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.
Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité/ LCHPNR, Département de Chimie, Faculté des Sciences de Monastir , 5000 Monastir, Tunisie.|Département de Chimie, Centre Québécois sur les Matériaux Fonctionnels, Université de Sherbrooke , Sherbrooke, Québec J1K 2R1, Canada.
Saoussen
S
Haddad
Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité/ LCHPNR, Département de Chimie, Faculté des Sciences de Monastir , 5000 Monastir, Tunisie.
Sarra
S
Boudriga
Département de Chimie, Centre Québécois sur les Matériaux Fonctionnels, Université de Sherbrooke , Sherbrooke, Québec J1K 2R1, Canada.
François
F
Porzio
Département de Chimie, Centre Québécois sur les Matériaux Fonctionnels, Université de Sherbrooke , Sherbrooke, Québec J1K 2R1, Canada.
Armand
A
Soldera
Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité/ LCHPNR, Département de Chimie, Faculté des Sciences de Monastir , 5000 Monastir, Tunisie.
Moheddine
M
Askri
Institut UTINAM - UMR CNRS 6213, Université de Franche-Comté , 16 Route de Gray, F-25030 Besançon, France.
Michael
M
Knorr
Institut de Chimie Moléculaire - UMR CNRS 6302, Université de Bourgogne , 9 Avenue A. Savary, F-21078 Dijon, France.
Yoann
Y
Rousselin
Institut de Chimie Moléculaire - UMR CNRS 6302, Université de Bourgogne , 9 Avenue A. Savary, F-21078 Dijon, France.
Marek M
MM
Kubicki
Anorganische Chemie, Technische Universität Dortmund , Otto-Hahn-Strasse 6, 44221 Dortmund, Germany.
Christopher
C
Golz
Anorganische Chemie, Technische Universität Dortmund , Otto-Hahn-Strasse 6, 44221 Dortmund, Germany.
Carsten
C
Strohmann
D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D061565:Cycloaddition Reaction; D007510:Isatin / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids; D011789:Quantum Theory; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry; D014961:X-Ray Diffraction
D001391:Azo Compounds; D010879:Piperazines; D011763:Pyrrolizidine Alkaloids; D013141:Spiro Compounds; D013882:Thiosemicarbazones; C512188:azomethine; D007510:Isatin