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Synlett 2007(5): 0729-0732  
DOI: 10.1055/s-2007-970770
LETTER
© Georg Thieme Verlag Stuttgart · New York

Deracemization of Acyclic α-Hydroxy Ketone Derivatives by Dynamic Resolution Using an Optically Active Host Compound

Kazutsugu Matsumoto*, Keiko Otsuka, Tomomi Okamoto, Hideto Mogi
Department of Chemistry, Meisei University, Hodokubo 2-1-1, Hino, Tokyo 191-8506, Japan
Fax: +81(42)5917360; e-Mail: mkazu@chem.meisei-u.ac.jp;
Further Information

Publication History

Received 12 December 2006
Publication Date:
08 March 2007 (online)

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Abstract

The dynamic resolution of racemic acyclic α-hydroxy ketone derivatives is accomplished using an optically active host compound, TADDOL, under basic conditions to give the corresponding optically active ketones.

Key words

acyclic ketones - deracemization - enantiomeric resolution - host-guest systems - optically active compounds

12

The substrate (±)-1 was easily prepared from (±)-lactic acid in four steps. The details of this synthesis have been reported in ref. 13.

14

The absolute configuration of 1 was confirmed by comparing the obtained optical rotation value with the reported value: Lit. [21] [α]D 24 -45.9 (c 1.16, CHCl3), S-form.

15

The ee of 1 was determined by HPLC analysis with CHIRALCEL OJ (Daicel Chemical Industries, Ltd.); eluent, hexane-2-PrOH = 180:1; flow rate, 0.5 mL min-1; t R = 40 (R) and 50 (S) min.

16

The deracemization did not occur for the reactions using the other TADDOL derivatives bearing a cyclopentane ring and a dimethyl group [(-)-2,2-tetramethylene- and 2,2-dimethyl-α,α,α′,α′-tetraphenyl-1,3-dioxolan-4,5-dimethanol, respectively], (+)-1,1′-bi-2-naphthol, and (-)-hydrobenzoin as chiral host compounds under the same conditions.

17

Although the ee of (S)-1 increased according to the extension of the reaction time (42% ee for one day), the reaction for over three days gave almost the same result as that of the three-day reaction. We then decided that the racemizations in all cases were carried out for three days.

18

The reaction using EtOH, i-PrOH, t-BuOH, and cyclohexane as an alternative mix solvent with H2O gave only the racemate 1.

19

A white solid was obtained by filtration when a sat. NH4Cl aq and EtOAc were not added to the reaction mixture. ESI-TOFMS analysis of the collected solid showed the peak of [1 + 2 + Na]+ ion (m/z = 721.3 for C46H50O6Na) in the same manner as the case of the optical resolution. [13] The peak would mean the construction of the 1:1 inclusion complex (1 and 2) in the reaction mixture.

20

The ee of the products can be improved by a sequential optical resolution using (-)-2 without a base. [13]