CHEMISTRY OF NOVEL COMPOUNDS POSSESSING MULTIFUNCTIONAL CARBON-ATOMS .10. SYNTHETIC STUDIES OF EFFICIENT AND PRACTICAL CHIRAL DERIVATIZING AGENTS BASED ON THE ALPHA-CYANO-ALPHA-FLUOROPHENYLACETIC ACID STRUCTURE

In order to develop efficient chiral derivatizing agents (CDAs) which can be obtained readily in optically active form, synthetic studies of alpha-cyano-alpha-fluorophenylacetic acid (CFPA) analogs, 3a-e and CF NA (14a), were made, Carboxylation of 6a-e obtained from 4a-e gave 3a- e in low yield, Alternatively, benzyl cyanides 5b-e were converted suc cessfully to the esters 7b-e, 8b-e, and 9b-e, which were fluorinated w ith FClO3 to produce the fluoro esters 10b-e, 11b-e, and 12b-d, in goo d yields. However, the attempted ester cleavage of these compounds did not give 3b-e, Carboxyl group introduction into 5e afforded 13, and f luorination with either F-2 or FClO3 gave complex mixtures. Carboxylat ion of the naphthyl analog 16 obtained from 15 did not give 14a. Howev er, fluorination of 18 derived from 17 proceeded readily to give 19, w hich was hydrolyzed to produce 14a, Optically active(-)-14a was obtain ed through enzymatic hydrolysis. The racemic acid 14a was condensed wi th three representative chiral nucleophiles to give 14b-d. From the H- 1- and F-19-NMR spectra of these derivatives, it was concluded that CF NA (14a) is potentially a much better CDA than the well-known alpha-me thoxy-alpha-(trifluoromethyl)phenylacetic acid (MTPA).