PEPPSI™-IPr

The aforementioned PEPPSI-IPr pre-catalyst 16 has also been used in the Suzuki-Miyaura reaction. This pre-catalyst allowed the easy preparation of hindered biaryls and drug-like heteroaromatic compounds in good to excellent yields (Scheme 6.27). 

Scheme 4 Reactivity of Pd-PEPPSI-SIPr (26) and Pd-PEPPSI-IPr (27) in KTC coupling...

A year later. Organ et reported the synthesis and characterization of well-defined NHC-Pd pre-catalysts 23,24, and 27. Pd-PEPPSI-IPr (27) was found to be the most active, successfully coupling all combinations of alkyl and aryl centers (i.e., sp —sp sp —sp sp —sp sp2—sp2) (Scheme 28). Since the o-donor abilities of IMes and IPr carbenes are similar, improvements in catalyst performance were attributed to the increased steric bulk around the metal centre. Organohalides (i.e.. Cl, Br, I) and pseudohalides (i.e., triflates, tosylates, mesylates) were used in this study and proved to be excellent oxidative addition partners, all resulting in high yield of the... 

In 2010, Organ and co-workers investigated the activity of Pd-PEPPSI-IPr (27) and Pd-PEPPSI-IPent (29) in the synthesis of di-, tri-, and tetra-ort/io-substituted biaryl and heterobiaryl products. With a few exceptions, 29 was found to be the optimal pre-catalyst system, generating various biaryl and heterobiaryl products possessing a variety of functional groups and/or orf/io-substituents (Scheme 29). In particular, a number of tetra-ort/jo-substituted biaryl compounds were synthesized in excellent... 

Orfho-disubstituted aryl iodides as representative examples of sterically hindered substrates are more challenging in palladium-catalyzed coupling reactions. In this respect it is interesting to note that Martin et al. reported a synthesis of sterically hindered aryl ketones by using the NHC palladium complex PEPPSI-iPr [34]. Several diaryl ketones were produced in moderate to good yields by this method (Scheme 4.18). 

The use of the well-defined PEPPSI-IPr precatalyst led to a significant improvement with respect to the rate and the substrate scope of the Negishi alkyl-alkyl coupling reactions (Scheme 3.62). This precatalyst can also be used to promote the cross-couphng of alkyl or aryl halides and sulfonates with arylzinc chloride reagents at room temperature by judicious choice of the solvent and additive (LiCl or LiBr) [236]. 

Scheme 3.62 Use of PEPPSI-IPr precatalyst in the Negishi alkyl-alkyl coupling with alkylzinc reagents [235].

Scheme 3.63 A general one-pot orthogonal double Negishi alkylation using PEPPSI-IPr and...

The influence of a range of salt additives in reactions between wBuZnBr and alkyl bromides catalyzed by PEPPSI-IPr (156-iPr) has been investigated. It has been found that bromide salts tend to be superior to chloride or iodide salts and the influence of the cation is minor [270]. The higher order zincate ZnjnBujBrj " has been suggested to be the active transmetallation agent. Its formation depends not... 

Much recent attention has been paid to the development of new ligand systems providing enhanced reactivity. As for nickel, catalytic systems of interest can be obtained with bulky NHC ligands. The family of PEPPSI (pyridine-enhanced precatalyst, preparation, stabilization, and initiation) precatalysts is well suited for crowded or poorly reactive electrophiles such as aromatic chlorides 67 (Scheme 5.12) [53]. As illustrated with the formation of 69 from biaryhnagnesium bromide 68, in the presence of PEPPSI-IPr (70) (2 mol%), reactions take place with high yields at room temperature in THF. It has been proposed that the pyridine attaches to and detaches from the Pd(0) complex in solution and therefore slows down the rate of palladium black formation and deactivation of the catalyst... 

Palladium complexes of monophosphine hgands such as PCyj or NHC ligands (PEPPSI-IPr catalyst 70) are efficient catalysts for the more challenging alkylations... 

In air, a vial equipped with a stir bar was charged with PEPPSI-IPr (70) (6.8mg,... 

Keywords Allyl bromides, benzyl bromides, diborylmethane derivative, Pd-catalysts such as [Pd-PEPPSI-IPr] (l)/Pd[P(f-Bu)3l2 (2), aq. KOH, dioxane, room temperature, Suzuki-Miyaura cross-coupling (SMC) reaction, C-C bond formation, regio- and chemoseletivity, homoallylboronates, alkylboronates... 

Finally, Greaney recently reported the use of PEPPSI-IPr in the direct arylation of oxazoles, although the scope of this reaction was limited. ... 

Greaney reported the use of PEPPSI-IPr in the direet arylation of oxazoles, although the scope of this reaction was limited. Huynh investigated dipalladium Janus-type triazole-based NHC eomplexes sueh as 79 (Figure 9.16) for arylation of imidazoles. These catalysts had a reasonably good substrate scope, but were less effective with aryl ehlorides. There was evidence... 

S)-(l-(3-(l,3-dimethyl-lH-pyrazol-5-yl)benzyl)pyrrolidin-2-yl)methanol To a 2-dram, round-bottom vial was added sequentially 3-formylphenyl MIDA boronate (0.4 M (THF suspension), 0.5 mL, 0.2 mmol), sodium triacetoxyborohydride (0.8 M (THF suspension), 0.5 mL, 0.4 mmol) and (5)-Prolinol (0.8 M (THF), 0.5 mL, 0.4 mmol), and the reactions were shaken at ambient temperature for 18 h. To the reaction vial was added a solution of aqueous K2CO3 (2 M, 1 mL, 2 mmol) and the reaction was then transferred to a 2-5 mL microwave vial containing 5-bromo-l,3-dimethyl-l//-pyrazole (0.4 mmol). To the vial was added a solution of PEPPSI-IPr in MeCN (0.1 M, 10 pmol), and the vials were irradiated in a microwave reactor at 150 °C for 20 min and analyzed by high-profile liquid chromatography (HPLC)-mass spectrometry (MS). To the microwave vial was added... 

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