The Photocatalyst-free Cross Dehydrogenative Coupling Reaction Enabled By Visible-light Directly Excitation Of Substrate

Tetrahydroisoquinolines(THIQs)is a common biological scaffold in natural products,and it has a wide range of applications in the design and synthesis of drug molecules.Therefore,the efficient construction of tetrahydroisoquinoline frameworks has attracted extensive attention from chemists.In the few ten years,the construction of tetrahydroisoquinoline skeletons has been widely reported.Among these synthetic methods,the photocatalytic CDC reaction to construct tetrahydroisoquinoline compounds has the advantages of high atom utilization,greenness,and pollution-free,it meets the development needs of green chemistry.Recently,scientists have found that by forming EDA complexes or forming enamine intermediates,photoreactions can be achieved without photosensitizers,avoiding the participation of photosensitizers that are expensive and complicated in synthesis steps,thereby reducing the cost of photoreaction.Based on this,we developed a new light-mediated photosensitizer-free cross-dehydrogenation coupling reaction and achieved a more environmentally friendly,efficient and inexpensive construction of tetrahydroisoquinoline framework.In this paper,the visible light-promoted CDC reaction of THIQ compounds was mainly studied,and a light-mediated synthesis method of photosensitizer-free THIQ was developed.Through the optimization of reaction conditions such as reaction light source,reaction solvent,the equal of L-Proline,finally determined the blue LED lamps of 20 W 427 nm as the best reaction light source,Me OH was used as best solvent,and the best feeding ratio of L-Proline was 0.2 equal,air atmosphere was the best reaction conditions.We not only investigated the substrate suitability of N-aryl-substituted tetrahydroisoquinolines,but also investigated the substrate suitability of different nucleophiles such as ketones,phosphites and indoles.The reaction mechanism was reasonably speculated through the calculation of optical switching experiment,TEMPO capture experiment,UV absorption spectrum,fluorescence lifetime of THIQ and reaction quantum yield.