Arene 1,2,3-Trifunctionalization Via Tandam Aryne 1,2-Difunctionalization-Friedel-Crafts Cyclization

As a class of highly active and widely used organic intermediates for efficient preparation of polysubstituted aromatic compounds,arynes play an important role in the synthesis of natural products and drug molecules,its broad application of which attracted much attention.In recent years,along with the discovery of a mild and highly efficient method for preparing arynes,namely Kobayashi's method,the chemistry of aryne has achieved rapid development.Since the structure of an aryne intermediate contains a formal carbon-carbon triple bond,it can only introduce a nucleophilic functional group and an electrophilic functional group at the 1,2-position of the aromatic ring when a nucleophilic reaction occurs.It is the triple-bond nature on the active site of an aryne that only permits an aryne species to undergo difunctionalization reactions at the vicinal positions of its aromatic ring in various transformations.To achieve functionalization at other positions of an arene ring at the same time using simple aryne intermediate becomes very challenging.In order to solve the above limitation,in 2016,our research group reported a cascade chemical transformation,in which traditional single aryne vicinal difunctionalization could be combined with a Claisen rearrangement.Consequently,1,2,3-trisubstituted arenes were achieved in this domino process.Inspired by our previous work,my project envisages that the bifunctionalization of single arynes might be able to connect with intramolecular Friedel-Crafts cyclization reaction to achieve the formation of three carbon-carbon bonds on the consecutive positions of an arene ring.To reach this goal,we synthesized a series of vinylogous amides with no free N-H bond on their structures and studied their reactivity with Kobayashi aryne precursor.However,due to the demand of an intramolecular Friedel-Crafts alkylation reaction on the aspects of both reactivity and selectivity,we did not obtain the desired product yet with the current substrates.Although we have not obtained conclusive results for this proposal at present,we believe that in our future study,we might have a chance to accomplish our goal through both in-depth mechanistic study and further design on the substrate structures.