Regio- and Stereoselective Synthesis of Spiropyrrolizidines and Piperazines through Azomethine Ylide Cycloaddition Reaction

A series
of original spiropyrrolizidine derivatives has been prepared
by a one-pot three-component [3 + 2] cycloaddition reaction of (E)-3-arylidene-1-phenyl-pyrrolidine-2,5-diones, l-proline, and the cyclic ketones 1H-indole-2,3-dione
(isatin), indenoquinoxaline-11-one and acenaphthenequinone. We disclose
an unprecedented isomerization of some spiroadducts leading to a new
family of spirooxindolepyrrolizidines. Furthermore, these cycloadducts
underwent retro-1,3-dipolar cycloaddition yielding unexpected regioisomers.
Upon treatment of the dipolarophiles with in situ generated azomethine ylides from l-proline or acenaphthenequinone,
formation of spiroadducts and unusual polycyclic fused piperazines
through a stepwise [3 + 3] cycloaddition pathway is observed. The
stereochemistry of these N-heterocycles has been confirmed by several
X-ray diffraction studies. Some of these compounds exhibit extensive
hydrogen bonding in the crystalline state. To enlighten the observed
regio- and stereoselectivity of the [3 + 2] cycloaddition, calculations
using the DFT approach at the B3LYP/6-31G­(d,p) level were carried
out. It was found that this reaction is under kinetic control.