Nucleophilic attack by hydride on

The reactivity of these metal hydride-metal carbonyl reactions can be correlated with the nature of the reactants in a manner consistent with the proposed mechanism nucleophilic attack by hydride on coordinated CO. Thus reactions involving the highly nucleophilic group IV hydride, Cp gZrHg, are much faster than those of group V metal hydrides. On the other hand, the relatively electrophilic neutral binary metal carbonyls all react with Cp2NbH under mild conditions (20-50° C), whereas more electron-rich complexes such as cyclopentadienylmetal carbonyls (Cp2NbH(C0), CpV(CO) ) or anionic carbonyls (V(CO)g ) show no reaction under these conditions. 

As shown in Figure 16.10, this reaction mechanism involves nucleophilic attack by —SH on the substrate glyceraldehyde-3-P to form a covalent acylcysteine (or hemithioaeetal) intermediate. Hydride transfer to NAD generates a thioester intermediate. Nucleophilic attack by phosphate yields the desired mixed carboxylic-phosphoric anhydride product, 1,3-bisphosphoglycerate. Several examples of covalent catalysis will be discussed in detail in later chapters. 

In contrast, spectroscopic and crystal structure analysis indicates that nucleophilic attack of hydride on 72 occurs on the face of the ligand which is coordinated to the metal (Scheme 17). No intermediate species could be detected for this latter reaction. Monitoring of the reduction of the rhenium analog 74 with sodium borohydride indicated the intermediacy of a rhenium formyl complex 75, presumably formed by attack on a coordinated carbon monoxide. Signals for 75 eventually disappear and are replaced by those of the (diene)rhenium product 76 (Scheme 18)95. 

The NAD+-dependent alcohol dehydrogenase from horse liver contains one catalytically essential zinc ion at each of its two active sites. An essential feature of the enzymic catalysis appears to involve direct coordination of the enzyme-bound zinc by the carbonyl and hydroxyl groups of the aldehyde and alcohol substrates. Polarization of the carbonyl group by the metal ion should assist nucleophilic attack by hydride ion. A number of studies have confirmed this view. Zinc(II) catalyzes the reduction of l,10-phenanthroline-2-carbaldehyde by lV-propyl-l,4-dihy-dronicotinamide in acetonitrile,526 and provides an interesting model reaction for alcohol dehydrogenase (Scheme 45). The model reaction proceeds by direct hydrogen transfer and is absolutely dependent on the presence of zinc(II). The zinc(II) ion also catalyzes the reduction of 2- and 4-pyridinecarbaldehyde by Et4N BH4-.526 The zinc complex of the 2-aldehyde is reduced at least 7 x 105 times faster than the free aldehyde, whereas the zinc complex of the 4-aldehyde is reduced only 102 times faster than the free aldehyde. A direct interaction of zinc(II) with the carbonyl function is clearly required for marked catalytic effects to be observed. 

Trialkylborohydride reducing agents differ from borohydride in their ability to transfer hydride directly to a carbonyl ligand without prior substitution in the coordination sphere. They are used to synthesize formyl complexes " . When formyl complexes lose CO and undergo hydride migration from the formyl ligand to the metal, a transition-metal hydride results. The process is formally similar to nucleophilic attack by [OH] on a carbonyl ligand, followed by loss of CO and formation of a transition-metal hydride. Examples of hydride syntheses via formyl complexes are ... 

Methyllithium attacked the sulfur atom of naphthothiete 205 to give 231 and oligomers 232 and 233 via 8-mercaptomethyl-l-lithionaphthalene. Treatment with lithium aluminum hydride followed by methylation gave 234. Treatment of thiete 215 with triphenylphosphine leads to ring-expanded products possibly via nucleophilic attack by phosphorus on sulfur. ... 

Although single-electron transfer is proposed in the reduction of aromatic ketones by AIH3, BH3, and LAH-pyridine [AG2], the reductions of aldehydes and ketones by alumino- and borohydrides and boranes occur mostly by nucleophilic attack of hydride on the carbonyl carbon. This process has been the subject of numerous theoretical [ESI, HWl, N2, W2] and mechanistic [CBl, N5, W2, W4] studies. 

The cation [(C5H5)Mo(CO)(NO)(allyl)] exists as an equilibrating mixture of isomers VII and VIII. Nucleophilic attack on a terminal carbon of cation VII would lead to the olefin complex IX if attack occurred onto the carbon trans to the NO ligand, or to complex XI if attack occurred onto the carbon trans to the CO ligand. Cation VIII, however, would give complex X by attack on the carbon atom trans to CO and complex XII by attack onto the carbon trans to NO. The olefin complexes IX and X rapidly equilibrate by rotation about the Mo-olefin bond as do the olefin complexes XI and XII. Nucleophilic attack by hydride or cyanide shows little regioselectivity, and both diastereoisomeric pairs IX X and XI XII are formed . 

C6H5R)(PF3)3] (R = H, Ph) afforded the highly fluxional agostic diene complex (20), characterised by X-ray diffraction for R = Ph. The nucleophilic attack of hydride on a variety of (Ti<5-arene)chromium tricarbonyl complexes has been studied and the X-ray crystal structure of (21), derived from the reaction with [Cr( n6-dibenzofuran)(CO)3], has been reported . 

Another standard example is the nucleophilic attack by lithium aluminum hydride (LAH) on a ketone or aldehyde (Scheme 10.8). Each hydrogen in LiAlH4 is partially negatively charged, and therefore the Al-H a bonds are nucleophilic. After the nucleophilic attack by hydride, the resulting alkoxide anion coordinates with the A1 species. These two steps are repeated three more times. Finally, dilute acid is added to supply a proton to the alkoxide anion (electron pushing not shown). 

Structure determination of 2-benzenesulfonyl-3-trimethylsilylbicyclo[2.2.2]octa-2,5-diene (197) demonstrates that the electron-deficient double bond is pyramidalized in the exo direction. Nucleophilic attack by hydride (a conjugate reduction) on... 

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