Visible-Light-Induced Acylarylation Of Unactivated Alkenes Toward 3-(Arylmethyl) Chroman-4-Ones

Objective:Chroman-4-ones are widely found in natural products and active bio-molecules,and have significant physiological activities.In the recent years,the radical-initiated cascade cyclization strategy has attracted great attention of scientists in the construction of chroman-4-one scaffold and other（hetero）cyclic frameworks.Most of the existing radical-initiated cascade cyclization strategies are based on the external radical-initiated,while there are only a few examples of internal acyl radical-initiated.In addition,these strategies are solely based on the elaboration of uneasily available and relatively unstable o-（allyloxy）arylaldehydes or carboxylic acid thioesters.Therefore,this thesis aims to develop a method for the construction of chroman-4-ones by internal acyl radical-initiated acylation of unactivated alkenes using readily available and relatively stable substrates.Methods:2-Allyloxybenzoic acid 1a and 4-cyanopyridine 2a were used as model substrates to explore the optimal reaction conditions for the synthesis of chroman-4-ones under different conditions.With the optimized reaction conditions in hand,we investigated the scope and limitations of this reaction.Then a plausible mechanistic pathway for this photocatalytic acylarylation is proposed by free radical capture experiment and cyclic voltammetry experiment,and further derivatization of the product was studied.Results:After a series of condition screening of the reaction conditions,the optimal reaction conditions were obtained as follows:under the protection of argon,alkenoic acid（0.1 mmol）and cyanoarenes（0.15mmol）as substrates,3DPAFIPN（2 mol%）as photocatalyst,P（p-tol）₃（0.2mmol）,Me CN（2 ml）as solvent,and the reaction was irradiation under 30W blue LED at room temperature for 24 h.Finally,33 4-chromone derivatives were synthesized with a yield of 17-72%,and the scale-up reaction and further derivatization of the synthesized products were carried out.At the same time,a challenging three-component alkene acylarylation reaction was explored.Conclusion:In this thesis,we have developed a novel visible-light-driven photoredox-neutral alkene acylarylation with cyanoarenes,enabling metal-and oxidant-free access to structurally diverse 3-（arylmethyl）chroman-4-ones as well as other cyclic ketone analogs.Furthermore,the resulting chroman-4-ones can be scale-up synthesized and also readily parlayed into skeletally diverse compounds such as chromone and 2H-chromene.In addition,the developed powerful protocol involves phosphoranyl radical-mediated acyl radical-initiated cascade cyclization followed by radicalradical coupling with the persistent aryl radical,enabling the concomitant introduction of ketone and aromatic fragments to organic molecules.