PALLADIUM-CATALYZED COUPLING OF ACID CHLORIDES WITH

Palladium-Catalyzed Coupling of Acid Chlorides with Organotin Reagents (E)-Ethyl-4-(4-n1trophenyl)-4-oxo-2-butenoate A, F. Renaldo, J, W. Labadie, and J. K. Stille, Department of Chemistry, Colorado State University, Ft. Collins, CO 80523... 

Palladium, benzylchlorobis(triphenylphosphine)-, trans-, 67, 86 Palladium-catalyzed aryl-aryl coupling, 66, 70 PALLADIUM-CATALYZED ALLYLIC AMINATION, 67,105 PALLADIUM-CATALYZED CHLOROACETOXYLATION, 67, 105 PALLADIUM-CATALYZED COUPLING OF ACID CHLORIDES WITH ORGANOTIN REAGENTS, 67, 86 PALLADIUM-CATALYZED COUPLING OF ARYL HALIDES, 66, 67 PALLADIUM-CATALYZED syn-ADDITION OF CARBOXYLIC ACIDS,... 

The palladium-catalyzed coupling of acid chlorides with tetraalkyllead derivatives gave the ketones in high yields under mild conditions (Scheme 13.28) [51]. Even with only 0.6 equiv. tetrahutyllead high yields (78-99%) were obtained. 

PALLADIUM-CATALYZED COUPLING OF ACID CHLORIDES WITH ORGANOTIN REAGENTS ETHYL (E)-4-(4-NITR0-PHENYL)-4-0X0-2-BUTENOATE... 

An alternative approach to multicomponent heterocycle synthesis involves the use of palladium catalysis to construct keto-alkynes for cycloaddition reactions. Muller has demonstrated the power of this approach in the construction of a range of aromatic heterocycles. For example, the palladium-catalyzed coupling of acid chlorides with terminal alkynes provides a method to assemble 36. The trapping of this substrate can provide routes to aromatic heterocycles. As an example, the addition of amidines provides a multicomponent synthesis of pyrimidines (Scheme 6.69) [97]. This same substrate 36 is available via the carhonylative coupling of aryl halides with terminal alkynes, providing a four-component synthesis of pyrimidines (98j. 36 can also be employed in 1,3-dipolar cydoaddition reactions. For example, cydoaddition... 

Labadie JW, Stille JK (1983) Mechanisms of the palladium-catalyzed couplings of acid chlorides with organotin reagents. J Am Chem Soc 105 6129-6137... 

Recent work has led to the use of bulk electron-rich phosphine ligands to facilitate palladium-catalyzed processes with problematic oxidative addition. For examples, see (a) Littke, A.F. Fu, G.C. A convenient and general method for Pd-catalyzed Suzuki cross-couplings of aryl chlorides and arylboronic acids. Angew. Chem., Int. Ed. Engl. 1998, 37, 3387-3388. (b) Shen, W. Palladium catalyzed coupling of aryl chlorides with arylboronic acids. Tetrahedron Eett. 1997, 38, 5575-5578. (c) Old, D.W. Wolfe,... 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

Alonso DA, Najera C, Pacheco MC (2004) Synthesis of ynones by palladium-catalyzed acylation of terminal alkynes with acid chlorides. J Org Chem 69 1615-1619 D Souza DM, Miiller TJJ (2008) Catalytic alkynone generation by Sonogashira reaction and its application in three-component pyrimidine synthesis. Nat Protoc 3 1660-1665 Karpov AS, Miiller TJJ (2003) A new entry to a three component pyrimidine synthesis by TMS-ynones via sonogashira-coupling. Org Lett 5 3451-3454... 

This classification is illustrated in Scheme 365. The synthesis of imidazoles under this classification is rare mainly due to the difficulty of C-C bond formation. A palladium-catalyzed coupling of imines 1415, 1417 and acid chloride 1416 to synthesize substituted imidazoles 1418 belongs to this category of ring formation. AT-Alkyl and AT-aryl imines can be used, as can imines of aryl and even nonenolizable alkyl aldehydes. A plausible reaction mechanism involving 1,3-dipolar cycloaddition with miinchnones is illustrated in Scheme 366 <2006JA6050>. 

Labadie, J. W., Tueting, D., Stille, J. K. Synthetic utility of the palladium-catalyzed coupling reaction of acid chlorides with organotins. J. 

Disilanes have been used in stoichiometric amounts as reductants in the palladium-catalyzed coupling of electron deficient aryl chlorides. By this procedure, trimellitic anhydride acid chloride (70) was converted to the high temperature polymer precursor biphenyl dianhydride (71) in 85% yield with concomitant decarbonylation (see Scheme 35 [128]). 

The palladium catalyzed coupling of imine, carbon monoxide and acid chloride is reported as a new route to prepare peptide-based imidazoline-carboxylates. Mechanistic studies suggest this process proceeds via the palladium catalyzed generation of l,3-oxazolium-5-oxide intermediates, which react with imine to generate the observed products. 

Various palladium(O) monophosphine complexes of 1,6-diene have been prepared from tmedaPd(CHj)2, PRj, and the corresponding 1,6-dienes. These molecularly defined Pd complexes catalyzed the Suzuki coupling of aryl chlorides with phenyl-boronic acid more efficiently than traditional Pd(Il)-PRj pre-catalysts. Best results were achieved with the 1,6-diene complex containing Buchwald s ligand (26). With only 0.05 mol% of the catalyst, good to excellent yields of biaryls were obtained from activated (2-chlorobenzonitrile, 97%), non-activated (4-chlorotoluene, 82%, chlorobenzene, 87%) and deactivated (4-chloroanisole, 72%) aryl chlorides (Equation 54) [66]. 

In Suzuki reaction, cross-coupling of aryl- or vinyl-boronic acid with an aryl or vinyl halide catalyzed by a palladium complex, is one of the most versatile reactions for the construction of carbon-carbon bonds, in particular for the formation of biaryls. Recent developments have expanded the possible applications of this reaction enormously. Microwave-assisted Suzuki reactions can now be performed in many different ways and have been incorporated into a variety of challenging synthesis. Under microwave-heated condition, the Suzuki coupling of aryl chlorides with bo-ronic acids was performed in an aqueous media using the air and moisture-stable palladium catalyst. A drastic reduction of the reaction time to 15 min and the formation of products in good yields were achieved (Miao et al, 2005). 

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