Abstract
Straightforward regio- and diastereoselective synthesis of bi-spirooxindole-engrafted rhodanine analogs
5a
–
d
were achieved by one-pot multicomponent [3 + 2] cycloaddition (32CA) reaction of stabilized azomethine ylide (AYs
3a
–
d
) generated in situ by condensation of L-thioproline and 6-chloro-isatin with (
E
)-2-(5-(4-chlorobenzylidene)-2,4-dioxothiazolidin-3-yl)-
N
-(2-morpholinoethyl)acetamide. The bi-spirooxindole-engrafted rhodanine analogs were constructed with excellent diastereo- and regioselectivity along with high chemical yield. X-ray crystallographic investigations for hybrid
5a
revealed the presence of four contiguous stereocenters related to C11, C12, C19 and C22 of the spiro structure. Hirshfeld calculations indicated the presence of many short intermolecular contacts such as Cl...C, S...S, S...H, O...H, N...H, H...C, C...C and H...H interactions. These contacts played a very important role in the crystal stability. The polar nature of the 32CA reaction was studied by analysis of the conceptual DFT reactivity indices. Theoretical study of this 32CA reaction indicated that it takes place through a non-concerted
two-stage one-step
mechanism associated with the nucleophilic attack of AY
3a
to the electrophilic ethylene derivative.