Selectivity in acylation

Results obtained in the acylation of aromatic sulfonamides with acetic acid, in the presence of SnOTf based catalysts are presented in Table 48.4. The rate of the sulfonamide acylation follows the seqnence benzenesnlfonamide > p-nitrobenzenesulfonamide > />-methoxybenzenesnlfonamide, and is very sensitive towards the nature of the aromatic hydrogen substituent (the selectivity in acylated />-methoxybenzenesnlfonamide did not exceed 7% irrespective of the catalyst nature this corresponds to an approximate relative yield... 

The salt effects of alkali metal salts on reactivity and selectivity in acylation reactions were systematically studied by Kobayashi and coworkers [98]. In the presence of excess LiClO4 the Friedel-Crafls reaction proceeded most effectively with a catalytic amount of Al(OTf)3 to give acylation regioselectively at the 6 position of the naphthalene ring (Scheme 6.76). 

Table 1 Effects of catalysts on site-selectivity in acylation of octyl p d glucopyranoside OH ...

Scheme 10 Dependence of the distance between the NHNs and OH groups in the site-selectivity in acylation of (a) 26 and (b) 24...

Yoshida K, Shigeta T, Furuta T, Kawabata T (2012) Catalyst-controlled reversal of chemo-selectivity in acylation of 2-aminopentane-1.5-diol derivatives. Chem Commun 48 6981... 

Interesting results have been obtained in intramolecular acylation reactions involving pyrrole and thiophene derivatives. A muscone synthesis involves selective intramolecular acylation at a vacant a-position (Scheme 18) (80JOC1906). In attempts to prepare 5,5-fused systems via intramolecular acylation reactions on to a jS-position of a thiophene or a pyrrole, in some cases ipso substitution occurs with the result that rearranged products are formed (Scheme 19) (82TH30200). 

Table 10.10. Substrate and Position Selectivity in Friedel-Crafts Acylation Reactions...

It is thus apparent that the selectivity of a reagent toward thiophene and benzene can differ appreciably, and this difference in selectivity is also strongly noticeable in the proportions of 2- and 3-isomers formed. Although in certain reactions no 3-isomer has been detected, appreciable amounts have been found in other reactions. Thus 0.3% of the 3-isomer has been found in the chlorination of thiophene.- Earlier results indicated that 5-10% 3-nitrothiophene is formed in the nitration of thiophene and a recent gas-chromatographic analysis by Ostman shows that the mononitrothiophene fraction contains as much as 16% of the 3-isomer. It appears that gas-chromatographic analysis should be very useful for the detection of small amounts of 3-isomers in other substitution reactions. However, from routine analyses of IR spectra, it appears to the present author that the amount of 3-isomers formed in acylation, formylation, and bromina-tion of thiophene are certainly less than a few per cent. 

One particular feature of ionic liquids lies in their solvation properties, not only for hydrophobic compounds but also for hydrophilic compounds such as carbohydrates. Park and Kazlauskas reported the regioselective acylation of glucose in 99 % yield and with 93 % selectivity in [MOEMIM][BF4] (MOE = CH3OCH2CH2), values much higher than those obtained in the organic solvents commonly used for this purpose (Entry 18) [22] (Scheme 8.3-4). 

Introduction of the C-6 acyl side chain proceeded with only modest selectivity in the presence of l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 4-DMAP, giving a 3 2 mixture of C-6 and C-7 acylated products (Scheme 26).60 However,... 

One of the simplest ways to prepare a chitin gel is to treat chitosan acetate salt solution with carbodiimide to restore acetamido groups. Thermally not reversible gels are obtained by AT-acylation of chitosans N-acetyl-, N-propionyl- and N-butyryl-chitosan gels are prepared using 10% aqueous acefic, propionic and bufyric acid as solvents for treatment with appropriate acyl anhydride. Both N- and 0-acylation are found, but the gelation also occurs by selective AT-acylation in the presence of organic solvents. 

For a review of selectivity in this reaction, that is, which group preferentially attacks when the reagent contains two or more, see Olah, G.A. in Olah, Ref. 240, vol. 1, p. 881. This review also covers the case of alkylation vs. acylation. 

Selective acylations of many carbohydrates have been achieved by the azolide method. A short review on acylation of carbohydrates is given in reference [188]. Of special interest is the selectivity of acylation by azolides, as demonstrated by the following examples. 

A few further general examples of zinc catalytic activity or reactivity include the following. Other zinc-containing systems include a zinc phenoxide/nickel(0) catalytic system that can be used to carry out the chemo- and regioselective cyclotrimerization of monoynes.934 Zinc homoenolates have been used as novel nucleophiles in acylation and addition reactions and shown to have general utility.935,936 Iron/zinc species have been used in the oxidation of hydrocarbons, and the selectivity and conditions examined.362 There are implications for the mechanism of metal-catalyzed iodosylbenzene reactions with olefins from the observation that zinc triflate and a dizinc complex catalyze these reactions.937... 

One or both carbonyls in /3-diketones can be reduced, as well as the carbonyl function in acyl cyanides (210). Similar treatment of a,/3-unsat-urated ketones and aldehydes can lead to the saturated carbonyl products via selective reduction of the olefinic bond (207, 208, 210) see Eq. (51) in Section III,A,4. Some terpenes (a- and /3-ionone, pulegone) were reduced in this way (208). Platinum(II) phosphine complexes have been used for the hydrosilylation of saturated ketones and could be used for the reduction (211). 

Ethoxycarbonyl chloride is, by virtue of resonance involving the ester function, less reactive than acetyl chloride, and the reagent has found application for selective O-acylation in the steroid field.34 With this reagent, methyl 4,6-O-benzylidene-a-D-glucopyranoside yielded35 2- and 3-esters in the ratio 24 1, and the related benzyl-thiocarbonyl chloride gave the 2-ester in 58% yield.36... 

Lack of selectivity in the reaction of the /3-D-glucoside derivative with one molar equivalent of benzylthiocarbonyl chloride has also been noted 40% of the 2,3-diester and 40% of the starting material were isolated.40 Similarly, unimolar benzoylation of phenyl 4,6-0-benzylidene-/3-D-glucopyranoside gave only 9% of the 3-ester, together with 47% of the 2,3-diester.41 Acylation of benzyl 4,6-0-benzylidene-/8-D-glucopyranoside with acetic anhydride-pyridine-pyridine hydrochloride yielded,42 in contrast to the reaction with the... 

Acyl azides show selectivity for acylation at secondary (rather than primary) hydroxyl groups in nucleosides. Thus, on reaction with an excess of N-(benzyIoxycarbonyl)glycyIglycyl azide in 1,4-dioxane-water at 8° and pH 9, adenosine gave the 2 (3 )-0-(aminoacyl) and 2, 3 -di-0-(aminoacyl) derivatives.183 Furthermore, adenosine and uridine were converted into a variety of 2 (3 )-esters of aromatic amino acids by reaction with the appropriate acyl azide.184... 

The symmetrical anhydride is less reactive and consequently more selective in its reactions than the O-acylisourea. Although the latter can acylate both N- and O-nucleophiles, the symmetrical anhydride will only acylate V-nuclcophilcs. This means that the hydroxyl groups of the side chains of serine, threonine, and tyrosine that have not been deprotonated are not acceptors of the acyl group of the symmetrical anhydride. An additional feature of this approach to carbodiimide-mediated reactions is that it avoids a possible side reaction between the carbodiimide and the iV-nucleophilc, which gives a trisubstituted guanidine [(C6HuN)2C=N-CHR5CO-... 

A further step towards improved selectivity in aldol condensations is found in the work of David A. Evans. The work of Evans [3a] [14] is based in some early observations from Meyers laboratory [15] and the fact that boron enolates may be readily prepared under mild conditions from ketones and dialkylboron triflates [16]. Detailed investigations with Al-propionylpyrrolidine (31) indicate that the enolisation process (LDA, THE) affords the enolate 32 with at least 97% (Z>diastereoselection (Scheme 9.8). Finally, the observation that the inclusion of potential chelating centres enhance aldol diastereoselection led Evans to study the boron enolates 34 of A(-acyl-2-oxazolidones (33), which allow not only great diastereoselectivity (favouring the 5yn-isomer) in aldol condensations, but offer a possible solution to the problem of enantioselective total syntheses (with selectivities greater than 98%) of complex organic molecules (see below, 9.3.2), by using a recyclisable chiral auxiliary. 

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