Oxidative cross-coupling reactions

Oxidative cross-coupling reactions of alkylated derivatives of activated CH compounds, such as malonic esters, acetylacetone, cyanoacetates, and certain ketones, with nitroalkanes promoted by silver nitrate or iodine lead to the formation of the nitroalkylated products.67 This is an alternative way of performing SRN1 reactions using a-halo-nitroalkanes. 

CATALYTIC OXIDATIVE CROSS-COUPLING REACTION OF 2-NAPHTHOL DERIVATIVES... 

Table 8.2 Asymmetric oxidative cross-coupling reaction with CuCl-(5)Phbox...

As already shown in Scheme 101, oxidative cross-coupling reactions of two different phenols using DDQ are quite interesting from the viewpoint of natural products synthesis. A mixture of 2,6-di(icri-butyl)phenol (1 equiv.) and 2,6-dimethylphenol (1 equiv.) was also oxidized with Mn(OAc)3 (4 equiv.) to give the desired cross-coupled dimer 674, although the yield (26-10%) was not satisfactory (Scheme 131) . 

Pd-Catalyzed Aryl-Aryl Bond Formation via Oxidative Cross-Coupling Reaction. .. 175... 

Scheme 13 Pd-catalyzed oxidative cross-coupling reaction...

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... 

Following their earlier success with the oxidative allylic alkylation reaction, Li and co-workers examined the oxidative cross-coupling reaction between activated methylenes 46 with benzylic C-H bonds of 55 (Scheme 30) [53]. 

Scheme 33 Oxidative cross-coupling reaction between cyclic alkanes and P-ketoesters...

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],... 

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. 

Subsequently, we studied the relationship between the oxidant and the mechanism of the Pd-catalyzed oxidative cross-coupling reactions. Through an extensive study of reaction kinetics and competition reactions, we demonstrated that oxidative coupling conditions employing heteropoly acids and O2 are distinctly different from those mediated by more conventional oxidants such as Cu(OAc)2 or AgOAc (Scheme 7). We concluded that the heteropoly acid-mediated reactions proceed via a Pd(II)/Pd(IV) mechanism. To the best of our knowledge, this is the first example of a Pd(IV)-mediated oxidative coupling reaction. 

The Wang group also realized enantioselective oxidative cross-coupling reactions between tertiary amines and the activated olefins by merging Cu(OTf)2 with quinine as the best cooperative catalysts/ A Morita-Baylis-Hillman-type mechanism is in operation. It was notable that molecular oxygen was employed as the sole oxidant. As shown in Scheme 2.12, the reactions between Ai-aryl THIQs and the a,p-unsaturated aldehydes or ketones 30 proceeded smoothly to afford the a-functionalized products 31 in up to 81% yield and 99% ee. 

In 2010, Gong and co-workers reported a Lewis acid-catalyzed enantioselective oxidative cross-coupling reaction of 3-indolylmethyl C—H bonds... 

Oxidative Cross-Coupiing Reactions C(sp )-organozincs can also take part in palladium-catalyzed oxidative cross-coupling reactions. C(sp )-C(sp) couplings, not easy to achieve by more classical approaches involving haloalkynes, are readily performed. 

Manganese-Catalyzed Oxidative Cross-Coupling Reactions... 

As in all C-C cross-coupling reactions, the Negishi reaction mechanism consists in three steps (Fig.4.1) oxidative addition, transmetalation, and reductive elimination. The former and the latter are common to all the other cross-coupling reactions, whereas the transmetalation step is particular of this reaction. Unfortunately, this transmetalation has been less studied compared to the ones in the Stille [12-17] or Suzuki reactions, [18-21] in spite of the fact that the transmetalation between organozinc and palladium complexes is also involved in other relevant processes, such as the hydroalkylation of styrenes, [22] the asymmetric allylation of aryl aldehydes, [23] the coupling propargylic benzoates and aldehydes, [24] or the double-transmetalation oxidative cross-coupling reaction [25, 26]. 

---