Synthesis and spectroscopic and structural characterization of spiro[indoline-3,3'-indolizine]s formed by 1,3-dipolar cycloadditions between isatins, pipecolic acid and an electron-deficient alkene.

Five new spiro[indoline-3,3'-indolizine]s have been synthesized with high regio- and stereospecificity in one-pot three-component reactions between a substituted indole-2,3-dione, (S)-pipecolic acid and trans-3-benzoylacrylic acid, and subsequently characterized using a combination of elemental analysis, IR and 1H and 13C NMR spectroscopy, mass spectrometry and crystal structure analysis. (1'SR,2'SR,3RS,8a'RS)-2'-Benzoyl-5-fluoro-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C23H21FN2O4, (I), and (1'SR,2'SR,3RS,8a'RS)-2'-benzoyl-5-methyl-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C24H24N2O4, (II), are isomorphous, as are (1'SR,2'SR,3RS,8a'RS)-2'-benzoyl-1-methyl-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C24H24N2O4, (III), and (1'SR,2'SR,3RS,8a'RS)-2'-benzoyl-5-chloro-1-methyl-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C24H23ClN2O4, (IV). Within each isomorphous pair, the spiro ring systems show some conformational differences. In each of (I) and (II), the molecules are linked into complex sheets by a combination of four types of hydrogen bond, and in each of (III) and (IV), a combination of O-H...O and C-H...π(arene) hydrogen bonds links the molecules to form a chain of centrosymmetric rings. In (1'SR,2'SR,3RS,8a'RS)-2'-benzoyl-1-hexyl-2-oxo-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizine]-1'-carboxylic acid, C29H34N2O4, (V), a combination of five hydrogen bonds links the molecules into sheets of alternating R22(16) and R66(46) rings. A mechanism is proposed for the formation of compounds (I)-(V) and some comparisons with related structures are made.