title: Chemoselective synthesis of ketones and ketimines by addition of organometallic reagents to secondary amides.
abstract: The development of efficient and selective transformations is crucial in synthetic chemistry as it opens new possibilities in the total synthesis of complex molecules. Applying such reactions to the synthesis of ketones is of great importance, as this motif serves as a synthetic handle for the elaboration of numerous organic functionalities. In this context, we report a general and chemoselective method based on an activation/addition sequence on secondary amides allowing the controlled isolation of structurally diverse ketones and ketimines. The generation of a highly electrophilic imidoyl triflate intermediate was found to be pivotal in the observed exceptional functional group tolerance, allowing the facile addition of readily available Grignard and diorganozinc reagents to amides, and avoiding commonly observed over-addition or reduction side reactions. The methodology has been applied to the formal synthesis of analogues of the antineoplastic agent Bexarotene and to the rapid and efficient synthesis of unsymmetrical diketones in a one-pot procedure.
authors.affiliation: Department of Chemistry, Université de Montréal, PO Box 6128, Station Downtown, Montréal, Québec, Canada                 H3C 3J7.
authors.forename: William S
authors.initials: WS
authors.lastname: Bechara
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pelletier
authors.forename: André B
authors.initials: AB
authors.lastname: Charette
mesh_terms: D000577:Amides / Q000737:chemistry*; D000077610:Bexarotene; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D013764:Tetrahydronaphthalenes / Q000737:chemistry
chemical_list: D000577:Amides; D007097:Imines; D007659:Ketones; D008698:Mesylates; D009570:Nitriles; D009942:Organometallic Compounds; D013764:Tetrahydronaphthalenes; C542835:ketimine; D000077610:Bexarotene; C012077:trifluoromethanesulfonic acid