Synthesis of optically active polyheterocycles containing pyrrolidine, imidazole, and 1,2,3-triazole rings

Optically active polyheterocycles containing pyrrolidine, imidazole, and 1,2,3-triazole units were obtained via a multistep synthesis with the [3+2] cycloaddition of Boc-protected (S)-(pyrrolidin-2-yl)methyl azide with 2-ethynylimidazoles in the presence of CuI (CuAAC reaction) as the key step. Typical for terminal alkynes, the reactions occurred regioselectively and 1,4-disubstituted 1,2,3-triazoles were formed exclusively. The deprotection of the pyrrolidine N-atom was performed by treatment with TFA under standard conditions.

Figure optionsDownload as PowerPoint slide

4-(1,4,5-Trimethyl-1H-imidazol-2-yl)-1-[((S)-pyrrolidin-2-yl)methyl]-1,2,3-triazoleC13H20N6Ee = 100%[α]D25 = −26 (c 0.5, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

4-(1,4-Dimethyl-5-phenyl-1H-imidazol-2-yl)-1-[((S)-pyrrolidin-2-yl)methyl]-1,2,3-triazoleC18H22N6Ee = 100%[α]D25 = −19 (c 0.625, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

4-(1-Methyl-4,5-diphenyl-1H-imidazol-2-yl)-1-[((S)-pyrrolidin-2-yl)methyl]-1,2,3-triazoleC23H24N6Ee = 100%[α]D25 = −29 (c 0.5, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

4-(1-Butyl-4,5-dimethyl-1H-imidazol-2-yl)-1-[((S)-pyrrolidin-2-yl)methyl]-1,2,3-triazoleC16H26N6Ee = 100%[α]D25 = −32 (c 0.5, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)

4-(1-Butyl-4-methyl-5-phenyl-1H-imidazol-2-yl)-1-[((S)-pyrrolidin-2-yl)methyl]-1,2,3-triazoleC21H28N6Ee = 100%[α]D25 = −16 (c 0.625, CH2Cl2)Source of chirality: (S)-prolineAbsolute configuration: (S)