Ruthenium-Catalyzed Direct Arylations

Ruthenium-Catalyzed Direct Arylations with Oi nometallic Reagents 

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Ruthenium-Catalyzed Direct Arylations Through C-H Bond Cleavages... 

Abstract Stoichiometric cycloruthenation reactions of substrates containing Lewis-basic functionalities set the stage for efficient ruthenium-catalyzed C-H bond functionalization reactions. Thereby, selective addition reactions of C-H bonds across alkenes or alkynes enabled atom-economical synthesis of substituted arenes. More recently, ruthenium-catalyzed direct arylation reactions were examined, which display an unparalleled scope and, hence, represent economically and environmentally benign alternatives to traditional cross-coupling chemistry. 

Scheme 17 Ruthenium-catalyzed direct arylation of aldimine 42...

Scheme 18 Ruthenium-catalyzed direct arylation with phenyl bromide (47)...

Scheme 19 Ruthenium-catalyzed direct arylation with heteroaryl bromide 50...

More recently, a phosphine ligand-free ruthenium-catalyzed direct arylation with aryl bromides as electrophiles was disclosed. Notably, the use of inexpensive RuCl3(H20)n as catalyst in NMP as solvent allowed for economically attractive C-H bond functionalizations of pyridine, oxazoline and pyrazole derivatives, also with more sterically hindered orfftosubstituted aryl bromides as electrophiles (Scheme 21) [79, 80],... 

Scheme 23 Ruthenium-catalyzed direct arylation with ort o-substituted aryl chloride 63...

Scheme 26 Ruthenium-catalyzed direct arylation/hydrosilylation sequence...

Scheme 28 Ruthenium-catalyzed direct arylations with chloride 74 and tosylate 75...

Unfortunately, experimental studies on the working mode of ruthenium-catalyzed direct arylations with organic (pseudo)halides are scarce. However, a beneficial effect of NaOAc on stoichiometric syntheses of ruthenacycles at ambient temperature was reported (see above) [49, 50], and suggested a cooperative depro-tonation/metalation mechanism [7, 30, 86] for the C-H bond activation step. Furthermore, recent computational DFT-calculations provided support for such a mechanistic rationale [87], Moreover, a transition state 83 was independently proposed to account for the high efficacy observed with (HA)SPO preligands in ruthenium-catalyzed direct arylation reactions (Scheme 31). 

Consequently, ruthenium-catalyzed direct arylations with aryl halides in less coordinating apolar solvents, such as toluene, were probed. Notably, a catalytic system derived from SPO preligand 59 enabled regioselective C-H bond functionalizations at the aromatic moieties of /V-aryl substituted 1,2,3-triazoles (Scheme 32) [88],... 

Scheme 33 Ruthenium-catalyzed direct arylation using carboxylic acid 88 as cocatalyst...

Scheme9.13 Ruthenium-catalyzed direct arylation ofthe ketone 29 with the arylboronicester 30 in pinacolone (32).

Scheme 9.14 Mechanism of ruthenium-catalyzed direct arylations of ketones (33) with a substituted boronic ester (37).

Ruthenium-catalyzed direct arylations of the arene 58 with the secondary phosphine oxide (l-Ad)2P(0)H (54) as preligand allowed for the use of inexpensive aryl chlorides as electrophiles (Scheme 9.22) [55], Importantly, the protocol proved applicable to both electron-deficient and electron-rich aryl chlorides. 

Scheme 9.21 Ruthenium-catalyzed direct arylation with bromobenzene (27).

Scheme 9.22 Ruthenium-catalyzed direct arylations with the aryl chlorides 64 and 65.

In ruthenium-catalyzed direct arylations, the directing abilities of 2-oxazolinyl, 2-imidazolinyl, and 1-pyrazolyl groups turned out to be comparable to those observed for 2-pyridyl substituents [60]. As a consequence, a number of nitrogen-containing five-membered heterocycles have been employed as directing groups in intermo-lecular ortho-arylation reactions [60, 62], As an example, the 2-aryloxazoline 76 was... 

These examples illustrated the potential of ruthenium complexes for selective intermolecular C—H bond functionalization reactions. Furthermore, they sowed the seeds of ruthenium-catalyzed direct arylation reactions, which proved to be rather broadly appUcable [124—127]. 

Ruthenium-Catalyzed Direct Arylations with Aryl (Pseudo) Halides... 

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