title: Indium-mediated asymmetric Barbier-type propargylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents.
abstract: We report a simple, efficient, and general method for the indium-mediated enantioselective propargylation of aromatic and aliphatic aldehydes under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 90%) and enantiomeric excess (up to 95%). The extension of this methodology to ketones demonstrated the need for electrophilic ketones more reactive than acetophenone as the reaction would not proceed with just acetophenone. Using the Lewis acid indium triflate [In(OTf)(3)] induced regioselective formation of the corresponding homoallenic alcohol product from acetophenone. However, this methodology demonstrated excellent chemoselectivity in formation of only the corresponding secondary homopropargylic alcohol product in the presence of a ketone functionality. Investigation of the organoindium intermediates under our reaction conditions shows the formation of allenylindium species, and we suggest that these species contain an indium(III) center. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA.
authors.forename: Terra D
authors.initials: TD
authors.lastname: Haddad
authors.forename: Lacie C
authors.initials: LC
authors.lastname: Hirayama
authors.forename: Jannise J
authors.initials: JJ
authors.lastname: Buckley
authors.forename: Bakthan
authors.initials: B
authors.lastname: Singaram
mesh_terms: D000098:Acetophenones / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D007204:Indium / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008698:Mesylates / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds; D010293:Pargyline / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000098:Acetophenones; D000447:Aldehydes; D007659:Ketones; D008698:Mesylates; D009942:Organometallic Compounds; D007204:Indium; D010293:Pargyline; C458239:propargyl bromide; C012077:trifluoromethanesulfonic acid; C038699:acetophenone