Intermolecular oxidative cross-coupling

Table 2 Selected data for optimization of an intermolecular oxidative cross-coupling...

After realizing that our hypotheses about oxidative cross-coupling reactions were not as unique as assumed, we quickly turned our attentirai to intermolecular oxidative amination reactions. In the carbazole example, regioselectivity was coti-trolled by the presence of a Lewis base that was attached near the C—H bmid that would be cleaved, resulting in a metallacyle intermediate. For die development of an intramolecular reaction, we chose to take advantage of the selectivity that is often observed in the selective metalation of electron-rich heteroarenes. At the time, the palladation of indoles was presumed to operate by an electrophilic aromatic substitution mechanism. (This has since been demonstrated to be incorrect, vide infra.) We hypothesized that regioselective palladation of an indole substrate could be followed by a subsequent C—N bond reductive elimination. At the time, the exact mechanism by which the intermediate containing Pd—C and Pd—N bonds could be formed was not clear, nor was the order of the two metalation steps, but the overall process seemed plausible. 

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. 

Palladium(0)-catalyzed cross-coupling of aryl halides and alkenes (i.e., the Heck reaction) is widely used in organic chemistry. Oxidative Heck reactions can be achieved by forming the Pd -aryl intermediate via direct palladation of an arene C - H bond. Intramolecular reactions of this type were described in Sect. 4.1.2, but considerable effort has also been directed toward the development of intermolecular reactions. Early examples by Fu-jiwara and others used organic peroxides and related oxidants to promote catalytic turnover [182-184]. This section will highlight several recent examples that use BQ or dioxygen as the stoichiometric oxidant. 

Some of the most useful synthetic transformations of terminal alkynes involve intermolecular and intramolecular homo- and cross-coupling reactions between their. sp-carbon centers, leading to butadiyne or polyyne derivatives. The two most widely used and practical systems are (i) oxidative homocoupling reactions, i.e. Glaser and Eglington reactions and (ii) heterocoupling reactions, i.e. Chodkiewicz-Cadiot coupling of a terminal alkyne with a haloalkyne. 

DeBoef and co-workers have reported a similar reaction, wherein direct C-H to C-H indole-arene cross-coupling can be controlled through the use of a particular oxidant (Scheme 34) [53,54], The basis of their selectivity concept is the formation of different polyvalent clusters between the Pd(OAc)2 and the AgOAc or Cu(0 Ac)2 oxidants respectively, and the subsequent reactivity of these complex in the aryla-tion reaction. The same group also demonstrated the utility of an intermolecular C-H to C-H coupling reaction. 

For a recent example of selective intermolecular oxidative palladium-catalyzed cross-coupling between indoles andarenes, see Stuart, D.R. and Fagnou, K. (2007) Science, 316, 1172-5. 

The intermolecular a-arylation of amides with aryl chlorides was unknown until very recently. Fortunately, the work developed by Walsh and coworkers [93] has demystified the theme. Aryl chlorides are generally less reactive than aryl bromides in oxidative additions nonetheless, aryl chlorides are less expensive and more readily accessible when compared with aryl bromides, making their use in cross-coupling reactions highly desirable. Walsh and coworkers reported the first deprotonative cross-coupling process for the intermolecular arylation of amides with aryl chlorides. Buchwald-type [94] precatalysts formed with Kwong s [95] indole-based phosphane ligand effectively catalyzes the... 

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