Stereoselective intramolecular cycloadditions of homochiral nitrilimines as a source of enantiopure 2,3,3a,4,5,6-hexahydro-pyrrolo[3,4-c]pyrazoles

Starting from the methyl esters of glycine, l-alanine, l-phenylalanine and (S)-2-phenylglycine, we developed a synthetic route to the title compounds in the enantiopure form by means of a stereoselective intramolecular 1,3-dipolar cycloaddition of homochiral nitrilimines 5a–d. Fair to good overall product yields and high cycloaddition diastereoselectivity were obtained.

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N,N-Diallyl-(S)-phenylglycine methylesterC15H19NO2[α]D25=-23.7 (c 0.26, CH2Cl2)Source of chirality: (S)-phenylglycine methylesterAbsolute configuration: (2S)

N-2(S)-Diallylaminopropanoyl-N′-phenylhydrazineC15H21N3O[α]D25=-16.4 (c 0.24, CHCl3)Source of chirality: N,N-diallyl-(S)-alanine methylesterAbsolute configuration: (2S)

N-2(S)-Diallylamino-3-phenyl-propanoyl-N′-phenylhydrazineC21H25N3O[α]D25=-9.4 (c 0.15, CH2Cl2)Source of chirality: N,N-diallyl-(S)-phenylalanine methylesterAbsolute configuration: (2S)

N-2(S)-Diallylamino-2-phenyl-ethanoyl-N′-phenylhydrazineC20H23N3O[α]D25=-12.2 (c 0.21, CH2Cl2)Source of chirality: N,N-diallyl-(S)-phenylglycine methylesterAbsolute configuration: (2S)

2-Phenyl-5-allyl-3a(R)-6(S)-methyl-2,3,3a,4,5,6-hexahydro-pyrrolo[3,4-c]pyrazoleC12H14N2O[α]D25=-106.0 (c 0.43, CH2Cl2)Source of chirality: the precursorAbsolute configuration: 3a(R),6(S)

2-Phenyl-5-allyl-3a(S)-6(S)-benzyl-2,3,3a,4,5,6-hexahydro-pyrrolo[3,4-c]pyrazoleC21H23N3[α]D25=-83.2 (c 0.51, CHCl3)Source of chirality: the precursorAbsolute configuration: 3a(R),6(S)

2-Phenyl-5-allyl-3a(R)-6(S)-phenyl-2,3,3a,4,5,6- hexahydro-pyrrolo[3,4-c]pyrazoleC20H21N3[α]D25=-76.1 (c 0.29, CHCl3)Source of chirality: the precursorAbsolute configuration: 3a(R),6(S)

2-Phenyl-5-allyl-3a(S)-6(S)-methyl-2,3,3a,4,5,6-hexahydro-pyrrolo[3,4-c]pyrazoleC15H19N3[α]D25=+112.7 (c 0.58, CHCl3)Source of chirality: the precursorAbsolute configuration: 3a(S),6(S)