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

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.