The development of enantioselective synthesis was initially slow, largely due to the limited range of techniques available for their separation and analysis.
Diastereomers possess different physical properties, allowing separation by conventional means, however at the time enantiomers could only be separated by spontaneous resolution (where enantiomers separate upon crystallisation) or kinetic resolution (where one enantiomer is selectively destroyed). The only tool for analysing enantiomers was optical activity using a polarimeter, a method which provides no structural data.
It was not until the 1950s that major progress really began. Driven in part by chemists such as R. B. Woodward and Vladimir Prelog but also by the development of new techniques.
The first of these was X-ray crystallography, which was used to determine the absolute configuration of an organic compound by Johannes Bijvoet in 1951.
Chiral chromatography was introduced a year later by Dalgliesh, who used paper chromatography to separate chiral amino acids.
Although Dalgliesh was not the first to observe such separations, he correctly attributed the separation of enantiomers to differential retention by the chiral cellulose. This was expanded upon in 1960, when Klem and Reed first reported the use of chirally-modified silica gel for chiral HPLC separation.