Carbenes and nitrenes in heterocyclic

Chemistry of Dihydroazines, 38, 1. Wentrup, C., Carbenes and Nitrenes in Heterocyclic Chemistry Intramolecular Reactions, 28, 231. 

Carbenes and Nitrenes in Heterocyclic Chemistry Intramolecular Reactions... 

General reviews on carbenes and nitrenes in heterocyclic chemistry and on the synthesis of saturated heterocycles have been published this year, and also specific reviews on 1,2-diazepines, 1,2-benzodiazepines, thiepins, dithiepins, and aza-azulenes." ... 

C. Wentrup, Carbenes and Nitrenes in Heterocyclic Chemistry. Intramolecular Reactions , Adv. Heterocycl. Synth, 1981, 28, 232. 

Wentrup, C, Carbenes and nitrenes in heterocyclic chemistry, AdvHeterocycl. Chem., 28,231,1981. 

The chemistry of short-lived intermediates is difficult to study because usually the species cannot be directly observed under the reaction conditions. Much of the knowledge is therefore obtained by deduction from product studies. In the present review we are dealing mainly with intramolecular gas-phase reactions, and the carbenes and nitrenes in question are most frequently generated from diazo-compounds and azides (or in heterocyclic systems valence isomers thereof, triazo-loazines and tetrazoloazines). It is known that diazo-compounds and azides deld carbenes and nitrenes, respectively, by low-temperature photolysis i>2). However, the cycloheptatrienylidenes and azepinylidenes invoked in many reaction mechanisms have not yet been observed by any spectroscopic means, and their existence is deduced exclusively from their chemistry. 

The formation of five- and six-membered heterocycles by radical cyclization is discussed in a comprehensive review <2004H(63)1903>. Representative examples of ring syntheses involving carbenoid (Table 6) or nitrenoid (Table 7) intermediates are given. In many cases, the free carbene or nitrene is probably not involved, and the distinction between insertion and addition reactions given in the tables is not always clear cut. Such reactions are particularly useful for the preparation of tricyclic compounds. The application of carbenes and carbenoids in the synthesis of heterocyles is summarized in a review <1996AHC(65)93>. 

Carbenes and nitrenes, intramolecular reactions in heterocyclic chemistry ... 

C-H alkylation and amination reactions involving metal-carbenoid and metal-nitrenoid species have been developed for many years, most extensively with (chiral) dirhodium(ll) carboxylate and carboxamidate complexes as catalysts [45]. When performed in intramolecular settings, such reactions offer versatile methods for the (enantioselective) synthesis of hetero- and carbocy-cles. In the past decade, Zhang and coworkers had explored the catalysis of cobalt(II)-porphyrin complexes for carbene- and nitrene-transfer reactions [46] and revealed a radical nature of such processes as a distinct mechanistic feature compared with typical metal (e.g., rhodium)-catalyzed carbenoid and nitrenoid reactions [47]. Described below are examples of heterocycle synthesis via cobalt(II)-porphyrin-catalyzed intramolecular C-H amination or C-H alkylation. 

In 1999, Bob Atkinson wrote [1] that aziridination reactions were epoxida-tion s poor relation , and this was undoubtedly true at that time the scope of the synthetic methods available for preparation of aziridines was rather narrow when compared to the diversity of the procedures used for the preparation of the analogous oxygenated heterocycles. The preparation of aziridines has formed the basis of several reviews [2] and the reader is directed towards those works for a comprehensive analysis of the area this chapter presents a concise overview of classical methods and focuses on modern advances in the area of aziridine synthesis, with particular attention to stereoselective reactions between nitrenes and al-kenes on the one hand, and carbenes and imines on the other. 

Natural products, synthesis via aziridine intermediates, 39, 181 New developments in the chemistry of oxazolones, 21, 175 Nitration of phenyl-substituted heterocycles, 58, 215 Nitrenes, carbenes and, intramolecular reactions of, 28, 231... 

By far the main part of the studies involves aromatic azides, however. These are the object of unrelenting interest. During the period considered, some reference works have been published, including a wide-scope review on the detection and role of intermediates, another one on pyr-idineazides and an account on the relation between nitrenes, carbenes, diradicals and zwitterions in the thermal and photochemical reaction operating in the decomposition of aromatic and heterocyclic azides. A recent, nice example illustrates the variety of paths followed. Thus, tetra-zolo[l,5-a]quinoxaline and tetrazolo[5.1-c]quinazoline equilibrate thermally with the corresponding azides. 

By analogy with the intramolecular insertion of phenylthiocarbenes, the reaction of (oo-oxido)diazoalkanes 93 resulted in the formation of cycloalkenes 94.38 However, the reaction was proven to proceed not via a carbene route b but a nitrene route a as shown in Scheme 26. The nitrene route is supported by the formation of heterocyclic products 98 and 99.39 This insertion reaction was used in the cydization step to the cyclopentene ring formation of isocarbacycline 97.40... 

The formation of fluorene from 2-biphenylcarbene is completely analogous to the carbazole formation described above. Contrary to earlier beliefs, the facile gas-phase rearrangement of diphenylcarbene to fluorene (Scheme 51) is not a direct process (path a),208 Other carbocyclic analogs of this reaction have been reported,10,329 and it has allowed the preparation of a number of heterocyclic compounds in high yields as well as a deeper understanding of the carbene-nitrene rearrangement.210 232... 

While major advances in the area of C-H functionalization have been made with catalysts based on rare and expensive transition metals such as rhodium, palladium, ruthenium, and iridium [7], increasing interest in the sustainability aspect of catalysis has stimulated researchers toward the development of alternative catalysts based on naturally abundant first-row transition metals including cobalt [8]. As such, a growing number of cobalt-catalyzed C-H functionalization reactions, including those for heterocycle synthesis, have been reported over the last several years to date (early 2015) [9]. The purpose of this chapter is to provide an overview of such recent advancements with classification according to the nature of the catalytically active cobalt species involved in the C-H activation event. Besides inner-sphere C-H activation reactions catalyzed by low-valent and high-valent cobalt complexes, nitrene and carbene C-H insertion reactions promoted by cobalt(II)-porphyrin metalloradical catalysts are also discussed. 

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