

Modern chemical transformations should be based on simple and innovative synthetic processes implying the containment of production costs, wastewaters, and reduced use of organic solvents. This can be attained, inter alia, by tandem (or cascade) reactions which allow for structural modifications of the organic compounds through the formation of several chemical bonds in a single, one-pot operation.
In the present project we plan to exploit the catalysis exerted by complexes of two transition metals of the IB group, i.e., copper and gold, for establishing novel and efficient synthetic procedures based on tandem reactions from alkenes and alkynes, which we have selected as ideal platforms for metal-catalyzed tandem reactions.
State of the art

One of the scientific goals of AMODIVE is to trap in a tandem fashion chiral alkyl-copper and boryl-copper intermediates with electrophiles not yet considered in order to create molecular diversity in a streamlined asymmetric fashion.

We plan to study the enantioselective gold-catalyzed rearrangement of suitably substituted propargyl vinyl ethers and propargyl esters to enable cascade processes entailing a [3.3]-rearrangement and either a Nazarov cyclization or a hydroarylation step, ultimately leading to nonracemic pentannulated N-heterocycles, carbocycles and aromatic structures. Carrying out the reaction in the presence of a (hetero)dienophile would add further chemical complexity to the final compounds

Dina Scarpi, Claudia Capanni, Samuele Visi, Cristina Faggi, and Ernesto G. Occhiato
The Journal of Organic Chemistry 2024, 89 (19), 14108-14119
DOI: 10.1021/acs.joc.4c01518
A one-pot synthesis of ring-fused, α-hydrazineyl-2-cyclopentenone derivatives is achieved by a gold(I)-catalyzed Rautenstrauch/hetero Diels–Alder/ring opening tandem reaction of suitable propargyl esters. By mixing the latter with a dialkylazodicarboxylate in the presence of a gold(I) catalyst, the 1,2-acyloxy migration/cyclization process (Rautenstrauch reaction) leads to cyclopentadienyl ester intermediates which are trapped by the heterodienophile present in situ. This provides strained intermediates which spontaneously undergo highly regioselective ring opening by a retro aza-Michael reaction promoted by the gold(I) catalyst, eventually yielding the target compounds. Six- and seven-membered ring-fused cyclopentenones bearing a pendant α-hydrazineyl moiety can be obtained in moderate to excellent yield (50–98%) by this approach, with a minimal erosion of the initial optical purity when using enantioenriched substrates.
Lucrezia Margherita Comparini, Giulio Gallorini, Lucilla Favero, Francesca Sardelli, Valeria Di Bussolo, Sebastiano Di Pietro, and Mauro Pineschi
The Journal of Organic Chemistry 2024 89 (21), 15652-15664
DOI: 10.1021/acs.joc.4c01769
We herein report an unprecedented ring-opening of unstrained cyclic aminals such as imidazolidines and hexahydropyrimidines by the use of Grignard and cuprate reagents to give secondary sulfonamides bearing diversely substituted tertiary amines in the β- or γ-position. This synthetic procedure can be carried out in a one-pot fashion without collateral reactions that are commonly associated with sp3-organometallic multicomponent Mannich-type reactions, indicating the fundamental role of sulfonamide protection of the second nitrogen atom in the generation of the cyclic aminal and in the ring-opening process. Computational density functional theory (DFT) data point to the formation of a transient iminium ion intermediate, in which the Lewis acidity of the cationic component of the organometallic reagent triggers the ring-opening process by coordination. The presented method allows the nucleophilic decoration of diamines including those bearing an adjacent chiral center to the tertiary amine not easily achievable by means of alternative standard synthetic procedures.

Dina Scarpi, Samuele Visi and Ernesto G. Occhiato
European Journal of Organic Chemistry 2025, 28 (17), e202500049 (GOLD OPEN ACCESS)
DOI: 10.1002/ejoc.202500049
The electrophilic α-hydrazination (generally referred to as α-amination) of carbonyl compounds with dialkyl azodicarboxylates is a powerful approach for the preparation of synthetically useful intermediates such as α-amino aldehydes and ketones, α-amino acids, and β-amino alcohols. Many methods for the enantioselective α-hydrazination have been published in the past and many new approaches have been disclosed in the last decade that deal with previously unresolved issues such as the direct enantioselective α-hydrazination of α-branched ketones. The enantioselective α-hydrazination is the field where most significant advances have been attained thanks to new approaches, catalysts and techniques. With this review we intend to cover the literature that appeared between 2015 and 2024. We will classify the various methods according to the strategies for the enantioselective formation of the new C−N bond, mainly based on the formation of chiral enamines, enols and enolates. Miscellaneous methods are grouped at the end of the review. Where relevant, the application of α-hydrazino carbonyl compounds to the synthesis of target molecules will also be illustrated.

Dina Scarpi, Giovanni Turchi, Matteo Fazzini, Lucilla Favero and Ernesto G. Occhiato
The Journal of Organic Chemistry 2025, 90, 20, 6743–6754
DOI: 10.1021/acs.joc.5c00433
An easy approach to the enantioselective synthesis of five-, six-, and seven-membered ring-fused cyclopentadienes (85–99% ee) is based on the Au(I)-catalyzed cycloisomerization of enantiomerically pure or enriched propargyl vinyl ethers, which occurs with complete central-to-axial-to-central chirality transfer. DFT calculations show that the formation of a nonplanar σ-Au(I)-pentadienyl cation intermediate having a helical configuration, which quickly cyclizes to form the target cyclopentadiene, accounts for the lack of erosion of the initial optical purity. From a synthetic point of view, when the cyclopentadienes are subjected to a quick 1,5-H shift and cannot be isolated as pure regioisomers, they can be trapped in situ by suitable dienophiles during or immediately after the gold(I)-catalyzed cycloisomerization to form more complex polycyclic compounds. The synthesis of an enantiomerically pure α-tertiary amine was realized to demonstrate the usefulness of this approach.

Francesca Sardelli, Lucilla Favero, Lucrezia Margherita Comparini, Valeria Di Bussolo, Sebastiano Di Pietro and Mauro Pineschi
Molecules 2026, 31(4), 731
DOI: 10.3390/molecules31040731
A mechanistically unusual CuCN-catalyzed electrophilic amidation of Grignard reagents with N-H containing O-allyl- and O-benzyl-hydroxamic acid derivatives as leaving groups to give secondary amides is reported. Computational DFT examination of the reaction points to the intermediate formation of electrophilic acyl nitrenoid species triggered by the presence of CuCN and magnesium salts. The work also provides some experimental evidence about the molecular composition and reactivity of organomagnesium cuprates, the structural nature of which remains a subject of ongoing debate.
S. Visi, C. Capanni, D. Scarpi, E. G. Occhiato “Synthesis of functionalized 2-cyclopentenones by the gold (I)-catalyzed Rautenstrauch reaction”, II Virtual Symposium on Pericyclic Reactions and Synthesis of Carbo- and Heterocyclic Systems, Messina, 28-29 Novembre 2024.
L. M. Comparini, G. Gallorini, F. Sardelli, L. Faveroa M. Pineschi “Ring-opening reactions of unstrained cyclic aminals with Grignard reagents”. Congresso Nazionale della Società Chimica Italiana SCI 2024 - Milano, 26-30 agosto 2024.
S. Di Pietro, M. C. Santangelo, L. Papa, M. A. Ali, M. Gary-Bobo, M. Pineschi, V. Di Bussolo, O. Maury. “Conjugation of Luminescent Lanthanide Probes with Bioactive Molecules: Imparting Selectivity of Action by Increasing Molecular Diversity”. Congresso Nazionale della Divisione di Chimica Organica della Società Chimica Italiana CDCO2025 - Cagliari, 21-25 settembre 2025
Ernesto G. Occhiato, Dina Scarpi, Giovanni Turchi, Lucilla Favero. “Central-to-Axial-to-Central Chirality Transfer in the Au(I)-Catalyzed Cycloisomerization of Propargyl Vinyl Ethers to Cyclopentadienes”. SMOS 12 - 12th Asian-European Symposium on Metal Mediated Organic Synthesis – Bologna 21-23 May 2025.
Samuele Visi, Dina Scarpi, Ernesto G. Occhiato. “Synthesis of Functionalized 2-Cyclopentenones by a Cascade Process Involving the Gold(I)-catalyzed Rautenstrauch Reaction” SMOS 12 - 12th Asian-European Symposium on Metal Mediated Organic Synthesis – Bologna 21-23 May 2025.
F. Sardelli, B. Baldini, L.M. Comparini, S. Di Pietro, M. Pineschi. “Development of copper-catalyzed regio- and stereoselective tandem functionalizations using strained heterocyclic rings”. Congresso Nazionale della Società Chimica Italiana SCI 2024 - Milano, 26-30 agosto 2024.
L. M. Comparini, F. Sardelli, L. Favero, S. Di Pietro, G. Daniele, M. Falasca, B. Polini, V. Citi, M. Pineschi. “Achieving molecular diversity to create new cost-effective drugs for diabesity and neurodegenerative diseases: a case study from our lab”. Congresso Nazionale della Divisione di Chimica Organica della Società Chimica Italiana CDCO2025 - Cagliari, 21-25 settembre 2025.
F. Sardelli, A. Del Vecchio, C. Campinoti, L.M. Comparini, F. Bellina, M. Pineschi. Development of novel protocols to create molecular diversity leveraging on nitroso-Diels Alder reactions. Congresso Nazionale della Divisione di Chimica Organica della Società Chimica Italiana CDCO2025 - Cagliari, 21-25 settembre 2025.
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University of Pisa University of Florence

Master Degree in Chemistry and Pharmaceutical Technology in 1990 at the University of Pisa.
-1991-1994 Ph.D Degree-Thesis Title: Reactions of 1,2-epoxides and their application to organic synthesis (Supervisor: Prof. Paolo Crotti).
1994-1996 Post-doc at the University of Pisa with Prof. Franco Macchia
1997 INDIVIDUAL MARIE-CURIE FELLOWSHIP at the Department of Organic and Molecular Inorganic Chemistry, University of Groningen, THE NETHERLANDS (supervisor Prof. Dr. Ben Feringa, Nobel Laureate Chemistry year 2016).
-1998-2002 ASSISTANT PROFESSOR (Ricercatore Universitario)
-2000 recipient of the Ciamician Medal, a prestigious award of the Organic Division of the Italian Chemical Society mainly for his achievements on new catalytic enantioselective carbon-carbon bond formation.
-2002 ASSOCIATE PROFESSOR of Organic Chemistry at the Department of Bioorganic Chemistry, University of Pisa.
-2017 FULL PROFESSOR of Organic Chemistry at the Department of Pharmacy, University of Pisa.
Member of the Editorial Advisory Board of the following Journals: Current Organic Chemistry (Bentham Science) and Molecules (MDPI). Member of the Scientific Committee of the A. Corbella International Summer School on Organic Synthesis (ISOS).
He has 116 publications in international peer-reviewed journals, including the most prestigious journals in chemistry.
Sum of the times cited=3915 (Scopus)
h-index=35 (Scopus)
Research activity: The main interest is about the development of new stereoselective synthetic methodologies. In particular, his research activity has been devoted to
1) Novel approach to the synthesis of heterocyclic scaffolds of biological/pharmaceutical interest
2) Development of new catalytic synthetic processes
3) Asymmetric catalysis using organometallic reagents and strained heterocyclic rings
Website: https://people.unipi.it/mauro_pineschi

Ernesto G. Occhiato graduated in Chemistry in 1989 at the University of Florence and carried out his Ph.D. studies in Chemical Science from 1991 to 1994 at the Department of Organic Chemistry, University of Florence (Italy), spending one year at the Department of Chemistry, University of Toronto (Canada) with Prof. Bryan Jones. After a CNR fellowship and post-doctoral studies from 1995 to 2000, he became Researcher at the University of Florence and from 2011 is Associate Professor of Organic Chemistry at the Department of Chemistry “U. Schiff”, University of Florence. He has the national scientific habilitation as Full Professor in Organic Chemistry from April 4th, 2017.
His scientific interests are focused on the development of novel synthetic methodologies based on transition metal (Pd, Au) and enzyme catalysis for the synthesis of naturally occurring hetero- and carbocyclic compounds and new molecular entities possessing biological activity (enzyme inhibitors, receptor ligands, and vaccine adjuvants). More recent interests include (a) the synthesis of hetero- and carbocycles by Au(I)-catalyzed cascade processes involving propargyl alcohol derivatives, (b) the synthesis of novel conformationally constrained unnatural amino acids for peptidomimetics, and (c) the synthesis of strigolactone analogues for the control of plant growth. He is author/co-author of 105 papers published in international peer reviewed journals. His h-index is 30.
Website: https://www.unifi.it/p-doc2-0-0-A-3f2a3d31332e29.html
Research unit of Pisa Research unit of Florence
Prof. Mauro Pineschi
Dott.ssa Lucrezia Margherita Comparini
Dott.ssa Lucilla Favero
Prof. Sebastiano Di Pietro
Prof. Ernesto Giovanni Occhiato
Dott.ssa Dina Scarpi
Dott. Giovanni Turchi