PAOLA PELUSO - icb.cnr.it · PAOLA PELUSO . CNR Researcher . Istituto di Chimica Biomolecolare ICB...

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PAOLA PELUSO CNR Researcher Istituto di Chimica Biomolecolare ICB - CNR Date and Place of birth June 20, 1965; Lecce, Italy Nationality Italian Email [email protected] ______________________________________________________________________________ Curriculum Vitae MAIN RESEARCH INTERESTS New Materials Design and applications of metal organic frameworks Applications of polysaccharide-based polymers for molecular recognition Chiral Chromatography and Molecular Recognition HPLC enantioseparations, method development, multimodal elution conditions Recognition mechanisms on polysaccharide-based chiral stationary phases Enantioseparation of atropisomeric compounds Design and preparation of new chiral stationary phases Organic Chemistry Chirality Stereochemistry Molecular recognition Organic Synthesis Bridged polycyclic compounds Heterocyclic chemistry Sulfone chemistry CURRENT RESEARCH (2009-2017) Synthesis and applications of 4,4’-bipyridine-based metal-organic frameworks (MOFs) Aubert, E.; Abboud, M.; Doudouh, A.; Durand, P.; Peluso, P.; Ligresti, A.; Vigolo, B.; Cossu, S.; Pale, P.; Mamane, V. Silver(I) coordination polymers with 3,3’,5,5’-tetrasubstituted 4,4’-bipyridine ligands: towards new porous chiral materials. RCS Advances 2017, 7, 7358-7367. Aubert, E.; Doudouh, A.; Peluso, P.; Mamane, V. Ordered water and bipyridine channels in a {[Cu(SiF6)(C10N2H8)2] (C10N2H8)2 (H2O)5}n porous coordination polymer. Acta Crystallogr. E 2016, E72, 1654-1658. Peluso, P.; Mamane, V.; Cossu, S. Homochiral metal-organic frameworks and their application in chromatography enantioseparations. J. Chromatogr. A 2014, 1363, 11-26 (invited review on Special Issue Enantioseparation 2014).

Transcript of PAOLA PELUSO - icb.cnr.it · PAOLA PELUSO . CNR Researcher . Istituto di Chimica Biomolecolare ICB...

PAOLA PELUSO CNR Researcher Istituto di Chimica Biomolecolare ICB - CNR Date and Place of birth June 20, 1965; Lecce, Italy Nationality Italian Email [email protected] ______________________________________________________________________________

Curriculum Vitae MAIN RESEARCH INTERESTS New Materials

• Design and applications of metal organic frameworks

• Applications of polysaccharide-based polymers for molecular recognition

Chiral Chromatography and Molecular Recognition

• HPLC enantioseparations, method development, multimodal elution conditions

• Recognition mechanisms on polysaccharide-based chiral stationary phases

• Enantioseparation of atropisomeric compounds

• Design and preparation of new chiral stationary phases

Organic Chemistry

• Chirality

• Stereochemistry

• Molecular recognition

Organic Synthesis

• Bridged polycyclic compounds

• Heterocyclic chemistry

• Sulfone chemistry

CURRENT RESEARCH (2009-2017) Synthesis and applications of 4,4’-bipyridine-based metal-organic frameworks (MOFs)

• Aubert, E.; Abboud, M.; Doudouh, A.; Durand, P.; Peluso, P.; Ligresti, A.; Vigolo, B.; Cossu, S.; Pale,

P.; Mamane, V.

Silver(I) coordination polymers with 3,3’,5,5’-tetrasubstituted 4,4’-bipyridine ligands: towards new

porous chiral materials.

RCS Advances 2017, 7, 7358-7367.

• Aubert, E.; Doudouh, A.; Peluso, P.; Mamane, V.

Ordered water and bipyridine channels in a {[Cu(SiF6)(C10N2H8)2]·(C10N2H8)2·(H2O)5}n porous

coordination polymer.

Acta Crystallogr. E 2016, E72, 1654-1658.

• Peluso, P.; Mamane, V.; Cossu, S. Homochiral metal-organic frameworks and their application in chromatography enantioseparations.

J. Chromatogr. A 2014, 1363, 11-26 (invited review on Special Issue Enantioseparation 2014).

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Halogen bond-driven enantioseparations • Peluso, P.; Mamane, V.; Aubert, E.; Dessì, A.; Dallocchio, R.; Dore, A.; Pale, P.; Cossu, S.

Insights into halogen bond-driven enantioseparations.

J. Chromatogr. A 2016, 1467, 228-238 (invited article on Special Issue Enantioseparation 2016).

• Peluso, P.; Mamane, V.; Cossu, S.

LC Enantioseparations of halogenated compounds on polysaccharide-based chiral stationary

phases: role of halogen substituents in molecular recognition.

Chirality 2015, 27, 667-684 (invited article on Special Issue Chirality in Separation Science and

Molecular Recognition).

• Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

Insights into the impact of shape and electronic properties on the enantioseparation of

polyhalogenated 4,4’-bipyridines on polysaccharide-type selectors. Evidence of stereoselective

halogen bonding interactions.

J. Chromatogr. A 2014, 1345, 182-192.

Synthesis and enantioseparation of atropisomeric 4,4’-bipyridines • Mamane, V.; Peluso, P.; Aubert, E.; Cossu, S.; Pale, P.

Chiral hexahalogenated 4,4’-bipyridines.

J. Org. Chem. 2016, 81, 4576-4587.

• Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

High-performance liquid chromatography enantioseparation of polyhalogenated 4,4’-bipyridines on

polysaccharide-based chiral stationary phases under multimodal elution.

J. Sep. Sci. 2014, 37, 2481-2489.

• Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

Optimization of the HPLC enantioseparation of 3,3’-dibromo-5,5’-disubstituted-4,4’-bipyridines using

immobilized polysaccharide-based chiral stationary phases.

J. Sep. Sci. 2013, 36, 2993-3003.

• Mamane, V.; Aubert, E.; Peluso, P.; Cossu, S.

Lithiation of prochiral 2,2’-dichloro-5,5’-dibromo-4,4’-bipyridine as a tool for the synthesis of chiral

polyhalogenated 4,4’-bipyridines.

J. Org. Chem. 2013, 78, 7683-7689.

• Mamane, V.; Aubert, E.; Peluso, P.; Cossu, S.

Synthesis, resolution, and absolute configuration of chiral 4,4′-bipyridines.

J. Org. Chem. 2012, 77, 2579-2583.

• Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

High performance liquid chromatography enantioseparation of atropisomeric 4,4’-bipyridines on

polysaccharide-type chiral stationary phases: impact of substituents and electronic properties.

J. Chromatogr. A 2012, 1251, 91-100.

Enantioseparations and molecular recognition mechanisms on polysaccharide-based CSPs • Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

Recent trends and applications in liquid phase chromatography enantioseparation of atropisomers.

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Electrophoresis 2017, 38, doi:10.1002/elps.201600502 (invited review on Special Issue Liquid Phase

Enantioseparations).

• Peluso, P.; Cossu, S.

Comparative HPLC enantioseparation of thirty six aromatic compounds on four columns of the Lux

series. Impact of substituents, shapes and electronic properties.

Chirality 2013, 25, 709-718.

• Peluso, P.; Fabbri, D.; Dettori, M. A.; Delogu, G.; Zambrano, V.; Cossu, S.

High-performance liquid chromatographic enantioseparation of atropisomeric biphenyls on seven

chiral stationary phases.

Curr. Org. Chem. 2011, 15, 1208-1229.

• Peluso, P.; Cossu, S.; Moretto, F.; Marchetti, M.

High performance liquid chromatographic enantioseparation of chiral bridged polycyclic compounds

on Chiralcel OD-H and Chiralpak OT(+).

Chirality 2009, 21, 507-518.

LANGUAGES • Italian

• English

EDUCATION 2003 PhD Degree in Chemical Sciences, Università Ca’ Foscari di Venezia in the group of Prof.

O. De Lucchi. Subject: Desymmetrization reactions of polycyclic alkenes.

1993 Laurea (MS Degree) in Chemistry, Università degli Studi di Pisa in the group of Prof. Rita

Menicagli. Subject: Synthesis and applications of new chiral stationary phases based on

1,3,5-triazine derivatives.

CAREER 2014-to date CNR Researcher, Istituto di Chimica Biomolecolare.

2009-2015 Member of the Internal Advisory Board, Istituto di Chimica Biomolecolare.

2008-2013 CNR Technologist, Istituto di Chimica Biomolecolare.

2001-2002 Research fellowship, Università Ca’ Foscari di Venezia. Subject: Desymmetrization

reactions of polycyclic alkenes.

1999-2000 Research fellowship, VIS Farmaceutici, Padova. Subject: Synthesis of biologically active

compounds.

1997-1998 Research fellowship, F.I.S. - Fabbrica Italiana Sintetici S.p.A., Vicenza. Subject: Synthesis of

pharmacologically active heterocyclic compounds.

1996 Research fellowship, CIBA-GEIGY S.p.A. Divisione Additivi, Bologna. Subject: Reactions of

hydrosilylation and oligomerization of organosilicon compounds.

1994-1995 CNR fellowship, Università degli Studi di Pisa. Subject: Carbonylation reactions of olefinic

substrates.

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Reviewer for the following international journals: Current Pharmaceutical Analysis, Current Analytical

Chemistry (Bentham Science Publishers); Chirality (Wiley), Journal of Chromatography A, Analytica Chimica

Acta (Elsevier); Analyst, Analytical Methods, New Journal of Chemistry (Royal Society of Chemistry); Journal

of the American Chemical Society (American Chemical Society); Materials (MDPI); Journal of Liquid

Chromatography and Related Techniques (Taylor & Francis).

COLLABORATIONS

• Università Ca’ Foscari di Venezia, Dipartimento di Scienze Molecolari e Nanosistemi.

Prof. Sergio Cossu

• Institut de Chimie de Strasbourg, UMR CNRS 7177, Equipe LASYROC.

Dr. Victor Mamane

• Université de Lorraine, UMR CNRS 7036.

Dr. Emmanuel Aubert

• Istituto di Metodologie Chimiche IMC – CNR

Dr.ssa Zeineb Aturki

INVITED CONFERENCES

• Université de Strasbourg (Faculté de Chimie), 2015.

High-performance liquid chromatography (HPLC) on polysaccharide-based chiral stationary phases.

Exploiting the size and shape of molecules to understand chiral recognition mechanisms.

• Istituto di Chimica Biomolecolare, Pozzuoli (NA) (ICB Seminar series 2015), CNR, 2015.

Cromatografia liquida ad alte prestazioni (HPLC) su fasi stazionarie chirali a base polisaccaridica:

enantioseparazioni, meccanismi di riconoscimento e high-throughput screening molecolare.

• Sassari Research Area, Seminar series 2009-2010, 2010. Molecular recognition in organic chemistry.

INTERNATIONAL CONGRESSES 2016

P. Spanu, A. De Mico, A. Cottarelli, F. Morelli, M. Zonfrillo, F. Ulgheri, P. Peluso, A. Mannu, F. Deligia, M.

Marchetti, G. Roviello, A. Reyes Romero, A. Doemling, M. P. Fuggetta, Synthesis and enantiomeric

separation of a novel spiroketal derivative: a potent human telomerase inhibitor with high in vitro anticancer

activity, XXIV EFMC International Symposium on Medicinal Chemistry. Manchester (UK), August 28 -

September 1, 2016.

2014

P. Peluso, V. Mamane, E. Aubert, S. Cossu, Exploiting halogen bonding interaction in high-performance

liquid chromatography enantioseparations, Chirality 2014. Praga (CZ), July 27-30, 2014.

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2012 P. Peluso, V. Mamane, E. Aubert, S. Cossu, High-performance liquid chromatography enantioseparation of

atropisomeric 4,4’-bipyridines on immobilized polysaccharide-based Chiralpak IA and Chiralpak IC: impact of

substituents and electronic properties, 4th EuCheMS Chemistry Congress. Praga (CZ), August 26-30, 2012.

V. Mamane, E. Aubert, P. Peluso, S. Cossu, Atropisomeric chiral 4,4’-bipyridines, 4th EuCheMS Chemistry

Congress. Praga (CZ), August 26-30, 2012.

2010 P. Peluso, D. Fabbri, M. A. Dettori, G. Delogu, S. Cossu, HPLC Enantioseparation of structurally related

chiral compounds on seven chiral stationary phases and computational analysis of the analyte structures,

Ischia Advanced School of Organic Chemistry IASOC 2010. Ischia (Na), September 25-29, 2010.

2001

G. Borsato, S. Cossu, O. De Lucchi, F. Fabris, P. Peluso, Cyclotrimerisation of polycyclic olefins: an

asymmetric approach to a symmetric molecule, 2nd Italian-Japanese Symposium of Organic Chemistry

(JISOC-2). Kyoto, Japan, November 28-30, 2001.

1998

S. Cossu, O. De Lucchi, P. Peluso, R. Volpicelli, Enantiotopic discrimination in the reaction of chiral

alcoholates with Cs-symmetric bis(phenylsulfonyl)alkenes, 2nd Italian-Spanish Symposium on Organic

Chemistry (ISSOC-2). Lecce, June 7-11, 1998.

1996 G. Uccello-Barretta, A. Iuliano, R. Menicagli, P. Peluso, E. Pieroni, P. Salvadori, 1,3,5-Triazine multiselectors

systems: a new tool for chiral discriminations, 8th International Symposium on Chiral Discrimination.

Edimburgh Scotland, June 30 - July 3, 1996. CNR GRANTS 2015 Short term mobility program (three weeks), Équipe LASYROC, CNRS, Université de

Strasbourg.

2010 Annual assignment (€ 1950,00) for training programmes and professional updates.

PARTICIPATION IN RESEARCH PROJECTS 2012-2015 Title: 3rd generation bio-refinery integrated in the territory (BIT3G), MIUR.

Role: Participating researcher.

2010-2012 Title: Diversità molecolare nella sintesi chimica di composti biologicamente attivi di

rilevanza sociale, Regione Sardegna.

Role: Participating researcher.

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2008-to date Title: Chiral liquid chromatography, ADIR-Dipartimento di Scienze Molecolari e

Nanosistemi, Università Ca' Foscari di Venezia.

Role: Participating researcher.

2000 Title: New syntheses of pharmacologically active 1,2-pyridazines, MIUR.

Role: Project coordinator

PARTICIPATION IN TEACHING PROGRAMS Years: 2009-to date

Project: “Alternanza Scuola/Lavoro”

Role: Teacher and laboratory training coordinator

Subject: Molecular recognition and chiral chromatography

High-performance liquid chromatography

Partners: Liceo Scientifico Statale “G. Marconi”, Sassari (2009-to date)

Liceo Classico Statale “D.A. Azuni”, Sassari (2016)

Year: 2009

Project: XIX Settimana della Cultura Scientifica e Tecnologica, Ministero dell’Istruzione,

dell’Università e della Ricerca (March 23th-29th).

Role: Teacher and laboratory training coordinator

Subject: Analysis of organic molecules by means of gas chromatography and GC-mass

spectrometry.

Partner: Liceo Scientifico Statale “G. Marconi”, Sassari

Istituto Tecnico Industriale “G.M. Angioy”, Sassari.

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PUBLICATIONS 36 articles and reviews in international journals (11 as corresponding author), h-index: 11. Total numbers of citations: 318 [Source: Google Scholar, February 2017]

2017

36. Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

Recent trends and applications in liquid phase chromatography enantioseparation of atropisomers.

Electrophoresis 2017, 38, doi:10.1002/elps.201600502 (invited review on Special Issue Liquid Phase

Enantioseparations).

The term Atropisomerism defines a type of enantiomerism that

arises from hindered rotation around an axis that makes two

rotational isomers enantiomers. Atropisomeric compounds are

present in nature, being important building blocks of many

biologically active compounds. Atropisomers have been

extensively studied in environmental and toxicological chemistry

and, in particular, separating them has become a need in specific

fields as organic synthesis and pharmaceutical research. High-

performance liquid chromatography has been fruitfully applied in this context, and, despite HPLC separation

on chiral stationary phase (CSP) is considered as mature technology nowadays, in the last years several

advancements and applications contributed to study compounds where axial chirality is of utmost

importance. Moreover, dynamic chromatography has been exploited as a versatile tool for kinetic studies of

systems with slow internal motion gaining essential information on their stereodynamic behaviour. On this

basis, current topics and trends in liquid phase chromatography enantioseparation of atropisomers are

presented herein with specific focus on new representative applications with HPLC, covering years 2010-

2016. Some examples concerning supercritical fluid chromatography (SFC) applications are also reported.

This review aims to provide the reader with a modern overview of the field in order to highlight the renewed

interest towards the chemistry of molecules with atropisomeric properties. A systematic compilation of all

published literature has not been attempted.

35. Aubert, E.; Abboud, M.; Doudouh, A.; Durand, P.; Peluso, P.; Ligresti, A.; Vigolo, B.; Cossu, S.; Pale, P.;

Mamane, V.

Silver(I) coordination polymers with 3,3’,5,5’-tetrasubstituted 4,4’-bipyridine ligands: towards new porous

chiral materials.

RCS Advances 2017, 7, 7358-7367.

Coordination polymers (CP) assembled from 3,3’,5,5’-

tetrasubstituted 4,4’-bipyridines and silver salts have been

prepared and characterized by X-ray diffraction. Silver-

CPs based on infinite Ag-bipyridine chains were obtained

where one or two halogen atoms strongly interacted with

Ag. A homochiral MOF was also prepared using the

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enantiopure 3,3′-dibromo-5,5′-bis(4-methoxyphenyl)-4,4′-bipyridine as ligand, while its racemic form only

formed a compact CP. Preliminary applications showed that the homochiral network is able to recognize the

enantiomers of rac-stilbene oxide and to control the cytotoxicity level of the Ag-based MOF toward a cell line

derived from adult human skin (HaCaT).

2016

34. Aubert, E.; Doudouh, A.; Peluso, P.; Mamane, V.

Ordered water and bipyridine channels in a {[Cu(SiF6)(C10N2H8)2]·(C10N2H8)2·(H2O)5}n porous coordination

polymer.

Acta Crystallogr. E 2016, E72, 1654-1658.

Water and 4,4'-bipyridine molecules can be accomodated inside the

channels of the porous coordination polymer [Cu(SiF6)(C10N2H8)2]n. Due

to the presence of these ordered species, the framework changes its

symmetry from P4/mmm reported in the literature to P21/c. These guests

4,4'-bipyridine forms chains where the molecules are bound by π··· π

stacking, filling pore of 6.5Å × 6.9 Å free aperture parallel to [100].

Ordered water molecules form infinite chain inside a second pore system

(1.6 Å × 5.3 Å free aperture) which is perpendicular to the first one.

33. Fuggetta, M. P.; De Mico, A.; Cottarelli, A.; Morelli, F.; Zonfrillo, M.; Ulgheri, F.; Peluso, P.; Mannu, A.;

Deligia, F.; Marchetti, M.; Roviello, G. N.; Reyes Romero, A.; Dömling, A.; Spanu, P.

Synthesis and enantiomeric separation of a novel spiroketal derivative: a potent human telomerase inhibitor

with high in vitro anticancer activity.

J. Med. Chem. 2016, 59, 9140-9149.

The synthesis, the enantiomeric separation and the characterization of new simple

spiroketal derivatives has been performed. The synthesised compounds have shown a

very high anticancer activity. Cell proliferation assay showed that they induce a

remarkable inhibition of cell proliferation in all cell lines treated, depending on culture

time and concentration. The compounds have also shown a potent nanomolar human Telomerase inhibition

activity and apoptosis induction. CD melting experiments demonstrate that spiroketal does not affect the G-

quadruplex (G4) thermal stability. Docking studies showed that telomerase inhibition could be determined by

a spiroketal interaction with the telomerase enzyme.

32. Peluso, P.; Mamane, V.; Aubert, E.; Dessì, A.; Dallocchio, R.; Dore, A.; Pale, P.; Cossu, S.

Insights into halogen bond-driven enantioseparations.

J. Chromatogr. A 2016, 1467, 228-238 (invited article on Special Issue Enantioseparation 2016).

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Although the halogen bond (XB) has been so far mainly studied in

silico and in the solid state, its potential impact in solution is yet to

be fully understood. In this study, we describe the first systematic

investigation on the halogen bond in solvated environment by high-

performance liquid chromatography (HPLC). Thirty three

atropisomeric polyhalogenated-4,4’-bipyridines (HBipys), containing

Cl, Br and I as substituents, were selected and used as potential XB donors (XBDs) on two cellulose-based

chiral stationary phases (CSPs) containing potential XB acceptors (XBAs). The impact of the halogens on

the enantiodiscrimination mechanism was investigated and iodine showed a pivotal role on the

enantioseparation in non-polar medium. Electrostatic potentials (EPs) were computed to understand the

electrostatic component of CSP-analyte interaction. Moreover, van’t Hoff studies for ten HBipys were

performed and the thermodynamic parameters governing the halogen-dependent enantioseparations are

discussed. Finally, a molecular dynamic (MD) simulation is proposed to model halogen bond in

polysaccharide-analyte complexes by inclusion of a charged extra point to represent the positive ‘σ-hole’ on

the halogen atom. On the basis of both experimental results and theoretical data, we have profiled the

halogen bond as a chemo-, regio-, site- and stereoselective interaction which can work in HPLC environment

besides other known interactions based on the complementarity between selector and selectand.

31. Mamane, V.; Peluso, P.; Aubert, E.; Cossu, S.; Pale, P.

Chiral hexahalogenated 4,4’-bipyridines.

J. Org. Chem. 2016, 81, 4576-4587.

The preparation of 27 isomers of chiral

hexahalogeno-4,4’-bipyridines by means of two

complementary methods is described. The first

one is convergent and based on the LDA-induced 4,4’-dimerization of trihalopyridines, whereas the second

method is divergent and achieved through regioselective halogenation reactions of 4,4’-bipyridine-2,2’-

diones. Iodine in 2,2’-positions of the 4,4’-bipyridines was introduced by a copper-catalyzed Filkenstein

reaction (Buchwald procedure) performed on 2,2’-dibromo derivatives. Selected compounds of this new

family of atropisomeric 4,4’-bipyridines were enantioseparated by chiral High Performance Liquid

Chromatography (HPLC) and the absolute configurations of the separated enantiomers were assigned by

using X-ray diffraction (XRD) analysis. The later revealed that various halogen bond type are responsible for

crystal cohesion.

2015

30. Peluso, P.; Mamane, V.; Cossu, S.

LC Enantioseparations of halogenated compounds on polysaccharide-based chiral stationary phases: role of

halogen substituents in molecular recognition.

Chirality 2015, 27, 667-684 (invited article on Special Issue Chirality in Separation Science and Molecular

Recognition).

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ABSTRACT Halogenated chiral molecules have become important in

several fields of science, industry, and society as drugs, natural

compounds, agrochemicals, environmental pollutants, synthetic products,

and chiral supports. Meanwhile, the perception of the halogen moiety in

organic compounds and its role in recognition processes changed. Indeed,

the recognition of the halogen bond as an intermolecular interaction

occurring when the halogen acts as a Lewis acid had a strong impact,

particularly in crystal engineering and medicinal chemistry. Due to this

renewed interest in the potentialities of chiral organohalogens, here we

focus on selected recent applications dealing with enantioseparations of halogenated compounds on

polysaccharide-based chiral stationary phases (CSPs), widely used in liquid chromatography (LC). In

particular, recently the first case of halogen bonding-driven high-performance LC (HPLC) enantioseparation

was reported on a cellulose-based CSP. Along with enantioseparations performed under conventional

HPLC, representative applications using supercritical fluid chromatography (SFC) are reported.

2014 29. Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

High-performance liquid chromatography enantioseparation of polyhalogenated 4,4’-bipyridines on

polysaccharide-based chiral stationary phases under multimodal elution.

J. Sep. Sci. 2014, 37, 2481-2489.

ABSTRACT An investigation on the high-

performance liquid chromatography

enantioseparation of 12 polyhalogenated 4,4’-

bipyridines on polysaccharide-based chiral

stationary phases is described. The overall study

was directed toward the generation of efficient

separations in order to obtain pure atropisomers

that will serve as ligands for building homochiral

metal organic frameworks. Four coated columns-

namely, Lux Cellulose-1, Lux Cellulose-2, Lux

Cellulose-4, and Lux Amylose-2-and two immobilized columns-namely, Chiralpak IC and IA-were used under

normal, polar organic, and reversed-phase elution modes. Moreover, Chiralcel OJ was considered under

normal-phase and polar organic conditions. The effect of the chiral selector and mobile phase composition

on the enantioseparation, the enantiomer elution order and the beneficial effect of nonstandard solvents

were studied. The effect of water in the mobile phase on the enantioselectivity and retention was

investigated and retention profiles typical of hydrophilic interaction liquid chromatography were observed.

Interesting phenomena of solvent-induced enantiomer elution order reversal occurred under normal-

phasemode. All the considered 4,4’-bipyridines were enantioseparated at the multimilligram level.

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28. Peluso, P.; Mamane, V.; Cossu, S.

Homochiral metal-organic frameworks and their application in chromatography enantioseparations.

J. Chromatogr. A 2014, 1363, 11-26 (invited review on Special Issue Enantioseparation 2014).

ABSTRACT The last frontier in the chiral stationary

phases (CSPs) field for chromatography

enantioseparations is represented by homochiral metal-

organic frameworks (MOFs), a class of organic-

inorganic hybrid materials built from metal-connecting

nodes and organic-bridging ligands. The modular nature of these materials allows to design focused

structures by combining properly metal, organic ligands and rigid polytopic spacers. Intriguingly, chiral

ligands introduce molecular chirality in the MOF-network as well as homochirality in the secondary structure

of materials (such as homohelicity) producing homochiral nets in a manner mimicking biopolymers (proteins,

polysaccharides) which are characterized by a definite helical sense associated with the chirality of their

building blocks (amino acids or sugars). Nowadays, robust and flexible materials characterized by high

porosity and surface area became available by using preparative procedures typical of the so-called reticular

synthesis. This review focuses on recent developments in the synthesis and applications of homochiral

MOFs as supports for chromatography enantioseparations. Indeed, despite this field is in its infancy,

interesting results have been produced and a critical overview of the 12 reported applications for gas

chromatography (GC) and high-performance liquid chromatography (HPLC) can orient the reader

approaching the field. Mechanistic aspects are shortly discussed and a view regarding future trends in this

field is provided.

27. Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

Insights into the impact of shape and electronic properties on the enantioseparation of polyhalogenated 4,4’-

bipyridines on polysaccharide-type selectors. Evidence of stereoselective halogen bonding interactions.

J. Chromatogr. A 2014, 1345, 182-192.

ABSTRACT Starting from the high-performance liquid chromatography

(HPLC) enantioseparation data collected by using twelve

polyhalogenated 2,2’-dichloro-3-substituted-5,5’-dihalo-4, 4’-bipyridines

as test probes on seven polysaccharide-based chiral stationary phases

(CSPs) under multimodal elution, the impact of substitution pattern,

shape and electronic properties of the molecules on the separation

behaviour was investigated through the evaluation of the

chromatographic parameters (k, α, Rs) and molecular properties

determined by means of quantum chemistry calculations. The

computational/chromatographic screening furnished relevant structure-

chromatographic behaviour relationships and some molecular interactions involved in the chiral

discrimination process could be identified. In particular, a halogen bonding interaction (I•••O) could

reasonably explain the high enantioseparation (α = 1.80, Rs = 8.2) observed for the 2,2’-dichloro-3,5’-diiodo-

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5-bromo-4,4’-bipyridine on Lux Cellulose-1. To the best of our knowledge, this is the first report supporting

the involvement of a stereoselective halogen bonding interaction in polysaccharide-based CSPs. Moreover,

having at disposal a sufficient set of data, the unknown absolute configurations of the eluted enantiomers of

3-methyl-, 3-thiomethyl- and 3-diphenylphosphinoyl-2,2’-dichloro-5,5’-dibromo-4,4’-bipyridines could be

deduced by chromatographic correlation with the enantiomer elution order (EEO) of the related compounds

of known absolute configuration.

2013 26. Peluso, P.; Cossu, S.

Comparative HPLC enantioseparation of thirty six aromatic compounds on four columns of the Lux® series.

Impact of substituents, shapes and electronic properties.

Chirality 2013, 25, 709-718.

ABSTRACT With the aim to define a combined

computational/chromatographic empirical approach useful for

the high-performance liquid chromatography (HPLC) method

development of new chiral compounds, 36 racemic aromatic

compounds with different chemical structures were used as test

probes on four polysaccharide-based chiral stationary phases

(CSPs) of the Lux series, namely Lux Cellulose-1, Lux

Cellulose-2, Lux Cellulose-4, and Lux Amylose-2, using

classical n-hexane/2-propanol mixtures as mobile phase.

Electrostatic potential surfaces (EPSs) determined using Density

Functional Theory (DFT) calculations were used to derive size, shape, and electronic properties of each

analyte. Then a comparative HPLC screening was carried out in order to evaluate the impact of substituents,

shapes, and electronic properties of the analytes on the chromatographic behavior as the column changes.

The four CSPs showed good complementary recognition ability. The elution sequence was determined in 30

cases out of 36. The success rate to afford baseline separations (Rs≥1.5) was estimated: 29 compounds out

of 36 showed baseline enantioseparation on at least one of the four selected CSPs. The combined

computational chromatographic screening furnished useful collective structure-chromatographic behavior

relationships and a map of the chiral discrimination abilities of the considered CSPs towards the analytes.

On this basis, the chromatographic behavior of new analytes on a set of polysaccharide-based CSPs can be

mapped through the qualitative correlation of chromatographic parameters (k, α, Rs) to computed molecular

properties of the analytes.

25. Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

Optimization of the HPLC enantioseparation of 3,3’-dibromo-5,5’-disubstituted-4,4’-bipyridines using

immobilized polysaccharide-based chiral stationary phases.

J. Sep. Sci. 2013, 36, 2993-3003.

13

ABSTRACT The HPLC enantioseparation of nine

atropisomeric 3,3’,5,5’-tetrasubstituted-4,4’-bipyridines

was performed in normal and polar organic (PO) phase

modes using two immobilized polysaccharide-based

chiral columns, namely, Chiralpak IA and Chiralpak IC.

The separation of all racemic analytes, the effect of the

chiral selector, and mobile phase (MP) composition on

enantioseparation and the enantiomer elution order

(EEO) were studied. The beneficial effect of

nonstandard solvents, such as tetrahydrofuran (THF), dichloromethane (DCM), and methyl t-butyl ether on

enantioseparation was investigated. All selected 4,4’-bipyridines were successfully enantioseparated on

Chiralpak IA under normal or POMPs with separation factors from 1.14 to 1.70 and resolutions from 1.3 to

6.5. Two bipyridines were enantioseparated at the multimilligram level on Chiralpak IA. Differently, Chiralpak

IC was less versatile toward the considered class of compounds and only five bipyridines out of nine could

be efficiently separated. In particular, on these columns, the ternary mixture n-heptane/THF/DCM (90:5:5) as

MP had a positive effect on enantioseparation. An interesting phenomenon of reversal of the EEO depending

on the composition of the MP for the 3,3’-dibromo-5,5’-bis-(E)-phenylethenyl-4,4’-bipyridine along with an

exceptional enantioseparation for the 3,3’-dibromo-5,5’-bis-ferrocenylethynyl-4,4’-bipyridine (α = 8.33, Rs =

30.6) were observed on Chiralpak IC.

24. Mamane, V.; Aubert, E.; Peluso, P.; Cossu, S.

Lithiation of prochiral 2,2’-dichloro-5,5’-dibromo-4,4’-bipyridine as a tool for the synthesis of chiral

polyhalogenated 4,4’-bipyridines.

J. Org. Chem. 2013, 78, 7683-7689.

ABSTRACT Lithiation of the achiral

tetrahalogenated 4,4′- bipyridine 1 with alkyllithiums

was investigated. n-BuLi was found to induce either

the chlorine-directed deprotolithiation reaction

alone or with a concomitant halogen−lithium

exchange furnishing after iodine trapping chiral 4,4′-bipyridines 2 and 6, respectively. The role of n-BuLi in

the deprotolithiation process of 1 was elucidated on the basis of isolated secondary derivatives. After

deprotolithiation, the lithiated species could be trapped by different electrophiles such as MeI, TMSCl,

MeSSMe, R3SnCl (R = Me or n-Bu), and PPh2Cl. Moreover, 4,4′-bipyridine 2 was submitted to cross-

coupling reactions (Suzuki and Sonogashira) which occurred selectively at the carbon−iodine bond. All

compounds of this new family of atropisomeric 4,4′-bipyridines were separated by chiral HPLC (high-

performance liquid chromatography), and the absolute configurations of obtained enantiomers were mainly

assigned by XRD (X-ray diffraction) using anomalous dispersion.

14

2012 23. Mamane, V.; Aubert, E.; Peluso, P.; Cossu, S.

Synthesis, resolution, and absolute configuration of chiral 4,4′-bipyridines.

J. Org. Chem. 2012, 77, 2579-2583.

ABSTRACT A chiral polyhalogenated 4,4′-bipyridine derivative is described allowing an easy access to a

new family of chiral 4,4′- bipyridines by site-selective cross-coupling reactions. The absolute configurations of

all the HPLC separated enantiomers were determined by X-ray diffraction and electronic circular dichroism

coupled with time-dependent density functional theory calculations.

22. Peluso, P.; Mamane, V.; Aubert, E.; Cossu, S.

High performance liquid chromatography enantioseparation of atropisomeric 4,4’-bipyridines on

polysaccharide-type chiral stationary phases: impact of substituents and electronic properties.

J. Chromatogr. A 2012, 1251, 91-100.

ABSTRACT The high performance liquid chromatography (HPLC) enantioseparation of eleven atropisomeric

4,4’-bipyridines was performed in the normal and polar organic phase mode using three cellulose-based

chiral stationary phases (CSPs), namely Lux® Cellulose-1, Lux® Cellulose-2, Lux® Cellulose-4, and two

amylose-based CSPs, Chiralpak® AD-H and Lux® Amylose-2. n-Hexane/2-propanol mixtures and pure

ethanol were employed as mobile phases. The combined use of Chiralpak® AD-H and Lux® Cellulose-2

allowed to enantioseparate all the considered bipyridines. Ten bipyridines were enantioseparated at the

multimilligram level allowing the elution sequence determination of the enantiomers as well as their future

use for the preparation of homochiral metal organic frameworks (MOFs). Moreover, the performance of the

CSPs regarding the same bipyridine was different and dependent on the backbone as well as on the side

chain of the polymer. The impact of substitution pattern, shape and electronic properties of the molecules on

the separation behavior was investigated through the evaluation of retention factors (k), separation factors

(α), resolution (Rs) and molecular properties determined using density functional theory (DFT) calculations.

In this regard, the substituents at the 3,3’,5,5’ positions of the 4,4’-bipyridyl rings exhibited a pivotal role on

the enantioseparation.

2011 21. Peluso, P.; Fabbri, D.; Dettori, M. A.; Delogu, G.; Zambrano, V.; Cossu, C.

High-performance liquid chromatographic enantioseparation of atropisomeric biphenyls on seven chiral

stationary phases.

Curr. Org. Chem. 2011, 15, 1208-1229.

ABSTRACT The HPLC enantioseparation of eight racemic atropisomeric biphenyls on commercially

available polymeric Chiralcel OD-H, Lux Cellulose-1, Lux Cellulose-2, Chiralcel OJ, Lux Amylose-2 and

Chiralpak OT(+) and on the brush-type Whelk-O1 columns, both in normal-phase mode and in polar organic

solvent mode, has been investigated. The attempts to enantioseparate the selected biphenyls on Whelk-O1

were unsuccessful. All compounds were well resolved on almost one of the polymeric columns. Lux

15

Cellulose-2 showed to be suitable for enantioseparation of all biphenyls. The effect of mobile phase,

temperature, type of chiral selector and analyte structure on enantioseparation are examined and discussed.

2-Propanol and ethanol were employed as mobile phase modifiers and their influence on the retention and

enantioseparation was investigated. Also a ternary mobile phase (n-hexane/2-propanol/methanol 91:6:3)

was employed to test the separation of the eight biphenyls. In some cases, the elution with pure ethanol

provided good enantioseparation in shorter elution times. The experimental data evidenced the

complemental chiral recognition capabilities of polysaccharide-based CSPs. Noteworthy, Lux Cellulose-1

and Chiralcel OD-H contain the same chiral selector, but the first one exhibited higher retention factors. The

evaluation of chromatographic data provided information about the chiral recognition mechanisms. In this

regard, we report on the effect of ortho and meta biphenyl substituents on the retention and

enantioseparation. In addition, computational evaluation of electrostatic potentials of analytes furnished a

very interesting piece of information about the enantioseparability as well as the chiral recognition

mechanisms on the evaluated chiral selectors.

2009

20. Peluso, P.; Cossu, S.; Moretto, F.; Marchetti, M.

High performance liquid chromatographic enantioseparation of chiral bridged polycyclic compounds on

Chiralcel OD-H and Chiralpak OT(+).

Chirality 2009, 21, 507-518.

ABSTRACT The HPLC enantiomeric separation of 29 racemic bridged polycyclic compounds was examined

on commercially available Chiralcel OD-H and Chiralpak OT(+) columns. The separations were evaluated

under normal-phase mode (hexane containing mobile phase) for Chiralcel OD-H and under normal-phase as

well as under reversed-phase mode (pure MeOH, temperature 58C) for Chiralpak OT(+). Almost all

compounds were resolved either on Chiralcel OD-H or on Chiralpak OT(+), in some cases on both. The use

of trifluoroacetic acid (TFA), as modifier of the hexanic mobile phase, had a beneficial effect on the

enantioseparation of some polar and acidic compounds on Chiralcel OD-H. The influence of small chemical

structural modifications of the analytes on the enantioseparation behavior is discussed. A structure-retention

relationship has been observed on both stationary phases. This chromatographic evaluation may provide

some information about the chiral recognition mechanism: in the case of Chiralcel OD-H, hydrogen bonding,

π-π and distereoselective repulsive are supposed to be the major analyte-CSP interactions. In the case of

Chiralpak OT(+), a reversed-phase enantioseparation could take place through hydrophobic interactions

between the aromatic moiety of the analytes and the chiral propeller structure of the CSP. The synthesis of

some unknown racemic bromobenzobicyclo[2.2.1] analytes is also described.

2006 19. Cossu, S.; Peluso, P.; Moretto, F.; Marchetti, M.

Conversion of γ-substituted bicyclo[2.2.1] (Z)-vinylsulfones to the corresponding (E)-allylsulfones.

Tetrahedron Lett. 2006, 47, 2253-2256.

16

ABSTRACT The preparation of bicyclo[2.2.1] (E)-allylsulfones starting from the corresponding (Z)-

vinylsulfones is described. Starting from 2,3-bis(phenylsulfonyl)norbornadiene 1, the Michael addition of

organometallic reagents followed by the base catalyzed isomerization affords (E)-allylsulfones in high yields.

The procedure allows to obtain vinylidenic norbornenes which are characteristic nuclei of valuable

biologically active compounds.

18. Cossu, S.; Peluso, P.; Alberico, E.; Marchetti, M.

Rhodium catalyzed hydroformylation of 2-phenylsulfonylbicyclo[2.2.1] alkenes: effect of the phenylsulfonyl

group.

Tetrahedron Lett. 2006, 47, 2569-2572.

ABSTRACT The preliminary results of the hydroformylation of 2-phenylsulfonyl substituted norbornene and

norbornadiene derivatives catalyzed by the unmodified Rh(CO)2acac system are presented. The reaction,

occurring under standard oxo conditions, gives polyfunctionalized exo norbornene- and exo

norbornanecarboxaldehydes. The effect of the phenylsulfonyl group has been evaluated: it has been found

that the steric properties of the sulfonyl substituent, more than the electronic ones, influence the

regioselectivity of the process.

17. Cossu, S.; Peluso, P.

Desymmetrization of meso 7-aza-2,3-bis(phenylsulfonyl) bicyclo[2.2.1]hept-2-ene: a re-examination. Kinetic

resolution of racemic 3-arylsulfonyl-7-aza-2-bromobicyclo[2.2.1]hepta-2,5-dienes.

Tetrahedron Lett. 2006, 47, 4015-4018.

ABSTRACT The inexpensive large scale preparation of N-methoxycarbonyl-7-aza-2,3-bis(phenylsulfonyl)

bicyclo[2.2.1]hept-2-ene and the re-examination of its stereoselective desymmetrization are reported.

Moreover, the kinetic resolution of N-protected 3-arylsulfonyl-7-aza-2-bromobicyclo[2.2.1]hepta-2,5-dienes

promoted by (R,R)-hydrobenzoin is described, representing a new tool to fix the absolute stereochemistry of

the 7-azabicyclo[2.2.1] skeleton.

2005 16. Cossu, S.; Peluso, P.

Diastereoselective desymmetrization of meso bis(phenylsulfonyl) polycyclic alkenes promoted by C2

symmetric chiral diolates: direct access to optically pure ketals and ketones.

Org. Chem.: an Indian J. 2005, 1, 1-17.

ABSTRACT The desymmetrization of meso 1,2-bis(phenylsulfonyl) substituted bridged polycyclic alkenes

promoted by C2 symmetric chiral diolates is reported. The phenylsulfonyl group exerts an

electronwithdrawing effect onto the C-C double bond, making the alkenylic function a good Michael acceptor:

enantiotopic Csp2 react with the enantiopure nucleophile which has been used in stoichiometric amount. The

stereoselective process leads to the formation of optically pure α-phenylsulfonylsubstituted polycyclic ketals,

17

which are valuable intermediate in the synthesis of polycyclic α-phenylsulfonylketones and ketones. The

kinetic resolution of a racemic mixture of a tolylsulfonylsubstituted polycyclic alkene is also reported.

15. Cossu, S.; Peluso, P.

Stereoselective desymmetrizations: role of symmetry, stereofacial discrimination and steric effects.

Org. Chem.: an Indian J. 2005, 1, 18-37.

ABSTRACT A stereoselective desymmetrization is a symmetry breaking synthetic operation and represents

a powerful synthetic tool not only for the preparation of new chiral synthons or building blocks, but also for

the applications in the target oriented synthesis, yielding enantiomerically enriched products. In this

microreview, after a brief historical overview of the origin of the method, through representative exxamples

that go back to the last six years, we describe the role of molecular symmetry and steric effects on the

stereotopic and stereofacial discrimination mechanisms. The most effective procedures to perform a

stereoselective desymmetrization of a non-chiral symmetric compound by nonenzymatic or enzymatic

methods are here presented.

2002 14. Samaritani, S.; Peluso, P.; Malanga, C.; Menicagli, R.

Selective amination of cyanuric chloride in the presence of 18-crown-6.

Eur. J. Org. Chem. 2002, 1551-1555.

ABSTRACT An interpretation of the role of 18-crown-6 in the selective di- and trialkylamination of 2,4,6-

trichloro-1,3,5-triazine is reported, and the usefulness of the procedure is shown.

13. Peluso, P.; Greco, C.; De Lucchi, O.; Cossu, S.

Synthesis of 2-mono- and 2,3-disubstituted polycyclic alkenes.

Eur. J. Org. Chem. 2002, 4024-4031.

ABSTRACT A range of mono- and disubstituted (−Br, −Cl, −SPh, −SO2Ph) polycyclic alkenes has been

prepared starting from alkenes by inexpensive and high-yielding synthetic routes.

12. Peluso, P.; De Lucchi, O.; Cossu, S.

Role of copper in the stereoselective metal-promoted cyclotrimerisation of polycyclic alkenes.

Eur. J. Org. Chem. 2002, 4032-4036.

ABSTRACT Copper-mediated stereoselective cyclotrimerisation of polycyclic alkenes is reported. The

mechanism involved provides strong support for the involvement of a Cu III intermediate in cross-coupling

reactions of sp2-carbon atoms.

18

2001 11. Cossu, S.; De Lucchi, O.; Peluso, P.; Volpicelli, R.

Improved selective synthesis of (Z)- and (E)-1,2-bis(phenylsulfonyl)chloroethylene.

Synth. Commun. 2001, 31, 27-32.

ABSTRACT The preparation of the title compounds (Z)- and (E)-1, which are synthetic substitutes for the

unstable bis(phenylsulfonyl)acetylene and key reagents for the asymmetric preparation of polycyclic ketones,

has been revisited and improved. Starting from inexpensive materials such as trichloroethylene, thiophenol,

and hydrogen peroxide, (Z)- and (E)-1 are selectively obtained in multigram quantity in 52% overall yields.

10. Ballini, R.; Bosica, G.; Cossu, S.; De Lucchi, O.; Peluso, P.

Observations in the alkylation of β-acetalic carbanions: monoalkylation vs. dialkylation and elimination.

Tetrahedron 2001, 57, 4461-4465.

ABSTRACT The reaction with methyl iodide and a base (t-BuOK) of 1,3-dioxolanes and 1,3-dithiolanes

substituted at the β-position with an electron-withdrawing substituent (EWG = -CO2Me, -SO2Ph, -SO2Ph-p-

NO2, SO2Ph-o-NO2) leads to mono- or dialkylated or ring opened products in good yield.

9. Cossu, S.; De Lucchi, O.; Paulon, A.; Peluso, P.; Zonta, C.

Anti-selective Heck cyclotrimerisation of polycyclic bromoalkenes.

Tetrahedron Lett. 2001, 42, 3515-3518.

ABSTRACT Vinyl halides can react as both substrate and reagent in the Heck reaction. In the case of

bicyclic vinyl halides, the reaction leads to cyclotrimers through an anti-selective process.

8. Cossu, S.; Cimenti, C.; Peluso, P.; Paulon, A; De Lucchi, O.

Enantiomeric discrimination in a reiterative domino coupling process: Cu (I)-mediated syn-cyclotrimerization

of racemic polycyclic trimethylstannyl bromonorbornadienes.

Angew. Chem. Int. Ed. 2001, 40, 4086-4089.

ABSTACT Herein we report a new CuI-mediated cyclotrimerization of racemic 3-bromo-2-

trimethylstannylalkenes which affords syn cyclotrimers through a reiterative enantiomeric discrimination

process.

2000 7. Peters, K.; Peters, E.-M.; Volpicelli, R.; Cossu, S.; De Lucchi, O.; Peluso, P.

Crystal structure of 2β,3β-bis(phenylsulfonyl)-2α-chlorobicyclo[2.2.1]hepta-5-ene, C7H7(SO2C6H5)2Cl.

Z. Kristallogr. NCS 2000, 215, 33-34.

6. Peters, K.; Peters, E.-M.; Volpicelli, R.; Cossu, S.; De Lucchi, O.; Peluso, P.

19

Crystal structure of 3α,4α-4',5'-diphenyl-3-(phenylsulfonyl)1R-[1α,2(4'R*,5'R*)spiro]bicyclo[2.2.1]hept-5-

ene,2'[1,3]dioxolane,[(C6H5SO2)C7H7][C2H2O2(C6H5)2].

Z. Kristallogr. NCS 2000, 215, 231-232.

5. Cossu, S.; De Lucchi, O.; Peluso, P.; Volpicelli, R.

Li+ and Na+ switch of enantioselectivity in the desymmetrisation of polycyclic bis(phenylsulfonyl)alkenes by

chiral alcohols.

Tetrahedron Lett. 2000, 41, 7263-7266.

ABSTRACT A complete switch of enantioselectivity is obtained in the desymmetrisation reaction of polycyclic

bis(phenylsulfonyl)alkenes by the change of the base from n-BuLi to NaH, thus allowing convenient access

to either enantiomer of polycyclic ketones with the same chiral auxiliary.

1999 4. Zonta, C.; Cossu, S.; Peluso, P.; De Lucchi, O.

Stereochemistry of the cyclotrimerisation of enantiopure polycyclic bromostannylalkenes: mechanistic

considerations on the coupling of alkenyl stannanes by copper (II) nitrate.

Tetrahedron Lett. 1999, 40, 8185-8188.

ABSTRACT The cyclotrimerisation of enantiopure l-bromo-2-trimethylstannylbenzonorbornadiene 2, contrary

to the expectations, affords predominantly the trimer anti-4. This observation suggests that the reaction

proceeds mainly via a Sn-Sn coupling to produce the dimer anti-5 and a tin-copper product that triggers

halogen-metal exchange on the dimer thus allowing a second coupling with the starling reagent eventually

leading to the anti- trimer. The little but consistent formation of the isomer syn-4 and meso dimer 5 can arise

from a racemisation of the bromine-copper-tin intermediate possibly via an alkyne structure.

3. Cossu, S.; De Lucchi, O.; Peluso, P.; Volpicelli, R.

Enantioselective synthesis of polycyclic ketones by desymmetrisation of bis(phenylsulfonyl)alkenes with

chiral alcoholates. Control of the absolute configuration by simple modification of the chiral auxiliary.

Tetrahedron Lett. 1999, 40, 8705-8709.

ABSTRACT Treatment of polycyclic bis(phenylsulfonyl)alkenes with chiral alcoholates, followed by acidic

work-up, affords enantioselectively ct-phenylsulfonyl ketones. The enantioselectivity is total with

monomethylated hydrobenzoin and of opposite configuration with respect to that obtained with hydrobenzoin

itself. Thus, starting from a bis(phenylsulfonyl)alkene, it is possible to obtain either the R or S polycyclic

ketone by the use of the same chiral auxiliary (hydrobenzoin) and a simple modification (methylation of one

of the hydroxy functions).

1997 2. Uccello-Barretta, G.; Iuliano, A.; Menicagli, R.; Peluso, P.; Pieroni, E.; Salvadori, P.

1,3,5-Triazine multiselector systems: new tools for chiral discrimination.

20

Chirality 1997, 9, 113-121.

ABSTRACT 2-Hexylamino-4-[(S)-1-(1-naphthyl)ethylamino]-6-L-valyl-L-valyl-L-valine isopropylester-1,3,5-

triazine (1), a molecule characterized by two different chiral selectors, and 2-hexylamino-4,6-bis-L-valyl-L-

valyl-L-valine isopropylester-1,3,5-triazine (2) and 2-ethoxy-4-hexylamino-6-[(S)-1-(1-naphthyl)ethylamino]-

1,3,5-triazine (3), systems in which a single kind of chiral selector is present, have been prepared. The

enantiodiscriminating ability in solution of the three compounds toward the N-3,5-dinitrobenzoyl derivatives of

1-phenylethylamine (4) or valine methylester (5) has been investigated by 1H nuclear magnetic resonance

(NMR) spectroscopy: 1 shows an improved versatility, relative to 2 and 3, as a chiral solvating agent for NMR

spectroscopy. On the basis of the indications obtained, the usefulness of 2-chloro-4-[(S)-1-(1-

naphthyl)ethylamino]-6-L-val-L-val-L-valine isopropylester-1,3,5-triazine (1a), a direct precursor of 1, as chiral

solvating agent for the determination by NMR of the enantiomeric compositions of derivatives of amines,

amino alcohols, amino acids, and carboxyl acids bearing a 3,5-dinitrophenyl moiety, has been demonstrated.

1994 1. Menicagli, R.; Malanga, C.; Peluso, P.

Selective mono- or dialkoxylation of 2,4,6-trichloro-1,3,5-triazine in solid-liquid phase transfer conditions.

Synth. Commun. 1994, 24, 2153-2158.

ABSTRACT In solid-liquid phase transfer conditions, both the primary and the secondary alcohols react

cleanly with 2,4,6-trichloro-1,3,5-triazine to give the corresponding mono or dialkoxy derivatives depending

on the reagent molar ratio.