A-Arylations palladium-catalyzed

Campos, K.R., Klapers, A., Waldman, J.H., Dormer, P.G., Chen, C.Y. (2006) Enantioselective, Palladium-Catalyzed a-Arylation of N-Boc-pyrrolidine. Journal of the American Chemical Society, 128, 3538-3539. 

A mild and efficient a-heteroarylation of simple esters and amides via nucleophilic aromatic substitution has been described <06OL1447>. Treatment of 2-chloro-benzo[//Jthiazole 99 with tert-butyl propionate in the presence of NaHMDS under nitrogen furnishes tert-butyl 2-(benzo[c(jthiazol-2-yl)propanoate 100. When the same reaction is preformed initially under nitrogen and then exposed to air, the hydroxylation product 101 is obtained. This method offers two desirable features that are either complementary or improvements to the palladium-catalyzed a-arylation reactions. First, heteroaryl chlorides... 

Scheme 6.43 Palladium-catalyzed a-arylation of esters and amides with organozinc reagents.

The push-spectator stabilization system enables one to employ various alkyl groups with different types of steric environment, which differentiate amino(alkyl) carbenes dramatically from the NHCs as ligands. Taking advantage of their steric and electronic properties, Bertrand et al. nicely demonstrated the utility of CAACs as ligands in the palladium catalyzed a-arylation of ketones. Depending on the nature of the aryl chloride used, dramatic differences were observed in the catalytic activity of Pd-complexes with CAACs featuring different types of steric environment [36]. 

Palladium-catalyzed a-arylation of ketones is performed with arylene dihalides and bifunctional aromatic ketones 148 to result in the bond formation at the r/) -a-carbon of the ketone, leading to polyketone 149. The reaction is carried out in the presence of Pd(0) and various phosphines. Several bidentate phosphines and bulky alkylphosphines such as dppf, BINAP, PCys, and P Bu3 are shown to be effective, while PPh3 results in no reaction. Arylene dibromide and diiodide are applicable as the co-monomers. The polymerization reaction is carried out in THE in the presence of NaO Bu at 75 °C under N2, and polymers 149 are isolated in 60-80% yields (M = 7000-15 000). Polyketone 149 is further transformed to conjugated polymer PPV by reduction of the ketone moiety with LiAlH4 followed by dehydration with an acid (Equation (69)). 

A. Culkin, J. F. Hartwig, Palladium-Catalyzed a-Arylation of Carbonyl Compounds and Nitriles, Acc. Chem. Res. 2003, 36, 234-245. 

This suggests that in the case that both intramolecular C- and 0-arylations are of geometrically equal possibility, the former preferentially takes place. The reaction of o-bromobenzaldehydes with dibenzylketones gives l,3-diaryl-2-naphthols that may be useful materials as bulky 0-ligands (Eq. 24) [62]. This cyclization involves palladium-catalyzed a-arylation and base-promoted dehy-drative condensation. Treatment of o-iodoanilines with ketones produces indole derivatives (Eq. 25) [63]. In this case, dehydrative condensation between the amino group and the carbonyl group occurs initially and the subsequent car-bopalladation (mechanism A) leads to the products. 

In the last years several publications appeared describing palladium-catalyzed a-arylations of ketone enolates for the synthesis of a-aryl ketones, involving ketone eno-lates, silyl enol ethers and intramolecular a-aiylation of ketone enolates . In this process, an enolate is generated from a ketone in the presence of an aryl halide, and a palladium catalyst couples this enolate with the aryl halide. Iwama and Rawal proposed... 

The exact mechanism of this process, however, remains unclear. It should be noted that the C-H activation in this case involves a C-H bond that is fairly acidic due to the carbonyl group, and the palladium-catalyzed a-arylation of esters by aryl halides is a well known process [68-71], Thus, one might argue that activation of this specific homobenzylic C-H bond may involve formation of a five-membered ring palladacycle, which undergoes P-hydride elimination, rather than palladium migration. 

Bulky imidazolium salts 76 and 77 were found to greatly accelerate the amination of aryl chlorides using nickel catalysts <01TL5689> and palladium catalysts <01JOC7729>. to be useful ligands in the palladium-catalyzed a-arylation of esters and protected amino acids <01JACS8410>, to be catalytic, environmentally benign solvents for the cyanide displacement... 

Palladium-catalyzed a-arylation of carbonyl derivatives and its applications in the synthesis of natural products 05CJO282. 

A variety of bases have been used in the palladium-catalyzed a-arylation of carbonyl derivatives. The pKa of the carbonyl moiety determines the choice of the base. The preferred bases for the a-arylation with ester derivatives are either NaHMDS (r-butyl propionate) or LiHMDS (f-butyl acetate) as KHMDS was reported to lead to lower yield because of competing hydrodehalo-genation. More sensitive substrates such as a-imino esters, malonates, or cyanoesters required the use of a milder base, as decomposition was observed with HMDS bases. 

For Heck reactions catalysed by Pd(OAc)2 associated with dppp, see Ref. [Ig] and (a) Cabri, W., Candiani, I. and Bedeshi, A. (1990) Ligand-controlled a-regioselectivity in palladium-catalyzed arylation of butyl vinyl ether. J. Org. Chem., 55, 3654-5 (b) Cabri, W., Candiani, L, De-Bernardinis, S. et al. (1991) Heck reaction on anthraquinone derivatives ligand, solvent, and salts effects. J. Org. Chem., 56, 5796-800 (c) Cabri, W., Candiani, L, Bedeshi, A. and Santi, R. (1991) Palladium-catalyzed a-arylation of vinyl butyl ether with aryl halides. Tetrahedron Lett., 32, 1753-6 (d) Cabri, W., Candiani, L, Bedeshi, A. et al. (1992) a-Regioselectivity in palladium-catalyzed arylation of acyclic enol ethers. J. Org. Chem., 57, 1481-6 (e) Cabri, W.,... 

Palladium-CatalYzed a-Arylation of Carbonyl Compounds and Nitriles I J5... 

The palladium-catalyzed a-arylation of ketones has become a useful and general synthetic method [106]. Initial studies required preformed zinc [378] or tin enolates [379]. On the other hand, Ni-mediated [380] or Ni-catalyzed couplings are also known. A great development of the reaction has occurred since 1997 based on the use of new catalysts with electron-rich alkylphosphines and NHCs as ligands [173, 381]. The reactions resemble cross-couphng processes in which the enolates behave as the nucleophilic organometaUic reagents (Scheme 1.47). 

Scheme 1.47 Proposed mechanism for the palladium-catalyzed a-arylation of carbonyl compounds.

Arylation of Enolates and Equivalents 381 Table 8.1 Palladium-catalyzed a-arylation of ketones with aryl chlorides. 

In 2006, Griebenow and coworkers [31] described the palladium-catalyzed a-arylation of ketones on a solid support using modified Buchwald-Hairtwig reaction conditions. The coupling of immobilized 4-bromobenzamide (prepared from polystyrene Rink amide resin and 4-bromobenzoic acid chloride) with several aromatic, heteroaromatic, and aliphatic ketones was investigated. 

Scheme 8.7 Palladium-catalyzed a-arylation of ketones using the catalyst generated from Pdj(dba)3 and...

Scheme 8.8 Palladium-catalyzed a-arylation of A/-tosyl-2 -aminoacetophenone with o-dibromobenzene, as described by SanMartin, Dominguez, and coworkers [30].

Scheme 8.9 Palladium-catalyzed a-arylation of ketones on solid support, as described by Griebenow and coworkers [31].

As can be seen so far, until 2001 (inclusive), phosphane ligands were the only ones used for the palladium-catalyzed a-arylation of ketones. However, issues such as high costs, nontrivial synthesis. 

In 2006, Ackermann and coworkers pointed out that bulky substituents on the nitrogen atoms of secondary chlorophosphanes facilitate the efficient palladium-catalyzed a-arylation of ketones bearing sp -hybridized C-H bonds in the a-position with electron-rich aryl chlorides (Scheme 8.23). The active catalyst for these reactions was generated from Pd(dba)2 and the bulky sterically hindered ligand shown in Scheme 8.23 [55]. 

Scheme 8.30 Palladium-catalyzed a-arylation of aldehydes with aryl bromides as described by Miura and...

In 2010, Dorta and coworkers [83] reported a new synthetic strategy to access functionalizable 3-allyl oxindoles bearing a chiral quaternary carbon stereocenter via a direct palladium-catalyzed a-arylation protocol. This elegant methodology, previously accessible only via a two-step procedure involving a Pd-catalyzed intramolecular a-arylation followed by an asymmetric Pd-catalyzed allylic alkylation [84], afforded impressive reactivities, and high chemoselectivities and enantioselectivities were also achieved in the synthesis of oxindoles using a new chiral Pd-NHC catalyst (Scheme 8.45). 

In 2009, Ackermann and coworkers reported a palladium catalyst derived from an air-stable secondary phosphane oxide (l-Ad)2P(0)H that enables efficient intramolecular a-arylations of amides with aryl chlorides. Good yields were obtained for several oxindole derivatives. The interesting fact was that they discovered an unprecedented intramolecular palladium-catalyzed a-arylation route to azaoxindoles (Scheme 8.50) [90]. 

Moradi and Buchwald reported an extensive study on the palladium-catalyzed a-arylation of esters [100], A number of esters could be functionalized with a wide range of aryl bromides or chlorides using PdfOAc) or Pd ldbalj as catalyst, the bulky phosphane ligands, and LiHMDS as base (Scheme 8.55). Of special importance was the use of LiHMDS as the base to obtain monoarylated products in a selective manner. Good to excellent yields were obtained on the desired arylated esters with high selectivity for monoarylation [100]. 

A few years later, Hama and Hartwig reported the palladium-catalyzed a-arylation of esters with bromo [102] and chloroarenes [103]. The coupling of esters with bromoarenes occurred under mild conditions and can be conducted easily without a drybox and on a substantial scale (a 10 g scale was described), using LiNCy as the base [102]. When chloroarenes were used, NaHMDS was the base of choice to obtain the desired products in high yield [103]. 

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