Main focus of the research is the design and synthesis of novel multi-site (pro)nucleophilic and (pro)electrophilic carbon matrices – mainly in the heterocyclic domain – and their exploitation in vinylogous and multivinylogous carbon-carbon bond-forming reactions.

Vinylogy concept: Firstly introduced by R. C. Fuson in 1935, the “Principle of Vinylogy” states that a given functional group within a molecule may relay its function (i.e. its electronic properties) to a distant point in the molecule provided that interposed conjugated unsaturated linkages are present. As an example, g-enolization of α,β-unsaturated carbonyl compounds provides ambident C-nucleophiles where the conventional “normal” C-a nucleophilicity may be usurped by that of the distant, vinylogous C-γ  carbon atom. Extending this concept, a conjugated polyenolate may be regarded as a multi-site C-nucleophile on the alternating α, γ,ε, ..., ω carbon sites. The synthesis of such pluripotent substrates and their use in chemo/regio/stereocontrolled synthesis is a formidable challenge in contemporary organic synthesis.

In recent past years, application of the vinylogy concept in asymmetric synthesis enabled us to access diverse collections of high-quality small-molecule scaffolds and targets ranging from unnatural and natural carbasugars and alkaloids to nucleosides, amino acids, peptidomimetics and heterocycles (e.g. γ-butenolides, pyrrolinones, 2-oxindoles). Thus, the exploitation of the “vinylogy concept” is a powerful opportunity to selectively accessing molecular diversity en route to biologically and pharmaceutically relevant molecules.

Main publications about this subject (2006-2016):

1. Marcantonio E., Guazzetti D., Bugatti K., Battistini L., Sartori A., Pelosi G., Curti C., Zanardi F. Turning the Imidazole Core into Three-Dimensional Ring Systems: Mild Organocatalytic Entry to Enantiopure 6,7-Dihydrobenzimidazoles, Chem. Eur. J. 2023, e202301200, https://doi.org/10.1002/chem.202301200

2. Marcantonio E., Zanardi F., Curti C. and Lombardo M. Mechanistic Insights into the Stepwise (4+2) Cycloaddition toward Chiral Fused Uracil Derivatives. Adv. Synth. Catal. 2023, 365; https://doi.org/10.1002/adsc.202300045 

3. Curti C., Sartori A., Battistini L., Zanardi F. Chapter 14: Merging Organocatalysis with Vinylogy – New Opportunities for Asymmetric,  Synthesis, Asymmetric Organocatalysis: New Strategies, Catalysts, and Opportunities, Volume 2, Wiley-VCH, 2022,  https://doi.org/10.1002/9783527832217.ch14

4. Curti C., Marcantonio E., Sartori A., Battistini L., Zanardi F., Accessing Chiral Dihydro- and Tetrahydriquinazoline-2,4-diones via [4+2]-cycloadditions: From Pioneering Studies To Asymmetric Organozatalyzed Syntheses, Targets In Heterocyclic Systems, Vol 26, 2022, Società Chimica Italiana, https://soc.chim.it/it/libri_collane/ths/vol_26_2022 

5. Marcantonio, E.; Curti, C.; Battistini, L.; Sartori, A.; Cardinale, L.; Pelosi, G.; Zanardi, F. Direct, Asymmetric Synthesis of Carbocycle-Fused Uracils via [4+2] Cycloadditions: a Noncovalent Organocatalysis Approach. Adv. Synth. Catal. 2021, 363, 1-10. DOI: 10.1002/adsc.202100082 

6. Curti C.; Rassu, G.; Lombardo, M.; Zambrano, V.; Pinna, L.; Battistini L.; Sartori, A-; Pelosi, G.; Zanardi F. Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach. Angew.Chem. Int. Ed. 2020, 59,20055–20064. DOI: 10.1002/anie.202007509

7. Curti, C.; Sartori, A.; Battistini, L.; Zanardi F. New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems. Chem. Rev. 2020, 120, 5, 2448–2612. DOI: 10.1021/acs.chemrev.9b00481

8. Curti, C.; Sartori, A.; Battistini, L.; Zanardi F. Exploring the Remote Reactivity of π-Extended Carbonyl Compounds: The Vinylogous Alkylidene Malononitrile Activation Strategy. Synlett 2018; 29(03): 266-281. DOI: 10.1055/s-0036-1589125 

9. Curti, C.; Battistini, L.; Sartori, A.; Rassu, G., Pelosi G., Lombardo, M.; Zanardi F. (E)‐3‐(Alkoxycarbonyl‐2‐Alkyliden)‐2‐Oxindoles: Multidentate Pronucleophiles for the Organocatalytic, Vinylogous Michael Addition to Nitroolefins. Adv. Synth. Catal. 2018, 360, 711 –721. DOI: 10.1002/adsc.201701164

10. Battistini, L.; Curti, C.; Rassu, G.; Sartori, A.; Zanardi, F. Enolizable Alkylidene Heterocyclic and Carbocyclic Carbonyl Systems­: Valuable Vinylogous Donor Substrates in Synthesis. Synthesis 2017, 49(11): 2297-2336. DOI: 10.1055/s-0036-1589487 

11. Curti, C.; Rassu, G.; Zambrano, V.; Pinna, L.; Brindani, N.; Pelosi, G.; Zanardi, F. Exploiting the Distal Reactivity of Indolyl-methylenemalononitriles: an Asymmetric Organocatalyzed [4+2] Cycloaddition with Enals Enables the Assembly of Elusive Dihydrocarbazoles. Chem. Eur. J. 2016, 22,12637 –12640. DOI: 10.1002/chem.201602793.

12. Brindani, N.; Rassu, G.; Dell’Amico, L.; Zambrano, V.; Pinna, L.; Curti, C.; Sartori, A.; Battistini, L.; Casiraghi, G.; Pelosi, G.; Greco, D.; Zanardi, F. Organocatalytic, Asymmetric Eliminative [4+2] Cycloaddition of Allylidene Malononitriles with Enals: Rapid Entry to Cyclohexadiene-Embedding Linear and Angular Polycycles. Angew. Chem. Int. Ed. 2015, 54, 7386-7390. DOI: 10.1002/anie.201501894.

13. Curti, C.; Sartori, A.; Battistini, L.; Brindani, N.; Rassu, G.; Pelosi, G.; Lodola, A.; Mor, M.; Casiraghi, G.; Zanardi, F. Pushing the Boundaries of Vinylogous Reactivity: Catalytic Enantioselective Mukaiyama Aldol Reactions of Highly Unsaturated 2-Silyloxyindoles. Chem. Eur. J. 2015, 21, 6433-6442. DOI: 10.1002/chem.201500083.

14. Curti, C.; Sartori, A.; Battistini, L.; Brindani, N.; Rassu, G.; Pelosi, G.; Lodola, A.; Mor, M.; Casiraghi, G.; Zanardi, F. Pushing the Boundaries of Vinylogous Reactivity: Catalytic Enantioselective Mukaiyama Aldol Reactions of Highly Unsaturated 2-Silyloxyindoles. Chem. Eur. J. 2015, 21, 6433-6442. DOI: 10.1002/chem.201500083.

15. Dell’Amico, L.; Rassu, G.; Zambrano, V.; Sartori, A.; Curti, C.; Battistini, L.; Pelosi, G.; Casiraghi, G.; Zanardi, F. Exploring the Reactivity of Cyclohexenylidene Malononitriles: Switchable Regioselectivity in the Organocatalytic Asymmetric Additin to Enals Giving Highly Enantioenriched Carbabicyclic Structures. J. Am. Chem. Soc. 2014, 136, 11107-11114. doi.org/10.1021/ja5054576 

16. Rassu, G.; Zambrano, V.; Pinna, L.; Curti, C.; Battistini, L.; Sartori, A.; Pelosi, G.; Casiraghi, G.; Zanardi, F. Direct and Enantioselective Vinylogous Michael Addition of α-Alkylidenepyrazolinones to Nitroolefins Catalyzed by Dual Cinchona Alkaloid Thioureas. Adv. Synth. Catal. 2014, 356, 2330-2336. Doi: 10.1002/adsc.201300964.

17. Ranieri, B.; Sartori, A.; Curti, C.; Battistini, L.; Rassu, G.; Pelosi, G.; Casiraghi, G.; Zanardi, F. 3-Alkenyl-2-silyloxyindoles in Vinylogous Mannich Reactions: Synthesis of Aminated Indole-Based Scaffolds and Products. Org. Lett. 2014, 16, 932-935. DOI: 10.1021/ol4036598

18. Sartori, A.; Dell’Amico, L.; Battistini, L.; Curti, C.; Rivara, S.; Pala, D.; Kerry, P. S.; Pelosi, G.; Casiraghi, G.; Rassu, G.; Zanardi, F. Synthesis, structure and inhibitory activity of a stereoisomer of oseltamivir carboxylate. Org. Biomol. Chem. 2014, 12, 1561-1569. doi.org/10.1039/C3OB42069H 

19. Rassu, G.; Zambrano, V.; Pinna, L.; Curti, C.; Battistini, L.; Sartori, A.; Pelosi, G.; Zanardi, F.; Casiraghi, G. Direct Regio-, Diastereo-, and Enantioselective Vinylogous Michael Addition of Prochiral 3-Alkylidene Oxindoles to Nitroolefins. Adv. Synth. Catal. 2013, 355, 1881-1886. DOI: 10.1002/adsc.201300168

20. Zanardi, F.; Rassu, G.; Battistini, L.; Curti, C.; Sartori, A.; Casiraghi, G. The Principle of Vinylogy as Applied to Heterocyclic Donor Systems. In Targets in Heterocyclic Systems – Chemistry and Properties (Attanasi, O. A., Spinelli, D. Eds.); Società Chimica Italiana: Roma, 2012, Vol. 16, p 56-89.

21. Curti, C.; Rassu, G.; Zambrano, V.; Pinna, L.; Pelosi, G.; Sartori, A.; Battistini, L.; Zanardi, F.; Casiraghi, G. Bifunctional Cinchona Alkaloid/Thiourea Catalyzes Direct and Enantioselective Vinylogous Michael Addition of 3-Alkylidene Oxindoles to Nitroolefins. Angew. Chem. Int. Ed. 2012, 51, 6200-6204. DOI: 10.1002/anie.201202027.

22. Rassu, G.; Zambrano, V.; Tanca, R.; Sartori, A.; Battistini, L.; Zanardi, F.; Curti, C.; Casiraghi, G. 3-Alkenyl-2-silyloxyindoles: an Enabling, yet Understated Progeny of Vinylogous Carbon Nucleophiles. Eur. J. Org. Chem. 2012, 466-470. DOI: 10.1002/ejoc.201101446

23. Ranieri, B.; Curti, C.; Battistini, L.; Sartori, A.; Pinna, L.; Casiraghi, G.; Zanardi, F. Diastereo- and Enantioselective Catalytic Vinylogous Mukaiyama-Mannich Reactions of Pyrrole-Based Silyl Dienolates with Alkyl-Substituted Aldehydes. J. Org. Chem., 2011, 76, 10291-10298. DOI: 10.1021/jo201875a

24. Sartori, A.; Dell’Amico, L.; Curti, C.; Battistini, L.; Pelosi, G.; Rassu, G.; Casiraghi, G.; Zanardi, F. Aqueous and Solvent-Free Uncatalyzed Three-Component Vinylogous Mukaiyama-Mannich Reactions of Pyrrole-Based Silyl Dienolates. Adv. Synth. Catal. 2011, 353, 3278-3284. DOI: 10.1002/adsc.201100572

25. Curti, C.; Battistini, L.; Sartori, A.; Lodola, A.; Mor, M.; Rassu, G.; Pelosi, G.; Zanardi, F.; Casiraghi, G. Catalytic, Asymmetric Hypervinylogous Mukaiyama Aldol Reactions of Extended Furan-Based Silyl Enolates. Org. Lett. 2011, 13, 4738-4741. DOI: 10.1021/ol2020626

26. Battistini, L.; Dell’Amico L.; Sartori, A.; Curti, C.; Pelosi, G.; Casiraghi, G.; Attanasi, O.A.; Favi, G.; Zanardi, F. On-Water Vinylogous Mukaiyama-Michael Addition of Heterocyclic 2-Silyloxydienes to 1,2-Diaza-1,3-dienes: One-Pot Three-Step Entry to Functionality-Rich Pyrroles. Adv. Synth. Catal. 2011, 353, 1966-1972. DOI: 10.1002/adsc.201100296.

27. Curti, C.; Battistini, L.; Ranieri, B.; Pelosi, G.; Rassu, G.; Casiraghi, G.; Zanardi, F. anti-Selective, Catalytic Asymmetric Vinylogous Mukaiyama Mannich Reactions of Pyrrole-Based Silyl Dienolates with N-Aryl Aldimines. J. Org. Chem. 2011, 76, 2248-2252. Doi: 10.1021/jo1021234.

28. Casiraghi, G.; Battistini, L.; Curti, C.; Rassu, G.; Zanardi, F. The Vinylogous Aldol and Related Reactions: Ten Years of Progress. Chem. Rev. 2011, 111, 3076-3154. DOI: 10.1021/cr100304n.

29. Curti, C.; Battistini, L.; Zanardi, F.; Rassu, G.; Zambrano, V.; Pinna, L.; Casiraghi, G. Uncatalyzed, Diastereoselective Vinylogous Mukaiyama Aldol Reactions on Aqueous media: Pyrrole vs Furan 2-Silyloxy Dienes. J. Org. Chem. 2010, 75, 8681-8684. DOI: 10.1021/jo101799e.

30. Curti, C.; Ranieri, B.; Battistini, L.; Gloria Rassu, G.; Zambrano, V.; Pelosi, G.; Casiraghi, G.; Zanardi, F. Catalytic, Asymmetric Vinylogous Mukaiyama Aldol Reactions of Pyrrole- and Furan-Based Dienoxy Silanes: How the Diene Heteroatom Impacts Stereocontrol. Adv. Synth. Catal. 2010, 352, 2011-2022. DOI: 10.1002/adsc.201000189.

31. Zambrano, V.; Rassu, G.; Roggio, A.; Pinna, L.; Zanardi, F.; Curti, C.; Casiraghi, G.; Battistini, L. Asymmetric Total Synthesis of 1-Deoxy-7,8-di-epi-castanospermine. Org. Biomol. Chem. 2010, 8, 1725-1730. DOI: 10.1039/b924721a.

32. Curti, C.; Sartori, A.; Battistini, L.; Rassu, G.; Zanardi, F.; Casiraghi, G. Asymmetric, catalytic, vinylogous aldol reactions using pyrrole-based dienoxy silanes. Enantioselective synthesis of a,b-unsaturated g-butyrolactam synthons. Tetrahedron Lett. 2009, 50, 3428-3431. doi.org/10.1016/j.tetlet.2009.02.181 

33. Casiraghi, G.; Zanardi, F.; Battistini, L.; Rassu, G. Advances in Exploring Heterocyclic Dienoxysilane Nucleophiles in Asymmetric Synthesis Synlett 2009, 1525-1542. 

34. Sartori, A.; Curti, C.; Battistini, L.; Burreddu, P.; Rassu, G.; Pelosi, G.; Casiraghi, G.; Zanardi, F. Direct-type vinylogous Mukaiyama-Michael addition reactions involving pyrrolinone donors. Tetrahedron 2008, 64, 11697-11705. DOI: 10.1016/j.tet.2008.10.007

35. Curti, C.; Sartori, A.; Battistini, L.; Rassu, G.; Burreddu, P.; Zanardi, F.; Casiraghi, G. Vicarious Silylative Mukaiyama Aldol Reaction: A Vinylogous Extension. J. Org. Chem. 2008, 73, 5446-5451. DOI: 10.1021/jo800741c

36. Zanardi, F.; Curti, C.; Sartori, A.; Rassu, G.; Roggio, A.; Battistini, L.; Burreddu, P.; Pinna, L.; Pelosi, G.; Casiraghi, G. Further Uses of Pyrrole-Based Dienoxysilane Synthons: A Full Aldol Approach to Azabicyclo[x.2.1]alkane Systems. Eur. J. Org. Chem. 2008, 2273-2287. doi.org/10.1002/ejoc.200800040 

37. Zanardi, F.; Sartori, A.; Curti, C.; Battistini, L.; Rassu, G.; Nicastro, G.; Casiraghi, G. Diastereoselective Synthesis of 4,5'-Bis-Proline Compounds via Reductive Dimerization of N-Acyloxyiminium Ions. J. Org. Chem. 2007, 72, 1814-1817. doi.org/10.1021/jo062406l 

38. Curti, C.; Zanardi, F.; Battistini, L.; Sartori, A.; Rassu, G.; Auzzas, L.; Roggio, A.; Pinna, L.; Casiraghi, G. New Enantioselective Entry to Cycloheptane Amino Acid Polyols. J. Org. Chem. 2006, 71, 225-230. doi.org/10.1021/jo0520137