Acylative kinetic resolution of racemic amines using N-phthaloyl-(S)-amino acyl chlorides

A comparative study of the kinetic resolution of racemic 2-methyl-1,2,3,4-tetrahydroquinoline and 2,3-dihydro-3-methyl-4H-1,4-benzoxazine using N-phthaloyl-(S)-amino acyl chlorides as chiral acylating agents is described. Temperature and solvent effects on the stereochemical features have been examined. It has been found that N-phthaloyl-(S)-phenylalanyl and N-phthaloyl-(S)-2-phenylglycyl chlorides bearing aromatic substituents close to the stereogenic centre are more stereoselective acylating agents than N-phthaloyl-(S)-alanyl chloride. For the preparative kinetic resolution of racemic amines N-phthaloyl-(S)-phenylalanyl chloride proved to be the most appropriate chiral acylating agent.

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(2S)-2-Methyl-N-[N′-phthaloyl-(2′S)-phenylalanyl]-1,2,3,4-tetrahydroquinolineC27H24N2O3[α]D20=+364 (c 1.0, CHCl3)Source of chirality: N-phthaloyl-(S)-phenylalanineAbsolute configuration: (2S,2′S)

(3S)-2,3-Dihydro-3-methyl-N-[N′-phthaloyl-(2′S)-phenylalanyl]-4H-1,4-benzoxazineC26H22N2O4[α]D20=+341 (c 1.0, CHCl3)Source of chirality: N-phthaloyl-(S)-phenylalanineAbsolute configuration: (3S,2′S)

(2S)-2-Methyl-N-[N′-phthaloyl-(2′S)-2-phenylglycyl]-1,2,3,4-tetrahydroquinolineC26H22N2O3[α]D20=+562 (c 1.0, CHCl3)Source of chirality: N-phthaloyl-(S)-phenylglycineAbsolute configuration: (2S,2′S)

(3S)-2,3-Dihydro-3-methyl-N-[N′-phthaloyl-(2′S)-2-phenylglycyl]-4H-1,4-benzoxazineC25H20N2O4[α]D20=+228 (c 1.0, CHCl3)Source of chirality: N-phthaloyl-(S)-phenylglycineAbsolute configuration: (3S,2′S)