10.1021/jo102374z.s001
Srinivasa Reddy Mothe
Srinivasa Reddy
Mothe
Prasath Kothandaraman
Prasath
Kothandaraman
Weidong Rao
Weidong
Rao
Philip Wai Hong Chan
Philip
Wai Hong Chan
Rapid Access to Halohydrofurans via Brønsted Acid-Catalyzed Hydroxylation/Halocyclization of Cyclopropyl Methanols with Water and Electrophilic Halides
American Chemical Society
2011
NXS
2O
cis product selectivity
method
cyclopropyl methanols
moiety
halohydrofuran
Br ønsted acid catalyst
electrophilic halide source
electrophilic halide sources
2011-04-15 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Rapid_Access_to_Halohydrofurans_via_Br_nsted_Acid_Catalyzed_Hydroxylation_Halocyclization_of_Cyclopropyl_Methanols_with_Water_and_Electrophilic_Halides/2662810
A one-pot, two-step method to prepare 3-halohydrofurans efficiently by TfOH-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with H<sub>2</sub>O and <i>N</i>-halosuccinimide (NXS, X=1, Br, Cl) or Selectfluor is described. The reactions proceed rapidly under mild and operationally straightforward conditions with a catalyst loading as low as 1 mol % and afford the 3-halohydrofuran products in moderate to excellent yields and, in most cases, with preferential <i>cis</i> diastereoselectivity. The method was shown to be applicable to cyclopropyl methanols containing electron-withdrawing, electron-donating, and sterically demanding functional groups and electrophilic halide sources. The mechanism is suggested to involve protonation of the alcohol substrate by the Brønsted acid catalyst and ionization of the starting material. This results in ring-opening of the cyclopropane moiety and in situ formation of a homoallylic alcohol intermediate, which undergoes subsequent intramolecular halocyclization on treating with the electrophilic halide source to give the halohydrofuran. The observed <i>cis</i> product selectivity is thought to be determined by the reaction proceeding through an in situ generated unsaturated alcohol intermediate that contains a (<i>Z</i>)-alkene moiety under the kinetically controlled conditions.