2-Phenylpropionic acid, resolution

Racemic a-phenylethyl bromide is carbonylated under phase-transfer conditions with 5 N NaOH and dichloromethane containing bis-(dibenzylideneacetone)Pd(O) and a chiral 2-substituted 3,1,2-oxaza-phospholane to give a-phenylpropionic acid in moderate ee (Scheme 83) (196). The reaction involves kinetic resolution of the bromide with a discriminative slow oxidative addition step. 

Further application of the in-situ generation of chiral quaternary ammonium fluorides from the corresponding hydrogen sulfates has also been shown in the facile preparation of optically active esters via the alkylative kinetic resolution of secondary alkyl halides. For example, simple stirring of the mixture of 3-phenylpropionic acid, l-(l-bromoethyl)naphthalene, (S,S)-6b (X = HS04 2 mol%) and KF-2H20 (5 equiv.)... 

CEC has also been used for the chiral analysis of pollutants, using a variety of chiral mobile phase additives. Cyclodextrin chiral selectors have been used for the chiral resolution of ibuprofen [49], 2-phenylpropionic acid and warfarin [50]. Other chiral selectors that have been resolved include warfarin on human semm albumin [51], ibuprofen on avidin [52], dichloroprop, ibuprofen, warfarin and thalidomide on vancomycin [53], ibuprofen and warfarin on teicoplanin [54], thalidomide and warfarin on... 

Dynamic resolution reactions couple the in situ racemization of a starting material with a kinetic resolution, thereby providing a route for the conversion of both enantiomers of starting material into one enantiomer of product. However, there is an important caveat the reaction product must be essentially inert to racemization. In control studies, 2-phenylpropionic acid (224 R = H) has been shown to racemize only slowly when treated with DABCO (l,4-diazobicyclo[2.2.2]octane) in water-DMSO (1 19) at 40 °C, whereas its phenyl ester (224 R = Ph) treated similarly was almost completely racemized in 7h. This work led to a procedure employing Candida cylindracea lipase (CCL) in which D,L-2-phenylpropanoic acid underwent a promisingly efficient dynamic kinetic resolution (Scheme 40). ... 

C6H5, —OH, or —H at the chiral centre of the mandelic acid for a methyl group we repeated our tests with DL-a-phenylethanol (III), and DL-2-phenylpropionic acid (VI) (eluant methanol) and with a-methyl-DL-mandelic acid (IV) and DL-lactic acid (V) (eluant methanol or water). Only in the case of a-methylmandelic acid (IV) (eluant methanol) was a weak resolution noticed (maximal 0.5%, optical total enrichment 0.1%). 

In the case of the remaining two APAs, the respective vertical resolution of the antimer pairs was higher ARp = 0.04 for naproxen and ARp = 0.10 for 2-phenylpropionic acid). Accordingly, the observed maximum deviations of the migration tracks were also higher. With naproxen, the maximum sum of the left- and the right-handed (i.e., horizontal) deviation was equal to 6 ( 2) mm, and in the case of 2-phenylpropionic acid, the analogous value was equal to 7 ( 2) mm. 

Figure 16.2-47. Resolution of racemic (R,S)-2-phenylpropionic alcohol with whole cells of Gluconobacter oxydans yielding (S)-2-phenylpropanoic acid and (R)-2-phenylpropionic alcohol.

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