Structural consequences of weak interactions in dispirooxindole derivatives

Spiro scaffolds are being increasingly utilized in drug discovery due to their inherent three-dimensionality and structural variations, resulting in new synthetic routes to introduce spiro building blocks into more pharmaceutically active molecules. Multicomponent cascade reactions, involving the in situ generation of carbonyl ylides from alpha-diazocarbonyl compounds and aldehydes, and 1,3-dipolar cycloadditon with 3-arylideneoxindoles gave a novel class of dispirooxindole derivatives, namely 1,1 ''-dibenzyl-5'-(4-chlorophenyl)-4'-phenyl-4',5'- dihydrodispiro[indoline-3,2'-furan-3',3 ''-indoline]-2,2 ''-dione, C44H33ClN2O3, (I), 1 ''-acetyl-1-benzyl-5 '-(4-chlorophenyl)-4 '-phenyl-4',5'-dihydrodispiro[indoline- 3,2'-furan-3',3 ''-indoline]-2,2 ''-dione, C39H29ClN2O4, (II), 1 ''-acetyl-1-benzyl-4',5'- diphenyl-4',5'-dihydrodispiro[indoline-3,2'-furan-3',3 ''-indoline]-2,2 ''-dione, C39H30N2O4, (III), and 1 ''-acetyl-1-benzyl-4',5'-diphenyl-4',5'-dihydrodispiro[ indoline-3,2'-furan-3',3 ''-indoline]-2,2 ''-dione acetonitrile hemisolvate, C39H30N2O4 center dot 0.5C(2)H(3)N, (IV). All four compounds exist as racemic mixtures of the SSSR and RRRS stereoisomers. In these structures, the two H atoms of the dihydrofuran ring and the two substituted oxindole rings are in a trans orientation, facilitating intramolecular C-H center dot center dot center dot O and pi-pi interactions. These weak interactions play a prominent role in the structural stability and aid the highly regio-and diastereoselective synthesis. In each of the four structures, the molecular assembly in the crystal is also governed by weak noncovalent interactions. Compound (IV) is the solvated analogue of (III) and the two compounds show similar structural features.