Phosphine-free palladium

Polyethylene glycol) (PEG) was used as a soluble polymeric support in the efficient preparation of the 2-benzazepine 58 via a phosphine-free palladium-catalysed Heck reaction from 57 <06T10456>. 

In a modified version of the Suzuki reaction arylboronates or boranes are utilized instead of arylboronic acid. Under the action of phosphine-free palladium catalysts NaBPh4 and tra(l-naphtyl)borane were found suitable phenyl-sources for arylation of haloaromatics in fully or partially aqueous solutions at 20-80 °C with good to excellent yields (Scheme 6.12) [32-34]. Aryl halides can be replaced by water-soluble diaryliodonium salts, At2IX (X = HSO4, BF4, CF3COO) in the presence of a base both Ar groups take part in the coupling [35]. 

Ahlquist, M. Fabrizi, G. Cacchi, S. Norrby, P.-O. The Mechanism of the Phosphine-Free Palladium-Catalyzed Hydroarylation of Alkynes. J. Am. Chem. Soc. 2006, 128, 12785-12793. 

Several important improvements of this methodology have been reported since 1994. A broad range of organotins were used in the reactions with aryl-, heteroaryl-, or alkenyliodonium salts in aqueous organic solvents. This reaction (Equation (2)) takes place at room temperature in the presence of phosphine-free palladium... 

Zhou, L. and Wang, L. (2006) Functionalized Ionic Liquid as an Efficient and Recyclable Reaction Medium for Phosphine-Free Palladium-Catalyzed Heck Reaction. Synthesis, 2653-2658, DOI 10.1055/S-2006-942466. 

Methylisoxazole-5-carboxylic acid was converted into the corresponding 5-carboxamides and 5-(l/7-pyrazol-l-ylcarbonyl) derivatives in satisfactory yields by treatment with thionyl chloride and amines or pyrazoles <2002SC425>. A three-component assembly of isoxazole-5-carboxylic acid chloride, 1,1-dimethylallene, and bis-pinacolatodiboron, catalyzed by a phosphine-free palladium complex, gave 2-acylallylboronate derivatives regiose-lectively (Equation 47) <2003JA12576>. On the other hand, a mild procedure allowed the preparation of /3,7-unsaturated ketones by simple reaction of 3-aryl-5-methylisoxazole-4-carboxylic acid chlorides with allyl bromide and indium in DMF (Equation 48) <1997TL8745>. 

In sharp contrast to the predominant formation of 1 1 adducts, reactions of 1,3-dienes with various disilanes in the presence of phosphine-free palladium catalyst provide bis-silylative dimerization products 63 in high yields (Eq. 30) [58,59]. In comparison with the Pd(OAc)2 and PdCl2(ArCN)2 catalysts originally found [58], the use of Pd(dba)2 (dba dibenzalacetone) in DMF was found to be more effective in enabling the reaction to proceed at room temperature [59]. Worthy of note is that head-to-head coupling products 63 having carbon-carbon double bonds with E-geometry are exclusively formed in these reactions. 

The cross-coupling reactions of various aryl halides and triflates with vinyl- or arylboronic acids and esters (Suzuki cross-coupling reaction) was also carried out in water in the presence of tetrabutylammonium bromide and a base such as Na2C03, using a phosphine-free palladium catalyst to give biaryl derivatives [Eq. 18)1 [108,109]. More recently, Casalnuovo [101] and Gen t [102,110] have performed this reaction using water-soluble palladium catalysts PdCla (tppms)2 and Pd(OAc)2/tppts in water/acetonitrile. 

Wang X, Gribkov DV, Sames D (2007) Phosphine-free palladium-catalyzed C-H bond arylation of free (N-H) -indoles and pyrroles. J Org Chem 72 1476-1479... 

The complex (1) proved to be an efficient, stable phosphine-free palladium catalyst for the carbonylation of various aryl iodides with different aliphatic alcohols as well as less reactive phenols to give the corresponding esters in excellent yield as shown in Table 12.3. 

Transition metal catalyzed processes are useful tools for the synthesis of functionalized thiophenes. Thus for instance, a phosphine-free, palladium catalyzed coupling protocol for the synthesis of 2-arylbenzo[d]thiophenes from various 3-substituted benzo[6]thiophenes and aryl bromides or iodides has been reported <04T3221>. Likewise, 2,2 -bithiophenes have been 5,5 -diarylated directly with aryl bromides in the presence of Pd(OAc)2, bulky phosphine ligands and CS2CO3 <04T6757>. A series of electron-deficient and relatively electron-rich benzo[6]thienyl bromides have been shown to participate in palladium catalyzed amination reactions, as exemplified by the interesting conversion of 63 to the tetracyclic system 64 upon reaction with 2-aminopyridine 65 <04EJO3679>. 

Allyl alkyl carbonates, prepared from various alcohols except simple primary ones, are converted into aldehydes or ketones in the presence of a phosphine-free palladium catalyst. Acetonitrile as coordinating solvent is necessary for the success of this reaction. A mechanism via palladium alkoxides was proposed (Scheme 8). Ruthenium hydride complexes work similarly. A similar mechanism operates for the palladium-catalyzed decomposition of allylic carbonates. The reaction can be utilized for the mild deprotection of amines, e.g., for peptide synthesis shown in equation (20). 

In a continuation of their work, they also reported the cross-eoupling reactions between MBH acetates and bimetallic reagents (Si-Si, Ge-Ge) catalyzed by a phosphine-free palladium complex. Substituted-2-carbonylallylsi-lanes 375 and allylgermanes 376 were isolated in high yields with regio- and stereoselectivity (Scheme 3.167). ... 

Mino, T., Shirae, Y, Sasai, Y. et al. (2006) Phosphine-free palladium catalyzed Mizoroki-Heck reaction using hydrazone as a ligand. J. Org. Chem., 71, 6834—9. 

Daniel, S., Rao, P.P., Nandakumar, M. and Rao, T.P. (2005) Synthesis of heterogeneous phosphine-free palladium-based catalyst assemblies via sohd phase extrachon and their charac-terizahon. Mat. Chem. Phys., 90, 99-105. 

The reaction suffered from low yields due to the instability of the starting enol triflate. However, phosphine-free palladium was recognized as an excellent catalyst for carrying out the reaction at low temperature (see the discussion in Section IV A). The overall yield of four steps from TES diazo ester is 58%. 

In sharp contrast to the predominant formation of l l-adducts, reactions of 1,3-dienes with various disilanes in the presence of phosphine-free palladium catalyst provide bis-silylative dimerization product in high yield (Scheme... 

Besides the Hartwig-Buchwald reaction, amination can be achieved by a Pd-catalyzed variant of the Ullmann reaction in the presence of copper salts. Though the scope of this reaction is much narrower, it does not require expensive phosphine ligands and thus is more economical. The arylation of diphenylamine with water-insoluble aryl iodides can be achieved in aqueous microemulsions in the presence of phosphine-free palladium catalyst and copper(I) iodide (Scheme 58). 

Yang and Cheng observed an unusual variant of allene diborylation where an aryl or alkenyl halide can act as a co-catalyst with a phosphine-free palladium catalyst [51]. As shown with the formation of allylboronate 29, the addition is completely regiose-lective and highly stereoselective (Equation 17). Examples with aryloxy-substituted allenes were also successfully demonstrated. Notably, Pd(dba)2 does not promote the diboration of allenes without the co-catalyst, and a new mechanism involving oxidative addition of an I-B bond to the palladium center was proposed to rationalize these observations. 

It should be noted that cross-coupling in the presence of phosphine complexes of palladium usually requires high amounts of catalyst, with initial loadings of 25-30 mol% not being uncommon. An entirely new approach to the Suzuki reaction is phosphine-free palladium catalysis. The use of palladium catalysts without the addition of phosphine ligands for cross-coupling with organoboron compounds in aqueous media opened a new chapter in the story of this powerful synthetic method. This approach allows catalyst efficiency to be dramatically increased, and the reaction to be performed under milder conditions. 

Wallow, T.I. Novak, B.M. (1994) Highly efficient and accelerated Suzuki aryl couplings mediated by phosphine-free palladium sources, J. Org. Chem., 59, 5034-7. 

Interestingly, the procedure of hydroxycarbonylation by using lithium formate and acetic anhydride as internal condensed sources of carbon monoxide can be carried out in the presence of a recoverable and reusable phosphine-free palladium-carbon aerogel catalyst [61]. To support high-speed chemistry and automated organic synthesis, an operationally simple and environmentally safe hydroxycarbonylation of vinyl triflates can... 

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