Synthesis, resolution, and diastereoselectivity of the chiral auxiliary trans-2-(9H-fluoren-9-yl)cyclohexanol

Matthew A Cheney, University of Texas at El Paso

Abstract

The synthesis of the chiral auxiliary trans-2-(9 H-fluoren-9-yl)cyclohexanol was performed using fluorene, potassium tert-amylate, n-butyl lithium, and cyclohexene oxide in benzene. After deprotonation at the methylene position of fluorene, the fluorenyl anion attacks cyclohexene oxide to produce enantiomers of the chiral auxiliary in 33% yield. ^ The enzymatic esterification of this chiral auxiliary was carried out using Candida rugosa lipase and several acids. The reactions were conducted in cyclohexane at 40°C and observed by chiral column High Pressure Liquid Chromatography. Using lauric acid, the reaction was enantioselective with an enantiomeric ratio, E, of 11 at an enantiomeric excess, e.e., of 89% at 60% conversion. Using pyruvic acid, the reaction was not enantioselective and also difficult to reproduce. On one occasion was racemic chiral auxiliary esterified into pyruvate ester. Racemic trans-2-(9 H-fluoren-9-yl)cyclohexyl pyruvate ester was synthesized using DMAP and DCC in a 28% yield. ^ The diastereoselectivity of the chiral auxiliary was measured by reducing the pyruvate ester with NaBH4 in anhydrous THF, producing trans-2-(9H-fluoren-9-yl)cyclohexyl lactate ester. The diastereomeric excess, d.e., was found to be 87% by silica column HPLC. ^

Subject Area

Chemistry, Organic|Chemistry, Pharmaceutical

Recommended Citation

Cheney, Matthew A, "Synthesis, resolution, and diastereoselectivity of the chiral auxiliary trans-2-(9H-fluoren-9-yl)cyclohexanol" (2007). ETD Collection for University of Texas, El Paso. AAI1445694.
http://digitalcommons.utep.edu/dissertations/AAI1445694

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