Resolution/Deracemization of Chiral α-Amino Acids Using Resolving Reagents with Flexible Stereogenic Centers (original) (raw)

2009, Journal of the American Chemical Society

Procedure for preparation of N-(2-benzoyl-phenyl)-2-bromo-2-methylpropanamide 3 3 Characterization of N-(2-benzoyl-phenyl)-2-bromo-2 methylpropanamide 3 3 Procedure for preparation of (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenylethylamino)-acetamide 5 4 Characterization of (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)acetamide 5 4 General Procedure for the formation of diastereomeric Ni(II) complexes of Schiff bases with α-amino acids 7a-f, 8a-f. 5 Characterization of Ni(II) Complex of (S)-alanine Schiff Base with (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 7a 5 Characterization of Ni(II) Complex of (R)-alanine Schiff Base with (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 8a 6 Characterization of Ni(II) Complex of (S)-2-Aminobutyric Acid Schiff Base with (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 7b 7 Characterization of Ni(II) Complex of (S)-Phenylalanine Schiff Base with (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 7c 8 Characterization of Ni(II) Complex of (R)-Phenylalanine Schiff Base with (R)-N-(2benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 8c 9 Characterization of Ni(II) Complex of (S)-Valine Schiff Base with (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 7d 10 S2 Characterization of Ni(II) Complex of (R)-Valine Schiff Base with (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 8d Characterization of Ni(II) Complex of (S)-Phenylglycine Schiff Base with (R)-N-(2-benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 7e Characterization of Ni(II) Complex of (R)-Phenylglycine Schiff Base with (R)-N-(2benzoylphenyl)-2,2-dimethyl-2-(1-phenyl-ethylamino)-acetamide 8e General Procedure for Decomposition of complexes 7 and 8, isolation of target amino acids 6, and recovery of chiral ligand 5. X-ray crystal structure of Ni(II) Complex 7a X-ray crystal structure of Ni(II) Complex 7c X-ray crystal structure of Ni(II) Complex 7d X-ray crystal structure of Ni(II) Complex 8d X-ray crystal structure of Ni(II) Complex 7e X-ray crystal structure of Ni(II) Complex 7f X-ray crystal structure of Ni(II) Complex 8f S3 General Methods. Unless otherwise noted all reagents and solvents were obtained from commercial suppliers and used without further purification. All of the reactions were carried out under Nitrogen atmospheres. Unless indicated 1 H and 13 C NMR spectra, were taken in CDCl 3 solutions at 299.95 and 75.42 MHz respectively, on an instrument available from the University of Oklahoma NMR Spectroscopy Laboratory. Chemical shifts refer to TMS as the internal standard. Yields refer to isolated yields of products of greater than 95% purity as estimated by 1 H and 13 C NMR spectroscopy. All new compounds were characterized by 1 H, 13 C NMR, highresolution mass spectrometry (HRMS-ESI), and melting point. Condensation of o-amino-benzophenone 1 and 2-bromo-2-methylpropanoyl bromide 2 yielding N-(2-benzoyl-phenyl)-2-bromo-2-methylpropanamide 3: A solution of acid module 2 (104.64 mmol) in acetonitrile (2 mL/1 g of 2) was slowly added to a slurry of phenone module 1 (102.32 mmol) and potassium carbonate 70.71 g (511.61 mmol) in acetonitrile 240 mL. The reaction was stirred at ambient temperature (room temperature water bath) for one hour, and upon completion (monitored by TLC), the acetonitrile was evaporated under vacuum. Water 200 mL was then added to the crude mixture and extracted with dichloromethane 200 mL three times. The organic portions were combined, dried and concentrated under vacuum to afford the corresponding α-bromoamide product 3 in 98% yield and greater than 99% chemical purity.