Palladium aliphatic substitution

Palladium-catalyzed amination has also been used to prepare aminoquinazolines substituted in the benzo ring <2002JA1594, 2003TL7533>. The reactions were peformed on solid support and involved amination of all four chloro isomers with 4-methoxyaniline <2002JA1594>, or the amination of 6-bromo or 6- or 7-chloroquinazoline derivatives with a variety of aliphatic amines <2003TL7533>. 

The triflate 125 is formed from the hydroxy precursor (Equation 131) and undergoes a variety of nucleophilic substitution processes <2006TL4437>, including Suzuki and Stille couplings (Equations 132 and 133, respectively). Amination of 125 with aliphatic amines occurs under thermal conditions, using either conventional or microwave heating (Equation 134), but the reactions of 125 with less reactive amines require palladium catalysis (Equation 135). 

The cross-coupling route to allylsilanes is effective with either aromatic or aliphatic a-silylated Grignard reagents16, and palladium catalysts are more reactive and stereoselective than the corresponding nickel complexes. Unsubstituted or i+monosubstituted alkenyl bromides work well but the Z-substituted bromides give lower yields and an inferior enantiomeric excess. The enantiomeric excess increases quite markedly with decreasing temperature, and optimum results are obtained at 0 C or below. 

A highly regioselective amination of 6-aryl-2,4-dichloropyrimidines has been developed using palladium catalysis. The reaction which works well with secondary aliphatic amines and with anilines gives the 4-substituted products.46 Palladium catalysis has also been used in the regioselective coupling of 2,3-dibromopyridine with a series... 

A palladium-catalyzed three-component reaction with 2-iodobenzoyl chloride or methyl 2-iodobenzoate, allene and primary aliphatic or aromatic amines to prepare fV-substituted 4-methylene-3,4-dihydro-1 (27/)-isoquinolin-1 -ones was disclosed <02TL2601>. A synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via a Cp2TiMe2-catalyzed, intramolecular hydroamination/cyclization of aminoalkynes was also reported <02TL3715>. Additionally, a palladium-catalyzed one-atom ring expansion of methoxyl allenyl compounds 79 to prepare compounds 80 that can serve as precursors to isoquinolones was reported <02OL455,02SL480>. 

The keto group of a keto ester may be preferentially reduced by catalytic hydrogenation. Excellent yields of hydroxy esters are obtained. Copper-chromium oxide catalyst has been employed in the preparation of methyl p-(a-hydroxyethyl)-benzoate and several aliphatic -hydroxy esters. The last compounds have also been made by hydrogenation over nickel catalysts.Substituted mandelic esters are prepared by catalytic reduction of aromatic a-keto esters over a palladium catalyst. Similarly, platinum oxide and copper-chromium oxide have been used in the aliphatic series for the preparation of the a-hydroxy diester, diethyl... 

Substituted 5,6,7,8-tetrahydroquinazolines are dehydrogenated to 2-substituted quinazolines by heating with palladium on charcoal in Decalin or without a solvent. The reduction in Decalin takes place in good yield when the substituent at the 2-position is amino and in lower yield where it is aliphatic or aromatic. " ... 

The palladium-catalyzed system can be extended to the acylation of siloxycyclopropanes with aroyl chloride/carbon monoxide or aryl triflate/carbon monoxide, which gives 1,4-diketones. Contrary to the case of doubly oxygen-substituted cyclopropanes vide infra), the acylation of 1-siloxycyclopropanes is restricted to aroyl chlorides and is not applicable to aliphatic or a, -unsaturated acyl chlorides. For the reactions with aryl triflates, tetrakis(triphenylphos-phane)palladium(O) is used as catalyst, while the reactions with aroyl chlorides employ bis(triphenylphosphane)palladium(II) chloride and ( / -allyl)chloropalladium dimer/triphenyl phosphite as catalysts. In these reactions, aroylpalladium(II) species may undergo ring opening of the siloxycyclopropanes. 

Palladium-catalyzed arylative and acylative ring openings (vide supra) can be successfully applied to 1-alkoxy-l-siloxycyclopropanes. Thus, ) -arylated esters and 4-oxo esters, respectively, are synthesized. Yields are generally higher and the reaction conditions milder for doubly oxygen-substituted cyclopropanes than for siloxycyclopropanes. For acylation, the procedure can be extended from aroyl chlorides to aliphatic acyl chlorides and carbon monoxide is no longer necessary for successful acylation. 

Palladium-catalyzed acylations offer a useful chemoselectivity. Since alkenylsilanes do not react, this allows the formation of silyl-substituted ketones which could not readily be made by classical aliphatic Friedel-Crafts acylations (equation 27). " ... 

Allylic acetoxylation with palladium(II) salts is well known however, no selective and catalytic conditions have been described for the transformation of an unsubstituted olefin. In the present system use 1s made of the ability of palladium acetate to give allylic functionalization (most probably via a palladium-ir-allyl complex) and to be easily regenerated by a co-oxidant (the combination of benzoquinone-manganese dioxide). In contrast to copper(II) chloride (CuClj) as a reoxidant,8 our catalyst combination is completely regioselective for allcyclic alkenes with aliphatic substrates, evidently, both allylic positions become substituted. As yet, no allylic oxidation reagent is able to distinguish between the two allylic positions in linear olefins this disadvantage is overcome when the allylic acetates are to... 

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