Hydride relay

Besides acting as a hydride relay, the Lewis acid fragment can also participate in substrate activation. This possibility was first illustrated by Owen and co-workers while investigating the reactivity of the Rh complex 44b with sterically demanding phosphines (Scheme 14). No reaction is observed in the absence of Hj, but under 2.5bar of Hj, rhodium hydride complexes 43c,d are formed along with tricy-clo[2.2.1.0 ]heptane. This transformation involves the addition of Hj, the cleavage of the Rh B interaction and the formation of a C—H bond (presumably via reductive... 

When /J-hydride elimination in the carbopalladation relay is completely blocked as in norbornene 116 and norbornadiene 117, the coupling with 6 -bromostyrene 113 furnished the respective cyclopentannelation products 118 and 119 exclusively and in good yields. 

Eklund et al. suggested that the side chains of Ser 48 and His 51 act as a proton relay system to remove the proton from the alcohol, in step b of Eq. 15-7, leaving the transient zinc-bound alcoholate ion, which can then transfer a hydride ion to NAD+, in step c.52 The shaded hydrogen atom leaves as H+. The role of His 51 as a base is supported by studies of the inactivation of the horse liver enzyme by diethyl pyrocarbonate57 and by directed mutation of yeast and liver enzymes. When His 51 was substituted by Gin the pKa of 7 was abolished and the activity was decreased ten-fold.58... 

Dunn has also proposed a mechanism involving this charge relay system in ternary complex formation, but with the substrate displacing the zinc-bound water, as shown in Scheme 9.1443 Hydride transfer from NADH, to form an alcoholate anion, has been shown to occur before protonation.1398 As well as not requiring penta-coordinate zinc, this mechanism differs from Dworschack and Plapp s in postulating the formation of an alcoholate anion. 

This mechanism, accounting for the observed pH perturbations, does not directly consider the proton charge relay system involving Ser-48 and His-51. However it is probable that this system is important in facilitating, by charge distribution, formation of the alcoholate anion and hydride transfer to NAD+, and in the reverse reaction, neutralization of the alcoholate anion and alcohol dissociation. 

As indicated in the previous example, carbopalladation does not necessarily culminate in /i-hydride elimination as the expected outcome of reactions under Heck conditions. In those cases where the initial carbopalladation can be reversed at a later stage in the sequence fascinating options for catalytic processes may evolve. In particular, Catellani (for an overview see [67]) has established that norbornene, a strained olefin, which is reversibly introduced and eliminated, might efficiently serve as a relay to open new pathways for Pd-mediated processes. Indeed, most of the processes were explored and conducted both in a stoichiometric and in a catalytic fashion. 

Scheme 14] is adopted in which the hydride is delivered syn to the hydroxy function. This stereochemistry is independent of additional stereogenic centers in the 2-position [reactions (37 vs 38), Scheme 14]. It also works in a relay fashion to create all-flnti-l,3,5-triols [reaction (39), Scheme 14] [33]. The application of a different borohydride reagent (Et2BOMe-i-NaBH4) results in the formation of complex 14-2 and, hence, in an anfi-attack of the hydride to generate syn-... 

In order to prepare the relay intermediate (30), lucidusculine was converted into napelline by hydride reduction. Dihydronapelline (43) was then prepared by hydrogenation with platinum oxide in acetic acid. Removal of the /V-ethyl group by treatment with mercuric acetate in aqueous acetic acid followed by oxidation with chromium trioxide in pyridine afforded the triketolactam (44). This was converted into the diketo-acetal intermediate (30) by conventional methods. 

Fig. 89. Preparation of very pure hydrogen from titanium hydride, a) quartz reactor tube ) molybdenum boat containing Ti c) heating winding d) radiation shield e) radiation shields for protection of stoppers f) glass wool g) apparatus for conducting reactions with the very pure hydrogen product the tube contains a boat for the reactants and is surroimded by an electric furnace. This part may be omitted if the hydrogen product is to be used elsewhere m) pressure-sensing switch r) relay.

The second coordination sphere refers to atoms or functional groups that are in close proximity to the metal site, but that are not directly bound to the metal (shown in yellow in Figure 7.3). As a result, direct interactions of the second coordination sphere may occur with substrate molecules bound to the metal (e.g., interaction of a pendant amine with an H2 or hydride ligand), but not with the metal center itself This second coordination sphere can modify some of the energies of the catalytic intermediates, but an additional important role is the ability of the second coordination sphere to facilitate the movement of protons between the active metal site and species in solution. In this role the second coordination sphere acts as a relay for proton transfer. 

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