Metalation-deprotonation step

The most common site for metalation of the carbon framework is C5 of the pyrimidines, C and U. For these reactions to occur, basic reaction conditions are generally required to assist in a deprotonation step. The first structurally characterized species was the di-Pt111 complex of 1-methyluracil, which also featured N3- and 04-binding (Pt-C5 distance... 

The diastereoselectivity observed during the addition of (61c) to isobutyraldehyde stands in marked contrast to the significantly lower selectivity (1.5 1) that was previously observed when the chiral 2-methyloxazoline (59) was used as the nucleophilic partner (vide supra). The enhanced diastereoselection in the reaction involving (61c) is presumably a consequence of internal lithium chelation, which enhances both the selectivity in the deprotonation step as well as the diastereofacial selectivity in the nucleophilic addition to the aldehyde. For example, in separate experiments it was determined that metallation of (61c) proceeded with a (Z) ( ) diastereoselectivity of >9 1. Subsequent reaction of this (Z)-azaenol-ate with isobutyraldehyde via the chelated, chair-like transition state depicted in (64 R = Me), in which steric interactions between the reacting residues are minimized, would lead preferentially to the anti isomer (62c). For the additions involving (59), examination of the related transition state (64 R = H) clearly reveals that the facial selectivity should be somewhat less. 

To take advantage of the attractive features of proton-coupled transport, we (9-12) and others (14-17) have utilized crown ether compounds with pendant carboxylic acid groups. The mechanism of proton-coupled transport of a monovalent metal cation across an organic liquid membrane is illustrated in Figure 1. Thus the carrier, which remains in the organic membrane, is deprotonated at the organic phase-alkaline aqueous source phase interface and complexes the metal cation (Step 1). The electroneutral complex... 

The results indicate that the rate- and regio-determining step involves concerted metalation-deprotonation, as shown in (23), to give an aryl palladium intermediate. This is followed by substitution of the pyridine ligand, L, by the alkene and insertion of the alkene double bond into the palladium—aryl bond. The absence of ortho-substituted product results from steric repulsion between the ring substituent,... 

Reactions with aikynes may aiso result in the formation of cyclized products. Thus a ruthenium-catalysed reaction with aromatic amides has been used to give isoquinoline derivatives. On the basis of values of the kinetic isotope effect, A h/ d> proposed that the rate-determining step is a concerted acetate-assisted metalation-deprotonation process to yield the intermediate (30), followed by aikyne insertion and ring closure. The reaction of arylketones with alkynes may yield indenols when catalysed by rhodium cyclopentadienyl in the presence of silver and copper salts. The reaction proceeds regioselectively, so that reaction of acetophenone with 1-phenyl-1-propene... 

The nature of the C-H activation step has been widely discussed in several studies. There are three accepted pathways for the mechanism of the C-H cleavage oxidative addition, electrophilic substitution, and concerted metallation-deprotonation (CMD). ° The reaction of [RuCl2(arene)]2 complexes with heteroarenes or benzylamines in the presence of a base has been shown to favour the formation of stable ruthenacycles. This evidence confirmed the crucial role of the base in the... 

Based on the existence of numerous hydroxamate-containing secondary metabolites such as mycelianamide, it can be further proposed that the tryptophyl oxidation proceeds through a hydroxamic acid intermediate (shown in Scheme 10). This functionality, an excellent chelator of (a non-heme) Fe(lll), for instance, could further function to assist the elimination of water to form the imino portion of the azadiene. Since the prolyl methine (pKa>30) must also be removed at the active site of an enzyme, a metal-coordinated amide might also be essential to lower the activation barrier for the deprotonation step. Finally, the intramolecular Diels-Alder cycloaddition might enjoy a catalytic effect of aza-diene-metal coordination. 

A more appealing strategy for arene C—H functionalizations involves the use of simple benzene derivatives lacking DGs. The overall pathway for such transformations entails metal mediated C—H activation to afford the metal-aiyl intermediate Ai M followed by subsequent functionalization of Ai M to release the desired product (Scheme 24.1). The C—H activation step can proceed via oxidative addition, sigma bond metathesis, or concerted metalation deprotonation pathway. The exact mechanism of C—H cleavage is dependent on the nature of the metal and the ancUlaiy ligands [1,3]. 

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