Oxygen oxidative cross-couplings

Soonafterward, Buchwald and coworkers reported an efficient Pd-catalyzed oxidative cross-coupling of A-acetanilides with simple arenes in a similar manner [70]. In the presence of 5-10 mol% Pd(OAc)2 and 10-20 mol% DMSO, the cross-coupling reaction took place smoothly between anilides and 4—11 equiv. of simple arenes in TFA under an oxygen atmosphere (Scheme 23). The reaction conditions could tolerate a wide range of substrates. The metal-free oxidant represents a great advantage of the current catalytic system. 

Oxidative Cross-coupling. Molecular oxygen has been employed as the bulk oxidant in numerous Pd(0) and Pd(II)-catalyzed oxidation processes. Another example is the cross-coupling of organoboranes with olefins, in an oxidative Heck-type reaction. Both Pd(OAc)2 and Pd2(dba)3 were productive in this process affording the desired product in 85-87% yield. It was found that O2 was crucial for this reaction as very little product was formed under anaerobic conditions. The authors infer that these results suggest that O2 plays a pivotal role in the Pd(II)-catalyzed reaction though the reoxidation of Pd(0) species to Pd(II) (eq 51). ... 

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. 

Oxidative Cross-Coupling (Chan-Evans-Lam Reaction) The coupling of phenols with aryl boronic acids has been accomplished (Scheme 20.37). Initially, Chan and coworkers studied an equivalent amount of CulOAc) for the coupling reaction [58]. Subsequently, Evans and coworkers found the use of MS 4 A led to improvement in the yield of the target product [106]. Later, Lam and coworkers made the process catalytic using oxygen as an oxidant [107]. Their mechanistic aspects have been recently demonstrated [108]. 

Numerous examples of unwanted or deliberate Pd-mediated homocoupling of organometallic reagents have been reported (Scheme 8.14) [38, 122, 123]. Suitable oxidants include a-halo ketones [116, 124, 125] (which can, therefore, not be used as electrophilic component in cross-coupling reactions), oxygen [120, 124, 126], 1,2-diiodoethene [127], 2,3-dibromopropionic acid esters [119], and CuCl2 [128]. 

The matrix of the phenomenological coefficients must be positive definite for example, for a two-flow system, we have L0 > 0, Ip >0, and Z/.p Z,pZpo > 0.1,0 shows the influence of substrate availability on oxygen consumption (flow), and Ip is the feedback of the phosphate potential on ATP production (flow). The cross-coupling coefficient Iop shows the phosphate influence on oxygen flow, while Zpo shows the substrate dependency of ATP production. Experiments show that Onsagers s reciprocal relations hold for oxidative phosphorylation, and we have Iop = Zpo. 

The development of C-H activation for cross-coupling reactions has been advanced rapidly. Extensive efforts have been devoted to the mechanistic studies in this field to shed light on the mechanism. The use of oxygen or air as sole oxidant has been successfully realized in a palladium-catalyzed cross-coupling reaction involving C-H activation. We have the right to believe that palladium-catalyzed double C-H activation would be a good alternative for the synthesis of biaryls. With further improvements in catalyst turnover, selectivity, and oxidant, the method should ultimately be able to find industrial applications. 

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