Transformations of (S )-1-Acyl-3-[(E )-(dimethylamino)methylidene]-5-(methoxycarbonyl)pyrrolidin-2-ones. A One- Step Synthesis of (S)-N - Benzoyl-3-(1-heteroaryl-5-hydroxy - 1H - pyrazolyl-4)alanine Esters

S)-1-Benzoyl-3-[(E)-(dimethylamino)methylidene]-5-(methoxycarbonyl)pyrrolidin-2-one (1) and (S)-1-tert-butoxycarbonyl-3-[(E)-(dimethylamino)methylidene]-5-(methoxycarbonyl)pyrrolidin-2-one (2) were transformed in one step with various hydrazines (3-10) into the corresponding (S)-3-(1-substituted 5-hydroxy-1H-pyrazolyl-4)alanine methyl esters (11-19).Since most of β-heteroarylalanines are non-proteinogenic amino acids widely found in nature, several synthetic methods for their preparation have been reported in last few decades. 1 Among them, the synthesis of 3-pyrazolylalanines has attracted considerable attention. 23-(Pyrazolyl-1)alanine for example, was used as constituent of highly potent renine inhibitors. 3Due to their potential biological activity, Young and coworkers developed a 'ring switching' strategy to the synthesis of 3-(pyrazolyl-4)alanines from (S)-3formylpyroglutamates and hydrazines. 4 Previously, we have shown that 3-dimethylamino-and 3-cyanopropenoates can serve as versatile reagents for the preparation of a variety of heterocyclic systems. 5,6On the other hand, we recently reported a 'ring switching' synthesis of 3-phenyl-3-(pyrazolyl-1)alanine esters with known relative configuration starting from rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone. 7In this connection, we have recently reported the utilization of 5-substituted (S)-1-acyl-3-[(E)-(dimethylamino)methylidene]pyrrolidin-2-ones, (S)-3-[(E)-(dimethylamino)methylidene]pyrrolidin-2-ones, and their 3-(E)-cyanomethylidene analogs for the preparation of heteroarylalanine and heteroaryllactic acid derivatives and their analogs. 8-10 In continuation of our work in this field, we report an improved 'ring switching' strategy for the synthesis of novel (S)-N-acyl-3-(1-heteroaryl-5-hydroxy-1H-pyrazolyl-4)alanine esters (11-19) from easily available (S)-1-acyl-3-[(E)-(dimethylamino)methylidene]-5-(methoxycarbonyl)pyrrolidin-2-ones (1) and (2).