Electroorganic synthesis, 56. Synthesis of advanced prostaglandin precursors by Kolbe electrolysis, I. – Preparation of (1′R,4′S,3RS)-3-(cis-4-acetoxycyclopent-2-enyloxy)-3-ethoxypropionic acid

✍ Scribed by Weiguny, Jens ;Schäfer, Hans J.

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 964 KB
• Volume: 1994
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199419940302

✦ Synopsis

Abstract

The key intermediate of a novel synthesis of prostaglandin precursors, (1′R,4′S,3__R__/S)‐3‐(cis‐4‐acetoxycyclopent‐2‐enyl oxy)‐3‐ethoxypropionic acid (3), is prepared by two different synthetic sequences: In a first strategy transacetalization of ethyl 3,3‐diethoxypropionate (6) with (1__R__, 4__S__)‐4‐acetoxy‐1‐hydroxy‐2‐cyclopentene (7) leads to the formation of the mixed acetal 8. By subsequent hydrolysis and acylation 8 could be converted into acid 3 in six steps in 6% overall yield. However, the generation of acid 3 by bromoalkoxidation of 3‐ethoxyacrylates 13d, e and subsequent electrochemical reduction proved to be more efficient. In this reduction it is possible to debrominate the α‐bromo esters 14d, e and to remove the 2‐haloethyl ester group in one step. Using this reaction sequence, we could synthesize acid 3 in five steps in 38% overall yield. magnified image