Heck palladium-catalyzed reactions

The use of ionic liquids as reaction media for the palladium-catalyzed Heck reaction was first described by Kaufmann et ak, in 1996 [85]. Treatment of bromoben-zene with butyl acrylate to provide butyl trans-cinnamate succeeded in high yield in molten tetraallcylammonium and tetraallcylphosphonium bromide salts, without addition of phosphine ligands (Scheme 5.2-16). 

Beller, M. et al., First palladium-catalyzed heck reactions with efficient colloidal catalyst systems, J. Organomet. Chem., 520, 257, 1996. 

Palladium-catalyzed Heck reactions are important in synthetic organic chemistry (253,254). Under conventional reaction conditions, a palladium black deposit was formed from the deterioration of the homogeneous palladium complex catalyst after the reaction. Recovery and recycle of the palladium catalyst are usually not realistic. 

To demonstrate this concept, let us consider the first optimization cycle for the palladium-catalyzed Heck reaction in the presence of bidentate ligands. The literature shows us some promising leads (14-18), with yields > 95% and TOFs > 1000, but much of the catalyst space is unexplored territory. 

A microwave-assisted synthesis of several isomeric pyrrolopyridines ([2,3-3], [2,3-c], [3,2-3], and [3,2-r ]) has been reported starting from aminohalopyridines <2005S2571>. Intramolecular palladium-catalyzed Heck reactions leading to substituted pyrrolo[3,2-3]pyridines from ketones and aminopyridines have been described <2003JME4702>. 

Members of the she same compound class, arylethenylpurines, can also be prepared in a two step sequence. The cross-coupling of a halopurine with vinyl-tributylstannane leads to the formation of a vinylpurine, which in turn can undergo palladium catalyzed Heck reaction with a series of aryl halides (8.20.),28 The two step procedure is of particular interest, since the alternate approach, the Heck reaction of halopurines and arylethenes is of very limited scope. 

Mukhopadhyay, S., Rothenberg, G., (oshi, A., Baidossi, M. and Sasson, Y. (2002) Heterogeneous palladium-catalyzed Heck reaction of aryl chlorides and styrene in water under mild conditions. Adv. Synth. Gated., 344, 348. 

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. 

The remarkable affinity of the silver ion for hahdes can be conveniently applied to accelerate the chiral palladium-catalyzed Heck reaction and other reactions. Enantioselectivity of these reactions is generally increased by addition of silver salts, and hence silver(I) compounds in combination with chiral ligands hold much promise as chiral Lewis acid catalysts for asymmetric synthesis. Employing the BINAP-silver(I) complex (8) as a chiral catalyst, the enantioselective aldol addition of tributyltin enolates (9) to aldehydes (10) has been developed." This catalyst is also effective in the promotion of enantioselective allylation, Mannich, ene, and hetero Diels-Alder reactions. 

The palladium-catalyzed Heck reaction of a vinyl or aryl halide with an alkene... 

In this context, a functionalized ionic liquid, 1-(2-hydroxyethyl)-3-methyl imidazolium tetrafluoroborate [hemim][BF4], is reported as an efficient and recyclable reaction medium for the palladium catalyzed Heck reaction. The olefination of iodoarenes and bromoarenes with olefins generates the corresponding products in good to excellent yields under phosphine-ffee reaction conditions. After separation of the product, fresh starting materials are charged into the recovered ionic liquid which entraps the palladium catalyst. The reactions still proceed quantitatively for six cycles, without significant loss of catalytic activity. " The effect of both the cation and the anion on the chemical yield is shown in Figure 28. 

Direct (instead of stepwise) transition metal catalyzed dicarboration is achieved by a modification of the palladium-catalyzed Heck reaction 2 4-85,86 116 if the final dehydropal-ladation step is suppressed. This step usually occurs after alkene insertion into an aryl - or a vinyl-palladium bond formed from the corresponding halide or triflate. 

The Industrial Potential of the Palladium Catalyzed Heck Reaction. Eisenstadt, A., 2nd International Conference Organic Process Research and Development, New Orleans, USA, 21-23 April 1999. 

Heck couplings of aryl halides with alkenes in room temperature ionic liquids have been reported [44]. Dialkylimidazolium and n-hexylpyridinium hexafluoro-phosphate and tetrafluoroborate ionic liquids were used as solvents, Pd(OAc)2 and PdCl2 as catalysts, and an amine as base. Addition of ligands such as triphe-nylphosphine, tri-o-tolylphosphine, and triphenylarsine usually had a negative affect on product yield. Addition of cosolvents such as DMF was not necessary. Palladium-catalyzed Heck reactions involving aryl bromides have been performed... 

Examples of specialized uses of palladium-catalyzed Heck reaction include the synthesis of the ergot metabolite claviciptic acid, where two sequential vinylations were carried out by taking advantage of the greater reactivity of a 3-iodo over a 4-bromo substituent (Scheme 127) <87JA4335>. 

SCCO2. A fluorinated phosphine ligand such as PPh(C6Fs)2 is also effective for the palladium-catalyzed Heck reaction in scC02. ... 

Schnyder, A., Aemmer, T., Indolese, A.E. et al. (2002) First application of secondary phosphines as supporting hgands for the palladium-catalyzed Heck reaction efficient activation of aryl chlorides. Adv. Synth. Catal., 344, 495-8. 

---