Ester group transfer, base-catalyzed

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

For acylations with reactive esters, such as formate or oxalate (see Section 3.6.4.5), sodium alkoxides are still the bases of choice, but sodium hydride, dimsyl sodium, sodium or potassium amide or sodium metal have all been used for the in situ generation of the enolate anion. A typical example is shown in Scheme 47. Acylation by esters results in the production of 1 equiv. of the alkoxide ion, along with the p-dicarbonyl compound proton transfer then results in the production of the conjugate base of the dicarbonyl compound. This process normally leads to the more stable anion in the acylation of an unsymme-trical ketone. The acyl group thus becomes attached to the less-substituted a-position of the ketone. The less stable 0-acylated products are normally not observed in such reversible base-catalyzed reactions. Methyl alkyl ketones are normally acylated on the methyl group where both a-carbons are substituted to the same extent, acylation occurs at the less-hindered site. Acylation is observed only rarely at a methine carbon as the more stable p-diketone enolate cannot be formed. 

Glucose-phosphate isomerase is one of the best studied enzymes catalyzing the interconversion of aldo- and ketohexose phosphates. An active site carboxyl group is a possible candidate for the base catalyzing the intramolecular proton transfer reaction. The affinity label 1,2-anhydro-D-mannitol 6-phosphate (8) inactivates the enzyme by forming an ester linkage between C-l of the affinity label and an active site carboxyl of a glutamic acid residue (98). 

Risse and S. Breunig, S. Transition metal catalyzed vinyl addition polymerizations of norbor nene derivatives with ester groups, Makromol. Chem. 193, 2915 (1992) C. Mehler and M. Risse, Addition polymerization of norbornene catalyzed by paUadium(2+) compounds. A pol3mierization reaction with rare chain transfer and chain termination, Macromol. 25, 4226 4228 (1992) R.G. Schulz, The chemistry of palladium complexes. III. The polymerization of norbornene systems cat alyzed by palladium chloride (1), Polym. Lett. 4, 541 (1966) C. Tanielian, A. Kiennemann, and T. Osparpucu, Influence de differents catalyseurs a base d elements de transition du groupe VIII sur la polymerisation du norbornene, Can. J. Chem. 57, 2022 (1979) A. Sen and T. W. Lai, Cat alytic polymerization of acetylenes and olefins by tetrakis(acetonitrile)paUadium(II) ditetrafluorobo rate, Organometallics 1, 415 (1982) C. Mehler and W. Risse, Pd(II) catalyzed polymerization of norbornene derivatives, Makromol. Chem. Rapid Commun, 12, 255 (1991). 

Based on this biological approach, the research group of MacMillan [11] and List [74] reported at the same time the reduction of enals catalyzed by chiral imidazolines 26. In both cases the key to success is the use of Hantzsch ester (92) as reducing agent. The Hantzsch ester can transfer simultaneously a hydride and a proton to the enal in a 1,4-addition process. 

Self-Condensation. Use of Electron-Release Caialyst (Cannizzaro reaction). Fundamentally, the base-catalyzed Cannizzaro reaction involves the reaction between two molecules of an aldehyde containing no a-hydrogen atoms. The overall result is the transfer of one aldehyde hydrogen to another aldehyde group, thus producing two radicals that could combine to form an ester. The presence of the basic catalyst prevents the ester formation, and an alcohol and a metal carboxylate result. The mechanism can be shown as follows ... 

The alternative selective cleavage of the allyl ester was achieved by Pd(0)-catalyzed allyl transfer. Because the Fmoc group is sensitive to morpholine, a very weak base must be used as the allyl-trapping nucleophile. IV-Methyl aniline was favorable, and its use as a scavenger nucleophile gave rise to the acid 29 in a high yield. 

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