Electron-rich, Sterically Hindered Phosphine Ligands

It is important to note that there are successful examples of biaryl coupling using electron-rich and sterically-hindered phosphine ligands on palladium(O). ... 

There is certain similarity in the order of reactivities between SnAt displacement reactions and oxidative additions in palladium chemistry. Therefore, the ease with which the oxidative addition occurs for these heteroaryl chlorides has a comparable trend. Even a- and y-chloroheterocycles are sufficiently activated for Pd-catalyzed reactions, whereas chlorobenzene requires sterically hindered, electron-rich phosphine ligands. 

Recently, the groups of Fu and Buchwald have coupled aryl chlorides with arylboronic acids [34, 35]. The methodology may be amenable to large-scale synthesis because organic chlorides are less expensive and more readily available than other organic halides. Under conventional Suzuki conditions, chlorobenzene is virtually inert because of its reluctance to oxidatively add to Pd(0). However, in the presence of sterically hindered, electron-rich phosphine ligands [e.g., P(f-Bu)3 or tricyclohexylphosphine], enhanced reactivity is acquired presumably because the oxidative addition of an aryl chloride is more facile with a more electron-rich palladium complex. For... 

The first example was published by Watanabe and coworkers. They successfully aminated both a- and [l-halothiophenes [185]. In a strategy employing the sterically hindered, electron-rich phosphine ligand P(r-Bu)3, NaOz-Bu as the base, and PdlOAcJj as the catalyst, 2,5-dibromothiophene was bisaminated with diphenylamine to afford 2,5-bis(diphenylamino)-thiophene (285). This method is also apphcable to 3-bromothiophene (69% yield), whereas the monoamination of 3,4-dibromothiophene was... 

The exo-selective gold-catalyzed cyclization of alkenyl carbamates, amides, or ammonium salts affords the corresponding pyrrolidine or piperidine derivatives. Here, cationic gold(I) catalysts bearing sterically hindered, electron-rich phosphine ligands such as P(r-Bu)2(o-biphenyl) were much more reactive than PhsPAuOTf... 

Aryl exchange occurs before transmetallation. Thus, the transmetal-lation rate constant which is low for steric and electronic reasons results in increasing the coupling product of phosphine-bound aryls (Eq. 51). Transmetallation is slowed down when electron-rich haloarenes and weak bases are used and accelerated with electron-deficient haloarenes because the transmetallation shown in Eqs. 16 and 17 involves nucleophilic substitution of Pd-X. The reported equilibrium ratio of 3/5 is 4/96 at 60 °C when Ar is p-methoxyphenyl. Thus, it is quite reasonable that the reaction accompanies a large amount of 6 when the rate constant of transmetallation ifej is lower than ky A strong base, polar solvent, and a sterically less hindered bidentate ligand, such as dppf, increase k. The formation of yields of 9 in p-iodoanisole higher than the bromo derivative... 

---