EDUCATION

2003.9 - 2007.6   Nankai University, College of Chemistry, B. S.

2007.9 - 2010.6   Nankai University, SKLEOC, M. S.

CONTACT

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DISSERTATION

a,a¢-Disubstituted Cyclohexanones>

Abstract

    Many pharmaceutical and naturally occurring bioactive compounds have more chiral centers. For example, Lycorine, an amaryllidaceae alkaloid, has a three contiguous stereogenic centers. Current access to compounds with multiple chiral centers is largely dominated by asymmetric carbon-carbon bond formation reactions. Catalytic asymmetric hydrogenation provides the corresponding hydrogenated compounds with no more than two chiral centers. It would be a very meaningful and challenging topic to study the asymmetric hydrogenation of racemic α,α'-disubstituted cyclohexanones via dynamic kinetic resolution (DKR) for achieving chiral cyclic alcohols with three contiguous stereogenic centers.

    Considering that a structure with three contiguous stereogenic centers in a cyclohexane ring is a general feature of amaryllidaceae alkaloids such as a Lycorine, we studied the hydrogenation of 2-alkyl-6-aryl disubstituted cyclohexanones. A new method for synthesis of 2-(2-ethoxy-2-oxoethyl)-6-arylcyclohexanones in 5 steps from the easily obtained cyclohexenone was developed.

    By using chiral spiro ruthenium complex [RuCl₂((S)-Xyl-SDP)((R,R)-DPEN)] as a catalyst, we successfully realized the highly efficient hydrogenation of 2-(2-ethoxy-2-oxoethyl)-6-arylcyclohexanones, offering the corresponding chiral dialcohols in high yields and excellent selectivities (> 99:1 cis,cis-selectivity, up to 99.9% ee). This result represents the first example of highly efficient catalytic asymmetric hydrogenation giving chiral compounds with three contiguous stereogenic centers. 2-Alkyl-6-arylcyclohexanones are also good substrates for this hydrogenation, and high yields and excellent cis, cis-selectivities (>99:1) were aobtained but with low to moderate enantioslectivities.

    In this dissertation, 32 new compounds have been synthesized. Their structures were confirmed by ¹H NMR, ¹³C NMR, and HRMS analysis. A crystal of 2-aryl-6-(2-hydroxyethyl)cyclohexanol suitable for X-ray diffraction was obtained and the absolute configuration of the hydrogenation product 2-aryl-6-(2-ydroxyethyl)cyclohexanol was determined by a single-crystal X-ray analysis. 

Key Words: disubstituted cyclohexanone, catalytic asymmetric hydrogenation, dynamic kinetic resolution (DKR), Ru(II)-SDPs/diamine catalyst

 PUBLICATION

1.Wen-Ju Bai, Jian-Hua Xie, Ya-Li Li, Sheng Liu, Qi-Lin Zhou*, Enantioselective synthesis of chiral β-aryloxyalcohols by ruthenium- catalyzed ketone hydrogenation via DKR, Adv. Synth. Catal. 2010, 352, 81-84.