Nucleophihc attack activation

FIGURE 14. Structure of E coli amine oxidase active site in the equilibrium turnover complex. Interactions and labelling as in Figure 12 except that the reduced form of the cofactor is labelled TPR and carries a nitrogen at the 5-position. The aldehyde product, labelled Prod, is retained in the channel to the enzyme surface. Water W4 is positioned for nucleophihc attack on C5 of the cofactor and W2 is retained as a link in a proton shuttle from 04 to dioxygen. 

Therefore, some conclusions have been generally accepted and have been summarized as follows the cycloaddition reaction is a stepwise reaction rather than a concerted one the reaction is initiated by nucleophihc attack of an imine to a ketene, giving rise to a zwitterionic intermediate a conrotatory eleclrocyclic ring-closure of the zwitterionic intermediate produces the final 2-azetidone product [85], As the stereochemistry of the structure of the P-lactams strongly affects their biological activity, the stereoselectivity of the process must be carefully considered. Uncatalysed as well as catalysed processes have been reported organometallic and organic catalysts have been utilized in procedures oriented to the syntheses of enantiopure P-lactams [90-92],... 

The titanium-tartrate complex was proven to have a dimeric structure by X-ray analysis [30,31 ]. The complex has been considered to maintain the dimeric structure also in solution. Based on the X-ray structure. Sharpless has proposed the transition state model 7 for the present epoxidation (Fig. 1). The coordination of the distal oxygen (O ) in the loaded TBHP activates the peroxy bond and facilitates the nucleophihc attack of the double bond as discussed in the beginning of this chapter. Both stereochemistry and substrate reactivity in this reaction can be reasonably explained with the model 7 [3,4,6,30,31]. The loaded substrate takes a conformation having a small dihedral angle (0-C-C=C, ca. 30°) to deliver its olefinic moiety in an appropriate space for the epoxidation. The -substituent... 

The (reversible) transformation of an a-ketocarboxyhc acid in presence of ammonia and one equivalent of NAD(P)H furnishes the corresponding a-amino acid and is catalyzed by amino acid dehydrogenases [EC 1.4.1.X] [962]. Despite major differences in its mechanism, this reaction bears a strong resemblance to carbonyl group reduction and it formally respresents a reductive amination (Scheme 2.133). As deduced for L-Leu-dehydrogenase [963], the a-ketoacid substrate is positioned in the active site between two Lys-residues. Nucleophihc attack by NH3 leads to a hemiaminal intermediate, which eliminates H2O to form an iminium species. The latter is reduced by a hydride from nicotinamide forming the L-amino acid. Since this mechanism is highly tuned for a-keto/a-amino acids, it is clear that a neutral Schiff base cannot be accepted as substrate. 

Additions to nonactivated olefins and dienes are important reactions in organic synthesis [1]. Although cycloadditions may be used for additions to double bonds, the most common way to achieve such reactions is to activate the olefin with an electrophilic reagent. Electrophilic activation of the olefin or diene followed by a nucleophilic attack at one of the sp carbons leads to a 1,2- or 1,4-addition. More recently, transition metals have been employed for the electrophilic activation of the double bond [2]. In particular, palladium(II) salts are known to activate carbon-carbon double bonds toward nucleophihc attack [3], and this is the basis for the Wacker process for industrial oxidation of ethylene to acetaldehyde [4]. In this process, the key step is the nucleophilic attack by water on a 7t-ethylenepalladium complex. 

Kuninobu, Takai, and coworkers [90] demonstrated that aromatic imines undergo ortho alkenylation under Re catalysis (Scheme 18.88). This reaction was proposed to proceed via C-H bond activation at the ortho position of imines, alkyne insertion into not Re-H but Re-C bond, intramolecular nucleophihc attack of the formed Re-C(sp ) bond on an imino carbon, and final reductive eUmination. 

In general, the initial formation of the a,p-unsaturated nitrile (72) via Knoevenagel condensation of an activated nitrile (69) with a carbonyl compound (71) mediated by a base ( B) is accepted as a proposed mechanism for the three-component Gewald reaction (G-3CR) (Scheme 12.24). Then, after deprotonation of that intermediate (72), it reacts with elemental sulfur (S ) following an S X mechanism, generating sulfated compound (74), which cyclizes to 75 via an intramolecular nucleophihc attack of the sulfur anion to... 

Neonicotenoid insecticidal action is enhanced by 0- -propyl O-(2-propynyl) phenylphosphonate (115) by dual inhibition of cytochrome P450 (CYP) and the nicotinic receptor (nAChR), and this is proposed to occur by oxidation to the epoxide, and then conversion to the ketene metabolite (Scheme 4.23), which acts by nucleophihc attack on the cytochrome P450 active site and the nAChR NMI binding site. Computational studies showed favorable docking of the ketene at the active site... 

NADH is a coenzyme, an organic molecule that can function only in the presence of an enzyme. The active site of the enzyme binds both the carbonyl substrate and NADH, keeping them in close proximity. NADH then donates H in much the same way as a metal hydride reagent that is, reduction consists of nucleophihc attack followed by protonation. 

The most important CO2 activation process is photosynthesis in green plants, in which solar photons drive a reaction that would otherwise be uphill thermodynamically the reduction of CO2 to carbohydrates coupled to water oxidation to O2. Many metalloenzymes are involved in these processes, such as ribulose diphosphate carboxylase that fixes CO2 via nucleophihc attack on an enolate anion from a sugar. Artificial photosynthesis takes the natural version as inspiration and seeks to photochemically reduce CO2 to fuels such as MeOH. Naturally, a catalyst is needed-Re(CO)3(bpy)X holds promise in this regard by converting CO2 to CO and HCOOH. ... 

The full energy diagram for the final mechanistic proposal is shown in Figure 8.10. The mechanism follows the proposal shown in Scheme 8.10. One of the acetate ligands in the square-planar complex 23 is replaced with the allylic substrate affording complex 28, which is converted to the C—H activation product 30 via transition state 29. The alkene switches from an in 30 to an q -allylic coordination in 31. Nucleophihc attack of the methyl nitroacetate anion via TS 32 affords complex 33. 33 is the corresponding Pd(0) complex coordinating the final product, which is replaced by benzoquinone and leads, after the recruitment of two acetate molecules in complex 35, to the stepwise oxidation via the transition states 36, 38, and 40 as well as the intermediates 37,... 

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