Combining the Enantioselectivity of a Cyclodextrin and a Diamide Selector in a Mixed Binary Gas-Chromatographic Chiral Stationary Phase PAVEL A. LEVKIN, ALEXANDER RUDERISCH, and VOLKER SCHURIG* Institute of Organic Chemistry, University of Tu ¨bingen, Tu ¨bingen, Germany ABSTRACT The present work reports on the investigation of a mixed binary chiral stationary phase (CSP) prepared by simultaneous attachment of permethylated-b- cyclodextrin (D selector) and resorcinarene with pendant L - or D-valine diamide groups (LV and DV selectors, respectively) to a polysiloxane matrix via platinum-catalyzed hydrosilylation. The gas-chromatographic investigation of a number of racemates on the four different CSPs (D, DV, DDV, and DLV) showed that the enantioselectivity of the individual chiral selectors was retained in the mixed binary CSPs. As a consequence, hydrocarbons, underivatized alcohols, ketones, and almost all proteinogenic amino acid derivatives could be separated simultaneously on each of the mixed CSPs. Matched and mismatched cases of enantioseparation on the mixed binary CSPs were observed but turned out to be of minor importance for enantiomeric separation. In general, more racemates were separated with a z 1.02 on the mixed phases as compared to the single phases. In order to analyze the influence of the presence of the diamide selector on the enantioselectivity of the cyclodextrin selector, a mixed ternary CSP containing the selec- tor D and a racemic mixture of the selectors DV and LV [D(DVLV)] was prepared and in- vestigated. Merits and limitations of the approach of mixed binary CSPs are discussed. A 2005 Wiley-Liss, Inc. Chirality 18:49 – 63, 2006. KEY WORDS: enantioselective GLC; Chirasil-b-Dex; Chirasil-CalixVal; mixed binary CSPs; matched case; mismatched case; unified column Up to now, a great number of diverse chiral selectors for the gas-chromatographic separation of enantiomers have been developed. 1 Most of them display enantioselectivity only toward particular classes of chiral compounds, how- ever, and there is still no universal chiral stationary phase (CSP) available that is capable of enantioseparation of a majority of racemates. Chirasil-b-Dex (permethylated b-cyclodextrin bonded to a polysiloxane matrix; cf. Fig. 1) is one of the most versatile inclusion-type selectors. 2–4 Apart from the fact that Chirasil-Dex is enantioselective toward many classes of chiral compounds, such as under- ivatized alcohols, ketones, lactones, and alkyl halides, it is one of the very few selectors capable of resolution of chi- ral saturated aliphatic hydrocarbons lacking any functional groups. 5 In spite of this, enantioselectivity of the Chirasil- b-Dex toward proteinogenic amino acid derivatives (like N-trifluoroacetyl ethyl esters) is quite moderate; only six out of 16 investigated specimens were enantioseparated with a z 1.02 using a standard temperature program. By contrast, the diamide-type selectors 6–8 Chirasil-Val 9 and Chirasil-Calix-Val 10 (cf. Fig. 1) proved to be especially useful for the enantioseparation of racemates capable of hydrogen bonding, such as derivatives of a-amino acids. However, these selectors fail to separate racemates lack- ing hydrogen-bonding functional groups. Taking into account the importance of the simultaneous enantiosepa- ration of chiral unfunctionalized hydrocarbons and chiral amino acids in the search for extraterrestrial homochirality in various space explorations (Rosetta, 5 Titan, 11,12 and Exo- Mars 13,14 ), it appears challenging to try to combine the enantioselectivities of the cyclodextrin inclusion-type se- lector and diamide-type selector by applying them simulta- neously in one gas-chromatographic column. In a lucid account, Pirkle and Welch treated the merits and limitations of coupling of dissimilar enantioselective columns or mixing of different CSPs for the separation of enantiomers in the realm of liquid chromatography. 15 No advantage is gained by using two coupled columns containing individual selectors or, as is considered equiv- alent, by using only one column containing mixed selec- tors. However, the coupled-column approach (and hence the mixed binary approach) was considered to be advanta- geous when more complex mixtures are encountered. 15 This clearly applies in attempts to enantioseparate different classes of compounds simultaneously. In the above trea- tise, undiluted chiral selectors are considered. 15 If the chi- ral selectors are diluted in a matrix (e.g., a polysiloxane), the enantioseparation factor a is rendered concentration- Contract grant sponsors: Deutsche Forschungsgemeinschaft, TL-Stiftung (Tu ¨bingen) *Correspondence to: Prof. Dr. Volker Schurig, Institute of Organic Chemistry, University of Tu ¨bingen, Auf der Morgenstelle 18, D-72076, Tu ¨bingen, Germany. E-mail: volker.schurig@uni-tuebingen.de Received for publication 22 July 2005; Accepted 19 September 2005 A 2005 Wiley-Liss, Inc. CHIRALITY 18:49–63 (2006) DOI: 10.1002/chir.20219 Published online 14 November 2005 in Wiley InterScience (www.interscience.wiley.com).