Protection 4- dimethylaminopyridine

PhCH20CO-imidazolyl, 4-dimethylaminopyridine, 16 h, it, 76% yield. Two primary amines were protected in the presence of a secondary amine. 

For example, the reaction of nitroalkanes with di-tert-butyl dicarbonate, (B0C)20, and 4-dimethylaminopyridine (DMAP) as catalysts in the presence of dipolarophiles at room temperature affords cycloadducts in improved yields compared with the Mukaiyama-Hosino method.58 The conversion of Eq. 6.32 gives a 90% yield by this procedure, whereas the conventional method using PhNCO gives a 79% yield of the same product. An additional advantage of this new method is that the use of (B0C)20 allows the reaction to be carried out with substrates that contain NH or OH groups without prior protection. The cycloaddition leads directly to protected N- or (9-Boc products (see Eq. 6.33). 

E Atherton, NL Benoiton, E Brown, RC Sheppard, B Williams. Racemisation of activated, urethane-protected amino-acids by jp-dimethylaminopyridine. Significance in solid-phase synthesis. J Chem Soc Chem Commun 336, 1981. 

N-Protected AAs were activated in situ with isopropenyl chloroformate to give an intermediate anhydride which reacted with Meldrum s acid in the presence of 4-dimethylaminopyridine (DMAP) to give the corresponding l,3-dioxane-4,6-dione. The reaction conditions are very stringent. Further transformation upon heating in an organic solvent yielded the pyrrole derivative (Scheme 15) [87JCS(P1)1177]. 

Protection of an alcohol function by esterification sometimes offers advantages over use of acetal or ether groups. Generally, ester groups are stable under acidic conditions. Esters are especially useful in protection during oxidations. Acetates and benzoates are the most commonly used ester derivatives. They can be conveniently prepared by reaction of unhindered alcohols with acetic anhydride or benzoyl chloride, respectively, in the presence of pyridine or other tertiary amines. 4-Dimethylaminopyridine (DMAP) is often used as a catalyst. The use of A-acylimidazolides (see Section 3.4.1) allows the... 

The electron-donating effect of pyridine substituents becomes especially evident with 4-dimethylaminopyridine. Methyl a-D-glucopyranoside reacts with 1.1 molar equiv. of trityl chloride, 1.5 molar equiv. of triethylamine, and a catalytic amount of 4-dimethylaminopyridine in DMF to give 88% of the 6-trityl ether after only several hours at room temperature [326], With the classical method, the yield was 61 % and some difficulties with the formation of addition complexes of the product with pyridine were encountered [326]. Surprisingly, pyridine still remains frequently used as a solvent in combination with this effective catalyst [327, 328]. Of the two secondary hydroxyl groups of methyl 4,6-O-benzyl-a-D-mannopyranoside [119] or methyl 4-0-benzyl-a-L-rhamnopyranoside [122], the equatorial OH-3 was protected first. Tritylation of methyl 2-0-benzyl-a-L-fucopyranoside (46) proceeded readily to give (47) in 70% yield [109]. 

Holton claimed in a patent application that (3/ ,45)-A-benzoyl-3-0-EE-(3-lactam 11 (5 equiv), obtained through tedious classical optical resolution of racemic t (. -3-hydroxy-4-phenylazetidin-2-one, could be directly coupled with 7-TES-bac-catin III (8) in the presence of 4-dimethylaminopyridine (DMAP) and pyridine and the subsequent deprotection afforded paclitaxel in ca. 82% yield.54 Although this procedure was proved to work by us and by others, the use of a large excess of (3-lactam is obviously inefficient. Moreover, the Holton procedure did not work at all when /V-f-Boc-(3-lactam 12 was used for our attempted syntheses of docetaxel and its 10-acetyl analogue. This is due to the lack of reactivity of the A-r-Boc-(3-lactam 12 toward the C-13 hydroxyl group of a protected baccatin III under the Holton conditions. The lack of reactivity is ascribed to the substantially weaker... 

Esterification.1 This reagent in combination with a catalytic amount of 4-dimethylaminopyridine (DMAP) is very effective for esterification of carboxylic acids with alcohols or thiols at room temperatures. However, reaction of aromatic and hindered acids requires several days at room temperature. French chemists report that only this method is useful for esterification of the protected baccatin III derivative (2) with (2R,3S)-N-benzoyl-0-(l-ethoxyethyl)-3-phenylisoserine (3) to provide the protected taxol derivative (4). A reaction conducted at 73° for 100 hours with 6 equiv. of 1 and 2 equiv. of DMAP produced 4 in 80% yield. Natural taxol, a cancer chemotherapeutic agent, is obtained by removal of the protective groups at C2 and C7 of 4. 

Depsipeptides. These esters can be prepared in 90-98% yield by coupling of BOC-protected amino acids with benzyl esters of an a-hydroxy acid by means of DCC and catalysis with 4-dimethylaminopyridine. The reaction is successful even with hindered substrates. ... 

The hydroxy 1,3-dioxolanone intermediate 28 is acid labile and is also unstable toward bases such as Et3N, (/-Pr)2NEt, imidazole, and N,N-dimethylaminopyridine, producing (5)-a-hydroxy-Y-butyrolactone 15. However, by carrying out the reduction of 27 at 0 °C and the protection of 28 using pyridine as the base, we were able to reproducibly perform these transformations on a large scale with comparable yields of isolated products. 

The use of 4-dimethylaminopyridine (DMAP) (18) as a catalyst for enhancement of carbodiimide-based peptide couplings has been proposed [43] but the potential for racemization is increased. This side reaction is more significant when the method is applied to the acylation of hydroxy-methyl-based resin [44]. If the amount of DMAP is reduced to 10% with respect to protected amino acids and carbodiimide and it is added to the resin when the active species is already formed, the racemization is reduced substantially. In most cases this procedure is a convenient method for incorporating the first amino acid in the resin [44]. Carbodiimides in the presence of DMAP have also been applied for the solid-phase formation of depside and depsipeptide bonds with low racemization [45,46]. 

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