The Oxidation of Secondary Hydroxyl Groups

scyllo-mositol (22a) exists in that chair form (22b) in which all hydroxyl groups are equatorial. For mpo-inositol (23a), the chair form 

Unfortunately, the nomenclature of the inositols is not standardized, and different systems have been used. In the present article, the system of Angyal and Anderson is employed, as set forth in this Series. Therefore, the isomers of the inositols and inososes will be characterized by prefixes. The optically active inositols are numbered according to the Angyal system.  

Catalytic oxidation was first apphed to the inositols by Heyns and Paulsen. It was found that jni/o-inositol (23), in nearly neutral solution at 60°, can be oxidized to a monoketone with platinum-on-carbon or with Adams catalyst. Oxidation stops at the monoketone stage, 5delding only insignificant proportions of ring-fission and further oxidation products. Only the axial hydroxyl group on C-2 is oxidized, affording scyUo-inosose 

Various blocked derivatives of myo-inositol (23) can be catalytically oxidized when the axial hydroxyl group is unsubstituted. Oxidations with Acetobader svboxydans are extremely sensitive to such substituents and are therefore, generally, not feasible. Sequoyitol (5-0-methyl-mj/o-inositol) 

If two axial hydroxyl groups in a molecule are sterically equivalent, they are oxidized at the same rate. Thus, the oxidation of epi-inositol (32) gives racemic ( )-epf-inosose (33, 34), which is also obtained by the oxidation of mi/o-inositol (23) with nitric acid. As expected, neo-inositol (35) yields pure neo-inosose (36) on catalytic oxidation. Hydrogenation of the 

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The oxidation of secondary hydroxyl functions to the carbonyl group is often an undesired side reaction. However, the oxidation of D-gluconic acid to 2-oxogluconic acid is a highly selective process (97% yield) when a Pt-Bi catalyst is employed.89 Such a procedure is of industrial interest. 

OH — X. Pi. carbohydrate hydroxyl group can be replaced by halogen (bromine, chlorine, iodine) by treatment in DMF with 2 eq. each of triphenylphosphine and an N-halosuccinimidc. The by-products are succinimide and triphenylphosphine oxide. Yields are generally high. Primary hydroxyl groups can be selectively replaced in the presence of secondary hydroxyl groups. 

The completion of the synthesis of key intermediate 2 requires only a straightforward sequence of functional group manipulations. In the presence of acetone, cupric sulfate, and camphorsulfonic acid (CSA), the lactol and secondary hydroxyl groups in 10 are simultaneously protected as an acetonide (see intermediate 9). The overall yield of 9 is 55 % from 13. Cleavage of the benzyl ether in 9 with lithium metal in liquid ammonia furnishes a diol (98% yield) which is subsequently converted to selenide 20 according to Grie-co s procedure22 (see Scheme 6a). Oxidation of the selenium atom... 

Scheme 31. Monosaccharide derivatives obtained by oxidation at secondary hydroxyl groups using PCC in the presence of 3A or 4A MS.

Oxidations with pyridinium cUorochromate PCC and pyridinium dichromate PDCY Oxidations with PCC and PDC of secondary hydroxyl groups of sugars and nucleosides is slow and incomplete. The reaction is markedly catalyzed by 3 A molecular sieves. Celite, alumina, and silica are not effective. CH2C12 is the most satisfactory solvent oxidations are slower in CICH2C H2CI and C6llf). The rate of oxidation increases in the order 5A< 10A<4A<3A. 

Bishop,141 interested in the relative reactivity of secondary hydroxyl groups without the complication of the veiy reactive primary hydroxyl group, condensed D-xylose under the conditions established by Ricketts and coworkers. A nondialyzable polyxylose having Pn 10-15 (by hypo-iodite oxidation) was isolated in 5.6% yield. Methylation and hydrolysis of a mole of q fraction having M + 55 2° gave 2,3,4-tri-O-methyl-D-xylose (3 moles), 2,3-di-O-methyl-D-xylose (7 moles), 2,4-di-O-methyl-D-xylose (1 mole), 3-O-methyl-D-xylose (5 moles), and D-xylose (1 mole). If, as was assumed, the D-xylose residues are in the pyranoid form, the ratio of (1—>4) (1— 2) (1— 3) bonds is 6.5 3 1. 

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