Highly Efficient and Robust Enantioselective Liquid-Liquid Extraction of 1,2-Amino Alcohols utilizing VAPOL- and VANOL-based Phosphoric Acid Hosts

The large-scale production of enantiopure compounds in a cost-effective and environmentally friendly manner remains one of the major challenges of modern day chemistry. The resolution of racemates via enantioselective liquid-liquid extraction was developed as a suitable solution but has remained largely underused due to a lack of highly efficient and robust chiral hosts to mediate the process. This paucity of hosts can in part be attributed to a feeble understanding of the underlying principles behind these processes hindering the design of more efficient selectors. Herein, we present an in depths study of a previously untested class of hosts, VAPOL and VANOL derived phosphoric acids, for the efficient enantioselective liquid-liquid extraction of 1,2-amino alcohols. A systematic investigation of extraction parameters was conducted revealing many key interactions, while DFT calculations illustrate the binding modes for the 1:1 complexes that are involved in chiral recognition. The resulting, now optimised, procedures, are highly robust and easy to implement. They are also easily scalable as was demonstrated by U-tube experiments.