Debenzylation, regioselective

In order to introduce the carboxylic function, azide 30 was regioselectively debenzylated at the primary hydroxyl group by controlled treatment with acetic anhydride and trifluoroacetic acid, (14) followed by saponification of the acetate at C-5. The product 31 was finally converted into the carboxylic acid 32 by Jones oxidation. 

Regioselective debenzylation can be achieved by treatment with Lewis acids such as ferric chloride and S11CI4 or under acetolysis conditions with acetic anhydride and sulfuric acid, and several examples are depicted in Scheme 2.3.9 Acetolysis results in cleavage of the most acid-sensitive benzyl group. In general, primary benzyl ethers can be selectively acetolysed in the presence of secondary benzyl ethers. The regioselectivity of the reaction can be explained as follows sulfuric acid protonates acetic anhydride followed by the formation of an acetyl ion and acetic acid. The acetyl ion reacts with the sterically most accessible oxygen which is at... 

Recently, a new intramolecular-type approach for the regioselective debenzylation or protection of a secondary hydroxyl group in disaccharides has been reported by Madsen and Bols [64]. 

Both acetal cleavage and regioselective debenzylation reactions can be successively induced by DIBAL by reaction of a mesylated spiroketal carbohydrate derivative to form a monodebenzylated bicyclic system (eq 49). ... 

Reaction of A,A-dimcthylsullamoyl aziridines 323 and 325 with primary amines furnishes substituted 1,2,5-thiadiazolidine 1,1-dioxides 324 and 326, respectively, in a regioselective manner <06SL833>. Aziridine 325 is made from ( I /t,6,S ,Z)-bicyclo[4.2. l]non-3-en-9-one in two steps /V,/V-dimethylsulfamoyl imine formation using dimethylsulfamide and subsequent reaction with trimethylsulfoxonium ylide. The product from the reaction with 4-methoxy-benzyl amine can be subsequently manipulated (debenzylation and derivatization) to give the alternative nitrogen substitution pattern in a controlled manner. 

Treatment of compound 22 with an excess of iodine in THF at 0 °C resulted in the formation of compound 23, the free hydroxyl group being favored in the nucleophilic attack to the iodonium ion. It is worth of note that, despite the presence of two double bonds, at 0 °C the reaction is regioselective. Increasing the temperature to 20 °C, the second iodocyclization with debenzylation occurs, affording compound 24 in 60% overall yield. 

Regioselective O-debenzylation. Of a number of Lewis acids, SnCl4 or TiCf, is the most effective for this reaction with polybenzylated sugars. The substrate... 

Rationalise the regioselectivity of the mono-debenzylation reaction carried out in step b. 

Similar utilization for cleavage of benzyl alcohols, ethers and esters has made this method the preferred one where regioselectivity is required, but for allylic cleavage double bond isomerization becomes a problem. A number of benzylic ethers and alcohols (equation 13), and benzhydric ethers and acetals (equation 14) have been cleaved in relatively high yield using cyclohexene in the presence of AlCb. Mild conditions of cleavage are frequently required for debenzylation of carbohydrates and a number of protected carbohydrates have been cleaved with formic acid as donor (equation 15). ... 

Debenzylation. Perbenzylated cyclodextrins (a-, P-, and y-forms) are partially debenzylated by Dibal-H in toluene in a regioselective manner to provide the mono-6-O-debenzylated or AD-di-0,(9-debenzylated derivative. 

The dependence of the a-deprotonation site on the kinetic acidity of the planar amine radical cation is best demonstrated by the sensitized ET photoreaction of iV-benzyl tertiary amines and A/-alkyl anilines in the presence of DCN, which leads to the efficient Af-debenzylation [38] and A/-dealkylation [39], respectively. These results are explained by considering the hydrolysis of the respective regioselective iminium cations produced during the reaction. The utility of these studies is demonstrated in the A -debenzylation [38] reaction of benzyl-protected tertiary amines and in the understanding of the mechanism of oxidative A -dealkylation [39] of tertiary amines by cytochrome P-450-depen-dent monooxygenases. 

Vasella and Peer have developed a regioselective synthesis of the protected six-membered cyclic L-fucose-derived nitrone 157 in view of the synthesis of a-L-fucosidase inhibitors [70]. The nitrone 157 has been transformed into the indolizidines 160 and 161 via a cycloaddition to an acrylate (Fig. 37). The reaction proceeded regioselectively and led to a 60 40 mixture of the diastereomeric isoxazoHdines 158 (55%) and 159 (34%) by exclusively axial C - C bond formation. Reductive cleavage of the N - O bond of the isoxazoHdines 158 and 159, followed by reduction with BH3 in THF with subsequent hydrogenolytic debenzylation in MeOH/HCl, afforded the indoUzidines 160 and 161 as their hydrochlorides. 

Figure 2.5.14 shows a synthetic route for pyriminobac-methyl [28]. The key step is ortho-lithiation reaction (step 3) of compound 21 protected by dimethylacetal and benzylation, followed by regioselective carbomethoxylation at the 2-position with methyl chloroformate via lithiated benzene prepared by n-butyllithium. Through several processes of deacetalization, methoxyimination of the acetyl group and debenzylation, compound 22 is condensed with DMSP 6 to give pyriminobac-methyl 15 [29]. 

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