Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a1-diazacyclopenta[cd]inden-2-ones.
Two cyclic azomethine imines, 7-methyl- and 7-phenyl-2-oxo-Δ7-hexahydropyrazolo[1,5-a]pyridin-8-ium-1-ide, were prepared in seven steps from the respective commercially available δ-keto acids. The addition of Grignard reagents followed by N-alkylation at position 1 afforded the 1,7,7-trisubstituted hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones, whereas 1,3-dipolar cycloadditions of these dipoles to typical acetylenic and olefinic dipolarophiles gave 4a-substituted 2a,2a1-diazacyclopenta[cd]indene derivatives as the first representatives of a novel heterocyclic system. Regio- and stereoselectivity as well as the mechanism of these [3 + 2]-cycloadditions were evaluated using computational and experimental methods. The data obtained were in agreement with the polar concerted cycloaddition mechanism via the energetically favorable syn/endo-transition states.
Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
Eva
E
Pušavec Kirar
Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
Miha
M
Drev
Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
Jona
J
Mirnik
Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
Uroš
U
Grošelj
Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
Amalija
A
Golobič
Medicinal Chemistry, Boehringer-Ingelheim Pharma GmbH&Co. KG, 88397 Biberach, Germany.
Georg
G
Dahmann
Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
Franc
F
Požgan
Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
Bogdan
B
Štefane
Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
Jurij
J
Svete