Beyond L-proline: Investigation of the properties of other natural amino acids in an organocatalytic warfarin synthesis

Proline is indisputably the model organocatalytic amino acid. However, other naturally occurring amino acids remain a potent and perhaps overlooked source of organocatalytic potential. In this work, we investigate the capacity of various natural amino acids to promote enantioselectivity in a synthesis of warfarin. We have identified L- and D-arginine as enantioselective catalysts for this reaction and have developed a recrystallization method to isolate the enantiomers of warfarin with high enantiopurity. In addition, we use methylated derivatives of arginine provide insight into the reaction mechanism.