Regio- and stereospecific assembly of dispiro[indoline-3,3′-pyrrolizine-1′,5′′-thiazolidines] from simple precursors using a one-pot procedure: synthesis, spectroscopic and structural characterization, and a proposed mechanism of formation

Abstract

The synthesis and characterization of three new dispiro[indoline-3,3′-pyrrolizine-1′,5′′-thiazolidine] compounds are reported, together with the crystal structures of two of them. (3RS,1′SR,2′SR,7a′SR)-2′-(4-Chlorophenyl)-1-hexyl-2′′-sulfanylidene-5′,6′,7′,7a′-tetrahydro-2′H-dispiro[indoline-3,3′-pyrrolizine-1′,5′′-thiazolidine]-2,4′′-dione, C28H30ClN3O2S2, (I), (3RS,1′SR,2′SR,7a′SR)-2′-(4-chlorophenyl)-1-benzyl-5-methyl-2′′-sulfanylidene-5′,6′,7′,7a′-tetrahydro-2′H-dispiro[indoline-3,3′-pyrrolizine-1′,5′′-thiazolidine]-2,4′′-dione, C30H26ClN3O2S2, (II), and (3RS,1′SR,2′SR,7a′SR)-2′-(4-chlorophenyl)-5-fluoro-2′′-sulfanylidene-5′,6′,7′,7a′-tetrahydro-2′H-dispiro[indoline-3,3′-pyrrolizine-1′,5′′-thiazolidine]-2,4′′-dione, C22H17ClFN3O2S2, (III), were each isolated as a single regioisomer using a one-pot reaction involving L-proline, a substituted isatin and (Z)-5-(4-chlorobenzylidene)-2-sulfanylidenethiazolidin-4-one [5-(4-chlorobenzylidene)rhodanine]. The compositions of (I)–(III) were established by elemental analysis, complemented by high-resolution mass spectrometry in the case of (I); their constitutions, including the definition of the regiochemistry, were established using NMR spectroscopy, and the relative configurations at the four stereogenic centres were established using single-crystal X-ray structure analysis. A possible reaction mechanism for the formation of (I)–(III) is proposed, based on the detailed stereochemistry. The molecules of (I) are linked into simple chains by a single N—H...N hydrogen bond, those of (II) are linked into a chain of rings by a combination of N—H...O and C—H...S=C hydrogen bonds, and those of (III) are linked into sheets by a combination of N—H...N and N—H...S=C hydrogen bonds.