title: Theoretical studies on the bifunctionality of chiral thiourea-based organocatalysts: competing routes to C-C bond formation.
abstract: The mechanism of enantioselective Michael addition of acetylacetone to a nitroolefin catalyzed by a thiourea-based chiral bifunctional organocatalyst is investigated using density functional theory calculations. A systematic conformational analysis is presented for the catalyst, and it is shown that both substrates coordinate preferentially via bidentate hydrogen bonds. The deprotonation of the enol form of acetylacetone by the amine of the catalyst is found to occur easily, leading to an ion pair characterized by multiple H-bonds involving the thiourea unit as well. Two distinct reaction pathways are explored toward the formation of the Michael product that differ in the mode of electrophile activation. Both reaction channels are shown to be consistent with the notion of noncovalent organocatalysis in that the transition states leading to the Michael adduct are stabilized by extensive H-bonded networks. The comparison of the obtained energetics for the two pathways allows us to propose an alternative mechanistic rationale for asymmetric C-C bond forming reactions catalyzed by bifunctional thiourea derivatives. The origin of enantioselectivity in the investigated reaction is also discussed.
authors.affiliation: Institute of Structural Chemistry, Chemical Research Center of the Hungarian Academy of Sciences, Pusztaszeri út 59-67, H-1025 Budapest, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hamza
authors.forename: Gabor
authors.initials: G
authors.lastname: Schubert
authors.forename: Tibor
authors.initials: T
authors.lastname: Soós
authors.forename: Imre
authors.initials: I
authors.lastname: Papai
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry; D008958:Models, Molecular; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010422:Pentanones / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000475:Alkenes; D007659:Ketones; D009574:Nitro Compounds; D010422:Pentanones; C008790:acetylacetone; D013890:Thiourea