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Chemoenzymatic Synthesis of Optically Pure Planar Chiral ( S )‐(–)‐5‐Formyl‐4‐hydroxy[2.2]paracyclophane
Author(s) -
Pamperin Dirk,
Schulz Christian,
Hopf Henning,
Syldatk Christoph,
Pietzsch Markus
Publication year - 1998
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199807)1998:7<1441::aid-ejoc1441>3.0.co;2-k
Subject(s) - chemistry , formylation , racemization , hydrolysis , kinetic resolution , biocatalysis , yield (engineering) , stereochemistry , cyclophane , organic chemistry , catalysis , enantioselective synthesis , reaction mechanism , molecule , materials science , metallurgy
The synthesis of optically pure ( S )‐5‐formyl‐4‐hydroxy‐[2.2]paracyclophane ( S )‐ 3 ( ee > 99 %) was achieved by a three‐step chemoenzymatic procedure consisting of (i) kinetic enzymatic resolution of ( R, S )‐4‐acetoxy[2.2]para‐cyclophane ( R, S )‐ 1 to produce optically pure starting material, which after (ii) hydrolysis was subjected to (iii) stereoselective ortho ‐formylation with an overall yield of 51 %. All attempts to use a biocatalyst directly for the preparation of optically pure disubstituted [2.2]para‐cyclophanes failed because of either total lack of activity (bioreduction) or low enantioselectivities of the enzymes screened (hydrolases). Using the chemoenzymatic approach from ( R, S )‐ 1 , optically pure ( S )‐ 1 and after subjecting ( S )‐ 1 to hydrolysis and finally to formylation ( S )‐ 3 was obtained. As confirmed by chiral GC, hydrolysis and formylation took place without racemization. During the optimization of the enzymatical part of the synthesis a strong influence of both the nature of the cosolvent and the pH of the buffer‐phase on the enantioselectivity value E were observed. Using a two‐phase system consisting of diethyl ether and phosphate buffer an E value higher than 100 was achieved at a pH of 7.0 and at room temperature.