title: General Approach to Nitrogen-Bridged Bicyclic Frameworks by Rh-Catalyzed Formal Carbenoid Insertion into an Amide C-N Bond.
abstract: Various nitrogen-bridged bicyclic skeletons are found in bioactive natural products and pharmaceuticals. The development of a new reaction to construct these molecular frameworks has attracted considerable attention in synthetic organic chemistry. We developed a novel synthetic method for obtaining a wide variety of nitrogen-bridged bicyclic compounds with a catalytic process, Rh-catalyzed formal carbenoid insertion into an amide C-N bond. Using 0.1-0.4 mol % Rh2(NHCO(t)Bu)4 catalyst, various azabicyclo[X.Y.Z]alkane derivatives were obtained in good to excellent yield, successfully demonstrating the broad substrate scope of the developed process. Experimental and computational studies to elucidate the reaction mechanism revealed that the formal insertion reaction of a carbenoid into an amide C-N bond proceeded via the formation of Rh-associated N-ylides, followed by an acyl group-selective Stevens [1,2]-shift through a concerted addition/elimination process on the sp(2)-hybridized carbon.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Harada
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kono
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nozaki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Menjo
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Hamada