Heck-oxidation reaction

Scheme 3.6 Domino Heck-oxidation reaction catalysed by a combination of chiral palladium catalysis and copper catalysis.

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

Popp BV, Stahl SS (2007) Palladium-Catalyzed Oxidation Reactions Comparison of Benzo-quinone and Molecular Oxygen as Stoichiometric Oxidants. 22 149-189 Prashad M (2004) Palladium-Catalyzed Heck Arylations in the Synthesis of Active Pharmaceutical Ingredients. 6 181-204 Prestipino C, see Zecchina A (2005) 16 1-35 Pretraszuk C, see Marciniec B (2004) 11 197-248... 

Following our first report on the palladium-catalyzed reaction of vinyl triflates with olefins (Heck-type reaction), oxidative insertion of palladium(O) into the carbon-oxygen bond of easily available vinyl triflates ... 

The transformations of 136 proceed cleanly upon treatment with a catalytic amount of Pd(PPh3)4, in the presence of triethylamine and molecular sieve (MS) 4 A it apparently is initiated by oxidative addition of the N(sp )-0 bond of 136 to the Pd(0) complex, and this is succeeded by two or even three intramolecular carbopalladations followed by / -hydride elimination. This Heck-type reaction is not affected by the configuration of the oxime derivatives probably due to a facile enough if/Z-isomerization of the alkylideneaminopalladium intermediate. 

As Scheme 23 illustrates, DMF reacts with POCI3 to form Vilsmeier reagent 158. Aryl-Pd-I species 159, generated by the oxidative addition of iodotoluene 160 to Pd(0) species, reacts with the reagent 158 to yield chloroiminium ion 162 via an adduct 161 through a hetero-Heck-type reaction mechanism, and liberates H-Pd-I species. Finally, the hydrolysis of chloroiminium ion 162 gives amide 163. 

Aliphatic amines can be readily oxidized by Pd(II) to imines or iminium salts and hydrido complexes. The latter can transfer hydrogen to alkenes, leading to the formation of alkanes as byproducts of the Heck reaction (last example, Scheme 8.18). Such reactions can be avoided by using alkali carbonates as base instead of aliphatic amines [148]. Treatment of stannanes or organoboron derivatives with electron-deficient alkenes under acidic reaction conditions can also lead to formal products of Michael addition instead of the products of a Heck-type reaction [149, 150] (Scheme8.19). 

As regards the rate determining step of the Heck coupling reaction, the oxidative addition has been assumed to be this step, although it has not been proven in all details. 

Ruthenium(O) complexes such as Ru(COD)(COT) catalyze the dehydrohalo-genative coupling of vinyl halides with olefins to give substituted conjugated dienes in a Heck-type reaction [11]. Thus, alkenyl halides readily react with activated olefins to produce dienes 16 (Eq. 7). Oxidative addition of vinyl halide, followed by regioselective insertion of an electron-deficient olefin and by -hydrogen elimination leads to the diene. 

Grigg et al. also introduced another Heck-type reaction. 2,6-Dibromo-hepta-1,6-dienes 80 cyclize to the same products 83 (n = 5) as do 2-bromo-1,6-dienes 78 (n = 5) when treated with the usual precatalyst mixture, yet containing a stoichiometric amount of triphenylphosphine [63,64], In this case, palladium dibromide rather than hydridopalladium bromide is eliminated in the final step of the cross-coupling reaction, and the palladium(II) salt is reduced by the phosphine to regenerate the reactive palladium(O) species. Completely selective exo-trig cyclizations occur in these examples, however, the respective cyclohexane derivatives with n = 6 are formed in poor yields. Additionally, it is sometimes difficult to separate the product from the phosphine oxide after aqueous work-up. This latter difficulty was circum-... 

The pioneering studies in this area were reported in 1999 by Narasaka, who demonstrated intramolecular heteroatom Heck-type reactions of 0-pentafluorobenzoyl oximes [97]. As shown below, treatment of unsaturated substrate 97 with a catalytic amount of Pd(PPh,y in the presence of triethyl amine provided pyrrole 98 upon workup with chlorotrimethylsilane. The mechanism of this reaction proceeds via oxidative addition of the N—O bond to afford 99, which undergoes alkene insertion into the Pd—N bond to provide alkyl-palladium complex 100. The exo-methylene product 101 is generated by [i-hydride elimination from 100, and isomerization to the desired pyrrole 98 occurs when chlorotrimethylsilane is added. 

Palladium is one of the most versatile and efficient catalyst metals in organic synthesis. Solubility in water is achieved by utilization of simple palladium(II) salts or water-soluble ligands, such as TPPTS and TPPMS. The active catalysts for Heck-type reactions are zerovalent palladium(O) species [3], which are often generated in situ by thermal decomposition of a Pd(II) precursor or by the application of a reducing agent, e.g., 1-6 equiv. of a phosphine in the presence of base generates Pd(0) and the phosphine oxide (Eq. 3) [4],... 

Following our first report on the palladium-catalyzed reaction of vinyl triflates with olefins (Heck-type reaction), oxidative insertion of palladium(O) into the carbon-oxygen bond of easily available vinyl triflates has proved to be a general method for the generation of o-vinyl palladium intermediates which can react directly with a variety of olefinic systems, carbon monoxide and alcohols or amines,or 1-alkynes, to give conjugated... 

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