Synthesis
The general procedure for the synthesis of benzophenone, L-Γ-methylisoleucine and (R)-2-amino-4,4-dimethylpentanoic acid from 4,4-dimethyl-2-oxopentanoic acid and 2,2-diphenylglycine was as follows: to a 5 mL reaction vial equipped with a magnetic stirrer were added, in order, 3-cyclohexyl-2-oxopropionic acid (1j, 0.0510 g, 0.30 mmol), 2, 2-diphenylglycine (2, 0.0681 g, 0.30 mmol), chiral pyridoxamine 6g (0.0195 g, 0.030 mmol), and MeOH-H2O (8:2, 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-bottomed flask and methanol was added until all solids were completely dissolved. Subsequently, silica gel (0.50 g) was added and the solvent was removed by concentration under reduced pressure at 20 °C. The resulting residue was purified by silica gel column chromatography (eluent ratio EtOH/ethyl acetate/25-28% ammonia = 100:58:16) to afford compound 3j (0.0401 g, 78% yield, 52% ee) as a white solid. To determine the enantiomeric excess of compounds 3b-k, they were 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 and then analyzed by HPLC.
References
[1] Tetrahedron Letters, 2016, vol. 57, # 41, p. 4612 - 4615
