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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
Author(s) -
Weiguny Jens,
Schäfer Hans J.
Publication year - 1994
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199419940302
Subject(s) - chemistry , yield (engineering) , hydrolysis , acylation , acetal , cyclopentene , stereochemistry , acid hydrolysis , organic chemistry , catalysis , materials science , metallurgy
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.