Visible Light Photocatalytic Radical-mediated Carbocyclization Of Unsaturated Hydrocarbons

Cyclic compounds are present in a vast number of natural products,pharmaceuticals,and functional materials.As compared to heterocycles,the construction of all-carbon rings is much more challenging.Recently,the radical-mediated carbocyclization has emerged as an efficient protocol for the access of carbocycles.Among these,many reports proceeding via 5-exo-trig closure have been documented,while other versions,such as 4-exo-trig,5-endo-trig,and 6-exo-trig,remain to be developed.By using hydrogen atom transfer（HAT）-mediated radical addition/cyclization cascade,a couple of visible light photocatalytic 4-exo,5-endo,6-exo-carbocyclizations of alkynes or alkenes have been accomplished,providing a direct and effective access to functionalized cyclobutanes,cyclopentenes,chroman-4-ones,and related compounds under very mild conditions,which should be valuable for the fast construction of synthetically challenging all-carbon rings.The main contents are summarized as follows:First,a visible light-induced 5-endo carbocyclization of terminal alkynes has been developed.According to the Baldwin’s rule,the 5-endo-trig radical cyclization of all carbon systems is elusive.By using SEt as a traceless directing group,a photocatalytic sulfonyl-carbocyclization of alkynes is achieved for the direct synthesis of decorated cyclopentenes and indenes.The reaction features mild conditions,good functional group tolerance,and high reaction efficiency.Additionally,it has been applied to the construction of a key motif of the GPR40 full agonist AM-6226.Mechanistic studies suggest a radical cascade involving a Markovnikov-type sulfonylation,1,5-HAT,5-endo-trig cyclization,andβ-elimination.Polar effects and radical delocalization caused by the sulfonyl group may be responsible for the occurrence of anti-Baldwin 5-endo-trig radical cyclization,thus laying further groundwork for the use of uncommon 5-endo-trig radical annulation in rapidly assembling five-membered carbocycles.Afterward,a photocatalytic 4-exo carbocyclization of terminal alkynes is developed,with an aim to seek a novel method for the construction of the synthetically important but challenging cyclobutanes which are difficult to access via traditional methods due to their strained,small ring structure.By using SEt as the transient directing group as well,a visible light mediated trifluoromethylative carbocyclization of terminal alkynes is realized,providing a direct approach to trifluoromethylated cyclobutyl aldehydes.The reaction displays excellent diastereoselectivity and good functional group compatibility.Mechanistic studies indicate that a pathway involving radical addition,1,5-HAT,4-exo-trig cyclization,single electron transfer（SET）oxidation,hydroxylation,and elimination of RSH from the hemithioacetal.DFT calculations suggest that the hyperconjugativeπ→σ^*_C-F interactions of trifluoromethylated vinyl sulfides may account for the realization of thermodynamically unfavorable 4-exo-trig radical cyclization.Finally,a photocatalytic acyl-fluoroalkylation of unactivated alkenes has been conducted.Due to its thermodynamically reason,the 6-exo-trig radical cyclization of aldehydes is rarely reported.By using difluoroacetic acids as the difluoroalkylation reagent and Ph I（OAc）₂ as the oxidant,a visible-light-induced acyl-difluoroalkylation of unactivated alkenes featuring a 6-exo-trig of aldehydes has been developed,affording difluoroalkylated cyclic ketones,including chroman-4-ones and indanones,in moderate to excellent yields.Various functional groups such as F,Cl,Br,Ac,CN,OR,esters,and amides are well tolerated.The catalytic cycle comprises radical fluoroalkylation of C-C double bonds,6-exo-trig cyclization,1,2-HAT,and oxidative deprotonation.It represents a new advance on acylation of carbon-centered radicals using aldehydes as the acyl donor.In summary,a couple of 4-exo,5-endo,or 6-exo radical carbocyclization of alkynes or alkenes has been successfully developed,which produce decorated cyclobutanes,cyclopentenes,chroman-4-ones and related compounds in a single reaction,thus providing a highly efficient route to construct complex molecules bearing all-carbon rings.