title: Highly stereoselective [4+2] and [3+2] spiroannulations of 2-(2-oxoindolin-3-ylidene)acetic esters catalyzed by bifunctional thioureas.
abstract: A new Michael-Michael cascade reaction between 2-(2-oxoindolin-3-ylidene)acetic esters 1 and nitroenoates 2, catalyzed by bifunctional thioureas, is investigated. The combination of the two Michael reactions results in a novel and facile [4+2] or [3+2] spiroannulation process, which is characterized by the following features: 1) two carbon-carbon bonds and four stereocenters, including a quaternary spiro carbon, are formed under mild conditions; 2) an unprecedented and stereochemically defined substitution pattern on the spirocarbocyclic unit is obtained; 3) the double-bond configuration of the donor-acceptor nitroenoate 2 determines the absolute configuration of the spiro center, whereas the remaining stereocenters are formed under control of the catalyst. The effect on the final stereochemical outcome of structural variations of each starting material, catalyst, and experimental conditions is analyzed in detail. In particular, the use of specifically designed chiral nitroenoates enables diverse polyfunctional spirocyclohexane derivatives containing six consecutive stereogenic centers to be constructed. To our knowledge, this is the first asymmetric organocatalytic strategy enabling both five- and six-membered β-nitro spirocarbocyclic oxindoles.
authors.affiliation: Alma Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna (Italy).
authors.forename: Magda
authors.initials: M
authors.lastname: Monari
authors.affiliation: Alma Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna (Italy).
authors.forename: Elisa
authors.initials: E
authors.lastname: Montroni
authors.affiliation: Alma Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna (Italy).
authors.forename: Andrea
authors.initials: A
authors.lastname: Nitti
authors.affiliation: Alma Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna (Italy).
authors.forename: Marco
authors.initials: M
authors.lastname: Lombardo
authors.affiliation: Alma Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna (Italy).
authors.forename: Claudio
authors.initials: C
authors.lastname: Trombini
authors.affiliation: Alma Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna (Italy). arianna.quintavalla@unibo.it.
authors.forename: Arianna
authors.initials: A
authors.lastname: Quintavalla
mesh_terms: D002384:Catalysis; D007211:Indoles / Q000737:chemistry*; D009574:Nitro Compounds / Q000737:chemistry; D000078183:Oxindoles; D013141:Spiro Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013890:Thiourea / Q000737:chemistry*
chemical_list: D007211:Indoles; D009574:Nitro Compounds; D000078183:Oxindoles; D013141:Spiro Compounds; C022960:2-oxindole; D013890:Thiourea
keywords: Michael addition; asymmetric catalysis; domino reactions; organocatalysis; spiro compounds