Chlorofluoroacetic Acid as a Highly Versatile Derivatizing Agent: Assignment of Stereochemistry to Esters of Chiral Alcohols

Abstract

Stereochemistry of a series of diastereomeric esters obtained from chiral alcohols 1a-21a by derivatization with (S)- or (R)-chlorofluoroacetic acid was correlated with their LC and GC separation (∆tr) and NMR resolution (∆δ). Both the chromatographic and NMR spectral behavior of respective diastereomers was found to follow systematic rules reflecting their steric arrangement. Moreover, identical conformations of the esters seem to be preferred in solution as well as in the chromatographic processes. Reasons underlying this behavior are discussed.

Chiral derivatives of 2‐(1‐naphthyl)‐2‐phenylacetic acid

“…The data from NMR as well as X-ray analysis are in good agreement, corroborating that conformation in a crystal as well as in a solution in a nonpolar solvent is similar. 13 The crystallographic analysis also shows very close similarity between the X-ray structure (Fig. 2C) and the optimized one ( Fig.…”

“…Applying the steric model of diastereomer/adsorbent interaction 13 and assuming that the interaction of both aromatic rings with the adsorbent's surface will be similar, the elution order difference (Dt r ) of 1b-20b diastereomers may thus be reasonably explained.…”

“…2 Low volatility and/or stability (GC), or inability to undergo the derivatization for steric reasons, may also be a limiting factor. 12,13 Generally, good separation and/or determination of diastereomers is certainly affected, among others, by the ability of the molecule to adopt the preferred conformation, while the distance of chiral centra is no less important. The incorporation of either bulky or polar groups or both into the molecule of a chiral auxiliary agent is the usual approach how to increase the stability of the representative conformation.…”