2-(1-Methylhydrazinyl)pyridine Assisted Cobalt-Catalyzed C-H Activation/Annulation Cascade Reaction And Synthetic Studies Towards Hamigeran G

The dissertation focuses on?i?2-?1-Methylhydrazinyl?pyridine as a new bidentate directing group assist the cobalt-catalyzed C-H activation/annulation cascade reaction,?ii?synthetic studies towards the natural product hamigeran G.To date,many types of bidentate directing groups have been reported,but,in some case,the lately removal of the directing group from the catalytic product require harsh reaction conditions or lengthy reaction steps.Here,we design and synthesize the 2-?1-Methylhydrazinyl?pyridine,a novel bidentate directing group,which react with benzoyl chloride derivatives to produce benzoyl hydrazone compounds,and successfully achieved:?1?Cobalt catalyzed hydrazide C-H bond activation/cyclization cascade reaction with alkynes;?2?Cobalt catalyzed hydrazide C-H bond activation/cyclization cascade reaction with allens;?3?Cobalt-catalyzed polyfunctionalization of allenes.To our surprised that the N-N bond in the product can be cleaved by SmI₂ under mild conditions,with the halogen on the aromatic ring toleranced.Hamigeran G-type natural products is a novel natural product,which were isolated from the New Zealand sponge tarangaensis by the Northcote in 2015.Activities study show that the kind of natural product are cytotoxic to the HL-60 early young mitochondrial cell line.Based on our group's experiment on the synthesis of important bioactive and structrial complexed natural products,We designed a route to synthesis of this family natural product.Firstly,we used o-bromobenzaldehyde as a model substrate to synthesis the allene compound 5-206 by the Sonogashira coupling reaction and organozinc reagents reacted with the aldehyde groups.Lately,a rhodium-catalyzed Pauson-Khand reaction was used as the key step to synthesis the tricyclic backbone of this kind of natural product.After obtaining the tricyclic backbone,we tried the[3+2]reaction,Mukaiyama hydration reaction,high pressure hydrogenation,and SeO₂ oxidation as the key procedure to modify the tricyclic backbone,and achieved the important intermediate alcohol5-223.But,for other reasons,subsequent conversions have not been achieved.At the same time,we also used 3,5-dihydroxytoluene and 4-methylsalicylic acid as starting materials to synthesize the tricyclic backbone of hagigeran G type natural products in two different routes.