Transition Metal-Mediated Transformation of Ynamides and Application to Organic Synthesis

N-Alkynylamide (ynamide) is recognized as a polarized alkyne, due to the delocalization of lone-pair electrons on the nitrogen atom to the carbon-carbon triple bond, and it is widely used in recent organic synthesis. We conducted the studies on the efficient and useful molecular transformation of ynamides with transition metal catalysis, and several new methods of ynamide transformation were developed. First, we demonstrated new synthetic protocol of enamide from ynamide. Thus, γ-siloxyenmides were efficiently prepared by the nickel(0)-catalyzed regio- and stereoselective coupling of ynamide, aldehyde and silane. Moreover, regioselective synthesis of tri- and tetra-substituted enamides was achieved by palladium-catalyzed silaboration of ynamide. On the other hand, 2-amino-1,3-dinenes were synthesized by ruthenium-catalyzed formal hydrovinylation of ynamide with ethylene. Carboxylation of ynamide with CO2 mediated by nickel(0) complex gave α-substituted-β-aminoacrylate, which was transformed into β2-amino acid derivative in a enantioselective manner by rhodium-catalyzed asymmetric hydrogenation. Finally, the first total synthesis of (−)-herbindoles A, B and C was achieved by [2+2+2] cyclization of dialkynylynamide.