Pd catalytic cycle

In the past decades, Pd-catalyzed C—H bond functionalization has witnessed significant progress, owing to their emerging potential for providing a direct approach towards target molecules. Many excellent examples of direct functionalization of inert C—H bonds in the total synthesis of natural products and bioactive compounds have been reported in the literature. Until now, there are mainly three mechanistic schemes which have been developed to achieve C—H bond functionalization reactions, namely Pd"/Pd , Pd VPd, and Pd /Pd" catalytic cycles (Figure 5.1). 

Figure 5.1 Summaries of Pd-catalyzed C—H bond functionalization (a) Pd"/Pd catalytic cycle, (b) Pd"/Pd catalytic cycle, (c) Pd /Pd" catalytic cycle.

Pd-catalyzed enantioselective C—H bond functionalization featuring a Pd /Pd catalytic cycle was first reported by Wang and co-workers. They employed phenylacetic acid derivatives as model substrates to construct structurally valuable benzofuranones via C—H bond activation. Based on the previous findings that MPAA ligands can facilitate asymmetric C—H bond functionalization reactions, they found Ac-Gly-OH was the optimal ligand. 

Another type of Pd-catalyzed asymmetric C—H bond activation involving a Pd°/Pd catalytic cycle has progressed rapidly in recent years. Due to its economic and ecological benefits as a result of being free from external oxidants, many scientists have devoted much attention to this type of reaction. 

The pioneer work of enantioselective C(sp )—H bond functionalization featuring a Pd /Pd catalytic cycle was first reported by Baudoin, Clot, and cowvorkers. The electronwvithdrawing group in the ortho position of substrate 83 was crucial to obtaining the p-arylation product (Scheme 5.31). Furthermore, aryl chlorides are also able to be the coupling partners although the reactions have to be performed at an elevated temperature. The intermolecular arylation products were synthesized in moderate yields and ee. However, it provides a blueprint for developing more efficient catalytic systems. 

As discussed earlier, aU of the reactirais in eqs. (2-6) have been proposed to proceed via Pd catalytic cycles. Thus, it is of great interest and potential relevance to establish the viability of carbon-chalcogen bond-forming reductive eliminatirai from Pd centers. In addition, it is important to understand the effects of steric and electronic factors as well as the influence of ancillary ligands on the mechanisms of reductive elimination from Pd to design improved catalytic transformations. 

A very interesting Pd"aminoacetoxylation reaction of alkenes was recently developed jointly by the Sorensen and Lee groups [60]. In a representative example, treatment of 75 with Pd(OAc)2 and PhI(OAc)2 provides oxazohdinone 76 in 65% yield with >20 1 dr (Eq. (1.33)). This transformation is heheved to proceed via a Pd"/Pd catalytic cycle that is initiated by antLatninopaUadation of the alkene to afford 77. The intermediate Pd complex is then oxidized by PhI(OAc)2 to alkyl Pd intermediate 78, which undergoes C—O bond-forming reductive elimination to afford 76. 

Tremont suggested that the C-C coupling step of the catalytic reaction involves either a a-bond metathesis with the electrophilic attack of the alkyl halide on the Pd-Ar bond or a Pd"-Pd catalytic cycle as illustrated in Scheme 19.4. 

Pd"" -Catalyzed Direct Arylations Synthetic Scope Aryl iodides, aryl stannanes, and aryl iodonium reagents have all been successfully employed for the direct conversion of -Ar-H -Ar Ar Pd catulytic cyclcs. For example, the Pd-catalyzed reaction of naphthalene with PhSnClj in the presence of CuCl affords the phenylated product in modest yield as a mixture of the a/p isomers (Scheme 24.9) [13]. This transformation can be applied toward the phenylation of other electron-neutral arenes, albeit, with poor efficiencies. Interestingly, reactions of naphthalene and xylenes yield products via preferential arylation of the more steri-cally hindered C—H bond. Preliminary mechanistic studies suggest a Pd" catalytic cycle for these reactions. 

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