Renzo Luisi

Renzo Luisi
Università degli Studi di Bari Aldo Moro | Università di Bari · Department of Pharmacy - Drug Sciences

Professor

About

197
Publications
13,255
Reads
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4,104
Citations
Citations since 2016
82 Research Items
2666 Citations
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
Introduction
I'm Full Professor of Organic Chemistry at the University of Bari. I'm enthusiastic of my research activity and I'm open to collaborations with other colleagues on topics related to organometallic synthesis, flow chemistry and molecular dynamics.
Additional affiliations
April 2012 - September 2012
The University of Manchester
Position
  • Professor
January 2011 - December 2013
University of Bari
Position
  • Microtechnology and modern spectroscopic and diffractometric techniques aimed at developing and understanding sustainable stereoselective synthetic processes.
Description
  • Stereoselective synthesis by microreactor technology.
Position
  • Physical methods in organic chemistry

Publications

Publications (197)
Article
Direct synthesis of NH-sulfoximines from sulfides has been achieved through O and NH transfer in the same reaction, occurring with complete selectivity. The reaction is mediated by bisacetoxyiodobenzene under simple conditions and employs inexpensive N-sources. Preliminary studies indicate that NH-transfer is likely to be first, followed by oxidati...
Article
The almost unexplored four-membered heterocycles azetidines, represent a particularly interesting class of molecules, among the family of saturated nitrogen heterocycles. Although often challenging to synthesize, substituted azetidines strongly attract chemists because of their importance in catalysis, stereoselective synthesis and medicinal chemis...
Article
Tertiary butyl esters find large applications in synthetic organic chemistry. A straightforward method for the direct introduction of the tert-butoxycarbonyl group into a variety of organic compounds has been developed using flow microreactor systems. The resultant flow process was more efficient, versatile and sustainable compared to the batch.
Article
The transfer of nitrogen atoms is extremely valuable in the preparation of medicinal compounds. Here, a new system for NH transfer is developed to prepare sulfoximines, which are emerging as valuable motifs for drug discovery. This is achieved using readily available sources of nitrogen without the requirement for pre-activation or for metal cataly...
Article
Full-text available
The reactivity profile of lithiated N-Boc-2-arylazetidines has been investigated filling a gap in the chemistry of this kind of four-membered heterocycles. Two unexpected and unprecedented results have been observed: an “ortho-effect” accounting for a regioselective functionalization of the azetidine ring, and a self-condensation leading to new and...
Preprint
Two unprecedented transformations of 2-azetines are reported. Varied C2-functionalized 2-azetines, prepared under continuous flow conditions, acted as linchpin for the preparation of either -aminocarbonyls or C3-thiolated azetidines. Interestingly, the two transformations occurred following an ionic or radical pathway depending on the reaction con...
Article
The growing interest in novel sulfur pharmacophores led to recent advances in the synthesis of some S(IV) and S(VI) motifs. However, preparation and isolation of uncommon primary sulfinamidines, the aza‐analogues of sulfinamides, is highly desirable. Here we report a multistep continuous flow synthesis of poorly explored NH 2 ‐sulfinamidines by nuc...
Article
Full-text available
An efficient synthetic route to construct diverse pyrazole-based chalcones from 1-phenyl-1H-pyrazol-3-ols bearing a formyl or acetyl group on the C4 position of pyrazole ring, employing a base-catalysed Claisen–Schmidt condensation reaction, is described. Isomeric chalcones were further reacted with N-hydroxy-4-toluenesulfonamide and regioselective...
Article
In recent years, fluoroiodomethane (CH2FI) has emerged as an easy-to-handle, non-ozone depleting agent and readily available platform for monofluoromethylation strategies. Recent applications in nucleophilic substitutions, lithiation reactions, transition-metal catalyzed transformations, radical processes, and 18F-radiolabelling chemistry showcase...
Article
The use of flow technology as enabling tool for accessing to 1-azabicyclo[1.1.0]butanes bearing strained 3-, 4-, and 5-membered O-heterocycles with C3(N-het)-C2(O-het) connectivity is reported. Reactivity and chemoselectivity (N-ring vs O-ring)...
Article
Full-text available
In this work it is demonstrated that enantiomerically enriched N-alkyl 2-oxazolinylazetidines undergo exclusive α-lithiation, and that the resulting lithiated intermediate is chemically stable but configurationally labile under the given experimental conditions that afford enantioenriched N-alkyl-2,2-disubstituted azetidines. Although this study re...
Article
Full-text available
We report an improved approach for the integration of flow synthesis and continuous chromatography, for applications in the end-to-end preparation of pharmaceutically-relevant small molecules. It involves the combination of sequential...
Article
Recent years have seen a marked increase in the occurrence of sulfoximines in the chemical sciences, often presented as valuable motifs for medicinal chemistry. This Review covers the most recent advances in the synthesis of NH‐sulfoximines, including extensive developments in both S−N and S−C bond formations. Moreover, flow chemistry processes for...
Article
Full-text available
Recent years have seen a marked increase in the occurrence of sulfoximines in the chemical sciences, often presented as valuable motifs for medicinal chemistry. This has been prompted by both pioneering works taking sulfoximines containing compounds into clinical trials and the concurrent development of powerful synthetic methods. This review cover...
Preprint
Vinyl sulfones and sulfonamides are valued for their use as electrophilic warheads in covalent protein inhibitors. Conversely, the S(VI) aza-isosteres thereof, vinyl sulfoximines and sulfonimidamides, are far less studied and have yet to be applied to the field of protein bioconjugation. Herein, we report a range of different synthetic methodologie...
Preprint
Vinyl sulfones and sulfonamides are valued for their use as electrophilic warheads in covalent protein inhibitors. Conversely, the S(VI) aza-isosteres thereof, vinyl sulfoximines and sulfonimidamides, are far less studied and have yet to be applied to the field of protein bioconjugation. Herein, we report a range of different synthetic methodologie...
Article
The reaction between configurably stable -lithiated oxiranes (and aziridines) and 3-substituted cyclobutanones allows to obtain enantiomerically enriched cyclobutanols (er > 98:2). These adducts, subjected to base-mediated Payne rearrangement lead to...
Article
Full-text available
The reported flow-batch approach enables the easy preparation of 2 H -azirines and their stereoselective transformation into highly functionalized NH -aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustai...
Chapter
Organolithium compounds, first reported more than a century ago are still capturing the interests of synthetic chemists not only because are very useful reagents for the selective construction of CC and CX bonds, but also because lithiation chemistry can always reveal new and interesting aspects that stimulate creativity and design in modern synthe...
Chapter
Nitrogen-containing four-membered heterocycles are extremely important in modern organic synthesis. The rigidity brought about by these heterocyclic scaffolds can be exploited in medicinal chemistry and modern drug discovery programs. In this chapter, recent advances on the synthesis and reactivity of azetidines, azetines, azetes, and azetidinones...
Article
Strained compounds are privileged moieties in modern synthesis. In this context, 1‐azabicyclo[1.1.0]butanes are appealing structural motifs that can be employed as click reagents or precursors to azetidines. We herein report the first telescoped continuous flow protocol for the generation, lithiation, and electrophilic trapping of 1‐azabicyclo[1.1....
Article
Strained….in Flow! The first telescoped continuous flow protocol for the generation, lithiation, and electrophilic trapping of 1‐azabicyclo[1.1.0]butane is reported. Several structurally unique C3‐functionalized 1‐azabicyclo[1.1.0]butanes were prepared using this strategy starting from readily available starting materials. Abstract Strained compou...
Preprint
Full-text available
The reported flow-batch approach enables the easy preparation of 2 H -azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithiums. The protocol has been developed using cyclopentylmethylether (CPME) as an environmentally responsible solvent, resulting into a sustainable,...
Article
The formation of hydrazinium salts by N−N bond formation has typically involved the use of hazardous and difficult to handle reagents. Here, mild and operationally simple conditions for the synthesis of hydrazinium salts are reported. Electrophilic nitrogen transfer to the nitrogen atom of tertiary amines is achieved using iodosylbenzene as oxidant...
Article
In this work we report a new synthetic tactic for the straightforward preparation of hardly accessible sulfinamidines and sulfinamide esters, by using a simple metal-free protocol. The process is robust and uses readily available sulfenamides as the S-donor and sulfonyloxycarbamates as the N-source. The scope and mechanism have also been investigat...
Article
Full-text available
Indole derivatives are among the most useful and interesting heterocycles employed in drug discovery and medicinal chemistry. In addition, flow chemistry and flow technology are changing the synthetic paradigm in the field of modern synthesis. In this review, the role of flow technology in the preparation of indole derivatives is showcased. Selecte...
Article
Since their discovery in the late 1960s, 1-azabicyclo[1.1.0]butanes have demonstrated to be interesting precursors of azetidines, because of the peculiar reactivity of the C3-N bond that allows the double functionalization in 1,3 positions. In particular, the recent advances reported by Baran, Lopchuck, Aggarwal, and others witnesses the synthetic...
Article
A synthesis of unprecedented and stable glycosyl sulfoximines is reported. The developed strategies represent the first example of highly stereoselective sulfoximine formation directly from thioglycosides. This synthetic protocol has been tested on several β-thioglycosides bearing different aromatics and alkyls as S-substituents, and bearing glucos...
Article
A straightforward flow synthesis of α-chloro aldehydes has been developed. The strategy involves, for the first time, the thermal unstable chloroiodomethyllithium carbenoid and carbonyl compounds. A batch versus flow comparative study showcases the superb capability of flow technology in prolonging the lifetime of the lithiated carbenoid, even at -...
Article
The external quenching method based on flow microreactors allows the generation and use of short‐lived fluoro‐substituted methyllithium reagents, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. Highly chemoselective reactions have been developed, opening new opportunities in the synthesis of fluorinated mol...
Article
The external quenching method based on flow microreactors allows the generation and use of short‐lived fluoro‐substituted methyllithium reagents, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. Highly chemoselective reactions have been developed, opening new opportunities in the synthesis of fluorinated mol...
Chapter
In view of the expanding interest in fluorinated heterocycles, the installation of a fluoroalkyl group in a molecule represents a challenging task in organic synthesis. Nowadays, convenient strategies for introducing CF2X groups are still on demand because halodifluoromethylated compounds are useful synthetic intermediates in medicinal and agrochem...
Article
Nuclear Magnetic Resonance (NMR) is an analytical technique extensively used in almost every chemical laboratory for structural identification. This technique provides statistically equivalent signals in spite of using spectrometer with different hardware features and is successfully used for the traceability and quantification of analytes in food...
Article
In the field of organic synthesis, the advent of flow chemistry and flow microreactor technology represented a tremendous novelty in the way of thinking and performing chemical reactions. Just as the classical flask and glass connectors, are still in use, after centuries, in our synthetic laboratories; flow devices will need to conquer the bench of...
Chapter
Flow chemistry and heterogenous catalysis hold incredible potential from a sustainability point of view and from a green perspective. In fact, if heterogenous catalysts are required by the chemical industry for their efficiency, on the other hand, heterogenous flow catalysis would allow performing greener and more efficient chemistry at an industri...
Article
Full-text available
The production of biodiesel at the industrial level is mainly based on the use of basic catalysts. Otherwise, also acidic catalysis allowed high conversion and yields, as this method is not affected by the percentage of free fatty acids present in the starting sample. This work has been useful in assessing the possible catalytic pathways in the pro...
Article
In a flow microreactor, aryllithiums bearing a piperidylmethyl group were generated using n ‐BuLi by precise residence time control and effective temperature control, and then selectively borylated with boronic esters such as 2‐isopropoxy‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolane (BpinO i Pr) and trimethyl borate B(OMe) 3 by fast mixing. Moreover, th...
Article
A facile microwave assisted three-component protocol allows the synthesis of chiral aryl-1,2-mercaptoamines in water in a few minutes with high yields, bypassing the use of toxic aziridine intermediates. The chiral...
Article
Full-text available
A new synthetic route to N-alkyl-2-acylazetidines was developed through a highly stereoselective addition of organolithiums to N-alkyl-2-oxazolinylazetidines followed by acidic hydrolysis of the resulting oxazolidine intermediates. This study revealed an unusual reactivity of the C=N bond of the oxazoline group when reacted with organolithiums in a...
Article
In the field of organic synthesis, the advent of flow chemistry and flow microreactor technology represented a tremendous novelty in the way of thinking and performing chemical reactions, opening the doors to poorly explored or even impossible transformations. In this concept review, we would like to highlight the impact of flow chemistry for explo...
Article
This work reports the preparation of propranolol according to a flow process. Propranolol has been prepared paying attention to tackle the formation of the by-product tertiary amine, resulting from an additional ring opening of the starting epoxide. Remarkably, the use of catalytic amount of water resulted beneficial for the yield and purity of the...
Article
NH‐ und O‐Transfer: Praktische Reagentien für den NH‐ und O‐Transfer ermöglichen die direkte Synthese von NH‐Sulfonimidamiden aus Sulfenamiden. In nur zwei Schritten wurden unterschiedlich funktionalisierten Sulfonimidamide aus kommerziell erhältlichen Substraten in hoher Ausbeute hergestellt. Zudem wurden Alkoxyamino‐λ⁶‐sulfannitrile isoliert, und...
Article
Sulfonimidamides are intriguing new motifs for medicinal and agrochemistry, and provide attractive bioisosteres for sulfonamides. However, there remain few operationally simple methods for their preparation. Here, for the first time the synthesis of NH‐sulfonimidamides is achieved directly from sulfenamides, themselves readily formed in 1 step from...
Article
Full-text available
Continuous flow chemistry is radically changing the way of performing chemical synthesis, and several chemical and pharmaceutical companies are now investing in this enabling technology [...]
Article
The use of graphene derivatives as supports improves the properties of heterogeneous catalysts, being graphene oxide (GO) the most frequently employed. In order to explore greener possibilities as well as to get some insights into the role of the different graphenic supports (GO, rGO, carbon black, and graphite nanoplatelets), we prepared, under th...
Article
An unprecedented direct fluorocyclopropanation of allylic alcohols is successfully achieved. This simple method involves the not so elusive fluoroiodomethyllithium, a carbenoidic intermediates, that under the developed conditions discloses its electrophilic...
Article
Full-text available
The discovery of alternative fuels that can replace conventional fuels has become the goal of many scientific researches. Biodiesel is produced from vegetable oils through a transesterification reaction that converts triglycerides into fatty acid methyl esters (FAME), with the use of a low molecular weight alcohol, in different reaction conditions...
Article
An expeditious, high-yielding synthesis of rare α-fluoroepoxides and α-fluoroaziridines through the addition of the unkown fluoroiodomethyllithium (LiCHIF) - formed via deprotonation the commercially available fluoroiodomethane with a lithium amide base - to carbonyl-like compounds is documented. The ring-closure reactions, leading to α-fluorinated...
Article
Full-text available
We report herein a synthetic protocol for the preparation of 1,3-dibromo-1,1-difluoro-2-propanone, a new synthon used for the first time in a reaction with aromatic amines and sodium thiocyanate, leading to thiazoles which are useful candidates in drug discovery programs. The new synthon allows to introduce a bromodifluoromethyl group at the C4 of...
Article
Full-text available
Flow chemistry and heterogenous catalysis hold incredible potential from a sustainability point of view and from a green perspective. In fact, if heterogenous catalysts are required by the chemical industry for their efficiency, on the other hand, heterogenous flow catalysis would allow performing greener and more efficient chemistry at an industri...
Article
Full-text available
The development of a multistep continuous-flow process, consisting of a direct α-lithiation stage and subsequent hydroxylation by aerobic oxidation, is reported. The protocol is applied to the synthesis of cyclopentylmandelic acid (CPMA), the main building block for the anticholinergic glycopyrronium bromide (glycopyrrolate). We demonstrate the saf...
Article
The present study reports, for the first time, synthesis and structural features of azetidine borane complexes, as well as their reactivity in lithiation reactions. A temperature-dependent stereoselectivity has been disclosed in the reaction of borane with N-alkyl-2-arylazetidines, allowing for a stereoselective preparation of azetidine borane comp...
Article
A convenient synthesis of 2- and/or 3-oxazolines has been developed depending on the structure and stereochemistry of the starting amino alcohol. PhI(OAc)2 acted as oxidant on the intermediate imine, as supported by NMR investigation. The findings demonstrate a new route providing access to unusual 3-oxazolines.
Article
[Figure not available: see fulltext.][InlineMediaObject not available: see fulltext.] Noteworthy stereoselective approaches toward the synthesis of densely substituted azetidines are reported. This microreview covers a selection of the latest efficient methods for the functionalization of azetidine cores by metalation, C–H activation, radical or bi...
Article
Aryl thiols can be selectively converted to sulfonimidates or sulfonamides with three new S–X connections being made selectively in one pot. Using hypervalent iodine reagents in the presence of ammonium carbamate, NH- and O-groups are transferred under mild and practical conditions. Reducing the loading of ammonium carbamate changed the product dis...
Article
A continuous-flow reduction of (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide, involved in the synthetic pathway of Mirabegron, has been developed. This study demonstrated the possibility to safely handling BH3 complexes within microfluidic reactors using 2-MeTHF as greener alternative to traditional solvents, and without requiring any...
Article
The first direct and straightforward nucleophilic fluoromethylation of organic compounds is reported. The tactic employs a “fleeting” lithium fluorocarbenoid (LiCH2F) generated from commercially available fluoroiodomethane. Precise reaction conditions were devel-oped for generation and synthetic exploitation of such a labile spe-cies. The versatili...
Article
Sulfoximines are emerging as valuable new isosteres for use in medicinal chemistry, with the potential to modulate physicochemical properties. Recent developments in synthetic strategies have made the unprotected ‘free’ NH-sulfoximine group more readily available, facilitating further study. This account reviews approaches to NH-sulfoximines, with...
Article
NH-Sulfoximines are emerging as useful and important targets in drug discovery and synthetic organic chemistry. We report herein the development of an efficient, convenient, and sustainable continuous flow strategy, for the direct straightforward preparation of NH-sulfoximines using sulfides or sulfoxides as suitable starting material. The flow pro...
Article
Among the artificial switchable catalysts, those catalysts whose activity can be switched by an external stimulus, only few cases offer the possibility to develop an effective chiral switchable system that could selectively accelerate the formation of a given enantiomer in one state, whereas in the other state it prefers accelerating the formation...
Article
The regioselective functionalization of four- and six-membered cyclic sulfones was investigated using a lithiation/electrophile trapping strategy. The protocol features an interesting eco-compatibility profile because of the use of 2-MeTHF as a solvent (more eco-friendly than other organic solvents) and n-hexyllithium as a lithiating agent safer th...
Article
The functionalization of four-membered cyclic sulfoximine, based on a lithiation/electrophile trapping sequence, led to unprecedented C(2)-substituted N-Boc-1-imino-1λ⁶-thietane 1-oxide in moderate to good yields. Interestingly, the reaction proceeded with high stereocontrol showing a preferential bias for an introduction of the electrophile syn to...
Article
Open image in new window Alternative and complementary procedures were adopted for preparing 2-arylazetidine derivatives in moderate to good yields. Preliminary biological evaluation of 2-arylazetidines as ligands of nicotinic acetylcholine receptors allowed to identify chloro-substituted analogs as the most interesting congeners. The title compoun...
Article
Full-text available
Microreactor technology and flow chemistry could play an important role in the development of green and sustainable synthetic processes. In this review, some recent relevant examples in the field of flash chemistry, catalysis, hazardous chemistry and continuous flow processing are described. Selected examples highlight the role that flow chemistry...