Chemistry of Novel Compounds with Multifunctional Carbon Structure. VI. : Synthetic Studies and ¹⁹F-Nuclear Magnetic Resonance Investigation of Novel α, α-Disubstituted Fluoroacetates

Abstract

As a part of our work on synthetic studies of chiral monofluoro compounds and molecular design of efficient reagents for optical purity determination, we focused on novel α, α-disubstituted α-fluoroacetic acids (8a-d) (R¹=Me, Ph; R²=C≡CPh, Me, Bu). The ethyl esters (13a-d) were prepared by introduction of alkyl groups into the appropriate α-keto acids (9a, b) followed by fluorination of the corresponding hydroxy-esters (12a-d) with diethylaminosulfur trifluoride (DAST). For comparison with Mosher's reagent (2-methoxy-2-trifluoromethylphenylacetic acid, (MTPA)), the ethyl esters (13a-d) were converted into three representative diastereoisomers, (14a-d), (15a-d), and (16a-d), and ¹⁹F-nuclear magnetic resonance (¹⁹F-NMR) chemical shift differences between pairs of diastereoisomers (Δδ) were obtained. These α, α-disubstituted α-fluoroacetate derivatives have much larger Δδ values than the corresponding derivatives of MTPA, which strongly indicates that the acids (8a-d) can potentially be better reagents for ee determination than MTPA. The influence on the Δδ values of the steric effects which arise upon introduction of the two substituents (R¹ and R²) on the fluorine-bearing chiral center is also discussed.