Rhodium metal nitrenes

Copper-catalyzed decomposition of benzenesulfonyl azide in the presence of cyclohexene was the first reported evidence of a metal-catalyzed nitrene insertion reaction [25]. This seminal discovery was then followed by the pioneering work of Breslow and Gellman who introduced the use of iminoiodinanes as metal nitrene precursors as well as rhodium dimer complexes as catalysts [26,27]. They showed the formation of the corresponding benzosultam in 86% yield in the presence of rhodium (II) acetate dimer (Rh2(OAc)4) via an intramolecular metal nitrene C—H bond insertion reaction (Eq. (5.1)). 

Muller then intensively studied rhodium dimer complexes as catalysts for the intermolecular amination of alkanes using iminoiodinanes, typically PhI=NTs and PhI=NNs [28-30]. Good yields were obtained for amination of benzyUc, aDylic and tertiary C—H bonds, which are the most reactive C— H bonds towards metal nitrenes. For instance the amination of indane provided the corresponding benzylic amine in... 

This discovery has tremendously expanded the field of amination reactions, not only to perform intramolecular, but also intermolecular C—H insertion reactions. Today this approach is the most commonly used to prepare metal nitrenes, especially those derived from rhodium catalysts. N-Tosyloxycarbamates are alternative rhodium... 

Rhodium dimer complexes are the most widely used catalysts to perform C—H aminations. Other metal complexes that catalyze metal nitrene C—H insertion reactions, include metalloporphyrins [12, 39], silver [21, 40], copper [22], palladium [41] and gold [42] complexes. 

A number of reviews have appeared recently on C—H insertion of metal nitrenes [18-20], some of them specifically dedicated to rhodium catalysts [16, 24, 43]. 

In the presence of a chiral catalyst such as rhodium(II) (5)-/V l,8-naphthanoyl-tert-leucinate dimer, Troc-amino indane was produced with 56% yield and 2.57 1 enantiomeric ratio. In contrast to other methods, no hypervalent iodine reagent (typically used stoichiometrically or in excess and forming iodobenzene as by-product) is required for oxidation of the amine component. However, a slight excess of the aromatic alkane component (5 equiv) must be used to achieve good conversions. The reactivity of rhodium nitrenes generated from 2,2,2-trichloroethyl-/V-tosyloxycarbamate with aliphatic alkanes is similar to the one observed with metal nitrenes obtained from the oxidation of sulfamate with hypervalent iodine reagent. Troc-protected amino cyclohexane and cyclooctane were obtained, respectively, in 73 and 62% yields when 2 equiv of alkanes was used, whereas yields up to 85% were observed with 5 equiv (eq 3). 

Nitrene addition to alkenes can be aided by the nse of a transition metal, such as copper, rhodium, ruthenium, iron, cobalt, etc. NHC-Cu catalysts have been used in nitrene addition. For example [Cu(DBM)(IPr)] 147 (DBM = dibenzoyl-methane) was successfully employed in the aziridination of aliphatic alkenes 144 in presence of trichloroethylsulfamate ester 145 and iodosobenzene 146 (Scheme 5.38) [43]. 

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. 

Preliminary efforts to examine the mechanism of C-H amination proved inconclusive with respect to the intermediacy of carbamoyl iminoiodinane 12. Control experiments in which carbamate 11 and PhI(OAc)2 were heated in CD2CI2 at 40°C with and without MgO gave no indication of a reaction between substrate and oxidant by NMR. In Hne with these observations, synthesis of a carbamate-derived iodinane has remained elusive. The inability to prepare iminoiodinane reagents from carbamate esters precluded their evaluation in catalytic nitrene transfer chemistry. By employing the PhI(OAc)2/MgO conditions, however, 1° carbamates can now serve as effective N-atom sources. The synthetic scope of metal-catalyzed C-H amination processes is thus expanded considerably as a result of this invention. Details of the reaction mechanism for this rhodium-mediated intramolecular oxidation are presented in Section 17.8. 

Padwa has shown that rhodium-catalyzed oxidation of indolyl carbamate 67 employing either Phl(OAc)2 or Phl=0 follows a path similar to that of the D-aUal carbamate (Scheme 17.26) [95]. In principle, indole attack of the putative rhodium-nitrene generates zwitterion 68, which is trapped subsequently by an exogenous nucleophile. Spiro-oxazolidinone products (for example, 69) are isolated as single diastereomers in yields ranging from 50 to 85%. As an intriguing aside, Padwa has found that certain carbamates react with Phl=0 in the absence of any metal catalyst to furnish oxazoHdinone products. This result may have implications for the mechanism of the rhodium-catalyzed process, although it should be noted that control experiments by Espino and Du Bois confirm the essential role of the metal catalyst for C-H amination [57]. 

The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

Attempts to achieve asymmetric nitrene insertion reactions catalyzed by chiral transition metal complexes have also been performed [41,42]. The reaction of the nosyl-imine derivative as the nitrene donor with indane 61 catalyzed by the chiral rhodium complex 63 gave the optically active allyl amine 62 in good yield and moderate ee (Eq. (15)) [41],... 

This chapter on nitrene cyclization is a segue to the following several chapters that employ this tactic in powerful and widely used indole ring syntheses. The use of metals, such as palladium, rhodium, and ruthenium, to generate nitrenes or their equivalent and effect indole ring construction is discussed in later chapters. Soderberg has reviewed the synthesis of heterocycles via the generation... 

As with several indole-ring syntheses to be discussed, transition metals have been adapted to the Sundberg azide indole-carbazole synthesis. These include rhodium, ruthenium, palladium, and iron. Rather than discuss these elegant methods in the present chapter, 1 have relegated them to the respective chapters on metal-promoted indole synthesis. Two excellent reviews discuss the synthesis of nitrogen heterocycles via azides [59] and nitrenes [60]. 

By analogy with the rhodium carbene intermediate proposed in the C H insertion reaction with diazo compounds, C— H amination is believed to proceed via a rhodium nitrene species, although such an intermediate has never been characterized. However, as chiral dimeric rhodium complexes lead to the formation of enantioen-riched amination products, it suggests that the metal center is closely associated with the reactive nitrogen during the C—H insertion step. Both a rhodium nitrene or rhodium phenyliminoiodinane species may be involved (Figure 5.2). 

The coordination of the N-tosyloxycarbamate to the rhodium catalyst is required for the deprotonation to occur, as no reaction is observed between potassium carbonate and the N-tosyloxycarbamate alone. The formation of the rhodium nitrene may proceed through the formation of a sulfonyloxy metal species which rapidly liberates the tosylate group, or the deprotonation may be concerted with the departure of the leaving group. It is postulated that the formation of the rhodium nitrene is the rate-determining step, since the rate of C H insertion is the same for a deuterated and undeuterated substrate (Eqs. (5.28) and (5.29)). 

Like their carbene cousins, the insertion of nitrenes into C-H bonds is a useful method for functionalizing molecules (Scheme 8.148). " The nitrenes are typically generated by the oxidation of an amine derivative in the presence of the metal catalyst, most often, but not exclusively, a rhodium complex. Widely used oxidants are iodosobenzene diacetate and iodosobenzene. These react with the amine derivative to form an... 

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. 

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. 

Photochemical reactions of the iridium(m) and rhodium(m) complexes [M(NH3)6(N3)] + result in the production of a co-ordinated nitrene intermediate. In concentrated hydrochloric add the iridium(m) product is [Ir(NH3)6(NH2Cl)] +, as in the equivalent thermal reaction. These iridium(ra) and rhodium(m) complexes thus behave photochemically in a similar mmmer to hydrazoic acid and to organic azides. Their behaviour contrasts with that of some other transition-metal azide complexes, e.g. those of ruthenium(n), where an azido-radical is the photochemical intermediate. One can indeed group transition-metal azide complexes into three groups, with their thermal and photochemical reactions depending on the relative ease of oxidation or reduction (or neither) of the transition-metal centre. ... 

The very rich reactivity of nitrenes arising through their generation in the coordination sphere of metals such as copper and rhodium has been described. Difimctionalizations... 

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