Selective acetylations

Acetates. Because of the significant interest in selective acetylation reactions of sucrose, the need for a convenient and unambiguous method of identification has been recognized (34,35). The position of an acetyl group in a partially acetylated sucrose derivative can be ascertained by comparison of its H-nmr acetyl methyl proton resonances after per-deuterioacetylation with those of the assigned octaacetate spectmm. The synthesis of partially acetylated sucroses has generally been achieved either by way of selectively protected derivatives such as trityl ethers and cychc acetals or by direct selective acetylation and deacetylation reactions. 

Acetylsucrose [63648-81-7] has been prepared in 40% yield by direct acetylation of sucrose using acetic anhydride in pyridine at 40° C (36). The 6-ester has subsequently been obtained in greater than 90% yield, by way of 4,6-cycHc orthoacetate. Other selective methods for the 6-acylated derivatives include the use of alkyl tin reagents such as dibutyl tin oxide (37) and of dibutyl stannolane derivatives (38). Selective acetylation of sucrose by an enzymic process has also been described. Treatment of sucrose with isopropenyl acetate in pyridine in the presence of Lipase P Amano gave, after chromatography, 6-0-acetylsucrose (33%) and 4/6-di-O-acetylsucrose (8%). The latter compound has been obtained in 47% yield by the prolonged treatment (39). 

Pentafluorophenyl acetate is a highly selective acetylating reagent, useful for acetylations at hydroxyl and amino groups under mild conditions When applied to the acetylation of amino alcohols, it gives selective formation of H acetyl derivatives at room temperature and M,0 diacetylated products under moderate heating in the presence of triethylamine [149]... 

Whereas treatment of ( )-29 with camphanic chloride achieves the selective esterification of the hindered C-9 hydroxyl group, the action of acetic anhydride on (+)- 29 results in the equally selective acetylation of the C-10 hydroxyl group It is not clear to what this discrepancy should be attributed, so we will not offer a rationalization here. This unexpected result is, however, most gratifying because TPAP-NMO oxidation27 of the remaining C-9 hydroxyl furnishes keto acetate 6 (88 % overall yield). You will note that the contiguous keto and acetate functions in 6 are both expressed in the natural product. 

Selective acetylations of hydroxyalkyl phenols by 1-acetylpyridinotriazolide were carried out with excellent results in 1 N aqueous sodium hydroxide solution 1283... 

Selective acetylation of the methylester of A acetyl-jS-D-neuraminic acid methyl-glycoside produces, roughly in a one to one ratio and in 74% yield, the two acetylation products shown 1191 ... 

For the syntheses of a large number of deoxypolypropionates requiring a,o -diheterofunctional intermediates, a couple of novel protocols, that are complementary with the conventional protocol using so-called Roche ester, have been developed (Scheme 33).199,200 More recently, the combined use of the ZACA reaction and the lipase-catalyzed kinetic resolution via selective acetylation has been shown to be practically attractive for the synthesis of enantio-merically pure compounds that cannot be readily purified by ordinary chromatography or recrystallization199,201 (Scheme 34). 

Compound 168 is a key intermediate for the synthesis of prostaglandin or prostacyclin compounds. Scheme 5-50 shows its preparation via a retro Diels-Alder reaction and subsequent treatment. Using enzyme-catalyzed acetylation, Liu et al.80 succeeded in the asymmetric synthesis of enantiomerically pure (+)/ (—)-156 and (—)-168 from the meso-Aio 164. When treated with vinyl acetate, meso-diol 164 can be selectively acetylated to give (+)-165 in the presence of Candida cyclindracea lipase (CCL). The yield for the reaction is 81%, and the enantiomeric excess of the product is 98.3%. 

CALB was again the favoured catalyst, selectively acetylating the pro-S alcohol (Scheme 1.47). To obtain the desired (5)-monoacetate in sufficient enantiopurity, the reaction was not terminated when all starting material had been consumed, but allowed to run a little further to transform a small portion of monoacetate to diacetate. This resulted in enantioenrichment of the desired (5")-monoacetate by the preferential acetylation of the unwanted (/f)-monoacetate to prochiral diacetate. 

A novel continuous-flow SCCO2 process for the kinetic resolution of 1-phenyethanol enantiomers (Figure 30) using Novozym 435 immobilized enzyme from Candida antarctica was described by Matsuda et al. [51], The lipase enzyme, selectively acetylated the R)-alcohol component. A mixture of starting material and vinyl acetate was passed through the enzyme with supercritical carbon-dioxide (Figure 31). The reaction zone was pressurized and heated, so the reaction could be performed imder supercritical conditions, synthesizing the desired (i )-acetate with 99.7% ee. and 47% yield. 

Coriolin (689), a metabolite of the Basidiomycete Coriolus consors, has attracted widespread interest because of its unusual anti-tumor activity and highly functionalized triquinane structure. Accordingly, a number of syntheses of689 have appeared on the scene. One of the earliest, due to Tatsuta, et al., begins with epoxide 690, whose preparation had been earlier realized in connection with their work on hirsutine (see Scheme LXIII). Deoxygenation of 690, hydrolysis, and cis-hydroxy-lation provided keto triol 691 (Scheme LXXII) The derived acetonide was transformed via 692 into tetraol 693 which could be selectively acetylated and dehydrated on both flanks of the carbonyl group. Deacetylation of 694 followed by epoxidation completed the synthesis. 

The 4-amino group of 31 was selectively acetylated under acidic conditions using acetic anhydride (1 equiv.) and methanesulfonic acid (1 equiv.) in acetic acid and f-butylmethyl ether to give 32. Deallylation of 32 using 10% Pd/C in the presence of ethanolamine in refluxing ethanol proceeded as before to afford 1, which was converted to the phosphate salt in 70% yield with high purity (99.7%). The overall yield of 1 from epoxide 23 was 35-38%. 

A range of enantiomerically pure (R)- and (S)-, (E)- or (Z)-oxime ethers of 2,3-dihydro[l,8]naphthyridine have been prepared from 2-amino-6-methylpyridine <2000EJM815>. The selective acetylation of the same compounds in the 1-, 4-, or 1,4-positions has also been reported <1996JHC1185>. 

A limitation on resolution is that the desired enantiomer is only half of the racemic starting material. Kurt Faber of the University of Graz has reported (Org. Lett. 2004,6,5009) a clever solution to this problem. On exposure of the sulfate 1 of a secondary alcohol to aerobically grown whole cells of Sulfolobus acidocaldarius DSM 639, one enantiomer of the sulfate was smoothly converted into the other enantiomer of the starting alcohol. The enzyme consumed the more reactive enantiomer > 200 times more rapidly than the less reactive enantiomer. For the last bit of conversion, the of the product alcohol will of course fall. One solution to this would be to run the reaction near 50% conversion, then hydrolyze the mixture to give high product alcohol 2. Exposure of the mixture to a lipase that selectively acetylated the minor enantiomer would then polish the of 2. 

Thus, to confirm the location of the two hydroxyl groups in inumakilactone A (28), this compound was selectively acetylated, and its diacetate selectively saponificated. The thus obtained 15- and 3-monoacetates were oxidized to the corresponding ketones with Jones reagent (Scheme 3) [40],... 

It is sometimes necessary either to acetylate the hydroxyl group first and then methylate this ester or to protect one hydroxyl group while another is alkylated, for instance. A promising technique of selective acetylation is therefore of interest when 5,7-dihy-droxyisoflavone (538) is heated with acetic anhydride-pyridine, the 7-acetoxy derivative is formed, but acetic anhydride-perchloric acid yields the 5-acetoxy isomer (79CC264). 

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