Marco Colella

Scopus Publications

Novel Sulfonium Reagents for the Modular Synthesis of Spiro[2.3]Hexanes and Heteroatom-Containing Analogues: Synthesis, Application, and Evaluation as Bioisosteres
Philipp Natho, Annarita Vicenti, Fabrizio Mastrolorito, Francesca De Franco, Lee Walsh‐Benn, Marco Colella, Ernesto Mesto, Emanuela Schingaro, Orazio Nicolotti, Antimo Gioiello, Renzo Luisi
Angewandte Chemie International Edition, 2026
Molecular scaffolds with a high fraction of sp 3 ‐hybridized centers have attracted considerable attention in medicinal chemistry as bioisosteres for a wide range of aromatic and nonstrained heterocycles. In particular, strained spiro‐heterocycles have garnered popularity for this purpose, although access to spiro[2.3]hexane analogues is underrepresented. We herein report modular access to nine different spiro[2.3]hexane analogues, including previously underdeveloped 5‐oxa‐1‐azaspiro[2.3]hexane and 1,5‐diazaspiro[2.3]hexane motifs. Our synthetic approach leverages novel cyclobutane‐, oxetane‐, and azetidine‐substituted sulfonium salts, which can undergo Johnson–Corey–Chaykovsky type reactions with alkenes, carbonyls and imines to provide access to the desired spiro[2.3]hexanes. Here, we also report the first comprehensive computational and predictive in silico evaluation of their bioisosteric potential, with validation provided by in vitro experiments.
Flow Chemistry Applied for Late-Stage Functionalization and Other Functional Group-Tolerant Manipulation
Philipp Natho, Marco Colella, Renzo Luisi
Late Stage Functionalization and Diversification in Organic Synthesis Methods and Applications, 2026
The introduction of flow technology as an alternative to classic batch systems in organic synthesis has allowed not only the improvement of already established chemistry but also enabled access to reactivity which was previously impossible or little explored. Flow technology allows precise control of reaction conditions, enabling often milder reaction conditions or higher functional group tolerance than batch protocols, making it ideal for the late-stage functionalization of natural products, Active Pharmaceutical Ingredients (APIs), or initial hit identification. In this chapter, we highlight the impact of flow technology on late-stage functionalization within the last five years, with a particular focus on the following four key areas: photochemical flow, electrochemical flow, flash technology, and homogeneous and heterogeneous catalysis in flow.
A Decade of NH-Transfer via Iodonitrene: A Journey of NH-Transfer from Sulfur and Nitrogen to Alkenes
Philipp Natho, Marco Colella, Renzo Luisi
Synlett, 2026
The incorporation of nitrogen atoms in lead compounds can significantly alter their physicochemical properties so that efficient methodologies for their introduction are highly sought after. In the last decade, electrophilic NH-transfer via in situ-generated intermediates from ammonia sources and hypervalent iodine reagents has attracted interest for its varied reactivity ranging from N-transfer to heteroatoms to core remodeling tactics. We herein describe the journey from the introduction of this tactic to its most recent application for the synthesis of NH-aziridines.
Strain Release of 1-Azabicyclo[1.1.0]butanes as a Gateway to Highly Functionalized Azetidines: New Strategies and Structural Motifs
Yuri Gelato, Philipp Natho, Marco Colella, Renzo Luisi
Chemistry A European Journal, 2026
Over the past decade, the interest of synthetic and medicinal chemists in the azetidine ring has continuously risen, given its impact on (positive) modulation of various physicochemical properties. In fact, the exploration of new azetidine‐based monocyclic, spirocyclic, and bridged scaffolds has led to the discovery of new potential 3D bioisosteres for 2D or nonstrained 3D rings frequently employed in drug discovery programs. A popular and recently revived strategy en route to azetidines relies on the use of 1‐azabicyclo[1.1.0]butanes as precursors, leveraging the inherent reactivity of the “spring‐loaded” transannular bond, connecting the bridgehead carbon to the nitrogen. This review provides an overview of synthetic advances since 2021, emphasizing newly accessed structural motifs, patterns in activation tactics, and use of enabling technologies such as photocatalysis and flow chemistry.
Iodonitrene-mediated synthesis of NH-aziridines
Yuri Gelato, Laura Marraffa, Francesco Pasca, Philipp Natho, Giuseppe Romanazzi, Arianna Tota, Marco Colella, Renzo Luisi
Trends in Chemistry, 2025
Azabicyclo[1.1.0]butyl-Substituted Sulfonimidoyl Fluoride: Electrophilic Hub Bridging Late-Stage Azetidine Incorporation with Sufex Chemistry
Defne Şerbetçi, Philipp Natho, Ernesto Mesto, Emanuela Schingaro, Marco Colella, et al.
Advanced Synthesis and Catalysis, 2025
The development of electrophilic strained small motifs is of increasing importance for chemical biology and drug discovery, enabling precise, late‐stage functionalization and targeted covalent inhibition. In this work, we report the efficient synthesis of a novel azabicyclo[1.1.0]butyl‐substituted sulfonimidoyl fluoride, a bench‐stable electrophilic hub combining strain‐release reactivity and SuFEx chemistry. The dual reactivity of this motif was demonstrated through selective ABB ring‐opening reactions, and SuFEx‐mediated ligations with diverse nucleophiles, including pharmaceutically relevant derivatives. Further derivatization of the resulting sulfonimidates and sulfonimidamides showcased the synthetic versatility of this system. These findings open avenues for the development of modular, multifunctional platforms in drug discovery.
Tunable Preparation of α-Aminoacyl Fluorides and α-Fluoroamides via Base-Induced Cascade Multiple-Cleavage Processes from Bromodifluorohydrin Reagents and Amines
Giulia De Santis, Andrea Maranzana, Federica Lauria, Mauro Spennacchio, Michael Andresini, Rosa Purgatorio, Marco Colella, Renzo Luisi, Leonardo Degennaro
Advanced Synthesis and Catalysis, 2025
A concise strategy for the divergent synthesis of α‐fluoroamides and α‐aminoacyl fluorides is developed via multiple bond‐cleavage processes of 2‐bromo‐2,2‐difluoro alcohols in the presence of amines. The transformation proceeds under mild conditions, displays a broad substrate scope, and features operational simplicity. Mechanistic studies, supported by density functional theory calculations, suggest the involvement of a putative gem‐difluoroepoxide intermediate that triggers a cascade of atom recombination events.
Generation and Use of Cyclopropenyllithium under Continuous Flow Conditions
Francesco Soddu, Iktedar Mahdi, Maria Chiara Cabua, Francesco Secci, Philipp Natho, Riccardo Tassoni, Paolo Dambruoso, Ernesto Mesto, Marco Colella, Renzo Luisi
Organic Letters, 2025
The cyclopropene scaffold has emerged as a valuable platform in modern synthesis. Here, we present a streamlined flow-based approach for the generation of cyclopropenyllithium and its functionalization with various electrophiles in a single, continuous flow process. This method eliminates the need for laborious temperature changes and cryogenic conditions, and significantly reduces the process time from starting material to products. Compared to traditional batch processes, our flow approach enables the use of a single organolithium reagent and operates efficiently at 0 °C, avoiding the cool-warm-cool temperature cycles typical of batch methods. This not only simplifies the workflow but also enhances practicality, scalability, and extends the accessible chemical space.
Strained spiro heterocycles as potential bioisosteres: an update on the synthesis of heteroatom-containing spiro[2.3]hexanes and spiro[3.3]heptanes
Philipp Natho, Marco Colella, Renzo Luisi
Chemical Communications, 2025
Developments in the synthesis and application of strained spiro heterocycles are discussed, given their potential as non-classical rigid three-dimensional bioisosteres in drug development.
Shifting Lithium Amide Reactivity to the Radical Domain: Regioselective Radical C−H Functionalization of 3-Iodooxetane for the Synthesis of 1,5-Dioxaspiro[2.3]hexanes
Philipp Natho, Marco Colella, Annarita Vicenti, Giuseppe Romanazzi, Faizan Ullah, Nadeem S. Sheikh, Andrew J. P. White, Francesco Pasca, Renzo Luisi
Angewandte Chemie International Edition, 2025
Strained spiro‐heterocycles (SSHs) have gained significant attention within the medicinal chemistry community as promising sp3‐rich bioisosteres for their aromatic and non‐spirocyclic counterparts. We herein report access to an unprecedented spiro‐heterocycle—1,5‐dioxaspiro[2.3]hexane. Our synthetic approach leverages a lithium‐amide induced single‐electron transfer to benzophenones generating an N‐centered radical and a ketyl radical anion—reminiscent of a frustrated radical pair. This pair works synergistically to selectively abstract the β‐hydrogen from 3‐iodooxetane, initiating an exergonic radical‐radical coupling reaction. This process enables the formation of the desired bond between the oxetane core and benzophenone derivatives, ultimately yielding the novel 1,5‐dioxaspiro[2.3]hexane core. The stability and synthetic utility of the novel 1,5‐dioxaspiro[2.3]hexane motif are showcased. An in‐depth mechanistic investigation is presented, including cyclic voltammetry studies, as well as computational calculations and experiments to support the mechanism of this new single electron synthetic tactic.
Generation and Use of Bicyclo[1.1.0]butyllithium under Continuous Flow Conditions
Elena Graziano, Marco Colella, Marcus Baumann, Renzo Luisi
Organic Letters, 2025
Continuous Flow Decarboxylative Monofluoroalkylation Enabled by Photoredox Catalysis
Francesco Pasca, Yuri Gelato, Michael Andresini, Defne Serbetci, Philipp Natho, Giuseppe Romanazzi, Leonardo Degennaro, Marco Colella, Renzo Luisi
Jacs Au, 2025
Synthesis of Aza-S(VI) Fluorides and Primary Sulfonimidamides from Sulfinylamines
Michael Andresini, Laura Marraffa, Defne Şerbetçi, Philipp Natho, Marco Colella, Leonardo Degennaro, Renzo Luisi
Advanced Synthesis and Catalysis, 2025
Iodonitrene-Mediated Nitrogen Transfer to Alkenes for the Direct Synthesis of NH-Aziridines
Yuri Gelato, Laura Marraffa, Francesco Pasca, Philipp Natho, Giuseppe Romanazzi, Arianna Tota, Marco Colella, Renzo Luisi
Journal of the American Chemical Society, 2025
1-Oxa-2,6-Diazaspiro[3.3]heptane as a New Potential Piperazine Bioisostere – Flow-Assisted Preparation and Derivatisation by Strain-Release of Azabicyclo[1.1.0]butanes
Elena Graziano, Philipp Natho, Michael Andresini, Fabrizio Mastrolorito, Iktedar Mahdi, Ernesto Mesto, Marco Colella, Leonardo Degennaro, Orazio Nicolotti, Renzo Luisi
Advanced Synthesis and Catalysis, 2024
A unified flow strategy for the preparation and use of trifluoromethyl-heteroatom anions
Mauro Spennacchio, Miguel Bernús, Jelena Stanić, Daniele Mazzarella, Marco Colella, James J. Douglas, Omar Boutureira, Timothy Noël
Science, 2024
Structure-based design of multitargeting ChEs-MAO B inhibitors based on phenyl ring bioisosteres: AChE/BChE selectivity switch and drug-like characterization
Gabriella La Spada, Daniela Valeria Miniero, Mariagrazia Rullo, Marco Cipolloni, Pietro Delre, Carolina Colliva, Marco Colella, Francesco Leonetti, Grazia Maria Liuzzi, Giuseppe Felice Mangiatordi, Nicola Giacchè, Leonardo Pisani
European Journal of Medicinal Chemistry, 2024
Synthesis of alcohols: streamlined C1 to Cn hydroxyalkylation through photoredox catalysis
Francesco Pasca, Yuri Gelato, Michael Andresini, Giuseppe Romanazzi, Leonardo Degennaro, Marco Colella, Renzo Luisi
Chemical Science, 2024
Taming 3-Oxetanyllithium Using Continuous Flow Technology
Philipp Natho, Marco Colella, Michael Andresini, Leonardo Degennaro, Renzo Luisi
Organic Letters, 2024
Continuous Flow Generation of Highly Reactive Organometallic Intermediates: A Recent Update
Mauro Spennacchio, Philipp Natho, Michael Andresini, Marco Colella
Journal of Flow Chemistry, 2024
Borylmetallation of alkynes made easy in flow
Marco Colella, Renzo Luisi
Nature Synthesis, 2024
Overlooked aza-S(iv) motifs: synthesis and transformations of sulfinamidines and sulfinimidate esters
Michael Andresini, Marco Colella, Leonardo Degennaro, Renzo Luisi
Organic and Biomolecular Chemistry, 2023
Sustainable continuous flow synthesis of β-aminocarbonyls via acid-catalyzed hydration of N-Boc-2-azetines
Michael Andresini, Marco Colella, Roberta Savina Dibenedetto, Elena Graziano, Giuseppe Romanazzi, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
Reaction Chemistry and Engineering, 2023
Forging C−S Bonds on the Azetidine Ring by Continuous Flow Photochemical Addition of Thiols and Disulfides to Azetines
Marco Colella, Yuri Gelato, Michael Andresini, Elena Graziano, Gianvito Vilé, Leonardo Degennaro, Renzo Luisi
European Journal of Organic Chemistry, 2023
Streamlining C1 Homologation Reactions Using Continuous Flow Technology: Focus on Diazomethane and Methyllithium Chemistry
Antimo Gioiello, Giada Ceccarelli, Marco Colella, Renzo Luisi
Homologation Reactions Reagents Applications and Mechanisms Volume 1 and 2, 2023
Synthesis and strain-release reactions of 1-azabicyclo[1.1.0]butanes: an update
Pantaleo Musci, Marco Colella, Michael Andresini, Leonardo Degennaro, Renzo Luisi
Arkivoc, 2023
A sustainable and chemoselective continuous flow hydrogenation of functionalized 2-azetines to azetidines
Elena Graziano, Debora Cannillo, Mauro Spennacchio, Pantaleo Musci, Luisa Pisano, Michael Andresini, Marco Colella
Tetrahedron Green Chem, 2023
Unlocking geminal fluorohaloalkanes in nucleophilic fluoroalkylation chemistry: generation and trapping of lithiumfluorocarbenoids enabled by flow microreactors
Mauro Spennacchio, Marco Colella, Michael Andresini, Roberta Savina Dibenedetto, Elena Graziano, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
Chemical Communications, 2023
(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl (R)-4-methylbenzenesulfonimidate
Arianna Tota, Michael Andresini, Marco Colella, Roberta Savina Dibenedetto, Leonardo Degennaro, Renzo Luisi
Molbank, 2022
Microwave-Assisted Treatment of Waste Wood Biomass with Deep Eutectic Solvents
Marco Colella, Giuseppe Romanazzi, Valentina Petrelli, Francesca Baldassarre, Giuseppe Ciccarella, Michelina Catauro, Piero Mastrorilli, Maria Michela Dell'Anna
Macromolecular Symposia, 2022
The synthetic versatility of fluoroiodomethane: recent applications as monofluoromethylation platform
Marco Colella, Pantaleo Musci, Michael Andresini, Mauro Spennacchio, Leonardo Degennaro, Renzo Luisi
Organic and Biomolecular Chemistry, 2022
Flow technology enabled preparation of C3-heterosubstituted 1-azabicyclo[1.1.0]butanes and azetidines: accessing unexplored chemical space in strained heterocyclic chemistry
Pantaleo Musci, Marco Colella, Michael Andresini, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
Chemical Communications, 2022
Dynamic Phenomena and Complexation Effects in the α-Lithiation and Asymmetric Functionalization of Azetidines
Pantaleo Musci, Marco Colella, Angela Altomare, Giuseppe Romanazzi, Nadeem S. Sheikh, Leonardo Degennaro, Renzo Luisi
Molecules, 2022
Lithium Complexes in Organic Synthesis
R. Luisi, L. Degennaro, M. Colella
Comprehensive Organometallic Chemistry IV Volume 1 15, 2022
11.02 - Lithium Complexes in Organic Synthesis
R. Luisi, L. Degennaro, M. Colella
Comprehensive Organometallic Chemistry IV Volume 1 15, 2022
Development of a Continuous Flow Synthesis of 2-Substituted Azetines and 3-Substituted Azetidines by Using a Common Synthetic Precursor
Marco Colella, Pantaleo Musci, Debora Cannillo, Mauro Spennacchio, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
Journal of Organic Chemistry, 2021
Sulfinimidate Esters as an Electrophilic Sulfinimidoyl Motif Source: Synthesis of N-Protected Sulfilimines from Grignard Reagents
Michael Andresini, Mauro Spennacchio, Marco Colella, Gianluca Losito, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
Organic Letters, 2021
Lithiated three-membered heterocycles as chiral nucleophiles in the enantioselective synthesis of 1-oxaspiro[2,3]hexanes
Andrea Cocco, Maria Grazia Rubanu, Maria Laura Sechi, Angelo Frongia, Pietro Mastrorilli, Leonardo Degennaro, Marco Colella, Renzo Luisi, Francesco Secci
Organic and Biomolecular Chemistry, 2021
N−N Bond Formation Using an Iodonitrene as an Umpolung of Ammonia: Straightforward and Chemoselective Synthesis of Hydrazinium Salts
Arianna Tota, Marco Colella, Claudia Carlucci, Andrea Aramini, Guy Clarkson, Leonardo Degennaro, James A. Bull, Renzo Luisi
Advanced Synthesis and Catalysis, 2021
Hypervalent iodine (III) reagents and ammonia as useful combination for highly chemoselective N-transfer to low-valent organosulfur compounds and amines
Michael Andresini, Marco Colella, Leonardo Degennaro, Renzo Luisi
Arkivoc, 2021
Continuous flow synthesis of heterocycles: A recent update on the flow synthesis of indoles
Marco Colella, Leonardo Degennaro, Renzo Luisi
Molecules, 2020
Fluoro-Substituted Methyllithium Chemistry: External Quenching Method Using Flow Microreactors
Marco Colella, Arianna Tota, Yusuke Takahashi, Ryosuke Higuma, Susumu Ishikawa, Leonardo Degennaro, Renzo Luisi, Aiichiro Nagaki
Angewandte Chemie International Edition, 2020
Flow Microreactor Technology for Taming Highly Reactive Chloroiodomethyllithium Carbenoid: Direct and Chemoselective Synthesis of α-Chloroaldehydes
Pantaleo Musci, Marco Colella, Alessandra Sivo, Giuseppe Romanazzi, Renzo Luisi, Leonardo Degennaro
Organic Letters, 2020
Synthesis of Biaryls Having a Piperidylmethyl Group Based on Space Integration of Lithiation, Borylation, and Suzuki–Miyaura Coupling
Yusuke Takahashi, Yosuke Ashikari, Masahiro Takumi, Yutaka Shimizu, Yiyuan Jiang, Ryosuke Higuma, Susumu Ishikawa, Hodaka Sakaue, Ibuki Shite, Kei Maekawa, Yoko Aizawa, Hiroki Yamashita, Yuya Yonekura, Marco Colella, Renzo Luisi, Toshihiro Takegawa, Chiemi Fujita, Aiichiro Nagaki
European Journal of Organic Chemistry, 2020
Flow Technology for the Genesis and Use of (Highly) Reactive Organometallic Reagents
Marco Colella, Aichiiro Nagaki, Renzo Luisi
Chemistry A European Journal, 2020
Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy-amino-λ6-sulfanenitrile Intermediate
Edward L. Briggs, Arianna Tota, Marco Colella, Leonardo Degennaro, Renzo Luisi, James A. Bull
Angewandte Chemie International Edition, 2019
Modular and Chemoselective Strategy for the Direct Access to α-Fluoroepoxides and Aziridines via the Addition of Fluoroiodomethyllithium to Carbonyl-Like Compounds
Serena Monticelli, Marco Colella, Veronica Pillari, Arianna Tota, Thierry Langer, Wolfgang Holzer, Leonardo Degennaro, Renzo Luisi, Vittorio Pace
Organic Letters, 2019
Synthesis and use of halodifluoromethyl heterocycles
Marco Colella, Pantaleo Musci, Renzo Luisi, Leonardo Degennaro
Targets in Heterocyclic Systems, 2019
Straightforward chemo- and stereoselective fluorocyclopropanation of allylic alcohols: Exploiting the electrophilic nature of the not so elusive fluoroiodomethyllithium
Marco Colella, Arianna Tota, Angela Großjohann, Claudia Carlucci, Andrea Aramini, Nadeem S. Sheikh, Leonardo Degennaro, Renzo Luisi
Chemical Communications, 2019
Stereo-and enantioselective addition of organolithiums to 2-oxazolinylazetidines as a synthetic route to 2-acylazetidines
Pantaleo Musci, Marco Colella, Flavio Fanelli, Angela Altomare, Luisa Pisano, Claudia Carlucci, Renzo Luisi, Leonardo Degennaro
Frontiers in Chemistry, 2019
Supported Catalysts for Continuous Flow Synthesis
Marco Colella, Claudia Carlucci, Renzo Luisi
Topics in Current Chemistry, 2018
1,3-Dibromo-1,1-difluoro-2-propanone as a Useful Synthon for a Chemoselective Preparation of 4-Bromodifluoromethyl Thiazoles
Marco Colella, Pantaleo Musci, Claudia Carlucci, Samuele Lillini, Mara Tomassetti, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
ACS Omega, 2018
Correction to: Use of hypervalent iodine in the synthesis of isomeric dihydrooxazoles (Chemistry of Heterocyclic Compounds, (2018), 54, 4, (428-436), 10.1007/s10593-018-2288-9)
Claudia Carlucci, Arianna Tota, Marco Colella, Giuseppe Romanazzi, Guy J. Clarkson, Renzo Luisi, Leonardo Degennaro
Chemistry of Heterocyclic Compounds, 2018
Use of Hypervalent Iodine in the Synthesis of Isomeric Dihydrooxazoles
Claudia Carlucci, Arianna Tota, Marco Colella, Giuseppe Ronamazzi, Guy J. Clarkson, Renzo Luisi, Leonardo Degennaro
Chemistry of Heterocyclic Compounds, 2018
Exploiting a "beast" in carbenoid chemistry: Development of a straightforward direct nucleophilic fluoromethylation strategy
Giovanna Parisi, Marco Colella, Serena Monticelli, Giuseppe Romanazzi, Wolfgang Holzer, Thierry Langer, Leonardo Degennaro, Vittorio Pace, Renzo Luisi
Journal of the American Chemical Society, 2017

Marco Colella

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Scopus Publications