title: Synthesis of chiral hexacyclic steroids via [8π + 2π] cycloaddition of diazafulvenium methides.
abstract: First examples of [8π + 2π] cycloaddition of 16-dehydropregnenolone (16-DPA) acetate with diazafulvenium methides leading to chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroids are reported. These hexacyclic steroids were obtained exclusively or selectively with the approach of the 1,7-dipole by the less hindered α-face of 16-DPA. Quantum chemical calculations at the DFT level were carried out, using the cycloaddition of 1-methyl- and 1-benzyl-diazafulvenium methides with N-phenylmaleimide as model reactions, in order to rationalize the stereochemistry outcome. The results indicate that endo cycloadditions of the more stable dipole conformation, having the 1-substituent pointing outward, are significantly more favorable than the alternative exo cycloaddition.
authors.affiliation: Centro de Química de Coimbra, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal. tmelo@ci.uc.pt.
authors.forename: Susana M M
authors.initials: SM
authors.lastname: Lopes
authors.forename: Cátia F O
authors.initials: CF
authors.lastname: Correia
authors.forename: Sandra C C
authors.initials: SC
authors.lastname: Nunes
authors.forename: Nelson A M
authors.initials: NA
authors.lastname: Pereira
authors.forename: Ana R F
authors.initials: AR
authors.lastname: Ferreira
authors.forename: Emanuel P
authors.initials: EP
authors.lastname: Sousa
authors.forename: Clara S B
authors.initials: CS
authors.lastname: Gomes
authors.forename: Jorge A R
authors.initials: JA
authors.lastname: Salvador
authors.forename: Alberto A C C
authors.initials: AA
authors.lastname: Pais
authors.forename: Teresa M V D
authors.initials: TM
authors.lastname: Pinho e Melo
mesh_terms: D002384:Catalysis; D003500:Cyclization; D061565:Cycloaddition Reaction; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007093:Imidazoles / Q000737:chemistry*; D045563:Indolequinones / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis*
chemical_list: D006571:Heterocyclic Compounds; D007093:Imidazoles; D045563:Indolequinones; D013256:Steroids; C113487:diazafulvene; C068040:quinone methide