Chelating electrophiles substitution with

The problem in the above example is to perform an enantiocontrolled electrophilic substitution in the a-position of a carboxylic acid derivative 1. To this end, chiral auxiliary 2, readily available in both (R) and (5) form from phenylalanine, is attached to the acid chloride 1 by amide formation. The amide 3 is converted into the (T )-enolatc 4, with the chelate ring forming... 

Certain other 1,3-dicarbonyl chelates were brominated with difficulty or not at all. For example, the trifluoro- and hexafluoroacetylacetonates (VI, R = CF3, R = CH3, and R = R = CF3) were not brominated under a variety of vigorous conditions. However, in the case of the chromium chelates of 1-phenyl-1,3-butanedione and dibenzoylmethane (VI, R = C( Hr), R = CH5, and R = R = C(iHr)), reaction with N-bromosuccinimide (NBS) was successful. That the electron density at the central carbon of the chelate ring is an important factor in the success or failure of these electrophilic substitutions is evident from the fact that the bis-(ethylenediamine)-2,4-pentanedionocobalt(III) cation cannot be brominated even under vigorous conditions. 

The electrophilic substitutions of acetylacetonate complexes have been taken as suggesting aromatic character in the chelate ring. Results with seventeen different 1,3-diketonatochromium(III) complexes were recently held to support this suggestion (176-178 equation 43).784 The bromination of tris(l,l,l-trifluoro-2,4-pentanedionato)chromium(III), previously claimed to be unreactive,785 has been reported.786... 

Chelation with metal ions dramatically affects the reactivity of the porphyrin macrocycle, and this can be used to advantage in many cases. For example, for efficient electrophilic substitution of the ring, metals can be chosen (vide infra) which effectively release electron density to the organic porphyrin ligand, while reductions are best carried out on metallo-porphyrins in which the metal tends to deplete the porphyrin ligand of its electron density by way of back-bonding. 

Early workers appeared to show that electrophilic substitution reactions could not be carried out on porphyrins, and began to question the aromaticity of porphyrins since this classical pre-requisite of aromatic character could not be accomplished. However, they had concentrated on reactions of metal-free systems, and since many electrophilic substitution reactions utilize acidic conditions (nitration, sulfonation), they were actually dealing with the non-nucleophilic porphyrin dication. But, as early as 1929, H. Fischer had realised that diacetylation of deuteroporphyrin-IX (Table 1) had to be carried out on a metal complex, such as the iron (III) derivative chelation with a metal ion which cannot be removed under the acid conditions of the subsequent reaction, effectively eliminates dication formation. A judicious choice of metal complex therefore needs to be made for any particular reaction. For example, though magnesium(II) produces an extremely reactive substrate for electrophilic substitution reactions, it is removed by contact with the mildest of acids and is, consequently, of little use for this purpose. 

Most tropolones give sparingly soluble, yellow or orange sodium salts, green cupric chelates, and colored ferric complexes. Although easily acetyl-ated or methylated and frequently precipitated by picric acid, tropolones only exceptionally react with carbonyl reagents. Electrophilic substitution reactions occur readily however, sulfonation or nitration is inhibited... 

The presence of chelating groups in those complexes is necessary to stabilize the intermediate aryl-palladium complex for isolation but it does not seem necessary to cause palladation. The chelating group does, however, tremendously accelerate the palladation. Aromatic compounds reactive to electrophilic substitution apparently undergo palladation with palladium acetate in acetic acid solution fairly readily at 100 °C or above. Of course, the arylpalladium acetates presumably formed, are not stable under these conditions, and they decompose very rapidly into biaryls and palladium metal 34,35,36) ag do aryl palladium salts prepared by the exchange route 24>. If the direct palladation is carried out in the presence of suitable olefins, arylation can be achieved, so far, however, only in poor yields, arid with concurrent loss of stereospecificity and formation of isomers and other side products 37.38). 

The distribution rates for iodination of monosubstituted benzene derivatives have been reported. Under conditions of thermodynamic control (elevated temperature), meta substitution is observed. Under conditions of kinetic control (room temperature), a significant preference for para substitution is observed for compounds containing oriha- puru-directing substituent groups. Ortho substitution results when chelation of TTFA with the directing substituent permits intramolecular delivery of the electrophile. For example, methyl benzoate gives almost exclusively or/ho-lhallation (95%). 

Aromatic compounds react with palladium(II) salts such as PdCOAc) and Na2PdCl4 via an electrophilic aromatic substitution process to give arylpalladium complexes. This type of reaction is most commonly observed with aromatic rings bearing a substituent that makes a fi e- or six-membered chelate ring with palladium in the metallation products (eq (87)) [118]. In this case, the electrophilic substitution occurs only at the ortho position to the chelating substituent. 

Alternatively, one of the metal-oxygen bonds in the acetylacetonate can cleave before or after electrophilic attack on the chelate ring that is undergoing cleavage, forming a five-coordinate intermediate. With the subsequent loss of a proton, a chelate ring with a 3-halo substituent is obtained. The trisacetylacetonates of Cr(III), Co(III), and Rh(III) were partially resolved on a 16-foot column of D-lactose hydrate. The optical activity of each of these chelates was measured before and after being subjected to a number of electrophilic substitution reactions. It was found that the substitution reactions did not cause total racemization, and therefore it was concluded that this alternative mechanism is unlikely (49). 

G.l.c. retention data over a ran of temperatures have been measured for Cr(hfa)3, Cr(tfa)3, and several other such chelates in three liquid phases and, together with other solution-phase data, have been used to show that the behaviour of these complexes in the liquid phase is determined solely by nonspecific van der Waals-type forces. " The electrophilic substitution reactions of fluorinated P-diketonato-chromium(iii) complexes have been studied under controlled conditions and the results obtained were shown to support the quasi-aromatic character of the six-membered chelate ring. Seven new tris(P-diketonato)chromium(iii) complexes have been prepared and characterized by magnetic, i.r., and electronic spectral studies. ... 

NH form e.g. 505). Most 4- and 5-hydroxy compounds of types (500) and (502) exist largely in these non-aromatic azolinone forms, although the hydroxyl form can be stabilized by chelation e.g. 506). The derived ambident anions react with electrophiles at O or C. Replacement of the hydroxyl group is sometimes possible provided electron-withdrawing groups are present as, for example, in 5-substituted 4-hydroxypyrazoles. 

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