Synthetic routes for a variety of halogenated (chiral) acetic acids from diethyl malonate

Abstract

Chiral halomethane is the smallest stable molecule with a single asymmetric C-atom and halogenated acetic acids often serve as precursors. We focus on a synthetic route to synthesise chiral halogenated acetic acids with F, Cl, Br, and H/D isotopic substitution at the a-C-atom starting from diethyl malonate.This reactant is easily available, cheap and allows the obtainment of target acids in a few reaction steps with great versatility. Among all of the possible fully halogenated acetic acids (more than one hundred, which are, in principle, accessible by this route), there are only a small number of chiral halogenated acetic acids, which have been synthesized following the devised synthetic route.

Absolute Configuration of Bromofluoroiodomethane after Preparative Gas Chromatographic Separation

“…amines and esters) of the corresponding acetic acids. [10] The VCD spectra were recorded on a BioTools ChiralIR 2X spectrometer. For detailed experimental procedures, see the Supporting Information.…”

Investigating Absolute Stereochemical Configuration with Coulomb Explosion Imaging

“…[13,15] A much more versatile and efficient synthesis has been described recently by starting from diethyl malonates. [16] The racemic CHBrClF was expanded by virtue of its room-temperature vapour pressure (without carrier gas) into the spectrometer and intersected with the laser. The high intensity of the laser pulse (around 6 • 10 14 W/cm²) can lead to up to fivefold ionisation and fragmentation into singly charged cations.…”

Absolute Configuration of Bromofluoroiodomethane after Preparative Gas Chromatographic Separation

“…The synthesis of small, halogen containing chiral molecules (C 1 and C 2 ) is difficult and has not been performed with high versatility in the past, however, we devised a versatile and efficient synthetic route to achieve this for chiral halogenated acetic acids. [10] Similarly difficult is the separation of enantiomers of such small compounds, where it is still a great challenge to crystallize the target molecules. Chiral derivatization and measurement of NMR anisotropy between two diastereomers can be used to determine the absolute configuration, [11] as well as enzymatic methods which rely on the enantio-preference of enzymes.…”