title: Intermolecular Noncovalent Hydroxy-Directed Enantioselective Heck Desymmetrization of Cyclopentenol: Computationally Driven Synthesis of Highly Functionalized cis-4-Arylcyclopentenol Scaffolds.
abstract: New computationally driven protocols for the Heck desymmetrization of 3-cyclopenten-1-ol with aryldiazonium tetrafluoroborates were developed. These new conditions furnished remarkable product selectivity originating from a resident hydroxyl group and the critical choice of the reaction solvent. Mechanistic insights gleaned from theoretical calculations of the putative transition states predicted toluene as an adequate solvent choice to attain high enantioselectivity by strengthening the noncovalent interaction of the substrate hydroxyl group and the chiral cationic palladium catalyst. Laboratory experiments validated the theoretical predictions, and by employing 2% MeOH/toluene as solvent, the Heck-Matsuda reaction provided exclusively the cis-4-arylcyclopentenols 3a-l in good to excellent yields in enantiomeric excesses up to 99%. The performance of the new PyOx ligand (S)-4-tert-butyl-2-(3,5-dichloropyridin-2-yl)-4,5-dihydrooxazole was also successfully evaluated in the Heck-Matsuda desymmetrization of 3-cyclopenten-1-ol. The synthetic potential of these highly functionalized cis-4-arylcyclopentenols is illustrated by a gold-catalyzed synthesis of cyclopenta[b]benzofuran skeletons.
authors.affiliation: Departamento de Química Orgânica, Universidade Estadual de Campinas, Cidade Universitária , Zeferino Vaz, Campinas 13083-970, SP, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: de Oliveira Silva
authors.affiliation: Departamento de Química Orgânica, Universidade Estadual de Campinas, Cidade Universitária , Zeferino Vaz, Campinas 13083-970, SP, Brazil.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Angnes
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo , Avenida Lineu Prestes, 748, Bl. 05 sup. Sl, 0552, Butantã, São Paulo, SP, Brazil.
authors.forename: Vitor H
authors.initials: VH
authors.lastname: Menezes da Silva
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo , Avenida Lineu Prestes, 748, Bl. 05 sup. Sl, 0552, Butantã, São Paulo, SP, Brazil.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Servilha
authors.affiliation: Department of Chemistry, Gomal University , Dera Ismail Khan 29050, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Adeel
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo , Avenida Lineu Prestes, 748, Bl. 05 sup. Sl, 0552, Butantã, São Paulo, SP, Brazil.
authors.forename: Ataualpa A C
authors.initials: AA
authors.lastname: Braga
authors.affiliation: Department of Chemistry, Center for Heterocyclic Compounds, University of Florida , Gainesville, Florida 32611, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Aponick
authors.affiliation: Departamento de Química Orgânica, Universidade Estadual de Campinas, Cidade Universitária , Zeferino Vaz, Campinas 13083-970, SP, Brazil.
authors.forename: Carlos Roque D
authors.initials: CR
authors.lastname: Correia