Esters reactivity enhancement

With the realization that the cycloamyloses form stable monomolecular inclusion complexes in solution came the idea that the inclusion process might affect the reactivity of an organic substrate. This idea was initially pursued by Cramer and Dietsche (1959b) who discovered that the rates of hydrolysis of several mandelic acid esters are enhanced by the cycloamyloses. More recently, the inclusion process has been shown to exert both accelerating and decelerating effects on the rates of a variety of organic reactions. The remainder of this article will be devoted to a discussion of these reactions in an attempt to review, compare, and unify the many intriguing facets of cycloamylose catalysis. 

Contrary to conventional reactivity arguments, which imply that substitution at carbonyls by electronegative atoms reduces electron density at the carbonyl carbon and hence promotes addition to carbonyls, a systematic study of 13C NMR shift data for ester carbonyls shows that electron density is actually greater at such carbons (reactivity enhancement is actually due to destabilisation of the ground states of the esters by the electron-withdrawing substituents).132,133 Our observations are in line with those of Neovonen et al. Electron-withdrawing nitrogen in... 

It was found that the transesterification of dimethyl H-phosphonate with 1,2-propane-diol yields 4-methyl-2-hydro-2-oxo-l,3,2-dioxaphospholane [56]. Obviously, the first stage of the reaction furnished methyl-2-hydroxypropyl H-phosphonate. Subsequent intramolecular transesterification of the methyl-2-hydroxypropyl phosphonate yielded 4-methyl-2-hydro-2-oxo-l,3,2-dioxaphospholane. The specific reactivity of these esters of H-phosphonic acid is determined by the presence of a P-hydroxyl gronp. The role of the P-hydroxyl gronp may be regarded as an intramolecular catalysis. The reactivity enhancement of P-hydroxylethyl esters of H-phosphonic acid probably can be explained through hydrogen bonding, which favors the intramolecular transesterification reaction. 

Electronic effects within the acid portion of the precursor have also been utilized for enhanced reactivity. The 4-hydroxybenzenesulfonate ester of octanoyloxyacetic acid, (15), undergoes efficient perhydrolysis at lower pHs because of the activation of the susceptible carbonyl by the beta-oxygen of the hydrophobic tail (100). 

If flammabiHty is an issue, Hquid chloroprene polymers (eg, Du Pont PB or Denki LCR-H-050) can be used. They cocure and, for that reason, are nonvolatile and nonextractable. They are particularly useful in hard compounds where they do not detract from physical properties as much as nonreactive plastici2ers (132,133). Methacrylate esters have been used as reactive plastici2ers (qv). Por example, hexa(oxypropylene)glycolmonomethacrylate can be used as a reactive plastici2er to enhance flex life without increasing hardness (134). 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

For the ordinary Diels-Alder reaction the dienophile preferentially is of the electron-poor type electron-withdrawing substituents have a rate enhancing effect. Ethylene and simple alkenes are less reactive. Substituent Z in 2 can be e.g. CHO, COR, COOH, COOR, CN, Ar, NO2, halogen, C=C. Good dienophiles are for example maleic anhydride, acrolein, acrylonitrile, dehydrobenzene, tetracya-noethylene (TCNE), acetylene dicarboxylic esters. The diene preferentially is of the electron-rich type thus it should not bear an electron-withdrawing substituent. 

Table 8 indicates substrate specifity as measured by rate enhancement. The most reactive ester is 1 which undergoes rate enhancement of more than 104 fold in the presence of 2 x 10-4 M of catalyst at pH 7.05. 

Alcohols react with carboxylic acids to give esters, a reaction that is common in both the laboratory and living organisms. In the laboratory, the reaction can be carried out in a single step if a strong acid is used as catalyst. More frequently, though, the reactivity of the carboxylic acid is enhanced by first converting it into a carboxylic acid chloride, which then reacts with the alcohol. We ll look in detail at the mechanisms of these reactions in Chapter 21. 

Racemic l-methyl-2-butenylboronates (E)- and (Z)-3 may be prepared selectively via reactions of the l-methyl-2-butenyl Grignard reagent with the appropriate borate ester. Use of triisopropyl borate provides a 96 4 mixture of (E)-3l(Z)-3 on a 0.36 mol scale15. Use of a bulkier borylating agent, such as 2-isopropyloxy-4,4,5,5-tetramethyl-l,3,2-dioxaborolane, reverses the selectivity, enabling a 91 9 mixture of (Z)-3/( )-3 to be obtained on a 0.5 mol scale. The diastereomeric purity of this mixture may be enhanced to 95 5 by treatment with 0.15 equivalents of benzaldehyde, since ( )-l-mcthyl-2-butenylboronatc ( )-3 is more reactive than (Z)-3. Repetition of this process provides (Z)-3 that is 98% isomerically pure. 

Especially for large-scale work, esters may be more safely and efficiently prepared by reaction of carboxylate salts with alkyl halides or tosylates. Carboxylate anions are not very reactive nucleophiles so the best results are obtained in polar aprotic solvents45 or with crown ether catalysts.46 The reactivity order for carboxylate salts is Na+ < K+ < Rb+ < Cs+. Cesium carboxylates are especially useful in polar aprotic solvents. The enhanced reactivity of the cesium salts is due to both high solubility and minimal ion pairing with the anion 47 Acetone is a good solvent for reaction of carboxylate anions with alkyl iodides48 Cesium fluoride in DMF is another useful... 

Lewis acid strength and hardness of the lithium cation. Both LiBH4 and Ca(BH4)2 are more reactive than sodium borohydride. This enhanced reactivity is due to the greater Lewis acid strength of Li+ and Ca2+, compared with Na+. Both of these reagents can reduce esters and lactones efficiently. 

Diborane also has a useful pattern of selectivity. It reduces carboxylic acids to primary alcohols under mild conditions that leave esters unchanged.77 Nitro and cyano groups are relatively unreactive toward diborane. The rapid reaction between carboxylic acids and diborane is the result of formation of a triacyloxyborane intermediate by protonolysis of the B-H bonds. The resulting compound is essentially a mixed anhydride of the carboxylic acid and boric acid in which the carbonyl groups have enhanced reactivity toward borane or acetoxyborane. 

Rhodium compounds have also been used as catalysts since the late 1960s and mechanistic studies date from the 1970s.534,578-582 The binuclear rhodium complex [(Ph3P)4Rh2(//-OH)2] was found to be an effective catalyst for the reductive carbonylation of nitrobenzenes to carbamate esters. Electron-withdrawing groups at the para-position enhance the reactivity of the substrate.583... 

C]-Cyanide is a secondary precursor, produced from 11C02, but nevertheless as a result of microwave-enhanced accelerations can be used to label a wide range of amines, acids, esters and alcohols. Such an example is illustrated in Scheme 13.12 [95-98]. Reactions with less reactive substrates can be achieved by increasing the polarity of the reaction medium through the addition of various salts. 

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