Michael addition reactions between various nucleophilic glycine equivalents and (S,E)-1-enoyl-5-oxo-N-phenylpyrrolidine-2-carboxamide, an optimal type of chiral Michael acceptor in the asymmetric synthesis of β-phenyl pyroglutamic acid and related compoun

(S)-5-Oxo-N-phenyl-1-[(E)-3-phenylacryloyl]pyrrolidine-2-carboxamide, easily prepared from inexpensive and readily available, in both enantiomeric forms, glutamic/pyroglutamic acid was designed as an optimal type of chiral Michael acceptor for reactions with a series of nucleophilic glycine equivalents. A study of the corresponding Michael addition reactions revealed that the new generation of modular glycine derivatives, as a counterpart to the Michael acceptor, provides for operationally convenient preparation of β-phenyl pyroglutamic acids and related compounds with virtually complete chemical and stereochemical outcomes.

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(S)-5-Oxo-N-phenyl-1-((E)-3-phenylacryloyl)pyrrolidine-2-carboxamideC20H18N2O3[α]D25=-43.5 (c 0.0008, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (S)

Ni(II) complex of (2R,3S,2′S)-3-phenyl-5-[5′oxo-N-phenylpyrrolidine-2′-carboxamide] glutamic acid Schiff base with 2-(picolinoylamino)-benzophenoneC41H33N5NiO6[α]D25=-413.2 (c 0.006, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (2R,3S,2′S)

Ni(II) complex of (2R,3S,2′S)-3-phenyl-5-[5′oxo-N-phenylpyrrolidine-2′-carboxamide] glutamic acid Schiff base with 2-(picolinoylamino)-acetophenoneC36H31N5NiO6[α]D25=-582.6 (c 0.0007, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (2R,3S,2′S)

Ni(II) complex of (2R,3S,2′S)-3-phenyl-5-[5′oxo-N-phenylpyrrolidine-2′-carboxamide] glutamic acid Schiff base with N-(2-benzoyl-phenyl)-2-dibutylamino-acetamideC45H44N5NiO6[α]D25=-70.0 (c 0.0011, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (2R,3S,2′S)

Ni(II) complex of (2R,3S,2′S)-3-phenyl-5-[5′oxo-N-phenylpyrrolidine-2′-carboxamide] glutamic acid Schiff base with N-(2-acetyl-phenyl)-2-dibutylamino-acetamideC40H47N5NiO6[α]D25=-974 (c 0.08, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (2R,3S,2′S)

Ni(II) complex of (2R,3S,2′S)-3-phenyl-5-[5′oxo-N-phenylpyrrolidine-2′-carboxamide] glutamic acid Schiff base with N-(2-benzoyl-phenyl)-2-piperidyl-acetamideC45H49N5NiO6[α]D25=-405.2 (c 0.0007, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (2R,3S,2′S)

Ni(II) complex of (2R,3S,2′S)-3-phenyl-5-[5′oxo-N-phenylpyrrolidine-2′-carboxamide] glutamic acid Schiff base with N-(2-acetyl-phenyl)-2-piperidyl-acetamideC40H47N5NiO6[α]D25=-432.8 (c 0.002, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (2R,3S,2′S)

Ni(II) complex of (2R,3S,2′S)-3-phenyl-5-[5′oxo-N-phenylpyrrolidine-2′-carboxamide] glutamic acid Schiff base with N-(2-benzoyl-phenyl)-2-dimethylamino-acetamideC39H37N5NiO6[α]D25=-1088 (c 0.05, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (2R,3S,2′S)

Ni(II) complex of (2R,3S,2′S)-3-phenyl-5-[5′oxo-N-phenylpyrrolidine-2′-carboxamide] glutamic acid Schiff base with N-(2-benzoyl-phenyl)-2-diethylamino-acetamideC41H41N5NiO6[α]D25=-416 (c 0.05, CHCl3)Source of chirality: l-pyroglutamic acidAbsolute configuration: (2R,3S,2′S)