Heck reaction ligand applications

Scheme 6.7 Application of bis-NHC chelating ligands in the Mizoroki-Heck reaction...

Zheng et al. treated potassium [l,2,4]diazaphospholides, obtained from the reaction of 3,5-disubstituted-[l,2,4]diazaphospholes with metallic potassium in THF, with [Cp RuCl]4 to afford [(T75-dp)RuCp ] type pseudoruthenocene complex (106) (Scheme 33). Sandwich structure with almost eclipsed orientation of two n-bonded ligands has been confirmed by X-ray crystal structure determination [110], Catalytic application of [(rf-dp)RuCp ] complexes in the Heck reaction has also been investigated [111]. 

Normally, the oxidative addition of an aryl chloride to Pd(0) is reluctant to take place. But such a process is greatly accelerated in the presence of sterically hindered, electron-rich phosphine ligands [e.g., P(/-Bu)3 or tricyclohexylphosphine]. In late 1990s, Reetz [76] and Fu [77] successfully conducted intermolecular Heck reactions using arylchlorides as substrates, as exemplified by the conversion of p-chloroanisole to adduct 77 [77], The applications of this discovery will surely be reflected on future Heck reactions of non-activated heteroaryl chlorides. 

Several important industrial applications of the Heck reactions are known. The world s largest producer of Naproxen is Albemarle and they make Naproxen using two homogeneously catalysed steps, a Heck reaction and a palladium catalysed hydroxycarbonylation. The last step is carried out using palladium without chiral ligand and the enantiomers obtained are separated, see Figure 13.18. 

Another significant development in oxazoline chemistry is the application of oxazoline-containing ligands for asymmetric catalysis, such as palladium-catalyzed allylic substimtions, Heck reactions, hydrogenations, dialkylzinc additions to aldehydes, and Michael reactions. The discovery of diastereoselective metalation of chiral ferrocenyloxazolines has further expanded the availability of chiral ligands for metal-catalytic reactions. 

The enantioselective Heck reaction has matured into a powerful method for asymmetric C-C bond formation and has proven its value in several total syntheses. One can expect that it will find many more applications in the future, even in industry. There is still an extensive space for chemists to design new suitable substrates and to search for new effective chiral ligands [23]. 

An indole alkaloid synthesis employing a bona fide intramolecular Heck reaction was documented in Sundberg s preparation of 5,6-homoiboga derivatives [90]. Several attempts to construct S,6-homoiboga derivative 191 using inter- or intramolecular Heck reaction conditions with phosphine ligands led to poor yields. Application of Jeffery s ligand-free" phase-transfer... 

Binap 3.43 is also a good ligand for palladium complexes. Although 71-allyl palladium-binap complexes have met limited applications in asymmetric allylation of malonate like derivatives [872], binap-PdCl2 complexes induce enantioselective Heck reactions [902] and 1,4-disilylations of a-enones [903],... 

Heck reaction has some important applications in industry because it is one of the effective tools for the formation of new C-C bonds [49]. The traditional Heck reaction is performed with a Pd catalyst with phosphine ligands in the presence of a base under an inert atmosphere. However, the expensive Pd complex is often lost at the end of the reaction, which limits the large-scale application of Heck reactions. On the other hand, phosphine ligands, especially the electron-rich ones, are often toxic, and water and air sensitive. For industrial application, it is important to have good strategies for catalyst-product separation and catalyst recycling. SIL catalyst is one of the promising alternatives for the development of eco-friendly processes. 

The polar path is apparently more common for Mizoroki-Heck reactions. With bidentate ligands, it serves as the basis for various regio- and enantio-selective protocols. However, owing to some peculiarities in the coordination chemistry of palladium, it has little or no application in the version with two stable monodentate ligands. Still, this path dominates in common Mizoroki-Heck reactions, where all ancillary ligands are labile or hemilabile and the coordination shell of palladium is largely undefined. 

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