Evolution of a multicomponent system: computational and mechanistic studies on the chemo- and stereoselectivity of a divergent process.
The evolution of a ternary molecular system (imine, diene and nitrile) is analyzed to disclose the pathways leading to a divergent synthetic outcome. The Lewis acid catalyzed reaction between cyclohexadiene, 2-phenyl-indol-3-one and acetonitrile yields the imino-Diels-Alder adduct as the major product together with minor amounts of the Mannich-Ritter-amidine product. The experimental and computational data show that the relative orientation of the initial reactants dictates the synthetic outcome. The exo approach between imine and diene leads to the Diels-Alder adduct in a concerted process, whereas the endo mode leads to a polarized intermediate, which is trapped by acetonitrile to yield the multicomponent adduct.
Department of Physical Chemistry and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Avda Diagonal 643, 08028 Barcelona (Spain), Fax: (+34) 934035987.
Salomé
S
Llabrés
Esther
E
Vicente-García
Sara
S
Preciado
Cristina
C
Guiu
Ramon
R
Pouplana
Rodolfo
R
Lavilla
F Javier
FJ
Luque
D000097:Acetonitriles / Q000737:chemistry; D053138:Cyclohexenes / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D058116:Lewis Acids / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry*; D013237:Stereoisomerism
D000097:Acetonitriles; D053138:Cyclohexenes; D007097:Imines; D058116:Lewis Acids; D009570:Nitriles
Diels-Alder reaction; Mannich-Ritter reaction; chemoselectivity; multicomponent reactions; stereoselectivity