Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

Cyclic annulation involving diaryliodonium salts is an efficient tool for the construction of two or more chemical bonds in a one-pot process. Ortho-functionalized diaryliodonium salts have showcased distinct reactivity in the exploration of benzocyclization or arylocyclization. With this strategy of ortho-ester-substituted diaryliodonium salts, herein, we utilized a copper catalyst to activate the C–I bond of diaryliodonium salts in the generation of aryl radicals, thus resulting in an annulation reaction with naphthols and substituted phenols. This approach yielded a diverse array of 3,4-benzocoumarin derivatives bearing various substituents.


Results and Discussion
To start the study, we used 2-naphthol (1a) and 1.1 equivalents of ortho-methyl formate-substituted diaryliodonium salt 2a as template substrates.The reaction was performed in the presence of 10 mol % Cu(OTf) 2 and 1.0 equivalent of K 2 CO 3 in DCE at a temperature of 80 °C.To our delight, the reaction afforded 3,4-benzocoumarin 3aa in a 27% yield (Table 1, entry 1).The structure of 3aa was confirmed through NMR spectroscopy and mass spectra analysis.Subsequently, we started to screen various bases such as Na 2 CO 3 , Cs 2 CO 3 , KOH, NaOt-Bu, LiHMDS, and DMAP (Table 1, entries 2-7).Fortunately, it was found that the reaction yield was increased to 50% in the absence of any base (Table 1, entry 8).Further investigations for assessing the influence of various solvents including dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), toluene, acetic acid (AcOH) and water (Table 1, entries 9-13) were carried out.However, polar solvents such as AcOH and H 2 O were proved to be unsuitable for this reaction.For catalysts, we found that Cu(OAc) 2 gave the best results (Table 1, entries [15][16][17][18].Finally, the reaction temperature and time were optimized, 3aa was produced in 61% yield at a temperature of 80 °C after 3 hours (Table 1, entry 15).
With the optimized reaction conditions in hand, we started to explore the substrate scope of the cyclization to construct a variety of 3,4-benzocoumarin derivatives.Our investigations commenced with 2-naphthol (1), and the results are presented in Table 2. Various substituted naphthols with a broad range of substituents on the naphthalene unit were well tolerated in the reaction, affording the corresponding products 3aa-aq in gener- These substituents included halogen (Br), methyl, phenyl, aldehyde, ester, and methoxy groups, all of which were compatible with the reaction conditions.Notably, compounds 3ab, 3ah, 3aj, 3am and 3ap bearing bromine are very useful modules for the synthesis of functional materials via cross-coupling reactions.Next, we extended our investigation to 1-naphthol in this reaction, and found that the arylation of 1-naphthol was achieved selectively at the C-2 position.The cascade cyclization resulted in the corresponding products 3an and 3ao in yields of 49% and 40%, respectively (Table 2, entries 14 and 15).When 5,6,7,8-tetrahydro-2-naphthol was subjected to the reaction, we obtained products 3ar and 3as as a mixture (40% and 10% yield, respectively, Table 2, entry 18).However, when naphthol bearing a strong electron-withdrawing group (such as a nitro group) in the para position was reacted, the corresponding product could not be obtained, but instead the O-arylated product 3at was obtained (Table 2, entry 19).Apart from naphthol, we also tested substituted phenols under the standard conditions.The corresponding products of 3au and 3av were produced in 34% and 39% yields, respectively, in which methoxy and tert-butyl groups were located in the para position to the hydroxy group (Table 2, entries 20 and 21).In the case of 3al, the mono-arylation of naphthol generated 3al' in 20% isolated yield, which is the reason for the low yield of 3al.
We subsequently turned our attention to explore the effect of structural diversity of the ortho-ester-substituted diaryliodonium salts.Firstly, a family of substituted diaryliodonium salts  were synthesized in a one-pot procedure.These ortho-substituted diaryliodonium salts were isolated as stable solids, whose structures were fully characterized by NMR spectroscopy.As shown in Table 3, we utilized 2-naphthol and 1-naphthol as template substrates to react with various unsymmetrical 2-estersubstituted diaryliodonium salts.Remarkably, iodonium salts 2  proved to be versatile in this reaction, regardless of the electronic nature and position of the substituents.The desired 3,4benzocoumarin products 3ba-ma were obtained in yields of 21-59%.Notably, substituents such as halogens (F, Cl, and Br), methyl, methoxy, and trifluoromethyl groups at the ortho-, meta-, or para-positions to the ester group were all well-tolerated (Table 3).
To gain further insights into the reaction mechanism, we conducted control experiments.Given the utility of diaryliodonium salts in radical chemistry, we introduced 2 equivalents of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 2 equivalents of butylated hydroxytoluene (BHT) into the template reaction.Remarkably, we observed that the desired product was not formed, suggesting a radical pathway.Subsequently, we investigated the bond-formation sequence in the benzocyclization reaction.A possible intermediate of 3al' was prepared and tested in the reaction under the standard conditions, however, product 3aa was not obtained.
Based on the literature known results and the experimental evidences [35,36], we proposed a plausible reaction mechanism (Scheme 2b

Conclusion
In summary, we have employed ortho-ester-substituted diaryliodonium salts in a cascade cyclization, the cyclization features a copper-catalyzed activation strategy involving the cleavage of the C-I bond and esterification.The resulting cascade of selective arylation/intramolecular cyclization facilitated the synthesis of 3,4-benzocoumarin derivatives.The protocol enables the efficient formation of two chemical bonds in one pot, representing a valuable tool for the synthesis of polycyclic benzocoumarins.Our ongoing research endeavours

Table 2 :
Scope of naphthols and phenols for the synthesis of 3,4-benzocoumarins.a,b .

Table 3 :
Scope of ortho-ester-substituted diaryliodonium salts.a (continued) ).The reaction started with the formation of radical intermediate A from diaryliodonium salt 2a.Naphthol 1a forms intermediate B with A after participation with the Cu(II) catalyst.Intermediate B generates C radical substitution.A final intramolecular transesterification yields the benzocoumarin product 3aa.