1H NMR spectroscopy in the presence of Mosher acid to rapidly determine the enantiomeric composition of amino acid benzyl esters, chirons susceptible to easy racemization

Abstract

Amino acid benzyl esters are very useful chiral synthons, whose enantiomeric purity needs to be carefully verified because of their susceptibility to easy racemization. Alternative to chiral HPLC, H NMR in the presence of a chiral solvating agent (CSA) can allow a more rapid and acceptably accurate determination of the enantiomeric composition, if explicit spectral non-equivalence of one or more protons of the analyte enantiomers is found. Here, we have studied the enantiodiscrimination of 13 amino acid benzyl esters byH NMR in the presence of (R)-Mosher acid and in different solvents proving that, for 5 of them (Ala, Pro, Glu, Met, Ser), efficient enantiodifferentiation can be achieved and ≤ 98% enatiomeric excesses accurately determined. Generally, as expectable, the best enantiodifferentiated proton was that on the amino acid stereogenic α-carbon, but also the spectral non-equivalence of methyl protons and of protons on the β-carbon and on the benzylic carbon could be exploited to distinguish the two enantiomers and to quantify the minor one. Structural feature favoring the amino acid ester enantiodiscrimination by the CSA seems to be low sterical hindrance at the amino acid β-carbon.

Efficient One‐Pot Reductive Aminations of Carbonyl Compounds with Aquivion‐Fe as a Recyclable Catalyst and Sodium Borohydride

“…[20] On our part, we needed a solvent stable under basic conditions, compatible with hydrides and, above all, apolar enough to avoid SB solubilisation and to exclude its reducing action during the DRA first stage. The choice, inspired by the recently reported replacement of banned solvents in L-amino acids esterification, [31][32][33] fell on the green ethers tert-amyl methyl ether (TAME), cyclopentyl methyl ether (CPME) and 2-methyl-tetrahydrofuran (Me-THF) and on pcymene, which is much less toxic than toluene. By the same protocol previously used in DCM, benzaldehyde was completely converted into benzylaniline and benzyl alcohol with a selectivity of 94 % in TAME, of 91 % in CPME, of 57 % in Me-THF and of 97 % in p-cymene.…”