Acylation selective

Akylsilanes are more reactive than vinylskanes in Friedel-Crafts reactions, as shown in the selective acylation of 2,3-disilylalkenes. The akylsilanes, a-skyloxyakyltrialkylsilanes, have been used as enolate equivalents in the preparation of 1,4-diketones (178). The mild reaction conditions required for these reactions tolerate many other functional groups, providing valuable synthetic routes. 

In a similar way, several cephalosporins have been hydrolyzed to 7-aminodeacetoxycephalosporanic acid (72), and nocardicin C to 6-aminonocardicinic acid (73). Penicillin G amidase from Pscherichia coli has been used in an efficient resolution of a racemic cis intermediate required for a preparation of the synthon required for synthesis of the antibiotic Loracarbef (74). The racemic intermediate (21) underwent selective acylation to yield the cis derivative (22) in 44% yield the product displayed a 97% enantiomeric excess (ee). 

Orthoesters. The value of cycHc orthoesters as intermediates for selective acylation of carbohydrates has been demonstrated (73). Treatment of sucrose with trimethylorthoacetate and DMF in the presence of toluene-/)-sulfonic acid followed by acid hydrolysis gave the 6-0-acetylsucrose as the major and the 4-0-acetylsucrose [63648-80-6] as the minor component. The latter compound underwent acetyl migration from C-4 to C-6 when treated with an organic base, such as / fZ-butylamine, in DMF to give sucrose 6-acetate in >90% yield (74). When the kinetic reagent 2,2-dimethoxyethene was used,... 

The antibacterial effectiveness of penicillins cephalospotins and other P-lactam antibiotics depends upon selective acylation and consequentiy, iaactivation, of transpeptidases involved ia bacterial ceU wall synthesis. This acylating ability is a result of the reactivity of the P-lactam ring (1). Bacteria that are resistant to P-lactam antibiotics often produce enzymes called P-lactamases that inactivate the antibiotics by cataly2ing the hydrolytic opening of the P-lactam ring to give products (2) devoid of antibacterial activity. 

Regioselective Acylation of Hydroxy Compounds. AUphatic diols can be selectively acylated at the primary position by a number of Upases in nonaqueous solvents. For example, PPL suspended in solutions of various diols in ethyl carboxylates catalyzes transesterification in a highly regioselective manner, producing primary monoesters in up to 97% yield (93). Similarly, chloramphenicol [56-75-7] (72) (R = NO2) can be acylated by a number of Upases to produce optically pure, water-insoluble 3-0-palmitate in a highly selective manner (94). 

ACOCH2CCI3, pyridine, porcine pancreatic lipase, 85% yield.These studies examined the selective acylation of carbohydrates. Mannose is acy-lated at the 6-position in 85% yield in one example. 

PvCl, Pyr, 0-75°, 2.5 days, 99% yield. In general, such extended reaction times are not required to obtain complete reaction. This is an excellent reagent for selective acylation of a primary alcohol over a secondaiy alcohol. "... 

Selective acylation can be obtained for one of two primary alcohols having slightly different steric environments. ... 

BzCN, Et3N, CH3CN, 5 min-2 h, >80% yield/ This reagent selectively acylates a primary hydroxyl group in the presence of a secondary hydroxyl... 

AcCl, NaOH, dioxane, Bu4N HSO, 25°, 30 min, 90% yield. Phase-transfer catalysis with tetra-n-butylammionium hydrogen sulfate effects acylation of sterically hindered phenols and selective acylation of a phenol in the presence of an aliphatic secondary alcohol. 

CgFgOAc, DMF, 25°, 1-12 h, 78-91% yield. These conditions allow selective acylation of amines in the presence of alcohols. If triethylamine is used in place of DMF, alcohols are also acylated (75-85% yield). 

AC2O, 18-crown-6, Et3N, 98% yield. The crown ether forms a complex with a primary amine, thus allowing selective acylation of a secondary amine. 

An acyl thiazolidone is also effective for the selective acylation (Ac, Pv, Bz) of primary alcohols." ... 

A,A-Diacetyl-2-trifluoromethylaniline, organic solvents, 3-24 h, rt or reflux, 54-99% yield. Acylation selectivity is a very sensitive function of steric effects this reagent selectively acylates pyrrolidine over piperidine (15 1). It is more selective than the diacetylaminoquinazolinones. ... 

Ac2NOMe selectively acylates a primary amine of a spermidine. ... 

Table Z14 Variation in selected acyl sugar concentrations as a function of latitude in Lycopersicon pennelli (from Shapiro et al., 1994)...

Lanthanide triflates have similar catalytic effects. Yb(03SCF3)3 and Lu(03SCF3)3, for example, were used in selective acylation of 10-deacetylbaccatin III, an important intermediate for preparation of the antitumor agent paclitaxel.111... 

In addition to acyl halides and acid anhydrides, there are a number of milder and more selective acylating agents that can be readily prepared from carboxylic acids. Imidazolides, the (V-acyl derivatives of imidazole, are examples.115 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with carbonyldiimidazole. 

A potential liability associated with such reductive hydroacylations resides in the fact that only one acyl residue of the symmetric anhydride is incorporated into the coupling product. For more precious carboxylic acids, selective acyl transfer from mixed anhydrides is possible. Mixed anhydrides derived from pivalic acid are especially convenient, as they may be isolated chromato-graphically in most cases. In practice, mixed anhydrides of this type enable completely branch-selective hydroacylation with selective delivery of the aromatic and a,()-unsalurated acyl donors (Scheme 19). 

Scheme 19 Selective acyl transfer in reductive hydroacylations involving mixed carboxylic anhydrides derived from pivalic acid...

Pyridinotriazolides were used for esterification in the presence of DBU under mild conditions, and for the selective acylation of steroids. 1271... 

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. 

Improved selective acylation of 4,6 4, 6 -di-0-benzylidene-a,a-trehalose was achieved in acetone by the following method, in which a gentle liberation of -acyl-imidazole occurs on the conversion of benzotriazolyl-iV-oxytris(dimethylamino)phos-phonium hexafluorophosphate with the carboxylic acid in the presence of triethylamine and addition of imidazole 1199 ... 

Further acylations/selective acylations of carbohydrates are compiled in Table 3—11. The acylations are carried out either by using imidazolides prepared in situ from the carboxylic acid and CDI (method A), or by using the isolated carboxylic acid imidazolides (method B). 

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