Rhodium-Catalyzed The Annulation Of Peresters And Alkynes Under External-Oxidant-Free Conditions

Transition-metal-catalyzed functionalization of inert C-H bonds has attracted signi?cant interest since it avoids the multistep preparation of starting materials and thus allows an overall streamlining of organic synthesis. Concerning the catalytic mechanism, it generally involves a high-oxidation-state metal species as a promoter and generates the desired products as well as low-oxidation-state metal species produced by reductive elimination. Therefore, stoichiometric or excessive amounts of oxidants are generally required to regenerate the active catalyst, which would provide a stoichiometric amount of waste and reduce the overall “greenness” of the process.To overcome this drawback, a novel redox-neutral strategy via the use of an oxidizing directing group(internal oxidant) has been recently pioneered by Cui and Wu group.Then, Hartwig, Yu, Glorius, Fagnou, Ackermann and other groups have developed various internal oxidants, however, which are limited to the oxidizing potential of N-O, N-N, and O-N bonds. Exploitations of other covalent bonds containing heteroatoms in the redox-neutral C-H activation are extremely rare.Isocoumarins are important structural motifs of various bioactive natural products.There existed three ways in the isocoumarin formation. With the development of C-H activation, constructions of isocoumarin have been broaden from annulation by arylcarboxylic acids and alkynes under external oxidant conditions to the annulation by N, N-diethyl-O-benzoylhydroxylamine and alkynes with the O N bond as an internal oxidant.Peresters are easily available and widely applied as oxidants or radical initiators in organic synthesis due to their weak O-O bond. We deduced that the O-O bond from the easily available aryl peresters could serve as an internal oxidant for the formation of isocoumarin derives through the transition-metal-catalyzed direct C-H activation. This method has innovations as follows: 1) As peroxides have been broadly applied as oxidants or radical initiators, it was the first time that using peroxides as the substrate of C-H activation reaction which has broaden theapplication of peroxides. 2) Since oxygen atom was a weak directing atom, using it to direct annulation has been a challenge in the research of the C H activation reaction.The successful overcoming of this difficulty has provided a valuable example for further researches. 3) It was the first report that using O O bond as an internal oxidant involving transition-metal-catalyzed C H activation reaction. Thus, it has the meaning of broaden the scope of internal oxidant. 4) Compared with previous constructions of isocoumarin, this method has advantages of using easily available substrates, without external oxidant as well as less toxic byproduct.According to the results obtained and literatures, the reaction mechanism was proposed as follows: The first step is the generation of the active [Rh III] species. Then an irreversible C-H activation of aryl perester through cyclorhodation gives intermediate A, which is subsequently coordinated and inserted with diarylalkyne to form intermediate C. C-O bond formation by elimination of intermediate C gives intermediate D. Product is released through the redox process of intermediate D and regenerates the active [Rh III] species(path I). Another pathway(path II) is also possible which involves a pivalic acid promoted intramolecular nucleophilic substitution leading to a C-O bond formation and O-O bond cleavage to afford product, tert-butyl alcohol, and a [Rh III] species. Since the protonation of O,O-tert-butyl group of intermediates E by pivalic acid makes it a better leaving group in path II, while the migration of the [RhI] to the adjacent oxygen would require a high energy 3-ring transition state in path I, path II seems to be more favorable in this transformation.