Palladium catalysts coupling reactions

The procedure in Section C is representative of the synthesis of non-natural a-amino acids featuring the palladium cross coupling reaction of a (1-alaninc organozinc derivative with aromatic electrophiles. This methodology has been successfully extended with modifications to both the electrophile and the catalyst as shown in the Table. 

Another palladium-catalyzed coupling reaction that has been successfully performed on soluble polymers is the Sonogashira coupling. Xia and Wang have presented an approach in which the PEG 4000 utilized simultaneously serves as polymeric support, solvent, and phase-transfer catalyst (PTC) in both the coupling and... 

With regard to application in the pharmaceutical industry, palladium-catalyzed coupling reactions offer the opportunity of shorter and more selective routes for a number of currently marketed and future drugs. Therefore, it is not surprising that since the early 1990s more and more palladium-catalyzed reactions are transferred from academic protocols to the industrial context (Beller et al. 2001 Beller and Zapf 2002 de Vries 2001). Selected examples of processes that are used nowadays or have been used in the pharmaceutical industry are shown in Scheme 3. In order to see more realizations of this type of chemistry, more active and productive palladium catalysts have to be developed because of the high price of palladium and most often the ligand system. 

A separate, quite thorough study of terminal alkyne hydrosilylation with platinum arrived at a similar set of conditions.39 This work utilized a one-pot hydrosilylation with the preformed platinum(O) complex (>Bu3P)Pt[(CH2=CH)Me2Si]20 ([(CH2=CH)Me2Si]20 = DVDS) and subsequent palladium-catalyzed coupling reaction to demonstrate that the platinum catalyst is compatible with cross-coupling conditions, providing a convenient hydrocarbation of terminal alkynes (Table 2). 

Arylation of cycloalkenes.1 Aryl halides undergo Heck coupling with cy-cloalkenes in the presence of a palladium catalyst. The reaction involves addition of an arylpalladium intermediate to the double bond followed by elimination of a palladium hydride. 

The added advantage of the C (1 )-stannylated glycals is their abUity to participate in palladium-catalyzed coupling reactions with organic halides, a process independently reported by Beau [75] and Friesen [81]. Vinyl stannane 237 can be benzylated, allylated or acylated provided that appropriate catalysts are used [75,77] and representative examples are given in Scheme 59. The C-arylation of... 

We have subsequently revisited this reaction and successfully optimized the Suzuki microwave-assisted coupling conditions using the Smith synthesizer. Several parameters were investigated, including the palladium catalysts, the reaction temperatures, and the reaction times (Table I). Optimization reactions were run in the Smith synthesizer using 50 mg of resin 7 and 6 equivalents of 4-methoxyphenylboronic acid to afford oxa-zolidinone 8. In just a few days, optimized conditions were identified that afforded the desired product in excellent yields and purities with reactions times of only 5-10 min.8... 

Diaryl ketones can also be prepared by coupling aryl iodides with phenylboronic acid (12-28), in the presence of CO and a palladium catalyst.This reaction has been extended to heteroaromatic systems, with the preparation of phenyl 4-pyridyl ketone from phenylboronic acid and 4-iodopyridine. 2-Bromopyridine as coupled with phenylboronic acid, CO and a palladium catalyst to give phenyl... 

Nickel- or palladium-catalyzed coupling reactions of alkyl Grignard or zinc reagents can be applied to heteroaromatic halides and sulfides. The characteristic features are, therefore, based on those described in the preceding sections and hence details are not repeated in this section. Aspects are summarized by the types of heteroaromatic compounds NiCh(DPPP) is used as catalyst, unless stated otherwise hereafter. 

Despite the multitude of functional groups present and the insolubility of the nucleosides in inert solvents, palladium-catalyzed coupling reactions have been used in their synthesis. Thus, the coupling of terminal alkynes with iodinated uracyl nucleosides proceeds in high yield in the presence of a Pd°-Cu catalyst in warm triethylamine, and several of the products obtained by this route have shown useful antiviral activity (Scheme... 

Though not proved, alkynyl-ketones could also be involved as reactive intermediates in the regioselective preparation of 3,5-diarylisoxazoles 19 through four-component coupling of terminal alkynes 17, hydroxylamine, carbon monoxide, and aryl iodides 18, in the presence of a palladium catalyst. The reaction proceeds at room temperature and an ambient pressure of CO in an aqueous solvent system <05OL4487>. 

Palladium-catalysed coupling reactions have been employed in two notable syntheses. A 5-halogenopyrimidine reacts with methyl acrylate in the presence of a palladium catalyst to give a methyl (E)-B-pyrimidinyl acrylate. Treatment with acid leads to (E)-B-(2,... 

Another palladium-catalyzed coupling reaction performed successfully on soluble polymers is the Sonogashira coupling. In a more recent report it was reported that PEG 4000 acts simultaneously as polymeric support, solvent, and phase transfer catalyst (PTC) in both steps, coupling and hydrolysis [72]. Poly(ethylene glycol) (PEG)-bound 4-iodobenzoic acid was readily reacted with several terminal alkynes under rapid microwave conditions (Scheme 16.50). Cleavage of the coupling products from the PEG support was achieved efficiently by simple saponification with brief microwave irradiation in an open beaker in a domestic microwave oven. 

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