title: Exploring the vinylogous reactivity of cyclohexenylidene malononitriles: switchable regioselectivity in the organocatalytic asymmetric addition to enals giving highly enantioenriched carbabicyclic structures.
abstract: Modulation of the complex reactivity of cyclohexenylidene malononitriles using diverse β-aryl-substituted enals and proper organocatalytic modalities resulted in divergent asymmetric reaction patterns to furnish angularly fused or bridged carbabicyclic frameworks. In particular, use of remotely enolizable dicyanodienes 1, under one-pot sequential amine/NHC catalysis, led to [3 + 2] cycloaddition to afford ε,δ-bonded spiro[4.5]decanone structures 5. Alternatively, modifying the standard amine catalysis by adding a suitable chemical stimulus (p-nitrophenol cocatalyst) switched the reactivity decidedly toward a domino [4 + 2] cycloaddition to afford γ',δ-bonded bicyclo[2.2.2]octane carbaldehydes 8. Products invariably formed in good yields, with rigorous chemo-, regio-, diastereo-, and enantiocontrol. Experimental evidence, including carbon isotope effects measured by (13)C NMR, were indicative of the rate (and stereochemistry) determining step of these transformations and suggested a stepwise mechanism for the [4 + 2] cycloadditive pathway.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma , Parco Area delle Scienze 27A, 43124 Parma, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Dell'Amico
authors.forename: Gloria
authors.initials: G
authors.lastname: Rassu
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Zambrano
authors.forename: Andrea
authors.initials: A
authors.lastname: Sartori
authors.forename: Claudio
authors.initials: C
authors.lastname: Curti
authors.forename: Lucia
authors.initials: L
authors.lastname: Battistini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pelosi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casiraghi
authors.forename: Franca
authors.initials: F
authors.lastname: Zanardi
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002384:Catalysis; D061565:Cycloaddition Reaction; D053138:Cyclohexenes / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry*; D013141:Spiro Compounds / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000447:Aldehydes; D001643:Bridged Bicyclo Compounds; D053138:Cyclohexenes; D009570:Nitriles; D013141:Spiro Compounds; C052568:cyclohexene; C030011:carbene; D008697:Methane