Rhodium direct arylation

When electronic effects dominate the reactivity of an aromatic substrate, regiose-lectivities can be accomplished in intermolecular direct arylation reactions. Thus far, this approach proved predominantly applicable to the functionalization of heteroarenes with the aid of either palladium- [21], copper-, or rhodium-catalysts [22-27],... 

Proch S, Kempe R (2007) An efficient bimetallic rhodium catalyst of the direct arylation of unactivated arenes. Angew Chem Int Ed 46 3135-3138... 

Arylation reactions of aromatic ketimines were developed, and in many cases the products of the reaction were isolated after subsequent hydrolysis. Therefore, these arylations constitute an indirect method for the preparation of arylated aromatic ketones, the direct functionalizations of which are often more difficult. Thus, direct arylation of imine 42 with sodium tetraphenylborate catalyzed by [RhCl(cod)]2 afforded a mixture of mono- and diarylated benzophenone imines (44 and 45) (Scheme 9.16) [53]. The formation of the corresponding amine 46 clearly indicated that 42 also acted as a hydride acceptor in this transformation. Most likely, the reaction occurs via initial coordination by the benzophenone imine to a phenylrho-dium intermediate followed by orfho-rhodation to afford the five-membered rhoda-cyde intermediate 47 (Scheme 9.16). Subsequent reductive elimination generates the monophenylated product 44 and a rhodium hydride, which then reduces imine 42 in the presence of ammonium chloride as proton donor to regenerate the catalytically active speties. 

Scheme 9.20 Rhodium-catalyzed direct arylation of 2-phenylpyridine (58).

A highly active catalytic system for direct arylation reactions of nonactivated arenes relied on a homobimetallic rhodium complex. Thus, treatment of [bis(2-pyridyl) amino]diphenylphosphane (109) with [Rh(cod)Cl]2 led to the formation of a complex 108, which, according to X-ray crystal structure analysis, consisted of [Rh(cod) Cl2] anion and a rhodium cation stabilized by two P,N-ligands (Scheme 9.34) [73]. This bimetallic rhodium complex (108) allowed the direct arylation of benzene (87) with the aryl chloride 106 with a turnover number (TON) of 780 under comparably mild reaction conditions. 

Intermolecular direct arylations of heteroarenes with aryl halides were thus far predominantly accomplished with palladium or rhodium complexes [31, 39,75, 76], Hence rhodium catalysts proved applicable to various electron-rich heteroarenes. In contrast, less expensive and more versatile palladium catalysts allowed for direct arylations of both electron-rich and electron-deficient substrates. Generally, the problem of achieving regioselectivities in direct arylation reactions of heteroarenes is less pronounced than it is for simple arenes, since in many cases the heteroatom can be considered as an endocyclic directing group. 

Scheme 9.39 Rhodium-catalyzed direct arylation of pyrrole (126) with the aryl iodide 40.

Scheme 9.40 Proposed mechanism of rhodium-catalyzed direct arylations of pyrroles.

In contrast, N-methylpyrrole underwent direct arylations atthe 3-position [93], and a comparable result was obtained in direct arylations of N-phenylpyrrole employing the electron-deficient rhodium complex 114, in combination with Ag2C03 under microwave irradiation [74b]. Selected examples of regioselective arylations of substituted five-membered heteroarenes are summarized in Table 9.3. 

Scheme 9.44 Rhodium-catalyzed direct arylation of lH-benzimidazole (157) with the aryl...

Scheme 9.45 Proposed mechanism for rhodium-catalyzed direct arylations of benzimidazoles.

Zhao P, Incarvito CD, Hartwig JF (2007) Directly observed transmetalation from boron to rhodium. /3-Aryl elimination from Rh(I) arylboronates and diarylbori-nates. J Am Chem Soc 129 1876... 

Other reported syntheses in this category include a copper-catalyzed preparation of 2-acylindoles from 2-bromobenzaldehydes (14EJ0511) and a rhodium-catalyzed direct arylation of a-diazoimines which furnishes... 

Oestxeich found that the direct arylation of indolines could be accomplished without over oxidation to the corresponding indole under palladium-catalysis with air (open flask), oxygen (balloon), or copper(II) acetate as the oxidant. Indolines can be unsubstituted or substituted as C2/C3 and the reaction performs well on gram scale (250, 18 examples, 18—90% isolated yield) (140L6020).A directed C2-functionalization/C7-alkenylation was discovered by Xu,Yi, and colleagues. With a rhodium catalyst, indole derivatives were functionalized with acetates at C2 (22 examples, 62—92% yield) the newly obtained products could be alkenylated at C7 with a rhodium/copper system (251,3 examples, 68—78% yield) (14CC6483). 

Scheme 1.38 Rhodium-catalyzed direct arylation of arene 100 (Oi, Inoue, 1998).

A comparable concept was applied in 1998 to rhodium-catalyzed oxidative direct arylations, which employed organometaUic compounds for regioselective direct arylations (Scheme 1.38) [128]. 

A comprehensive review on direct arylations with ruthenium and rhodium complexes is provided in Chapter 9 by Lutz Ackermann and Ruben Vicente, where... 

Rhodium-catalyzed direct arylations of 2-aryl pyridines were efficiently accomplished with arylstannanes through chelation-assistance (Scheme 9.3) [14]. This report constitutes an early example of a metal-catalyzed direct arylation with an... 

Scheme 9.3 Rhodium-catalyzed direct arylation with stannane 2.

Scheme 9.4 Rhodium-catalyzed direct arylation of imine 5 with boronate 6.

During studies on rhodium-catalyzed Suzuki-Miyaura cross-coupling reactions, Miura and coworkers reported more recently on the use of less-toxic tetraphenyl-borate 6 for the direct arylation of imines (Scheme 9.4) [16]. Unfortunately, rather low yields of mono- and di-arylated products were obtained, this being due to a reduction of the starting material via a sequence consisting of a rhodium hydride addition and subsequent protonation. The reduction of the imine is mandatory for the regeneration of a rhodium chloride species, and thereby for catalytic turnover. 

Highly efficient rhodium-catalyzed direct arylations were accomplished through the use of 2,2, 6,6 -tetramethylpiperidine-N-oxyl (TEMPO) as terminal oxidant [17]. Thereby, a variety of pyridine-substituted arenes was regioselectively functionalized with aromatic boronic acids (Scheme 9.5). However, in order for efficient catalysis to proceed, 4equiv. of TEMPO were required. The use of molecular oxygen as terminal oxidant yielded, unfortunately, only unsatisfactory results under otherwise identical reaction conditions. However, a variety of easily available boronic acids could be employed as arylating reagents. 

Scheme 9.5 Rhodium-catalyzed direct arylation of pyridine 1 with boronic acid 10.

Scheme 9.8 Rhodium-catalyzed direct arylation of phenol 18 with bromide 19.

Scheme 9.10 Chlorophosphine 24 as preligand in a rhodium

Scheme 9.11 Rhodium-catalyzed direct arylation of anisole (29) with aryl iodide 30.

Rhodium-catalyzed direct arylahons of arenes can be achieved in the absence of any directing groups. Thus, a rhodium complex displaying a strong it-accepting ligand [P(OCH(CF3)2]3 led to a direct arylation of anisole (29) using electron-deficient aryl iodide 30 under microwave irradiation (Scheme 9.11) [23]. As a... 

Scheme 9.12 Homobimetallic rhodium complex 35 for a catalytic direct arylation.

A homobimetallic rhodium catalyst derived from a P,N-ligand was found to allow for intermolecular direct arylations of unfunctionalized arenes [24]. Interestingly, aryl iodides, bromides-and even chlorides-could be employed as electrophiles, and a variety of valuable functional groups was tolerated by the catalytic system (Scheme 9.12). The C—H bond functionalization of toluene yielded ortho-, meta- and para-substituted regioisomers in a ratio of 71 19 10. Based on this observation and a Hammett correlation, a mechanism proceeding through radical intermediates was suggested. 

Intermolecular direct arylations of heteroarenes, such as indoles, pyrroles or (benzo)furans, were, thus far, predominantly achieved with palladium catalysts (see Chapter 10). However, rhodium complexes proved also competent for the direct functionaUzations of various valuable heteroarenes with comparable or, in some cases, improved catalytic performance. Thus, rhodium-catalyzed C—H bond functionalizations of various N-heterocycles, were elegantly developed by Bergman, Ellman and coworkers. Here, the use of a catalytic system comprising [RhCl(coe)2]2 and PCys led to direct arylations of unprotected benzimidazoles with aryl iodides... 

Scheme 9.13 Rhodium-catalyzed direct arylation of benzimidazole (37).

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