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

Abstract

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.