Study On The Synthesis Of 3-Aminoindenes Via Rhodium-catalysed C-H Bond Activation/cyclization

C-H bond widely presents in organic molecules,and transition metal catalyzed direct functionalization of C-H bonds is one of the most effective methods for constructing carbon-carbon and carbon-heteroatom bonds,due to avoiding the pre-functionalization of the substrates,which greatly shortens the reaction step and improves the atom utilization efficiency.The functionalization of inert C-H bonds under mild conditions reduces energy consumption and pollutant,and makes the chemical reactions environmentally friendly.However,direct functionalization of the inert C-H bond is not easy to control the regioselectivity of the reaction because there are more than one C-H bonds in most organic molecules.So a directing group is required to realize the region-selectivity.The further chemical transformation or removal of the directing group is also a challenge.Moreover,an additional oxidant is usually required for dehydrogenerative coupling reaction.On the other hand,indenamine is a key structural framework embedded in a large number of biologically active molecules and exhibits wide range of interesting pharmacological properties.As a result,developing the methology of the synthesis and transformation of indenamine-based compounds has become attractive for organic chemists.The traditional methods to build such a croe are mainly based on the conversion of functional groups.The substrates involved in the reaction are mostly halides or pseudohalides,etc.,which would produce a large amount of by-products,leading to waste and environmental pollution.Moreover,these reaction substrates need to be pre-prepared or pre-activated,which make the reactions suffer from multistep processes.Recently,organic synthetic chemists have made great efforts to construct indenamines by transition metal catalyzed C-H bond activation/cyclization.However,these strategies all focused on the cycloaddition of arylimines with alkynes,which is not beneficial to expand the substrate scope.Based on these problem mentioned above,in this thesis,we have mainly been studying a protocol to polysubstituted 3-aminoindenes from benzimidates and alkenes through rhodium-catalyzed C-H activation/carbocyclization(Scheme 1).Cheap and easily available α,β-unsaturated ketones or nitroalkene are applied as coupling partner.The acyl or nitro groups could be smoothly introduced to 3-aminoindenes at the C-2 position,which makes the products of this reaction particularly attractive for further transformation to synthesize various important molecules.The introduction of the imidate group as a directing group allows the activation of the C-H bond to occur selectively in the ortho position of the imidate group,and the imidate group can be converted to the amino group of the indenamine during the reaction without removing the directing group.The amino group is easy to further modify.Additional,this protocol exhibits good functional-group tolerance and excellent regioselectivity.The reaction mechanism was proposed based on the control experiments(Scheme 2).C-H bond activation,cyclization,and finally removal of one molecule of alcohol give the corresponding 3-aminoindene product,which avoid the externl oxidant.