Nitrenes, carbenes and, intramolecular

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... 

As shown in the previous two sections, rhodium(n) dimers are superior catalysts for metal carbene C-H insertion reactions. For nitrene C-H insertion reactions, many catalysts found to be effective for carbene transfer are also effective for these reactions. Particularly, Rh2(OAc)4 has demonstrated great effectiveness in the inter- and intramolecular nitrene C-H insertions. The exploration of enantioselective C-H amination using chiral rhodium catalysts has been reported by several groups.225,244,253-255 Hashimoto s dirhodium tetrakis[A-tetrachlorophthaloyl-(A)-/ r/-leuci-nate], Rh2(derived rhodium complex, Rh2(i -BNP)4 48,244 afforded moderate enantiomeric excess for amidation of benzylic C-H bonds with NsN=IPh. 

In summary, metal carbene and metal nitrene C-H functionalizations have undergone explosive growth over the last decade. Major advances have been made in both intermolecular and intramolecular versions of this chemistry. The reactions represent new strategic methods for synthesis, and with the foundation set, it is expected that the chemistry will be even more broadly used in synthesis in the future. 

Like carbene insertions into carbon-hydrogen bonds, metal nitrene insertions occur in both intermolecular and intramolecular reactions.For intermole-cular reactions, a manganese(III) meio-tetrakis(pentafluorophenyl)porphyrm complex gives high product yields and turnovers up to 2600 amidations could be effected directly with amides using PhI(OAc)2 (Eq. 51). The most exciting development in intramolecular C—H reactions thus far has been the oxidative cychzation of sulfamate esters (e.g., Eq. 52), as well as carbamates (to oxazolidin-2-ones), ° and one can expect further developments that are of synthetic... 

In contrast to considerations of 50 years ago, today carbene and nitrene chemistries are integral to synthetic design and applications. Always a unique methodology for the synthesis of cyclopropane and cyclopropene compounds, applications of carbene chemistry have been extended with notable success to insertion reactions, aromatic cycloaddition and substitution, and ylide generation and reactions. And metathesis is in the lexicon of everyone planning the synthesis of an organic compound. Intramolecular reactions now extend to ring sizes well beyond 20, and insertion reactions can be effectively and selectively implemented even for intermolecular processes. 

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

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

Carbenes and Nitrenes in Heterocyclic Chemistry Intramolecular Reactions... 

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. 

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

A range of studies have now appeared modeling complete catalytic cycles based on an initial C-H bond activation and the subsequent functionalization steps. The functionalization processes involve reactions with an insertion partner (an alkyne, an alkene, or a carbene/nitrene source) and lead to the formation of new heterocychc rings or direct replacement of the C—H bond with a new C-R group. In many cases, the focus of the computational studies is on these functionalization processes as well as the reoxidation steps (particularly with internal oxidants). The C-H activation in these catalytic processes is typically of the intramolecular AML A-6 type, although exceptions do exist, as will be detailed later. Input from parallel experimental studies, including the determination of kfj/ko KIEs, the observation of H/D exchange, competition experiments, and the isolation of key intermediates both complement and provide benchmark data... 

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. 

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