ISSN:
1434-193X
Keywords:
Planar chirality
;
Cyclophanes
;
Asymmetric synthesis
;
Biocatalysis
;
Lipases
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Type of Medium:
Electronic Resource
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