Catalysis nucleophilic attack

This thesis has been completely devoted to catalysis by relatively hard catalysts. When aiming at the catalysis of Diels-Alder reactions, soft catalysts are not an option. Soft catalysts tend to coordinate directly to the carbon - carbon double bonds of diene and dienophile, leading to an activation towards nucleophilic attack rather than to a Diels-Alder reaction . This is unfortunate, since in water, catalysis by hard catalysts suffers from a number of intrinsic disadvantages, which are absent for soft catalysts. 

As we ve just seen nucleophilic ring opening of ethylene oxide yields 2 substituted derivatives of ethanol Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions Other nucleophilic ring openings of epoxides like wise give 2 substituted derivatives of ethanol but either involve an acid as a reactant or occur under conditions of acid catalysis... 

Section 16 13 Under conditions of acid catalysis nucleophiles attack the carbon that can better support a positive charge Carbocation character is developed m the transition state... 

The acid-catalyzed additions of bromide and chloride ion to thiiranes occurs readily, with halide preferentially but not exclusively attacking the most substituted carbon atom of the thiirane. The reaction of 1-substituted thiiranes with acetyl chloride shows a slight preference for halide attack at the less substituted carbon atom (80MI50601). For further discussion of electrophilic catalysis of halide ion attack see Section 5.06.3.3.2. The reaction of halogens with thiiranes involves electrophilic attack on sulfur (Section 5.06.3.3.6) followed by nucleophilic attack of halide ion on carbon. 

We should distinguish between the phrases nucleophilic attack and nucleophilic catalysis. Nucleophilic attack means the bond-forming approach by an electron pair of the nucleophile to an electron-deficient site on the substrate. In nucleophilic catalysis this results in an increase in the rate of reaction relative to the rate in the absence of the catalyst. However, nucleophilic attack may not result in catalysis. Thus, if methylamine is reacted with a phenyl acetate, the reaction observed is amide formation, not hydrolysis, because the product of the nucleophilic attack is more stable than is the ester to hydrolysis. 

The rate equation for this reaction is expected to be v = A [RCOOR [MeNH2], but it is possible for terms like A [RCOOR ][MeNH2] or A "[RCOOR ] [MeNH2j[MeNH3 ] to be present. The k term could be a general base catalysis or nucleophilic attack, the k" term, general acid catalysis of nucleophilic attack. 

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. 

We have disclosed that the ligands 4c, 10, and 77, when complexed with a metal ion such as Zn2 +, Ni2+, or Co2+, become highly active toward the hydrolysis of p-nitrophenyl picolinate (7). The catalysis is most likely to occur through formation of a ternary complex in the transition state or in reactive intermediates. The metal ion in such a complex serves to activate the ligand hydroxyl group for nucleophilic attack and to orient the substrate into a favorable position to undergo the reaction. 

The preparation of mono- and di-tm-butylcyclopentadienes 1 and 2 starting from monomeric cyclopentadiene was reported first in 1963 [23]. It was noted that the nucleophilic attack of the cyclopentadienide anion on ferf-alkyl halide has to compete with elimination reaction giving isobutene. The yield of the di- and tri-fer/-butylcyclopentadienes 2 and 3 was therefore reported to be modest to low [23, 24], Recently an elegant improvement for this synthesis using phase transfer catalysis was presented (Eq. 1), but the availability of the tri-substituted derivative... 

Similar reaction mechanisms, involving general base and metal ion catalysis, in conjunction with an OH nucleophilic attack, have been proposed for thermolysin (Ref. 12) and carboxypeptidase A (Refs. 12 and 13). Both these enzymes use Zn2+ as their catalytic metal and they also have additional positively charged active site residues (His 231 in thermolysin and... 

Yamamoto Y,Nakamura I (2005) Nucleophilic Attack by Palladium Species. 14 211-240 Yasuda H (1999) Organo Rare Earth Metal Catalysis for the Living Polymerizations of Polar and Nonpolar Monomers. 2 255-283 Yasuda N, see King AO (2004) 6 205-246... 

In the pH range 2—3.5 the phosphonate (78) hydrolyses with loss of ROH at approximately 10 times the rate of comparable esters lacking the vicinal oxime function or in which this function is methylated on oxygen. An intramolecular general-acid catalysis mechanism was proposed, but it was not possible to exclude entirely an intramolecular nucleophilic attack at phosphorus. Intramolecular attack by the vicinal dimethylamino-group takes place preferentially at carbon rather than phosphorus in the phos-phonofluoridate (79). ... 

The second step, nucleophilic attack of an alcohol or phenol on the activated carboxylic acid RCOIm (carboxylic acid imidazolide), is usually slow (several hours), but it can be accelerated by heating[7] or by adding a base[8] [9] such as NaH, NaNH2, imidazole sodium (ImNa), NaOR, triethylamine, diazabicyclononene (DBN), diazabicycloimdecene (DBU), or /7-dimethylaminopyridine to the reaction mixture (see Tables 3—1 and 3—2). This causes the alcohol to become more nucleophilic. Sodium alcoholate applied in catalytic amounts accelerates the ester synthesis to such an extent that even at room temperature esterification is complete after a short time, usually within a few minutes.[7H9] This catalysis is a result of the fact that alcoholate reacts with the imidazolide very rapidly, forming the ester and imidazole sodium. 

It is difficult to effect attack on the carbonyl carbon atom of RC02H, (171), with nucleophiles of the general type Y , as they commonly remove proton instead, and the resultant RCO20 is then insusceptible to nucleophilic attack. Weaker nucleophiles of the form YH, e.g. ROH, do not suffer this inability, but their reactions with the relatively unreactive carbonyl carbon atom of RC02H are slow. The carbonyl character may be enhanced by protonation, however, i.e. by acid catalysis in, for example, esterification [(171) — (172)] ... 

Acid catalysis assists epoxide ring opening by providing a better leaving group (an alcohol) at the carbon atom undergoing nucleophilic attack. 

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