Cellulose and cellulose derivatives are biopolymers which are often used as stationary phases for the separation of enantiomers. Describing the mechanism of such separations is a difficult task due to the complexity of these phases. In the present study, we attempt to elucidate the types of interactions occurring between a diol intermediate for a LTD(4) antagonist and a tris(4-methylbenzoate)-derivatized cellulose stationary phase. Thermodynamic studies indicate that, at low temperatures, the enantioselectivity is entropy driven. At higher temperatures, the separation is enthalpy driven. DSC and IR experiments reveal that the transitions between the enthalpic and the entropic regions of the van't Hoff plots are a result of a change in conformation of the stationary phase. Investigation of chromatographic kinetic parameters reveals that, at low temperature, the second eluted enantiomer undergoes sluggish inclusion interactions. Subtle changes in the structure of the analyte indicates that π-π interactions do not contribute to enantioselectivity. Finally, molecular modeling of (R)- and (S)-diol and the stationary phase suggests that hydrogen bonding is a primary factor in the separation, and the calculated energy values obtained from the molecular modeling correlate well with the chromatographic elution order.

Addition of methylmagnesium chloride to ester 1 in the presence of cerium chloride gave significantly better yields of the tertiary alcohol 2 than the reaction performed in the absence of cerium chloride. The beneficial effect of added cerium chloride is postulated to be due to suppression of the enolization of the ketone intermediate. The use of properly "activated" anhydrous cerium chloride which is proposed to generate a less basic, more nucleophilic species to overcome this undesired reaction was found to be critical. The activated cerium chloride was identified as the known seven-coordinate THF solvate, [CeCl(m-Cl) 2 (THF) 2 ] n . Inactive crystal forms were also identified and the key parameters for formation of the active form were delineated.

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We show that complexation of B-chlorodiisopinocampheylborane (Dip-Cl) with 8-hydroxyquinoline results in an air- and moisture-stable complex. Using enantiomerically pure (+)-α-pinene, the (+,+)-Dip-quinoline complex, [(+)-C10H17]2B(η2-N,O-C10H6NO), was isolated and characterized by spectroscopic and crystallographic methods. When Dip-Cl is prepared from enantiomerically impure (+)-α-pinene a mixture of heterochiral, (+,−)-Dip-Cl, and homochiral, (+,+)-Dip-Cl and (−,−)-Dip-Cl, stereoisomers are formed. We have developed the 8-hydroxyquinoline complexation method for quantification of these stereoisomers by chiral HPLC. Since this is the first quantitative analysis of a reagent that exhibits asymmetric amplification, it enables us to verify part of Kagan's model for this phenomenon and evaluate the terms β and K which are measures of the relative amounts of stereoisomers. Our analysis shows that there is a preference for the formation of the heterochiral (+,−)-Dip-Cl isomer; therefore, the stereoisomers are not statistically distributed. This is beneficial for the asymmetric amplification process because it causes the heterochiral diastereomer to absorb the minor (−)-α-pinene enantiomer, thereby increasing the effective concentration of (+,+)-Dip-Cl that is formed from (+)-α-pinene. We also studied the distribution of stereoisomers as a function of the preparation temperature of the Dip-Cl reagent (0, 10, 20 °C). Increasing the preparation temperature increases the relative amounts of the homochiral stereoisomers, suggesting that the activation energy for the formation of the homochiral isomers is greater than for the heterochiral isomer. Thus, at higher preparation temperatures greater amounts of (−,−)-Dip-Cl are formed from (−)-α-pinene. However, there is a surprising benefit as higher levels of asymmetric induction are observed, especially when low enantiomeric purity α-pinene is used. In addition, the reduction reactions proceed slightly faster when Dip-Cl is prepared at higher temperature. In sum, the complexation of Dip-Cl with 8-hydroxyquinoline and subsequent analysis by chiral HPLC provides considerable insight into the asymmetric amplification process observed with this reagent. Moreover, we have shown how the conditions used for the preparation of the reagent affect the asymmetric amplification process.

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