Transition Metal-Catalyzed Reductions

Transition-metal catalyzed photochemical reactions for hydrogen generation from water have recently been investigated in detail. The reaction system is composed of three major components such as a photosensitizer (PS), a water reduction catalyst (WRC), and a sacrificial reagent (SR). Although noble-metal complexes as WRC have been used [214—230], examples for iron complexes are quite rare. It is well known that a hydride as well as a dihydrogen (or dihydride) complex plays important roles in this reaction. 

Scheme 2 Transition metal-catalyzed reductive aldol reaction...

After the initial two reports of Rh- and Co-catalyzed reductive aldol couplings, further studies did not appear in the literature until the late 1990s. Beyond 1998, several stereoselective and enantioselective reductive aldol reactions were developed, which are catalyzed by a remarkably diverse range of metal complexes, including those based upon Pd, Cu, Ir, and In. In this chapter, transition metal-catalyzed aldol, Michael, and Mannich reactions that proceed via transition metal hydride-promoted conjugate reduction are reviewed. 

For the reason of comparison and the development of new domino processes, we have created a classification of these transformations. As an obvious characteristic, we used the mechanism of the different bond-forming steps. In this classification, we differentiate between cationic, anionic, radical, pericyclic, photochemical, transition metal-catalyzed, oxidative or reductive, and enzymatic reactions. For this type... 

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. 

The reduction of protons is one of the most fundamental chemical redox reactions. Transition metal-catalyzed proton reduction was reviewed in 1992.6 The search for molecular electrocatalysts for this reaction is important for dihydrogen production, and also for the electrosynthesis of metal hydride complexes that are active intermediates in a number of electrocatalytic systems. 

It is well known that acrylates undergo transition metal catalyzed reductive aldol reaction, the silanes R3SiH first reacting in a 1,4 manner and the enolsilanes then participating in the actual aldol addition.57,58 A catalytic diastereoselective version was discovered by arrayed catalyst evaluation in which 192 independent catalytic systems were screened on 96-well microtiter plates.59 Conventional GC was used as the assay. A Rh-DuPhos catalyst turned out to be highly diastereoselective, but enantioselectivity was poor.59... 

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... 

There has been considerable recent research interest in the activation of carbon monoxide en route to more complex organic molecules. Among the various reactions that have been investigated and/or newly discovered, the transition metal catalyzed reduction of CO to hydrocarbons (Fischer-Tropsch synthesis) has enjoyed particular attention (l- ). Whereas most of the successful efforts in this area have been directed toward the development of heterogeneous catalysts, there are relatively few homogeneous systems. Among these, two are based on clusters (10,11) and others are stoichiometric in metal (12-17). In this report we detail the synthesis and catalytic chemistry of polystyrene ( ) supported... 

For a review encompassing the transition metal-catalyzed reductive coupling of carbonyl compounds, see Avalos, M. Babiano, R. Gintas, P. ... 

Malacria and co-workers76 were the first to report the transition metal-catalyzed intramolecular cycloisomerization of allenynes in 1996. The cobalt-mediated process was presumed to proceed via a 7r-allyl intermediate (111, Scheme 22) following C-H activation. Alkyne insertion and reductive elimination give cross-conjugated triene 112 cobalt-catalyzed olefin isomerization of the Alder-ene product is presumed to be the mechanism by which 113 is formed. While exploring the cobalt(i)-catalyzed synthesis of steroidal skeletons, Malacria and co-workers77 observed the formation of Alder-ene product 115 from cis-114 (Equation (74)) in contrast, trans-114 underwent [2 + 2 + 2]-cyclization under identical conditions to form 116 (Equation (75)). 

Alcohols have always been the major group of hydrogen donors. Indeed, they are the only hydrogen donors that can be used in Meerwein-Ponndorf-Verley (MPV) reductions. 2-Propanol (16) is most commonly used both in MPV reductions and in transition metal-catalyzed transfer hydrogenations. It is generally available and cheap, and its oxidation product, acetone (14), is nontoxic and can usually be removed readily from the reaction mixture by distillation. This may have the additional advantage that the redox equilibrium is shifted even more into the direction of the alcohol. As a result of sigma inductive electronic ef-... 

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 conclusion, the applicability of the transition metal catalyzed hydroformylation of easily accessible functionalized or non-functionalized unsaturated compounds is expanded by its implementation in reaction sequences, tandem reactions or domino reactions. The hydroformylation can be combined with simple functional group transformations, such as reduction or isomerization, or with C,0-, C,N- and, most importantly, C,C-bond forming reactions. It can be expected that more interesting examples and applications will be presented in the future. 

Boronic esters have been used in a wide range of transformations. These useful reagents have been transformed into numerous functional groups and are essential reagents for several C-C bond-forming reactions. Transition metal-catalyzed hydroboration of olefins often leads to mixtures of branched and linear products. Several groups have reported asymmetric reductions of vinyl boronic esters [50-52] with chiral rhodium P,P complexes however, the first iridium-catalyzed reduction was reported by Paptchikhine et al (Scheme 10) [53]. 

Several peroxidative reactions initiated by OH radical that may be generated by either y- and X-radiolysis of aqueous solutions or by transition metal-catalyzed reduction of H2O2 have been identified in free amino acids and short peptides. In this respect we may distinguish oxidizing reactions that involve the polypeptide backbone on the one hand... 

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... 

Transition metal-catalyzed allylic alkylation is generally considered to involve mechanistically four fundamental steps as shown in Scheme 1 coordination, oxidative addition, ligand exchange, and reductive elimination. A key step of the catalytic cycle is an initial formation of a (7r-allyl)metal complex and its reactivity. The soft carbon-centered nucleophiles, defined as those derived from conjugate acids whose pAj, < 25, usually attack the allyl ligand from the opposite side... 

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