Use of 1,3-Dioxin-4-ones and Their Related Compounds in Synthesis. Part 35. Synthesis of Optically Pure Fluoromalonamic Acids by Means of Asymmetric Fluorination of Chiral 1,3-Oxazine-4,6-diones

Abstract

Abstruct-Fluorination of chiral 5-substituted 1,3-oxazine-4.6-dionederivatives proceeded stereoselectively to give the 5-fluorooxazinediones, which were readily transformed to optically pure fluoromalonamic acids.Owing to their expected enhancement of biological activity, fluorinated organic compounds have attracted much attention in the field of medicinal chemistry.2Chiral substituted fluoromalonates are useful intermediates for construction of such compounds because of their bifunctionality and impossible racemization.However, the synthetic methods for these malonates so for reported are not satisfactory.Asymmetric hydrolysis of prochiral a-substituted a-fluoromalonate with lipase catalysis gives good results only when the a-substituent is relatively small one, such as methyl and ethyl groups.3Asymmetric fluorination of chiral monosubstituted This paper is dedicated to Emeritus Professor M. Hamana on the occasion of his 75th birthday.