title: Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles.
abstract: Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water-assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4-5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five- and six-membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4-oxadiazole derivatives having a unique hybrid isoxazoline-oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly-like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis.
authors.affiliation: Chulabhorn Graduate Institute, Chemical Biology Program, Kamphaeng Phet 6 Road, Laksi, Bangkok, 10210, Thailand.
authors.forename: Chatchai
authors.initials: C
authors.lastname: Kesornpun
authors.affiliation: Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Thammarat
authors.initials: T
authors.lastname: Aree
authors.affiliation: Chulabhorn Graduate Institute, Chemical Biology Program, Kamphaeng Phet 6 Road, Laksi, Bangkok, 10210, Thailand.|Chulabhorn Research Institute, Bangkok, 10210, Thailand.
authors.forename: Chulabhorn
authors.initials: C
authors.lastname: Mahidol
authors.affiliation: Chulabhorn Graduate Institute, Chemical Biology Program, Kamphaeng Phet 6 Road, Laksi, Bangkok, 10210, Thailand.|Chulabhorn Research Institute, Bangkok, 10210, Thailand.|Center of Excellence on Environmental Health and Toxicology (EHT), CHE, Ministry of Education, Thailand.
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
authors.affiliation: Chulabhorn Graduate Institute, Chemical Biology Program, Kamphaeng Phet 6 Road, Laksi, Bangkok, 10210, Thailand. prasat@cri.or.th.|Chulabhorn Research Institute, Bangkok, 10210, Thailand. prasat@cri.or.th.|Center of Excellence on Environmental Health and Toxicology (EHT), CHE, Ministry of Education, Thailand. prasat@cri.or.th.
authors.forename: Prasat
authors.initials: P
authors.lastname: Kittakoop
keywords: alkenes; cycloaddition; green chemistry; heterocycles; water