Synthesis
GENERAL STEPS: To a 5 mL reaction vial equipped with a magnetic stirrer was added 3-cyclohexyl-2-oxopropanoic acid (1j) (0.0510 g, 0.30 mmol), 2,2-diphenylglycine (2) (0.0681 g, 0.30 mmol), chiral pyridoxamine 6 g (0.0195 g, 0.030 mmol) and MeOH-H2O (8:2) , v/v) (3.0 mL). The reaction mixture was stirred at 20 °C for 3 days. Upon completion of the reaction, the mixture was transferred to a 25 mL round-bottom flask and methanol was added until all solids were completely dissolved. Silica gel (0.50 g) was then added. The solvent was removed by reduced pressure distillation at 20 °C and the resulting residue was purified by silica gel column chromatography (eluent ratio EtOH/ethyl acetate/25-28% ammonia solution = 100:58:16) to afford compound 3j (0.0401 g, 78% yield, 52% ee) as a white solid. To determine the enantiomeric excess of 3b-k, compound 3j was first treated with thionyl chloride in methanol and subsequently converted to N-benzoylmethyl ester by reaction with benzoyl chloride and finally analyzed by HPLC. For the determination of enantiomeric excess of compound 3a, it was converted to methyl ester by treatment with CH2N2 in methanol followed by HPLC analysis.
References
[1] Tetrahedron Letters, 2016, vol. 57, # 41, p. 4612 - 4615
