Development of the First Ruthenium-Iminium-SOMO Organocatalytic Cascade and Its Application in Total Synthesis of the Highly Bioactive Natural Products Viroallosecurinine and Norsecurinine
Final Report Abstract
Over the last few years, photoredox catalysis emerged as a powerful tool in organic synthesis. This new activation mode enables the rapid construction of novel molecular architectures. Visible-light-mediated sp3 C-H functionalization of small molecules allows the creation of an unparalleled synthetic platform for novel target structures. Along these lines, the C-H functionalization of benzylic ethers was investigated. In detail, it was reasoned that a catalytic system composed of Ir(ppy)2(dtbbpy)PF6 as photocatalyst and methyl thioglycolate as organocatalyst serve to abstract a hydrogen atom from benzyl methyl ether. The resulting alpha-benzyl ether radical could then react with a radical species formed through a single electron reduction of imine to provide amine. Application of this concept showed that under optimized reaction conditions, a variety of chiff bases were combined with benzyl methyl ether in high yield especially when they are derived from electron rich aldehydes. Furthermore, heterocyclic aromatics as well as halogen substituted substrates were prepared to establish a broad and synthetically attractive imine scope. In addition, the benzyl ether scope was defined with respect to diverse arene moieties and versatile protecting groups. In order to elucidate the mechanism, Stern-Volmer quenching studies were performed that suggest a reductive quenching of the photocatalyst. Finally, the rate of our new transformation was investigated with respect to the illumination surface. These studies demonstrated a photon dependence of this photoredox protocol.
Publications
- J. Am. Chem. Soc. 2014, 136, 16986−1698: Activation of C−H Bonds via the Merger of Photoredox and Organocatalysis: A Coupling of Benzylic Ethers with Schiff Bases
Dominik Hager and David W. C. MacMillan
(See online at https://doi.org/10.1021/ja5102695)
