title: Intramolecular additions of various pi-nucleophiles to chemoselectively activated amides and application to the synthesis of (+/-)-tashiromine.
abstract: [reaction: see text] Vilsmeier-Haack type cyclizations proved to be particularly efficient for generating parts of the polycyclic cores of many alkaloids, although only monocyclizations have so far been reported. With the goal of rapidly and efficiently constructing polycyclic alkaloids, we decided to exploit the Vilsmeier-Haack reaction by utilizing iminium ions successively generated and trapped with tethered nucleophiles. To develop such a strategy, we had to set the first cyclization. This constitutes a great challenge in itself because amide activation conditions are usually not compatible with tethered nucleophiles, except for indoles and aromatic rings which have already been reported. This paper describes the comprehensive study of intramolecular addition of silyl enol ethers, allylsilanes, and enamines to chemoselectively activated formamides, aliphatic amides, and lactams. Good to excellent yields were obtained for the 5-exo, 6-exo, and 6-endo modes of cyclization. Moreover, we demonstrated that the species in solution after the cyclization are iminium ions. This is highly encouraging for the development of bis-cyclization strategies. An expeditious total synthesis of (+/-)-tashiromine is also reported.
authors.affiliation: Laboratoire de synthèse organique et de développement de stratégies de synthèse Département de Chimie, Université de Sherbrooke 2500 boulevard Université, Sherbrooke, Québec, J1K 2R1, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bélanger
authors.forename: Robin
authors.initials: R
authors.lastname: Larouche-Gauthier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ménard
authors.forename: Miguel
authors.initials: M
authors.lastname: Nantel
authors.forename: Francis
authors.initials: F
authors.lastname: Barabé
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry*; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D000470:Alkaloids; D000577:Amides; D007212:Indolizines; C512155:tashiromine