Cis-Hydroxylation

Glucose undergoes a large number of seleetive, acid-catalyzed substitution reaetions at Cj. Sinee the role of aeid is to protonate the Ci hydroxyl and make it a better leaving group, it is not apparent why only this hydroxyl group gets replaeed. 

It is, in fact, interesting to note that the latter cyclohexanepentol, which has four adjacent cis-hydroxyl groups, reacts slowly with periodate. Perhaps further light will be thrown on this problem when the results of periodate oxidations of dl-1, 2, 3, 5/4-cyclohexanepentol (36), 1, 2, 4, 5/3-cyclohexanepentol (37), and (1 d)-1, 2, 3/4, 5-cyclohexanepentol (38) will be available. 

As noted at the end of Section 7.8, the prefixes cis- and trans- would be ambiguous when naming the diols derived from 1-methylcyclohexene because the ring has three substituents. Instead, a reference substituent r is chosen and other substituents are either cis (c) or trans (f) to that reference. For the two l-methyl-l,2-cyc ohexanediol isomers, the -OH group at Cl is the reference (r-1), and the -OH at C2 is either cis (c-2) or trans (t-2) to that reference. Thus, the diol isomer derived by cis hydroxylation is named l-methyl-r-l,c-2-cyc ohexanediol, and the isomer derived by trans hydroxylation is named l-methyl-r-l,t-2-cyclohexanediol. 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

This reaction is due to the combination of two cis hydroxyl groups of the compound with the boric acid to form a much stronger monobasic acid ... 

Concomitant protection of the amino group and the cis-hydroxyl group of the diol 342 was realized by treatment with formaldehyde to afford the oxazolidine 345, oxidation of which with silver carbonate on Celite gave the... 

Osmium(VIII) tetraoxide (0s04) is an effective reagent for the cis hydroxylation of olefins under stoichiometric conditions as well as in a variety of catalytic variants.213 Under both catalytic and stoichiometric conditions, the critical step is the formation of an osmium(VI) cycloadduct, the formation of which is dramatically accelerated in the presence of amine bases such as pyridine,214 i.e.,... 

Now it has been established that cis hydroxylation occurs because the following intermediate products of cyclic structure are first formed. 

When a-D-glucopyranose is dissolved these anomalies are not observed, for K K = 0.0109, a value practically equal to the mutarotation constant, 0.0107. In this case the influence of the intermediate product is overshadowed by the presence of a-D-glucofuranose, which exercises a very great influence on the conductivity because it is a five-membered ring with two adjacent cis hydroxyl groups. The mutarotation process may now be symbolized as follows ... 

From this point of view, both the pyranoses and the furanoses may participate in the mutarotation reaction, and both a- and /3-d 1uco-pyranose will have similar mutarotation constants. We may expect a heterocyclic five-membered ring with two adjacent cis hydroxyl groups to have a A of about 1000 units for 0.5 M solutions. In the case of D-glucose it is between 93 and 80 hence, the concentration of a-D-glucofuranose is probably less than 10 per cent. This quantity is sufficient, however, to explain the formation of derivatives of the furanoses. 

Since the hexitols are saturated aliphatic compounds, the asymmetric centers are generally assumed to have free rotation. Hence one cannot with certainty predict differences in reactivity between cis and trans" pairs of hydroxyl groups on the basis of steric hindrance. Thus one cannot say that D-mannitol, because of its two pairs of cis hydroxyl... 

Another, more efficient route43 to DL-lyxose and DL-xylose consisted in reduction of 24 with lithium aluminum hydride to the trans-alkene 29a, cis-hydroxylation of 29b, and acid hydrolysis of the products obtained (30 and 31, respectively). In an alternative approach to DL-ri-bose and DL-arabinose, l-ethoxy-l-penten-3-yn-5-ol (32) was used24 as the substrate. Reduction of 32a with lithium aluminum hydride afL... 

A very efficient, stereospecific synthesis of DL-ribose was based26 on the use of l,l-diethoxy-5-(tetrahydropyran-2-yloxy)-2-pentyn-3-ol as the substrate. Catalytic hydrogenation of this alkyne to the cts-alkene was accompanied by cyclization, to give 2-ethoxy-2,5-dihydro-5-(tetra-hydropyran-2-yloxy)furan (35). cis-Hydroxylation of the double bond in 35 was effected with potassium permanganate, yielding the ethyl DL-ribofuranoside derivative 36, which was hydrolyzed to DL-ribose. 

Stereospecific syntheses of the 1,1-diethyl acetals 45 and 47 were performed by Makin and coworkers.29 trans-5,5-Diethoxy-2-penten-l-ol (44) was cis-hydroxylated with potassium permanganate, to yield the diethyl acetal (45) of 2-deoxy-DL-threo-pentose. Epoxidation of 44 and alkaline hydrolysis of the epoxide 46 gave the diethyl acetal (47) of 2-deoxy-DL-en/thro-pentose. 

DL-cordycepose it was obtained in two steps, namely, epoxidation to 55 and mild, acid hydrolysis of the epoxide 55. For the synthesis of 53, substrate 54 was first brominated to the 2-bromo compound 57, which was dehydrobrominated with lithium amide, to afford the unsaturated acetal 58. cis-Hydroxylation of 58 under typical conditions then afforded 53. 

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