Ketones transition metal catalysts

Addition of HCN to unsaturated compounds is often the easiest and most economical method of making organonitnles. An early synthesis of acrylonitrile involved the addition of HCN to acetylene. The addition of HCN to aldehydes and ketones is readily accompHshed with simple base catalysis, as is the addition of HCN to activated olefins (Michael addition). However, the addition of HCN to unactivated olefins and the regioselective addition to dienes is best accompHshed with a transition-metal catalyst, as illustrated by DuPont s adiponitrile process (6—9). 

Flowever, ionic liquids acting as transition metal catalysts are not necessarily based on classical Lewis acids. Dyson et al. recently reported the ionic liquid [BMIM][Co(CO)4] [38]. The system was obtained as an intense blue-green colored liquid by metathesis between [BMIM]C1 and Na[Co(CO)4]. The liquid was used as a catalyst in the debromination of 2-bromoketones to their corresponding ketones. 

These transition-metal catalysts contain electronically coupled hydridic and acidic hydrogen atoms that are transferred to a polar unsaturated species under mild conditions. The first such catalyst was Shvo s diruthenium hydride complex reported in the mid 1980s [41 14], Noyori and Ikatiya developed chiral ruthenium catalysts showing excellent enantioselectivity in the hydrogenation of ketones [45,46]. 

Recently, great advancement has been made in the use of air and oxygen as the oxidant for the oxidation of alcohols in aqueous media. Both transition-metal catalysts and organocatalysts have been developed. Complexes of various transition-metals such as cobalt,31 copper [Cu(I) and Cu(II)],32 Fe(III),33 Co/Mn/Br-system,34 Ru(III and IV),35 and V0P04 2H20,36 have been used to catalyze aerobic oxidations of alcohols. Cu(I) complex-based catalytic aerobic oxidations provide a model of copper(I)-containing oxidase in nature.37 Palladium complexes such as water-soluble Pd-bathophenanthroline are selective catalysts for aerobic oxidation of a wide range of alcohols to aldehydes, ketones, and carboxylic acids in a biphasic... 

The other direction concerns the use of immobilized transition metal catalysts in the synthesis of libraries of organic compounds of interest in therapeutic drug discovery. One such strategy uses immobilized catalysts (e.g., scandium complexes), leading to efficient library syntheses of quinolines, amino ketones, and amino acid esters.72,73... 

The development of chiral phosphorus ligands has made undoubtedly significant impact on the asymmetric hydrogenation. Transition metal catalysts with efficient chiral phosphorus ligands have enabled the synthesis of a variety of chiral products from prochiral olefins, ketones, and imines in a very efficient manner, and many practical hydrogenation processes have been exploited in industry for the synthesis of chiral drugs and fine chemicals. 

Transition-metal catalysts are, in general, more active than the MPVO catalysts in the reduction of ketones via hydrogen transfer. Especially, upon the introduction of a small amount of base into the reaction mixture, TOFs of transition-metal catalysts are typically five- to 10-fold higher than those of MPVO catalysts (see Table 20.7, MPVO catalysts entries 1-20, transition-metal catalysts entries 21-53). The transition-metal catalysts are less sensitive to moisture than MPVO catalysts. Transition metal-catalyzed reactions are frequently carried out in 2-propanol/water mixtures. Successful transition-metal catalysts for transfer hydrogenations are based not only on iridium, rhodium or ruthenium ions but also on nickel [93], rhenium [94] and osmium [95]. It has been reported that... 

In summary, the reduction of ketones and aldehydes can both be performed with MPV and transition-metal complexes as catalysts. Reductions of alkenes, al-kynes, and imines require transition-metal catalysts MPV reductions with these substrates are not possible. 

As mentioned above, MPVO catalysts are very selective towards carbonyl compounds. Alkenes, alkynes or other heteroatom-containing double bonds are not affected by these catalysts, while they can be reduced by transition-metal catalysts. Examples of the reduction of a,/ -unsaturated ketones and other multifunctional group compounds are compiled in Table 20.3. 

Transition metals can display selectivities for either carbonyls or olefins (Table 20.3). RuCl2(PPh3)3 (24) catalyzes reduction of the C-C double bond function in the presence of a ketone function (Table 20.3, entries 1-3). With this catalyst, reaction rates of the reduction of alkenes are usually higher than for ketones. This is also the case with various iridium catalysts (entries 6-14) and a ruthenium catalyst (entry 15). One of the few transition-metal catalysts that shows good selectivity towards the ketone or aldehyde function is the nickel catalyst (entries 4 and 5). Many other catalysts have never been tested for their selectivity for one particular functional group. 

One of the very few examples of a practical application of a transition-metal catalyst in total synthesis is shown in Scheme 20.22 [107]. The chloroiridic acid catalyst (HjIrCfs) (6) reduces 71 to androsterone (72) by selective attack of the sterically less hindered ketone in the 3-position of 71. 

An interesting dependence on the nature of the transition metal catalyst employed for the dimerization has been observed for the substituted vinylallene 318 (R = phenyl or vinyl). Whereas its carbonylation in the presence of Rh(I) leads to the [4+ 1] cydoadduct 317, the change to Pd° opens up a [4 + 4 + l]route which furnishes the nine-membered ring ketone 319, the yields being good to excellent in both cases [132]. 

The first application of NMR diffusion measurements to determine the aggregation state of a transition metal catalyst concerned the chiral, tetranuclear Cu(i) catalysts 130-132, used in the conjugate addition reactions of anions to a,p-unsatu-rated cyclic ketones. Compounds 130-132 react wdth isonitriles to form 133-135, and do not degrade to lower molecular weight species (see Eq. (20)) [109]. 

During studies of the hydrogenolysis and isomerization of the 2-Me-oxa-cycloalkanes on transition metal catalysts, it was found that different metals have different regioselectivities (refs 1,2). On Cu and Ni catalysts, primarily the C-0 bond adjacent to the substituent is split, leading to the formation of a primary alcohol or aldehyde (ref. 3), while on Pt and Pd catalysts mainly the more distant C-0 bond undergoes cleavage (ref. 4) yielding a secondary alcohol or ketone (Scheme 1). 

Despite fruitful results of asymmetric hydrogenation of functionalized ketones, only limited examples have been reported for reaction of ketonic substrates with no functionality near the carbonyl group [1,162,254]. Transition-metal catalysts with a bidentate chiral phosphine, successfully used for functionalized ketones, are often ineffective for reduction of simple ketones in terms of reactivity and enantioselectivity [162b,c]. However, a breakthrough in this subject has been provided by the invention of a new chiral Ru catalyst system. 

Direct catalytic intermolecular a-allylic alkylation of aldehydes and cyclic ketones has been achieved using a one-pot combination of a transition metal catalyst, Pd(PPh3)4, and an organocatalyst a secondary amine which facilitates enamine catalysis.300... 

On the basis of this mechanism, it was surmised that substitution of Et3SiH by an appropriate organometallic reagent would provide access to ketones. Extensive screening of various transition metal catalysts and organometallic reagents have revealed suitable conditions, which are currently used in the Fukuyama-Coupling. 

When only 0.1 equiv of triethylamine was used, 3-(chlorosilyl)propyl ketone was formed as the major product in 86% estimated yield (based on NMR analysis). According to the authors mechanistic hypothesis, oxidative insertion of the transition metal catalyst occurs into the acid chloride, which is followed by ring insertion of the acylpalladium... 

Table 2. Examples of couplings of aromatic ketones with olefins using transition metal catalysts. ...

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

Oxidations of carbon-heteroatom species often results in the destruction of a stereogenic center, as in the oxidation of a secondary alcohol to a ketone. In some instances, this reaction can be coupled with another to provide a chiral product (see Chapter 21). One example is the enzymatic acetylation of one enantiomer of a secondary alcohol, where a redox reaction with a transition metal catalyst equilibrates the unreactive isomer of the alcohol (Scheme 9.1).10 12 The redox reaction can also be performed by an enzyme.13... 

The oxidative cleavage of alkenes to aldehydes and ketones is commonly achieved via ozonolysis. Transition-metal catalysts, including RUCI3, Ru04, and OSO4, together with stoichiometric oxidants also may be used for this... 

Cleavage of carbon-carbon bonds by transition-metal catalysts is one of the major challenges in organic and organometallic chemistry [43]. For that purpose, strained small-ring ketones are useful substrates. Recently, some synthetic... 

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