Monoacylation selective

A number of examples of monoacylated diols produced by enzymatic hydrolysis of prochiral carboxylates are presented in Table 3. PLE-catalyzed conversions of acycHc diesters strongly depend on the stmcture of the substituent and are usually poor for alkyl derivatives. Lipases are much less sensitive to the stmcture of the side chain the yields and selectivity of the hydrolysis of both alkyl (26) and aryl (24) derivatives are similar. The enzyme selectivity depends not only on the stmcture of the alcohol, but also on the nature of the acyl moiety (48). 

The low condensation of diacyl chloride and bis-orf/zo-aminophenol gave a polyhydroxy amide that was submitted to a thermal dehydration.185 187 The two functions of an aminophenol could be acylated, and the question of chemose-lective acylation has been discussed.188 The problem is not O-acylation versus N-acylation because the N-acylated product is tire more stable isomer, but the question is how to control N-monoacylation versus diacylation that could reduce the molecular weight. It has been shown that the condensation in the presence of inorganic salt (LiCl) in NMP gives selectively the N-monoacylated... 

Monoalkylation of a vic-glycol.1 Selective monoalkylation or monoacylation of the vic-glycol group of dimethyl L-tartrate is possible by conversion to the O-stannylene acetal (1) by reaction with dibutyltin oxide. The acetal is converted selectively to a mono derivative (3) by reaction with an alkyl halide or acyl chloride (excess) and CsF (about 2 equiv.). KF or Bu4NF are less effective than CsF. 

Rodens, S., Organotin-mediated monoacylation of diols with reversed chemoselectivity. Mechanism and selectivity. J. Org. Chem. 1996,61, 5257-5263. 

It is possible to obtain selective monoacylation even if the heteroaromatic base has more free reactive positions, by taking advantage of the protonation equilibria of the starting base and the reaction products. Thus with 4-cyanopyridine, which has two free reactive positions, the introduction of an acyl group in position 2 decreases the basic character and therefore allows selective monoacylation by the precipitation of the unprotonated reaction product. 

Fatty acids of sugars are potentially useful and fully green nonionic surfactants, but the lipase-mediated esterification of carbohydrates is hampered by the low solubility of carbohydrates in reaction media that support lipase catalysis in general. Because the monoacylated product (Figure 10.8) is more soluble in traditional solvents than is the starting compound, the former tends to undergo further acylation into a diester. In contrast, the CaLB-catalyzed esterification of glucose with vinyl acetate in the ionic liquid [EMIm][BF4] was completely selective. The reaction became much faster and somewhat less selective when conducted in... 

Dehydration of monoacylated diamines using POCl3 yielded substituted imidazolines 16 and 19 (Fig. 5). Selective acylation of the primary amino group of the diamines 14 and 17 was successfully achieved using a... 

Unsymmetric diamines can sometimes be acylated selectively at one amino group only, if one of the amino groups is sterically or electronically deactivated. If the difference in reactivity is only small, acylating agents of low reactivity will usually be required. Some polyamino heteroarenes can be monoacylated or monoalkylated with astonishingly high regioselectivity (Scheme 7.13), which is, however, difficult to predict. 

The monoacylation of symmetrical diols has been extensively investigated, and several useful methods have been developed. 1,2-Diols can be monoacylated readily, presumably because the product is acylated more slowly than the starting diol (Scheme 10.4). A variety of catalysts, for example lanthanide salts [10, 11], zeolites [12, 13], and tin derivatives [14, 15] have been used to further improve the selectivity of this reaction. Orthoesters have also been successfully used as acylating agents for the monoacylation of 1,2-diols [16],... 

Diols can also be selectively monoacylated by treatment with an acylating agent of low reactivity (vinyl, 2,2,2-trifluoroethyl, phenyl, or ethyl esters) in the presence of catalytic amounts of an esterase (Scheme 10.8) [27]. Surprisingly, these enzymatic... 

Clarke, P. A. Selective monoacylation of meso-and C2-symmetric 1,3- and 1,4-diols. Tetrahedron Lett. 2002, 43, 4761 1763. 

Ogawa, H. Amano, M. Chihara, T. Facile and highly selective monoacylation of symmetric diols adsorbed on silica gel with MeCOCl. Chem. Commun. 1998, 495—496. 

Green, J. Woodward, S. Selective monoacylation of 2,2 -binaphfhol as a route to new monothiobinaphthol-based Cu catalysts for conjugate addition. Synlett 1995, 155—156. 

J. F. Wang, T. Selective monoacylation of symmetrical diamines via prior complexation with boron. Org. Lett. 2003, 5, 3399-3402. 

The selective enzyme-catalyzed acylation of carbohydrates is of great interest, as of carbohydrates fatty acid esters of carbohydrates have important applications in detergents, cosmetics, foodstuff, and pharmaceuticals because of their surface-active properties. Monoacylated sugars have been synthesized by lipase-catalyzed transesterifications of activated esters in pyridine and by protease-catalyzed esterifications in DMF. A most remarkable new development... 

By contrast, however, 3,5-diamino-l,2,4-thiadiazoles are selectively converted into amides and sulfonamides in good yields. Thus, acetylation of 3,5-diamino-l,2,4-thiadiazole (53) with excess acetic anhydride yields the symmetrical derivative (133) whereas under similar conditions 3-amino-5-methylamino-l,2,4-thiadiazole and 3,5-diarylamino-l,2,4-thiadiazoles (65AHC(5)119) produce the monoacylated derivatives (134) and (135), respectively. Sulfonylation also results in the preferential formation of the 3-sulfonamides but reaction with excess reagent eventually produces the 3,5-disubstituted derivatives (136) and (137) in good yields (65AHC(5)119). 

The monoacylated derivative (6"-0-butyrate) was detected as the major product by H PLC analysis for all enzymatic reactions, while a diacylated derivative was also detected and confirmed by MS analysis [17]. As it can be seen in Table 9.3, higher regioselectivity of the process was observed in [bmim]BF4 than in [bmim]PF,5, while the selectivity was even lower in acetone. The lower regioselectivity of the enzymatic acylation of polyhydroxylated compounds in [bmim]PF,5 as well as in the organic solvent could be related to the lower solubility of unmodified phenolic substrates in these media, compared to that of their monoacylated derivatives [5, 16, 17]. On the other hand, the enhanced solubility of phenoHc substrates in [bmim]BF4 could explain the increased regioselectivity observed in this ionic liquid. 

The silver-catalyzed decarboxylation of a-oxo acids (carboxylic acids " ) by peroxy-disulfate leads to acyl " (alkyl radicals, which can effect selective homolytic acylation (alkylation of quinoxaline. This procedure is effective in monoacylation when multiple positions of high nucleophilic reactivity are available in the heterocyclic ring. " ... 

While most of the chemistry discussed in this chapter has been developed in the past decade, several important methods have withstood the test of time and have made important contributions in areas such as natural product synthesis. Methods such as cuprate acylation and the addition of organolithiums to carboxylic acids have continued to enjoy widespread use in organic synthesis, whereas older methods including the reaction of organocadmium reagents with acid halides, once virtually the only method available for acylation, has not seen extensive utilization recently. In the following discussion, we shall be interested in cases where selective monoacylation of nonstabilized carbanion equivalents has been achieved. Especially of concern here are carbanion equivalents or more properly organometallics which possess no source of resonance stabilization other than the covalent carbon-metal bond. Other sources of carbanions that are intrinsically stabilized, such as enolates, will be covered in Chapter 3.6, Volume 2. 

Hydroxylamines usually react with acid chlorides to give mixtures of N-, O- and poly-acylated products. In contrast reaction of tris(trimethylsilyl)hydroxylamine (65) with aliphatic acid chlorides leads selectively under /V-monoacylation to the corresponding hydroxamic acids (66 equation 26). While di-phenylphosphinic chloride (68) is attacked by the oxygen of hydroxylamine to yield 0-(diphenylphos-phinyl)hydroxylamine (67 Scheme 13), A -(diphenylphosphinyl)hydroxylamine (69) can be obtained by treatment of diphenylphosphinic chloride with 0-trimethylsilylhydroxylamine followed by removal of the silyl blocking group (Scheme 13). 0-Acylation of arylhydroxylamines can be achieved with acyl cyanides. ... 

Regioselective acylations of polyhydroxylated compounds such as carbohydrates, glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and proteases [13, 20]. One example is the Candida antartica lipase (immobilized on acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giving selectively the 2-C)-acetate 2 (eq. (1)). Using vinyl acetate for this transesterification the reaction was irreversibly pushed to the product side, since the liberated enol instantaneously isomerizes to acetaldehyde [21]. The sometimes unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or -fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed for the quasi-irreversible reaction courses. 

Acylation of 3,4,7,8-tetramethylglycoluril by the method of Sun and Harrison [34] leads to the monoacyl derivatives, which can be further selectively acylated with lithium diisopropylamide (LDA) and acyl chlorides. The resulting symmetrical or asymmetrical diacyl compounds undergo a base-catalyzed acyl transfer reaction. Consequently, the glycoluril acts as a temporary template that facilitates a condensation between acyl units. The absence of O-acylation products is explained by chelation of the lithium by the intermediate enolate. 

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