title: Palladium-catalyzed intramolecular C-O bond formation.
abstract: A number of oxygen heterocycles were synthesized using the palladium-catalyzed intramolecular etherification of aryl halides by employing di-tert-butylphosphinobiaryl ligands. The reaction proceeds under mild conditions using weak bases such as Cs(2)CO(3) or K(3)PO(4). A variety of functional groups are tolerated in the reaction, and enantioenriched alcohols can be coupled without erosion of optical purity. The mildness of the reaction conditions allows for the use of polyfunctionalized substrates. This method was used as the key step in the synthesis of MKC-242, an antidepressant currently in clinical trials. The synthesis of MKC-242 was achieved in 40% overall yield from commercially available sesamol and acrylonitrile.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Kuwabe
authors.forename: K E
authors.initials: KE
authors.lastname: Torraca
authors.forename: S L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D000928:Antidepressive Agents / Q000138:chemical synthesis*; D002384:Catalysis; D004146:Dioxanes / Q000138:chemical synthesis*; D004149:Dioxoles / Q000138:chemical synthesis*; D004987:Ethers / Q000138:chemical synthesis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis; D010100:Oxygen / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*
chemical_list: D000928:Antidepressive Agents; D004146:Dioxanes; D004149:Dioxoles; D004987:Ethers; D006571:Heterocyclic Compounds; D010165:Palladium; C096294:osemozotan; D010100:Oxygen