Current Organic Chemistry - Volume 15, Issue 10, 2011

In modern organic chemistry, nitrogen-containing molecules represent certainly a very important target. Organic nitrogen compounds can possess a variety of interesting properties and are widely used as synthetic intermediates, drugs, additives, crop protection products, advanced materials. Many methods have since long been exploited to create new C-N bonds and a number of useful aminating agents have been proposed and are now available. The focus of this special issue is on the recent development for the use of aminating agents and their application in organic synthesis, as well as for obtaining amino derivatives. The first review provided by us (Lucio Pellacani, Stefania Fioravanti, and Paolo A. Tardella, Dipartimento di Chimica, Universita degli Studi “La Sapienza”, Roma, Italy), comprises 126 references and highlights the variable behavior of ethyl nosyloxycarbamate with different substrates under a great deal of experimental conditions. In an umpolung-process this versatile reagent is able to furnish either a nucleophile or an electrophile according to the nature of the carbon to be attacked. Generally electrophilic amination takes place with nucleophilic substrates, while strongly electrophilic alkenes (good Michael acceptors) afford mainly aziridines, containing a cornucopia of various functions, that can be considered precursors of a number of multifunctionalized heterocylic systems. The second review, contributed by Roberto Ballini, Serena Gabrielli, Alessandro Palmieri, and Marino Petrini, SARRF Scienze e Tecnologie, Universita degli Studi di Camerino, Italy includes 92 references and focuses on the utilization of nitro alkanes as effective substrates for the preparation of important target compounds featured by the amino group. These will include simple primary amines, diamines, amino acids, piperidines, pyrrolidines and heteroaromatic derivatives. Delphine Karila and Robert H. Dodd, Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France wrote the third review. They presented an overview on the recent developments made in the area of metal-catalyzed iminoiodane-mediated aziridination of olefins, including 98 references, over the last seven years with regard to the various iminoiodanes which have been used, their in situ generation, the different metals which can be employed to catalyze the reaction, the new ligands, both chiral and non-chiral, which have been designed, the application of this reaction to total synthesis and to the preparation of pharmacologically active compounds. The fourth review came from Adelina Vallribera, Rosa María Sebastian, and Alexandr Shafir, Departament de Quimica, Universitat Autonoma de Barcelona, Cerdanyola del Valles, Barcelona, Spain. This manuscript with 101 references aimed to point out the usefulness of dialkyl azodicarboxylates in carbon-nitrogen bond formation by electrophilic reactions. Both metal catalyzed and organocatalyzed approaches are covered describing contributions in this area over the period 2005-2009. Sergio Cenini, Fabio Ragaini, Emma Gallo, and Alessandro Caselli, Dipartimento di Chimica Inorganica, Metallorganica e Analitica “Lamberto Malatesta”, Universita degli Studi di Milano, Italy contribute to the fifth review, including 99 references, which deals with synthetic methodologies reported in the last five years for the construction of N-heterocyclic products by intramolecular cyclization of organic azides. Particular emphasis is given on those transformations catalyzed by metal complexes. In the last review Devdutt Chaturvedi, Natural Products Chemistry Division, North-East Institute of Science and Technology (CSIR), Jorhat, Assam, India presented the recent developments in the synthesis of organic carbamates using a variety of reagents, including 220 references. Organic carbamates find a wide utility in various areas such as pharmaceuticals, agrochemicals, intermediates in organic synthesis, protection of amino group, and linker in combinatorial chemistry. It has been a great pleasure to be invited to act as Guest Editor of this Special Issue of Current Organic Chemistry. I wish to thank the Editor-in-Chief for the kind invitation and his office for the continuing support as well as all of the authors who contributed for their valuable work and am sure that the overall effort will be beneficial for many organic chemists and can provide inspiration to face new interesting challenges in the development of the chemical science. I also sincerely thank all the referees for their help and valuable comments. Finally I am particularly delighted to dedicate this issue to Professor Paolo Antonio Tardella on the occasion of his 75th birthday.

The purpose of this review is to illustrate the use of ethyl nosyloxycarbamate (NsONHCO2Et). This is a versatile aminating agent known for over 47 years and used to generate, in the presence of organic or inorganic bases under homogeneous conditions, a carbonyl nitrene, a reactive intermediate able to form new C-N or X-N bonds by electrophilic amination reaction of a remarkable variety of nucleophilic substrates. Interest in this reagent has been renewed most recently, during the past dozen years. Operating still in alkaline medium, but under generally heterogeneous conditions, has made possible new synthetic applications for the conjugate base of the same nosyloxycarbamate. These, developed mainly by our research group, allow to carry out direct syntheses of various nitrogenated compounds under mild conditions. The applications span from simple molecules to highly functionalized compounds and many new exciting regio- and stereoselective routes can be envisioned. In particular, it was possible to obtain aziridines containing a cornucopia of assorted functions and therefore able to provide access to more complex molecules under simple operational conditions by using an aminating agent cheap and easy to obtain.

The carbanion stabilizing effect of the nitro group makes nitroalkanes ideal reagents in carbon-carbon bond formation. Once introduced in a molecular framework, the nitro group is amenable to further transformations including reduction to primary amines. The aim of this review is to explore the utilization of nitroalkanes as effective substrates for the preparation of important target compounds featured by the amino group. These will include simple primary amines, diamines, amino acids, piperidines, pyrrolidines and heteroaromatic derivatives. A particular emphasis will be placed on the synthesis of enantioenriched amino derivatives mediated by organocatalysts or organometallic complexes.

The aziridination of olefins mediated by metal-catalyzed generation of nitrenes from iminoiodanes was first described almost a quarter century ago. Since then, great progress has been made in improving the efficiency, versatility and stereocontrol of this important reaction. This review will cover developments made in this area over the last seven years with regard to the various iminoiodanes which have been used, their in situ generation, the different metals which can be employed to catalyze the reaction, the new ligands, both chiral and non-chiral, which have been designed, the application of this reaction to total synthesis and to the preparation of pharmacologically active compounds.

This review focuses on the use of dialkyl azodicarboxylates in the formation of C-N bonds through catalyzed α-amination reactions. Both metal catalyzed and organocatalyzed approaches are covered in the present report.

A review of synthetic methodologies reported in the last five years that yield N-heterocyclic products by intramolecular cyclization of organic azides with a particular emphasis on transformations catalyzed by metal complexes is presented. These reactions have been classified according to the ring size of the formed heterocycle.

Organic carbamates represent an important class of compounds showing various interesting properties. They find wide utility in various areas as pharmaceuticals, agrochemicals (pesticides, herbicides, insecticides, fungicides etc.), intermediates in organic synthesis, protection of amino group in peptide chemistry, and as linker in combinatorial chemistry etc. Classical synthesis of carbamates involves use of harmful reagents such as phosgene, its derivatives and carbon monoxide. Recently, various kinds of synthetic methods have been developed for the synthesis of organic carbamates. In the present review, I would like to highlight the recent developments on the synthesis of organic carbamates using variety of reagents.

Heterocyclic compounds, five-membered components in particular, are of great significance in organic and pharmaceutical chemistry. This review highlights the substantial progress and examples, which have been made in the last decade to construct fivemembered heterocycles by transition metal-catalyzed cyclization of propargylic compounds. Propargylic compounds are versatile threecarbon building blocks in heterocyclic chemistry. They can be easily and efficiently prepared by nucleophilic addition of alkynyl anions to carbonyl compounds and the successive substitution reactions. Current trends have focused on and expanded the flexible applications of propargylic compounds in many aspects of organic syntheses. Heterocyclic syntheses involving transition metal complexes have become of common use in past decades because a transition metal-catalyzed reaction has a potential to directly build complicated molecules from readily accessible starting materials under mild conditions. Transition metal elements encompassing Ag, Au, Cu, Fe, Zn, Hg, Ru, Re, Ir, Rh, Ni, Pd, Pt, Sc and the like demonstrate intriguing catalytic activity in the aforesaid transformations. They are able to drive reactions either or both as Lewis acids and most commonly triple-bond activation agents by the formation of σ- or π-complexes. As a consequence, a variety of stages are set for new diversity-oriented routes to five-membered heterocycles such as furans, pyrroles, thiophenes, oxazoles, imidazoles, thiazoles, benzofurans, benzothiophenes, indoles and the like. Owing to the structural importance in biologically active natural and unnatural compounds, some of the nonaromatic five-membered heterocyclic compounds are also included with this review.

The purpose of this review article is to illustrate synthetic aspects of functionalized phosphorus derivatives containing an oximo moiety at the beta-position. First section will be focused on the synthesis of phosphine oxides, phosphonates or phosphonium salts containing an oxime group. The synthesis of these derivatives comprises the carbon-phosphorus single bond construction by reaction of haloximes with phosphorus derivatives, nucleophilic addition of phosphorus reagents to carbonyl compounds, or nucleophilic addition of phosphorus reagents to nitro olefins. This section will also concentrate on the most practical routes for the synthesis of the target compounds, through carbon-nitrogen double bond formation, which are as follows: condensation processes of carbonyl compounds and hydroxylamine derivatives or addition of hydroxylamines to allenes or alkynes. The preparative use of beta-oximo phosphorus derivatives as synthetic intermediates will be discussed in a second section, comprising olefination reaction, oxidation of oximes to nitrile oxides by reaction at the C-N double bond of the oxime moiety, oxidation of these substrates to nitrosoalkenes, reduction to the corresponding hydroxylamines and some reactions at the hydroxyl group of the hydroxyimino moiety.

S-Alkyl pyrimidine derivatives 2-5 were obtained by the reactions of ethyl 4-sulfanyl-6-methyl-2-phenylpyrimidine-5- carboxylate (1) with allyl bromide, propargyl bromide, epichlorohydrin and vinyl acetate (Scheme 1). On reaction of sulfanylpyrimidine 1 with iodine, hydrogen peroxide under different conditions afforded bisdisulphide, desulphrization, and 4-hydroxypyrimidines 6-8. Treatment of the sulfanylpyrimidine 1 with ethylbromoacetate followed by oxidation, and hydrazonlysis gave the thienopyrimidine dioxide derivative 10 and pyrazolopyrimidine 11, respectively (Scheme 2). Reaction of 1 with benzalidene derivatives in ethanol/TEA yielded pyridopyrimidine derivatives 12a,b and 13. On reaction with ethyl acrylate afforded thienopyrimidine 14 under the same condition. Furthermore, reaction of 1 with dimethyl amine/sulfur in absolute ethanol and with 4-chlorobenzaldhyde afforded the dihydrothienopyrimidine, and 6-styrylpyrimidinthione 15 and 16, respectively (Scheme 3). N-alkylated pyrazolopyrimidine 18 and pyridazinopyrimidine 19 were obtained by the reaction of 4-chloropyrimidine 17 with acetophenonehydrazone and hydrazones derivative of malononitrile in the presence of TEA (Scheme 4). All of the newly synthesized compounds were characterized by IR, 1H, 13C NMR and microanalysis.