1.2- Cyclopentanediol oxidation

Epoxides, like other ethers, are cleaved by nucleophiles under acidic conditions. For example, cyclopentene oxide produces a mixture of 1,2-cyclopentanediol stereoisomers when treated with water and sulfuric acid. 

The product of nucleophilic attack can be anticipated by examining the lowest-unoccupied molecular orbital (LUMO) on protonated cyclopentene oxide. From which direction (top or bottom) would a nucleophile be more likely to approach each epoxide carbon in order to transfer electrons into this orbital Explain. Does one carbon contribute more to the LUMO, or is the orbital evenly spread out over both epoxide carbons Assuming that LUMO shape dictates product stereochemistry, predict which stereoisomers will be obtained, and their approximate relative amounts. Is the anticipated kinetic product also the thermodynamic product (Compare energies of 1,2-cyclopentanediol stereoisomers to tell.)... 

Strong support for the cyclic ester intermediate comes from the measurement of the relative rates of oxidation by chromic acid of cis- and // fl/w-l,2-dimethyl-1,2-cyclopentanediol. In water and in 90 % acetic acid is 17,000 and... 

Glycols and related alcohols In contrast to aliphatic monoalcohols (1), 1,2-glycols and related compounds (2-methoxy alcohols, 1,2-amino alcohols) can be easily oxidized by the direct electrochemical method [12]. For example, 1,2-cyclopentanediol (9) affords diacetal (10) in 56% yield as the main product (Eq. 3). 

Aqueous acetic acid (rate of oxidation) [1, 145, after citation of ref. 5], Rocek and Westheimer58 reported that the oxidation of cm-l,2-dimethyl-1,2-cyclopentanediol (1) by chromic acid in water or 90% acetic acid to 2,6-heptanedione (2) is much faster than oxidation of the trans isomer (3). In water the oxidation of (1) to (2) is 17,000... 

Because glycol formation involves a back-side attack on a protonated epoxide, the result is anti orientation of the hydroxyl groups on the double bond. For example, when 1,2-epoxycyclopentane ( cyclopentene oxide ) is treated with dilute mineral acid, the product is pure rmns-1,2-cyclopentanediol. 

From (-)-cuparene (322), ve metabolites (328-332) all of which contained cyclopentanediols or hydroxycyclopentanones were obtained. An aryl methyl group was also oxidized to give primary alcohol, which was further oxidized to afford carboxylic acids (329-331) (Hashimoto et al., 2001a) (Figure 20.96). 

At this point, let us compare the stereochemistry of the glycol formed by acid-catalyzed hydrolysis of an epoxide with that formed by oxidation of an alkene with osmium tetroxide (Section 6.5A). Each reaction sequence is stereoselective but gives a different stereoisomer. Acid-catalyzed hydrolysis of cyclopentene oxide gives trans-l,2-cyclopentanediol osmium tetroxide oxidation of cyclopentene gives ds-1, 2-cyclopentanediol. Thus, a cycloalkene can be converted to either a cis glycol or a trans glycol by the proper choice of reagents. 

The simple workup procedure provides highly pure products (>97%) without the need for further purification of the crude material. The small excess of 4-methoxy-3-buten-2-one utilized in the reaction is conveniently hydrolyzed to water-soluble and/or highly volatile products (Eq. 7.10). The B-methoxy-9-BBN byproduct is oxidized to water-soluble cis-1,5-cyclopentanediol and boric acid. The whole sequence thus provides [18] clean products after simple extraction of the reaction mixture. 

Li and coworkers have described the gram-scale preparative desymmetrization of cyclohexene oxide, cyclopentene oxide, and N-benzyloxycarbonyl-3,4-epoxypyr-rolidine using the EH from Sphingomonas sp. HXN-200 expressed in the recombinant host E. coli (SpEH) [94]. Desymmetrization of 10 g of cyclohexene oxide (500 mM substrate concentration) with resting cells of E. coli (SpEH) (10 g cdw/1) afforded 10.3 g (89% isolated yield) of (lE,2R)-l,2-cyclohexanediol in 86% ee. Desymmetrization of the two other meso-epoxides (200 mM substrate concentration) afforded (1R,2R)-1,2-cyclopentanediol in 87% ee and 70.4% isolated yield and (3R,4R)-N-benzyloxy-carbonyl-3,4-dihydroxypyrrolidine in 93% ee and 94.1% isolated yield, respectively. 

The synthesis of rhynchophyllol by van Tamelen et a/P illustrates a biogenetic-type approach to oxindole alkaloids. A key feature of this synthesis is generation of the desired tetracyclic structure by an intramolecular Mannich cyclization of dialdehyde (B) produced by oxidative cleavage of the substituted cyclopentanediol (A). 

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