The Reaction Of Rhodium(?) Catalyzed Inert Bond Activation

Inert bond activation has been an important research area in organic chemistry,including unactivated C-H,C-F,C-O,C-N and C-C bond which exist widely in chemistry.The importance on the research of inert bond activation is that chemists can construct target material in one step from simple starting material avioding pre-functionalization of substrates.This flexible method can reduce reaction steps and time,improve reaction efficiency and save the reaction cost.However,due to the high bond energy and similar property,it's difficult to realize selective inert bond activation using traditional chemistry.Along with the development in transition metal catalysis,transition metal catalyst have shown specific catalytic activity and superior chemoselectivity.This gives chance to activate inert bond and has brought promotion in this area.Of course new difficulties and challenges are coming in the same time.Our group has been always committed to the research of inert bond cleavage,activation and functionalization,and has made some progress.On the bases of the literature report and our experiment reseach,my doctoral dissertation focuses on the Rhodium(1)catalyzed inert bond functionalization with high chemical selectivity,excellent functional group compatibility and good application value.In this dissertation,we study the C-H arylation to construct monophosphine ligand libraries,selective direct C7-arylation of indoles,aldehyde activation with transfer hydroformylation and decarbonylation of diaryl ketones.Part I:Rhodium catalyzed P-atom directed sp2 C-H arylation reaction has been established.The arylation of various commercial monophosphine ligands can not only adjust and control the spatial structure of the ligands,but also alter the electrical effects of coordination atoms.This simple and efficient synthesis method avoids the multi-step conversion required by traditional monophosphine ligand structure modification.Using[Rh(cod)Cl]2 as catalysis and LiOtBu as base,unmodified phosphine ligands reacted with various(hetero)aryl bromide or even aryl chloride efficiently without any extra ligand or oxidant.Aryl bromide containing electron-donating and withdrawing substituents or substituents with large steric hinderance are well tolerate.Both mono-arylation and di-arylation ligands can be selectively acquired through different conditions.In light of the widespread use of monophosphine ligands,this strategy of rapid construction of ligand libraries will have an irreplaceable advantage in reaction optimization and new reaction development.Part II:Direct C-H functionalization at indole benzene core has always been a hot and difficult topic in organic synthesis.Based on the study of P-atom directed C-H functionalization in our group,we have successfully realized Rh(I)catalyzed P-atom directed indole C7-arylation.With Rh(PPh3)3Cl as a catalyst and LiOtBu as base,broad range of indole derivatives react with various(hetero)aryl bromide generating C7-arylated products.The key to this high regioselective transformation lies in the selection of a class of easily removable N-PR2(R = tBu&Cy)dericting groups.This makes the reaction has good application value which is reflected in the synthesis of key intermediate in the total synthesis of nature product Dictyodendrin B.Besides,the product itself is a kind of electron-rich monophosphine ligand which has the potential value for synthetic application.Mechanistic studies by DFT calculations and several experiments suggest that the most favorable pathway involves direct arylation initiated by an oxidative addition of the aryl bromides to Rh(I)complex followed by tBuO anion-involved CMD process as the rate-determining step.This finding should be an important supplementary to the research of P-atom directed reactions.Part III:Aldehydes are one kind of important synthetic raw materials as well as important synthetic intermediates in biomedical and chemical producing area.Hydroformylation of unsaturated hydrocarbons is the most used process for the preperation of aldehydes,but the use of highly toxic syngas and high pressure reaction conditions greatly limit the synthesis of various types of aldehydes and their synthetic applications.Based on the literature research and experience accumulated by the our group in C-H activation,we have designed a new way to synthesis aldehydes using n-butyraldehyde instead of syngas.Rh(CO)2(acac)catalyzed C-CHO bond cleavage followed by n-butyraldehyde dehydroformylation afford the irreversible hydroformylation of alkynes and olefins which produce unsaturated and aliphatic aldehydes.This hydroformylation process reacted through aldehyde dissociation and recombination is easy to operate,which is of great significance for the synthesis and application of aldehydes.Part IV:C-C bond activation has always been one of the most challenging area in inert bond activation.Ketones,due to its abundent reaction forms,become an important research area in organic synthesis.There are some publications about C-C bond activation of ketones,but only be limited in active substrates or alkyl ketones.Diaryl ketones are difficult to proceed C-C bond activation because of the strong conjugative effect.Rhodium catalyzed P-atom directed decarbonylation of diaryl ketones has been developed by our group on the bases of our research in P-atom directing reactions.C-C bond activation was realised to give biaryl products using[Rh(cod)Cl]2 as catalyst and ZnI2 as a co-catalyst without extra ligand.We also found accidently that with the use of LiOtBu,C-H activation will first happend with aryl choloride of diaryl ketones followed with decarbonylation to give ortho-diaryl substituted anilines.We also tried to isolate the reaction intermediate and confirm its structure through single crystal analysis which further validate the reaction meachanism.Along with the development of transition metal catalyzed inert bond activation reaction,C-C bond activation should be an idea method for rapidly constructing target moleculars.