Ketone transition metal-catalyzed

In a different approach a super-high-throughput ee-assay was developed on the basis of chirally modified capillary array electrophoresis (CAE).90 CAE was used in the Human Genome Project, and commercially available instruments have been developed which comprise a high number of capillaries in parallel, for example the 96-capillary unit MegaBACE consisting of 6 bundles of 16 capillaries.91 The system can address a 96-well microtiter plate. It was adapted to perform ee-determinations of chiral amines, which are potentially accessible by catalytic reductive amination of ketones, transition metal catalyzed Markovnikov addition of ammonia, or enzymatic hydrolysis of acetamides (Scheme 14).90... 

For transition-metal-catalyzed hydrogenation of ketones and aldehydes, H2 or the combination of PrOH with a base has been widely used as the hydrogen source (Scheme 8). In case of using H2, the reaction is called hydrogenation, whereas the reaction using the combination of PrOH with a base is especially called transfer hydrogenation. ... 

Hydrido(alkoxo) complexes of late transition metals are postulated as intermediates in the transition metal-catalyzed hydrogenation of ketones (Eq. 6.17), the hydrogenation of CO to MeOH, hydrogen transfer reactions and alcohol homologation. However, the successful isolation of such complexes from the catalytic systems was very rare [32-37]. 

For transition-metal catalyzed hydroxylation of alkane C-H bonds, the reactions of alkanes with platinum(II) complexes were the most successful. In an aqueous solution of hexachloroplatinic acid and Na2PtCl4, alkanes were converted into a mixture of isomeric alkyl chlorides, alcohols, and ketones, and the platinum(IV) is reduced to platinum(II).7 The kinetics of the reaction with methane as the alkane have been described in detail.8... 

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

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... 

The transition metal-catalyzed domino reactions will undoubtedly have a splendid future which is underlined by the increasing number of publications in this area Steglich et al. presented an approach to arcyriacyanin A via a domino Heck reaction between a bromo(indolyl)maleiimide and 4-bromoindole.1811 The synthesis of 33 -bifurans by Ling et al. was achieved using a novel palladium-catalyzed domino dimerization and subsequent cyclization of acetylenic ketones.1821 Other applications of a combination of Heck reactions for domino processes are the syntheses of aza-heterocydes developed by our group.1831... 

Direct electrochemical allylation can be performed with some carbonyl compounds.Transition metal catalyzed couplings are however more efficient, notably in reactions involving ketones. 

Hydrogen transfer reactions from an alcohol to a ketone (typically acetone) to produce a carbonyl compound (the so-caUed Oppenauer-type oxidation ) can be performed under mild and low-toxicity conditions, and with high selectivity when compared to conventional methods for oxidation using chromium and manganese reagents. While the traditional Oppenauer oxidation using aluminum alkoxide is accompanied by various side reactions, several transition-metal-catalyzed Oppenauer-type oxidations have been reported recently [27-29]. However, most of these are limited to the oxidation of secondary alcohols to ketones. 

Ketone and ester enolates have historically proven problematic as nucleophiles for the transition metal-catalyzed allylic alkylation reaction, which can be attributed, at least in part, to their less stabilized and more basic nature. In Hght of these limitations, Tsuji demonstrated the first rhodium-catalyzed allylic alkylation reaction using the trimethly-silyl enol ether derived from cyclohexanone, albeit in modest yield (Eq. 4) [9]. Matsuda and co-workers also examined rhodium-catalyzed allylic alkylation, using trimethylsilyl enol ethers with a wide range of aUyhc carbonates [22]. However, this study was problematic as exemplified by the poor regio- and diastereocontrol, which clearly delineates the limitations in terms of the synthetic utihty of this particular reaction. 

A masked allylic boron unit can be revealed through a transition-metal-catalyzed borylation reaction. For example, a one-pot borylation/allylation tandem process based on the borylation of various ketone-containing allylic acetates has been developed. The intramolecular allylboration step is very slow in DMSO, which is the usual solvent for these borylations of allylic acetates (see Eq. 33). The use of a non-coordinating solvent like toluene is more suitable for the overall process provided that an arsine or phosphine ligand is added to stabilize the active Pd(0) species during the borylation reaction. With cyclic ketones such as 136, the intramolecular allylation provides cis-fused bicyclic products in agreement with the involvement of the usual chairlike transition structure, 137 (Eq. 102). 

In principle, one could write two mechanisms for the MPV reduction a stepwise mechanism involving a discrete hydride intermediate, and a direct hydride transfer from alkoxide to ketone. These alternatives are similar to the two mechanisms usually assumed for transition-metal-catalyzed transfer... 

The chemistry of cyclopropanol [7] has long been studied in the context of electrophilic reactions, and these investigations have resulted in the preparation of some 3-mercurio ketones. As such mercury compounds are quite unreactive, they have failed to attract great interest in homoenolate chemistry. Only recent studies to exploit siloxycyclopropanes as precursors to homoenolates have led to the use of 3-mercurio ketones for the transition metal-catalyzed formation of new carbon-carbon bonds [8] (vide infra). 

Hydroalkoxylation of Allenes In the year 2000, during their investigation of transition metal catalyzed reactions of allenyl ketones [29], Hashmi et al. discovered that gold(III) salts were able to lead the cydoisomerization and dimerization of these substrates (Equation 8.2) with a considerable improvement related to other assays with Ag (I) or Pd (II) catalysts [18]. 

The advancements in supramolecular catalysis are not limited to transitions-metal catalyzed reactions. Clarke and coworkers recently reported the preparation of a library of organocatalysts and their application in the asymmetric Michael addition of ketones to nitroalkenes [37]. They proposed use of a supramolecular catalyst formed... 

Numerous useful transition metal-catalyzed reactions of organic halides are now known. Practical syntheses of esters, acids, amides, aldehydes, olefins, ketones, and acetylenes have been described. In many instances the metal-catalyzed reactions are superior to more conventional, purely organic routes to the same compounds. 

Scheme 15. Transition metal-catalyzed reactions of allenyl ketones 43, 45 and 47.

Several related examples of transition metal-catalyzed addition of C-H bonds in ketones to olefins have been reported (Table 2) [11-14]. The alkylation of diterpenoid 6 with olefins giving 7 proceeds with the aid of Ru(H)2(CO)(PPh3)3 (A) or Ru(CO)2(PPh3)3 (B) as catalyst [11], Ruthenium complex C, Ru(H)2(H2)(CO) (PCy3)2, has catalytic activity in the reaction of benzophenone with ethylene at room temperature [12]. The alkylation of phenyl 3-pyridyl ketone 8 proceeds with A as catalyst [13], Alkylation occurs selectively at the pyridine ring. Application of this C-H/olefin coupling to polymer chemistry using ce,co-dienes such as 1,1,3,3-tetramethyl-l,3-divinyldisiloxane 11 has been reported [14]. 

The hydroacylation of olefins with aldehydes is one of the most promising transformations using a transition metal-catalyzed C-H bond activation process [1-4]. It is, furthermore, a potentially environmentally-friendly reaction because the resulting ketones are made from the whole atoms of reactants (aldehydes and olefins), i.e. it is atom-economic [5]. A key intermediate in hydroacylation is a acyl metal hydride generated from the oxidative addition of a transition metal into the C-H bond of the aldehyde. This intermediate can undergo the hydrometalation ofthe olefin followed by reductive elimination to give a ketone or the undesired decarbonyla-tion, driven by the stability of a metal carbonyl complex as outlined in Scheme 1. 

Research on intermolecular hydroacylation has also attracted considerable attention. The transition-metal-catalyzed addition of a formyl C-H bond to C-C multiple bonds gives the corresponding unsymmetrically substituted ketones. For the intermolecular hydroacylation of C-C multiple bonds, ruthenium complexes, as well as rhodium complexes, are effective [76-84]. In this section, intermolecular hydroacylation reactions of alkenes and alkynes using ruthenium catalysts are described. 

The use of C-H bonds is obviously one of the simplest and most straightforward methods in organic synthesis. From the synthetic point of view, the alkylation, alkenylation, arylation, and silylation of C-H bonds are regarded as practical tools since these reactions exhibit high selectivity, high efficiency, and are widely applicable, all of which are essential for practical organic synthesis. The hydroacylation of olefins provides unsymmetrical ketones, which are highly versatile synthetic intermediates. Transition-metal-catalyzed aldol and Michael addition reactions of active methylene compounds are now widely used for enantioselective and di-astereoselective C-C bond formation reactions under neutral conditions. 

Metal complexes enable one to employ molecules that are thermally unreactive toward cycloadditions by taking advantage of their ability to be activated through complexation. Most of the molecules activated by transition-metal complexes involve C-C unsaturated bonds such as alkynes, alkenes, 1,3-dienes, allenes, and cyclopropanes. In contrast, carbonyl functionalities such as aldehydes, ketones, esters, and imines seldom participate in transition-metal-catalyzed carbonylative cycloaddition reactions. Recently, such a transformation was reported via the use of ruthenium complexes. 

While most of the initial studies have involved the transition metal-catalyzed decomposition of a-carbonyl diazo compounds and have been reviewed [3-51], it appears appropriate to highlight again some milestones of these transformations, since polycyclic structures could be nicely assembled from acyclic precursors in a single step. Two main reactivities of metalo carbenoids derived from a-carbonyl diazo precursors, namely addition to a C - C insaturation (olefin or alkyne) and formation of a ylid (carbonyl or onium), have been the source of fruitful cascades. Both of these are illustrated in Scheme 27 [52]. The two diazo ketone functions present in the same substrate 57 and under the action of the same catalyst react in two distinct ways. The initially formed carbenoid adds to a pending olefin to form a bi-cyclop. 1.0] intermediate 58 that subsequently cyclizes to produce a carbonyl ylide 59, that is further trapped intramolecularly in a [3 + 2] cycloaddition. The overall process gives birth to a highly complex pentacyclic structure 60. 

Alkenes with a variety of substituents such as acetal, amine, amide, carbamate, ester, ether, isocyanate, ketone, oxirane, and snlfide can be hydrosilated, usually without affecting the ftinctional group. However, this is not always fine for example, allyl chloride gives a considerable amount of the reduction product (see equation 26). Table 4 lists representative examples of hydrosilation. It is not so remarkable in the case of radical hydrosilation, but reactivity is high for hydrosUane, which has electronegative group in the case of transition metal catalyzed hydrosilation. 

E. Ketone Enolates as Nucleophiles in Transition-metal Catalyzed Allylic... 

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