Lactonization/benzylic lactone hydrogenolysis

This compound, previously prepared174 in low yield from alginic acid, has been synthesized128 from 61 by oxidation at C-2, and stereospecific reduction of the intermediate methyl 5-0-benzyl-/3-D-nrab-ino-2-hexulofuranosidurono-6,3-lactone. Hydrogenolysis of the 5-0-benzyl group yielded the title compound in a superior yield. 

It is important to note that the one-step conversion of 27 to 28 (Scheme 4) not only facilitates purification, but also allows differentiation of the two carbonyl groups. After hydrogenolysis of the iV-benzyl group (see 28—>29), solvolysis of the -lactone-ring in 29 with benzyl alcohol and a catalytic amount of acetic acid at 70 °C provides a 3 1 equilibrium mixture of acyclic ester 30 and starting lactone 29. Compound 30 can be obtained in pure form simply by washing the solid mixture with isopropanol the material in the filtrate can be resubjected to the solvolysis reaction. 

Lactones (cyclic esters) are usually stable toward hydrogenolysis. However, the aromatic lactones contain benzylic C—O bonds and can be hydrogenolyzed. As an example, the hydrogenolysis of an aromatic lactone was performed over Ra-Ni in THF under 4 atm H2 pressure at 50°C for 30 hours.213... 

Catalytic hydrogenation of benzylic lactones 71 and 72 over 10% palladium on activated charcoal gave diacids 73 and 74 which were isolated as their corresponding dibenzhydryl esters 75 and 76 after treatment of the crude hydrogenolysis product with diphenyldia-... 

Lactonization Reaction of 1 with trityl tetrafluoroborate not only effects oxidative debenzylation as expected (4, 567), but also cyclization to 2, d/-aplysis-tatin, a brominated sesquiterpene. Attempted hydrogenolysis of the benzyl ether resulted only in hydrogenation of the double bond. 

Bycroft was able to achieve the synthesis of 110 via a slightly modified route (Scheme 1.22). ° Condensation of benzyl 7-hydroxyoctanoate (108) with 3,5-dimethoxyphenylacetyl chloride provided the expected diester 109. Hydrogenolysis of the benzyl ester gave the desired acid, which was induced to close to the lactone via intramolecular Friedel-Crafts acylation to afford 110. 

---