- In Former Members (Graduated in 2010)
- Last Updated on 07 April 2017
- Hits: 3253
2003.9 - 2007.6 Nankai University, College of Chemistry, B. S.
2007.9 - 2010.6 Nankai University, SKLEOC, M. S.
<Study on the Catalytic Asymmetry Hydrogenation ofa,a¢-Disubstituted Cyclohexanones>
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
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.