Coordination, hydride transfer

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

The aldehyde or ketone, when treated with aluminum triisopropoxide in isopropanol as solvent, reacts via a six-membered cyclic transition state 4. The aluminum center of the Lewis-acidic reagent coordinates to the carbonyl oxygen, enhancing the polar character of the carbonyl group, and thus facilitating the hydride transfer from the isopropyl group to the carbonyl carbon center. The intermediate mixed aluminum alkoxide 5 presumably reacts with the solvent isopropanol to yield the product alcohol 3 and regenerated aluminum triisopropoxide 2 the latter thus acts as a catalyst in the overall process ... 

RhCl(PPh3)3 is a very active homogenous hydrogenation catalyst, because of its readiness to engage in oxidative addition reactions with molecules like H2, forming Rh—H bonds of moderate strength that can subsequently be broken to allow hydride transfer to the alkene substrate. A further factor is the lability of the bulky triphenylphosphines that creates coordinative unsaturation necessary to bind the substrate molecules [44]. 

The mechanism of such reactions using unsaturated carboxylic acids and Ru(BINAP)(02CCH3)2 is consistent with the idea that coordination of the carboxy group establishes the geometry at the metal ion.26 The configuration of the new stereocenter is then established by the hydride transfer. In this particular mechanism, the second hydrogen is introduced by protonolysis, but in other cases a second hydride transfer step occurs. 

On the basis of these experimental results, a possible mechanism has been proposed for the reaction of 1-215 with Sml2 (Scheme 1.52). After formation of the syn-complex A, a rearrangement occurs to give the aldehyde B, which coordinates to the added aldehyde RCHO to afford complex C. Subsequent samarium-catalyzed nucleophilic attack of the secondary alcohol to the carbonyl of RCHO generates a hemiacetal, D. There follows an irreversible intramolecular 1,5-hydride transfer via... 

The reduction to methoxy-hydrido species (7) is thought to proceed via loss of CO from the dicarbonyl complex followed by addition of hydrogen to give the dihydrido carbonyl species (9). The next step suggested (37) is hydride transfer to the carbonyl carbon to give a formyl species in which both the carbonyl carbon and the carbonyl oxygen coordinate to the metal center, i.e., 10 ... 

The rate also varies with butadiene concentration. However, the order of the rate dependence on butadiene concentration is temperature-de-pendent, i.e., a fractional order (0.34) at 30°C and first-order at 50°C (Tables II and III). Cramer s (4, 7) explanation for this temperature effect on the kinetics is that, at 50°C, the insertion reaction to form 4 from 3, although still slow, is no longer rate-determining. Rather, the rate-determining step is the conversion of the hexyl species in 4 into 1,4-hexadiene or the release of hexadiene from the catalyst complex. This interaction involves a hydride transfer from the hexyl ligand to a coordinated butadiene. This transfer should be fast, as indicated by some earlier studies of Rh-catalyzed olefin isomerization reactions (8). The slow release of the hexadiene is therefore attributed to the low concentration of butadiene. Thus, Scheme 2 can be expanded to include complex 6, as shown in Scheme 3. The rate of release of hexadiene depends on the concentra-... 

The pyridine-catalysed lead tetraacetate oxidation of benzyl alcohols shows a first-order dependence in Pb(OAc)4, pyridine and benzyl alcohol concentration. An even larger primary hydrogen kinetic isotope effect of 5.26 and a Hammett p value of —1.7 led Baneijee and Shanker187 to propose that benzaldehyde is formed by the two concurrent pathways shown in Schemes 40 and 41. Scheme 40 describes the hydride transfer mechanism consistent with the negative p value. In the slow step of the reaction, labilization of the Pb—O bond resulting from the coordination of pyridine occurs as the Ca—H bond is broken. The loss of Pb(OAc)2 completes the reaction with transfer of +OAc to an anion. 

The cationic tantalum dihydride Cp2(CO)Ta(H)2]+ reacts at room temperature with acetone to generate the alcohol complex [Cp2(C0)Ta(H01Pr)]+, which was isolated and characterized [45]. The mechanism appears to involve protonation of the ketone by the dihydride, followed by hydride transfer from the neutral hydride. The OH of the coordinated alcohol in the cationic tantalum alcohol complex can be deprotonated to produce the tantalum alkoxide complex [Cp2(C0)Ta(01Pr)]. Attempts to make the reaction catalytic by carrying out the reaction under H2 at 60 °C were unsuccessful. The strong bond between oxygen and an early transition metal such as Ta appears to preclude catalytic reactivity in this example. 

Scheme 16.2 illustrates the catalytic mechanism proposed by Muetterties and coworkers [13]. Salient features of this mechanism are the coordination of benzene in the -fashion, to give a transient Col I( 4-C, iH, i)(PR3)2 complex, and the intramolecular hydride transfer to form the allylic intermediate Co(//3-Ctl l7) (PR3)2. Hydrogen addition would give an 4-1,3-cyclohexadiene complex that ultimately releases cyclohexane via H2 addition/hydride migration steps. Complete cis stereoselectivity of hydrogen addition was demonstrated by replacing H2 with D2. 

In the direct transfer mechanism, the metal ion coordinates both reactants enabling an intramolecular reaction, and activates them via polarization. Consequently, strong Lewis acids including Alln and the Lnln ions are the most suitable catalysts in this type of reactions. In the hydride mechanism, a hydride is transferred from a donor molecule to the metal of the catalyst, hence forming a metal hydride. Subsequently, the hydride is transferred from the metal to the acceptor molecule. Metals that have a high affinity for hydrides, such as Ru, Rh and Ir, are therefore the catalysts of choice. The Lewis acidity of these metals is too weak to catalyze a direct hydride transfer and, vice versa, the affinity of Alm and Lnm to hydride-ions is too low to catalyze the indirect hydrogen transfer. Two distinct pathways are possible for the hydride mechanism one in which the catalyst takes up two hydrides from the donor molecule and another in which the catalyst facilitates the transfer of a single hydride. 

The catalytic cycle of the reaction is depicted in Scheme 20.6 [31]. After the initial ligand exchange, the ketone (10) is coordinated to the metal ion of 11 (a), yielding complex 12. A direct hydride transfer from the alkoxide to the ketone takes place via a six-membered transition state (b) in which one alkoxy group is oxidized (13). The acetone (14) and the newly formed alcohol (15) are released... 

The mechanism of the Meerwein-Pondorf-Verley reaction is by coordination of a Lewis acid to isopropanol and the substrate ketone, followed by intermolecular hydride transfer, by beta elimination [41]. Initially, the mechanism of catalytic asymmetric transfer hydrogenation was thought to follow a similar course. Indeed, Backvall et al. have proposed this with the Shvo catalyst [42], though Casey et al. found evidence for a non-metal-activation of the carbonyl (i.e., concerted proton and hydride transfer [43]). This follows a similar mechanism to that proposed by Noyori [44] and Andersson [45], for the ruthenium arene-based catalysts. By the use of deuterium-labeling studies, Backvall has shown that different catalysts seem to be involved in different reaction mechanisms [46]. 

In the case of hydrogenation using [Ru(BINAP)Cl2]n as the catalyst precursor, the reaction seems to occur by a monohydride mechanism as shown in Scheme 6-31. On exposure to hydrogen, RuC12 loses chloride to form RuHCl species A, which in turn reversibly forms the keto ester complex B. Hydride transfer occurs in B from the Ru center to the coordinated ketone to form C. The reaction of D with hydrogen completes the catalytic cycle.67... 

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

Vinyl cations of type 28 with a-aryl or a-alkyl substituents and two P-silyl groups and with an anion of very low nucleophilicity can be generated at room temperature in non-coordinating solvents from 30 by a Si-H to C-H hydride transfer reaction. For 29 (R = t-butyl), an X-ray structure determination has been reported (43, 52, 53). 

On the basis of these results we embarked on a systematic study on the synthesis of vinyl cations by intramolecular addition of transient silylium ions to C=C-triple bonds using alkynyl substituted disila alkanes 6 as precursors.(35-37) In a hydride transfer reaction with trityl cation the alkynes 6 are transformed into the reactive silylium ions 7. Under essentially nonHnucleophilic reaction conditions, i.e. in the presence of only weakly coordinating anions and using aromatic hydrocarbons as solvents, the preferred reaction channel for cations 7 is the intramolecular addition of the positively charged silicon atom to the C=C triple bond which results in the formation of vinyl cations 8-10 (Scheme 1). 

The essential features of the catalytic cycle are summarized in Figure 12.6. After binding of NAD+ the water molecule is displaced from the zinc atom by the incoming alcohol substrate. Deprotonation of the coordinated alcohol yields a zinc alkoxide intermediate, which then undergoes hydride transfer to NAD+ to give the zinc-bound aldehyde and NADH. A water molecule then displaces the aldehyde to regenerate the original catalytic zinc centre, and finally NADH is released to complete the catalytic cycle. 

For unsaturated lactones containing an endocyclic double bond also the two previously described mechanisms are presumably involved and the regio-selectivity of the cyclocarbonylation is governed by the presence of bulky substituents on the substrate. Inoue and his group have observed that the catalyst precursor needs to be the cationic complex [Pd(PhCN)2(dppb)]+ and not a neutral Pd(0) or Pd(II) complex [ 148,149]. It is suggested that the mechanism involves a cationic palladium-hydride that coordinates to the triple bond then a hydride transfer occurs through a czs-addition. Alper et al. have shown that addition of dihydrogen to the palladium(O) precursor Pd2(dba)3/dppb affords an active system, in our opinion a palladium-hydride species, that coordinates the alkyne [150]. 

The consequences on the magnitude of the secondary a-deuterium KIE of coupling the motion of the nontransferring a-hydrogen into the reaction coordinate motion, as suggested by Kurz and Frieden, was investigated in some model calculations by Huskey and Schowen (1983). They used two different models to calculate the secondary isotope effects for the hydride transfer reaction (45). 

In an NMR study of the MPV reduction of acetophenone with Al(OtV)3, Shiner and Whittaker (118,119) showed that the trimer is more reactive than the tetramer. Furthermore, the rate-determining step is alcoholysis of the mixed alkoxide, and not hydride transfer. They proposed that the ketone coordinates directly with trimer or tetramer by expansion of die coordination number of aluminum, and not with monomeric aluminum alkoxide. 

If secondary isotope effects arise strictly from changes in force constants at the position of substitution, with none of the vibrations of the isotopic atom being coupled into the reaction coordinate, then a secondary isotope effect will vary from 1.00 when the transition state exactly resembles the reactant state (thus no change in force constants when reactant state is converted to transition state) to the value of the equilibrium isotope effect when the transition state exactly resembles the product state (so that conversion of reactant state to transition state produces the same change in force constants as conversion of reactant state to product state). For example in the hydride-transfer reaction shown under point 1 above, the equilibrium secondary isotope effect on conversion of NADH to NAD is 1.13. The kinetic secondary isotope effect is expected to vary from 1.00 (reactant-like transition state), through (1.13)° when the stmctural changes from reactant state to transition state are 50% advanced toward the product state, to 1.13 (product-like transition state). That this naive expectation... 

Thus the primary and secondary isotope eifects are all within the semiclassical limits and their relationship is in full accord with the semiclassical Swain-Schaad relationship. There is no indication from the magnitudes of the secondary isotope elfects in particular of any coupling between motion at the secondary center and the reaction-coordinate for hydride transfer. Thus the sole evidence taken to indicate tunneling is the rigorous temperature-independence of the primary isotope elfects. 

Huskey, W.P. and Schowen, R.L. (1983). Reaction-coordinate tunneling in hydride-transfer reactions. J. Am. Chem. Soc. 105, 5704-5706... 

The mechanism for the iridium-catalyzed hydrogen transfer reaction between alcohols and ketones has been investigated, and there are three main reaction pathways that have been proposed (Scheme 4). Pathway (a) involves a direct hydrogen transfer where hydride transfer takes place between the alkoxide and ketone, which is simultaneously coordinated to the iridium center. Computational studies have given support to this mechanism for some iridium catalysts [18]. 

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