phase. The Lux Amylose-2 column, in combination with alkyl sulfonic acid containing NP eluent systems, prevailed over the Chirobiotic T one, when used under the PI mode of elution, and hence can be considered as the elective choice for the enantioseparation of this class of rigid β-amino acids. Moreover, the extraordinarily high α (up to 4.60) and RS (up to 10.60) values provided by the polysaccharidic polymer, especially when used with camphor sulfonic acid containing eluent systems, make it also suitable for preparative-scale enantioisolations.