Synthesis of spiro[indoline-3,3′-pyrrolizines] by 1,3-dipolar reactions between isatins, L-proline and electron-deficient alkenes

Abstract

Two spiro[indoline-3,3′-pyrrolizine] derivatives have been synthesized in good yield with high regio- and stereospecificity using one-pot reactions between readily available starting materials, namely L-proline, substituted 1H-indole-2,3-diones and electron-deficient alkenes. The products have been fully characterized by elemental analysis, IR and NMR spectroscopy, mass spectrometry and crystal structure analysis. In (1′RS,2′RS,3SR,7a′SR)-2′-benzoyl-1-hexyl-2-oxo-1′,2′,5′,6′,7′,7a′-hexahydrospiro[indoline-3,3′-pyrrolizine]-1′-carboxylic acid, C28H32N2O4, (I), the unsubstituted pyrrole ring and the reduced spiro-fused pyrrole ring adopt half-chair and envelope conformations, respectively, while in (1′RS,2′RS,3SR,7a′SR)-1′,2′-bis(4-chlorobenzoyl)-5,7-dichloro-2-oxo-1′,2′,5′,6′,7′,7a′-hexahydrospiro[indoline-3,3′-pyrrolizine], which crystallizes as a partial dichloromethane solvate, C28H20Cl4N2O3·0.981CH2Cl2, (II), where the solvent component is disordered over three sets of atomic sites, these two rings adopt envelope and half-chair conformations, respectively. Molecules of (I) are linked by an O—H...·O hydrogen bond to form cyclic R 6 6(48) hexamers of \overline{3} (S 6) symmetry, which are further linked by two C—H...O hydrogen bonds to form a three-dimensional framework structure. In compound (II), inversion-related pairs of N—H...O hydrogen bonds link the spiro[indoline-3,3′-pyrrolizine] molecules into simple R 2 2(8) dimers.