Enantiomeric purity analysis alcohols

The BINAP derivative of the ort/io-cyclometallated iridium catalyst has been characterized by single crystal X-ray diffraction analysis [280]. Remarkably, although the reaction sequence depends upon oxidation of either the reactant alcohol or isopropanol, the enantiomeric purity of the homoallylic alcohol product... 

The enantiomeric purity is determined by chiral stationary phase, supercritical fluid chromatographic (CSP-SFC) analysis (Berger Instruments, Daicel Co. CHIRALCEL OD column 4% methanol, 180 psi, 3.0 mUmin flow rate detection at 220 nm). Racemic 1-phenylpropanol exhibited base-line separation of peaks of equal intensity arising from the R-isomer (tp, 2.74 min) and the S-isomer (tp, 3.10 min) whereas the synthetic alcohol showed these peaks in the ratio 97.7 / 2.3. This chromatographic method allowed for identification of the trace contaminants propiophenone (tp, 1.63 min) and benzyl alcohol (tp 3.40 min). 

Enantiomeric purity was determined to be 96-98% by 1H NMR analysis of the Mosher esters4 of the alcohols 4 and ent-4 obtained by reduction of the aldehydes 5 and ent-5. To an ice-cold solution of aldehyde 5 (0.10 g, 0.44 mmol) in 5 mL of methanol was added solid sodium borohydride (33 mg, 0.88 mmol). After the mixture was stirred for 30 min at this temperature, the TLC in (7 3) cyclohexane-ethyl acetate showed the clean formation of the alcohol 4. The mixture was treated with 0.05 mL of acetone and concentrated to dryness under reduced pressure. The residue was partitioned between water (10 mL) and ethyl acetate (10 mL) and the phases were separated. The aqueous phase was extracted with three 10-mL portions of ethyl acetate. The combined organic phases were dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by flash... 

Analysis of Reagent Purity the enantiomeric purity of the reagent can be evaluated by capillary GC analysis of its methyl ester on a chiral stationary phase, HPLC analysis of the corresponding l-(a-naphthyl)ethylamide, or by LiAlfli reduction to the corresponding alcohol, which is analyzed by chiral GC." ... 

Alcohok. When using the H NMR spectra of MTPA esters to determine the enantiomeric purity of alcohols, the MTPA methoxy peaks tend to be most useful. This technique can be sensitive enough to detect as little as 1% of the minor alcohol enantiomer. The enantiomeric purity of chiral alcohols (1) and (2) has been determined this way. The enantiomeric purity of primary alcohols (3) and (4), in which the asymmetric center is not the carbinol carbon, has also been determined by H NMR analysis of their MTPA esters. A slight variation of this methodology is the use of shift reagents like Eu(fod)3 to increase the chemical shift separation between diastereotopic MeO peaks this procedure has been used in the analysis of alcohols (S) and (6). ... 

Amines. In a manner similar to alcohols, the enantiomeric purity of primary and secondary amines can be assayed by H NMR analysis of their MTPA amides. The technique has been particularly useful for amino acid derivatives, e.g. (13), (14), and (15). ... 

Other Compounds. In theory, any chiral compound with a reactive functional group can be derivatized with (5)- or (R)-MTPA in order to assess its enantiomeric purity. An example is the derivatization of cyclic carbamates, followed by H NMR analysis (eq 1). Similarly, axially chiral biaryls bearing amine or alcohol substituents, e.g. (16) and (17), have been analyzed via the corresponding MPTA derivatives. ... 

The enantiomeric purity of carboxylic acids with remotely disposed chiral centers can be analyzed using 2-(anthracene-2,3-dicarboximido)cyclohexanol 36. Similar to the derivative with a carboxylic acid moiety on the cyclohexane ring 10 described earlier for the analysis of alcohols, the ester derivative of carboxylic acids with 36 positions the carbon chain of the substrate over the anthryl ring. Carboxylic acids with the stereocenter at C12 still show enantiomeric discrimination in the derivative with 36. ... 

Me02CCH0/H+ -7.90 eV, vide infra), by the BINOL-Ti catalyst (1) (Table 1). The reaction was carried out by simply adding an olefin and tfien freshly dehydrated and distilled fluoral (2a) at 0 C to the solution of the chiral titanium complex (1) prepared from (/ )- or (5)-BINOL and diisopropoxytitanium dihalide in the presence of molecular sieves MS 4A as described for die glyoxylate-ene reaction (5). The reaction was completed widiin 30 min. The ene-type product, namely homoallylic alcohol (3) was obtained along with the allylic alcohol (4) (entries 1-4). The enantiomeric purities of both products were determined to be more than 95% ee by 1h NMR analysis after transformation to the (5)- and (/ )-MTPA ester derivatives. Thus, the absolute configuration of the products was determined by the Mosher method (8). The sense of asymmetric induction is, therefore, exactly the same as observed for the glyoxylate-ene reaction the (/ )-catalyst provides the (/ )-alcohol products (5). 

Determination of Optical Yields. Optical yields of the siloxycyclopentenones derived from CPDK were determined by chiral HPLC (Chiracel OC column (J. T. Baker)) with the exception of the triphenylsilane derivative which was determined by optical rotation. 2-Butanol was derivatized to the corresponding diastereomeric urethanes with /Mnethylbenzylisocyanate according to literature procedures (32) the optical yield was then determined by G.C analysis using a Chirasil-L-Val column (Chrompack). The optical purity of the remaining alcohols (with the exception of a-tetralol optical rotation) was determined by chiral G.C. analysis of the underivatized alcohol using a CP-Cyclodextrin-B-2,3,6-M-19 column (Chrompack). Baseline resolution of the enantiomeric alcohols was achieved in all cases and it was observed that the / -isomer was eluted first without exception (confirmed by both optical rotation and G.C. analysis of independently prepared optically pure samples). 

Combination of a nonracemic isocyanate and a l,3-disul)sliluted distannoxane has provided a new method for determination of the optical purity of chiral alcohols (Scheme 12.174) [316]. When a chiral alcohol was reacted with commercially available (l )-l-(l-naphthyl)efhyl isocyanate in the presence of 1,3-disubstituted distannoxane, formation of the desired carbamates occurred rapidly, with acid-labile functional groups such as ester, THP and /Miydroxyketone remaining intact. Subsequent HPLC analysis of the resulting carbamate revealed a pair of well-separated peaks of diastereomers derived from both enantiomeric alcohols. 

When one needs to determine the optical purity of a compound that is not amenable to salt formation (i.e., not a carboxylic acid or amine), analysis by NMR becomes slightly more difficult. It is frequently necessary to determine the enantiomeric excesses of chiral secondary alcohols, for example. In these cases, derivatization of the alcohol through covalent attachment of an optically pure auxiliary provides the mixture of diastereomers for analysis. This requires reacting a (usually small, a few milligrams) sample of sample alcohol with the optically pure derivatizing agent. Sometimes, purification of the products is necessary. In the example shown below, a chiral secondary alcohol is reacted with (5)-2-methoxyphenylacetic acid [(5)-MPA] using dicyclohexylcarbodiimide (DCC) to form diastereomeric esters. After workup, the NMR spectrum of product mixture is acquired, and the res-... 

---