Enantioselective Synthesis of Ethyl 4,5,7,8,9‐Penta‐ O ‐acetyl‐2,6‐anhydro‐ 3‐deoxy‐ D ‐ erythro‐ L ‐ gluca ‐nononate: a 2‐Monodeoxygenated Derivative of `2‐Keto‐3‐deoxy‐ D ‐ glycero ‐ D ‐ galacto ‐nononic Acid'

A study aimed at developing an enantioselective synthesis of the title compound 23 , a 2‐monodeoxy analogue of the naturally occurring (+)‐2‐keto‐3‐deoxy‐ D ‐ glycero‐ D ‐ galacto ‐2‐nononic acid (KDN), is reported. From D ‐mannose as starting material, the chiral 1,3‐diene 10 , activated by a silyloxy substituent at C(2), was prepared in six steps ( Scheme 1 ). However, the intermediates were often contaminated with varying amounts of by‐products arising from overoxidation during cleavage with periodic acid. An alternative route starting from the inexpensive and readily available D ‐isoascorbic acid ( 12 ), though a little longer than the first, satisfactorily circumvented the purification problem and led to the desired dienes 17 in good yields ( scheme 2 ). The [Co II ( S , S )‐(+)‐salen]‐catalyzed hetero‐ Diels‐Alder reactions of the aforementioned dienes with ethyl glyoxylate proceeded smoothly at room temperature, giving the dihydropyrano adducts 18 in moderate yields ( Scheme 3 ). Dihydroxylation of 18a followed by reduction of the keto function gave the desired 4,5‐ trans dihydroxy moiety of the KDN framework ( Scheme 4 , see 21 ). The spectroscopic data of the penta‐ O ‐acetylated 2‐deoxy‐KDN ethyl ester 23 were consistent with those reported for the corresponding methyl ester derived from natural KDN.