Direct oxidative cross couplings

Although not directly relevant to this review, it should be noted that Sanford, Shi and Buchwald have also reported a palladium-catalyzed reaction for the chemo-and regioselective oxidative cross-coupling between ligand coordinated L-Cat-H substrates and simple arenes (Ar-H) [55-57]. 

Simultaneously, Shi and coworkers used an amide as a directing group in the oxidative cross-coupling reaction. Amide was used as a directing group to control... 

To extend the concept of trapping alkane radicals with other types of C-H bonds, Li and co-workers showed that aromatic C-H bonds of 64, with the aid of a pyridine directing group, can undergo oxidative cross-coupling reactions with cyclic alkanes 62 in the presence of tert-butyl peroxide and catalytic amounts of dichloro (p-cymene)ruthenium(II) dimer (Scheme 35) [62],... 

Also in 2010, DeBoef and Gorelsky reported a combination of experimental and computational work to elucidate the mechanism of C2-oxidative cross-coupling of indoles with benzene previously reported by DeBoef in 2008 [50]. The results of their work led to the conclusion that both C-H bond cleavage events proceeded via a single unifying mechanism—a concerted metallation-deprotonation process (Scheme 9). Furthermore, their experiments lead them to the conclusion that the palladation at indole takes place directly at the C2-position without C3-palladation and subsequent C3/C2-palladium migration as previously reported [27, 35] and described herein (vide supra). 

Early 2011 has produced additional advances in both scope and mechanistic understanding of oxidative cross-coupling reactions, as well as, an application of this chemistry to the synthesis of a pharmacologically relevant compound. With respect to advancing the scope of compatible reaction partners in oxidative crosscoupling reactions, Beifuss communicated the direct coupling of xanthines with simple benzene and its derivatives in which the regioselectivity for the simple arene... 

DeBoef demonstrated the utility of the C2-selective oxidative cross-coupling of indole and benzene previously reported by his group in the expedient synthesis of a botulinum neurotoxin inhibitor (Scheme 10) [53]. The streamlined synthesis featured an oxidative cross-coupling of methyl-AT-SEM-indole-6-carboxylate with benzene, and after further elaboration, a direct arylation of a thiophene moiety that had been incorporated into the molecule. This formal synthesis highlights the efficiency of transition metal catalyzed reactions at C-H bonds in the planning of synthetic routes. 

A ruthenium(II)-catalysed oxidative cross-coupling of phenylpyridine substrates with cycloalkanes has been reported (Scheme 31) [22]. The proposed mechanism involves directed metalation of phenylpyridine and formation of a ruthenium alkyl species in the presence of ferf-butyl peroxide as an oxidizing reagent. The reaction required an excess of oxidizing reagent (4 equiv. with respect to phenylpyridine) as... 

In 2010, Gouverneur and coworkers reported a novel cascade cyclization-intermolecular alkynylation reactions toward the synthesis of five-membered 0-heterocycles. /i-Alkynyl-y-butenolides 2 could be efficiently prepared from allenoates 1 and terminal alkynes in the presence of a gold catalyst with the use of Selectfluor as an external oxidant (Scheme 12.1) [5]. This process involves a direct C(sp)-H functionalization of terminal alkynes. This novel gold-catalyzed cascade cyclization oxidative cross-coupling process provides a basis for the development of novel cascade reactions combining traditional gold catalysis and intermolecular oxidative alkynylation. 

Copper-catalyzed C—H and C—X bond activations have attracted much attention because they can convert a C—H bond directly into a C—C or C—FG bond. These transformations meet the basic requirements of green chemistry [82], One elegant example of a cascade reaction related with the copper-catalyzed C—H bond activation is the copper-catalyzed C—H oxidation/cross-coupling of indole with a-amino carbonyl compounds (Scheme 5.80). 

Abstract This chapter highlights the use of iV-heterocyclic carbenes as supporting ligands in arylation reactions different than the more common cross-coupling reactions, including C-F bond activation, catalytic arylation, homocoupling, direct arylation and oxidative Heck reactions. 

In summary, these results demonstrate that air-stable POPd, POPdl and POPd2 complexes can be directly employed to mediate the rate-limiting oxidative addition of unactivated aryl chlorides in the presence of bases, and that such processes can be incorporated into efficient catalytic cycles for a variety of cross-coupling reactions. Noteworthy are the efficiency for unactivated aryl chlorides simplicity of use, low cost, air- and moisture-stability, and ready accessibility of these complexes. Additional applications of these air-stable palladium complexes for catalysis are currently under investigation. 

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