Catalyst-free rapid conversion of arylboronic acids to phenols under green condition

A catalyst-free and solvent-free method for the oxidative hydroxylation of aryl boronic acids to corresponding phenols with hydrogen peroxide as the oxidizing agent was developed. The reactions could be performed under green condition at room temperature within very short reaction time. 99% yield of phenol could be achieved in only 1 min. A series of different arenes substituted aryl boronic acids were further carried out in the hydroxylation reaction with excellent yield. It was worth nothing that the reaction could completed within 1 min in all cases in the presence of ethanol as co-solvent.


Introduction
][7] However, these methods generally require harsh reaction conditions and exhibit limited substrate scope.][10][11][12][13] The oxidative hydroxylation of aryl boronic acids have been widely reported and applied to afford phenols.A variety of oxidants have been applied, such as O2, 9,13 NaBO3, 14 H2O2, 8 PhI(OAc)2, 15 etc...In order to facilitate the oxidation process, diverse conditions were also developed such as metal-catalyst, 16 organo-catalyst, 17 photocatalyst, 13 catalyst-free or solvent-free 1 , 4 etc...In view of sustainable and green chemistry, it was environmentally important to reduce the waste and pollution in the oxidative hydroxylation reactions by using green oxidant and solvent.9] However, in most cases, longer reaction times and complex reaction systems were necessary.Herein, we report a catalyst-free condition for the transformation of aryl boronic acids to substituted phenols by using H2O2 as oxidant and solvent.H2O2 can be seen as a green reaction medium.In the previous reports, the oxidation employing H2O2 in the absence of catalyst is a very slow process. 12,20However, the transformation of aryl boronic acids to phenols was very fast in this work.Excellent yields could be obtained in one minute for most substrates.

Results and Discussion
Initially, we wished to expand new catalytic applications for Ag nanoparticle which was synthesized in our lab previously.With this in mind, we used the hydroxylation of phenylboronic acid (1a) to the phenol (2a) as model reaction catalyzed by the Ag nanoparticle in order to optimize reaction conditions.The phenylboronic acid was transformed completely by using 20mg Ag catalyst and 0.2 mL H2O2 as oxidant in water (Entry 1, Table 1).Next, we attempted to reduce the catalyst loading.Surprisingly, the oxidative hydroxylation of 1a also afforded the corresponding product 2a in almost quantitative yield using 0.4 mL H2O2 (13 equiv. in this case) (Entry 2, Table 1).Compared with previous report, just 85% yield was achieved by using 3 equiv.H2O2 as oxidant in 10 mL water. 12It was obvious that the reaction speed could be increased along with the concentration increases of H2O2 (Entry 3, Table 1).Furthermore, the reaction occurred very rapidly (complete in 1 min) with 99% yield when 1.6 mL H2O2 was used as sole solvent and oxidant (Entry 4, Table 1).The pure product was easy to isolate without chromatography.A series of different substituted aryl boronic acids was subjected to the oxidative process under the optimized conditions, and the results are summarized in Table 2.Both the electron-withdrawing (2b-2h, table 2) and electron-rich (2i-2k, table 2) aryl boronic acids afforded the corresponding product in excellent yield in 3-12 minutes.The results demonstrates that the electronic nature of the substrates had no obvious influence on the yield.However, no products were detected when the arylboronic acids with para-substituents (2l-2r, table 2) and di-ortho substituents (2p, 2q, table 2).The relatively low yields could be reasonably attributed to the substrates which was difficult to dissolve in H2O2 as sole solvent.
In order to prove our assumption, various solvents which could co-solve with water such as MeOH, EtOH, acetone were added to the hydroxylation of boronic acids.Excellent yields could then be achieved in many cases.To our delight, when EtOH was employed as the co-solvent, a quantitative yield could be obtained in one minute.In view of the environmentally friendly features of EtOH.Hence, the scope of the substrates was further tested with EtOH as co-solvent.Surprisingly, phenyl boronic acids with electron-rich and electronwithdrawing groups were converted into the corresponding product in quantitative yields, and it is worth noting that the reaction occurs very rapidly (1 min in all cased).Table 3. Catalyst-free hydroxylation of boronic acids in EtOH a a Reaction conditions: phenylboronic acid (1 mmol), H2O2 (1.6 mL) and EtOH (1 mL) at room temperature, 1 min.b Isolated yield.
Based on the literature reports, we have proposed a plausible mechanism for catalyst-free ipsohydroxylation.Firstly, phenylboronic acid reacted with hydrogen peroxide to form adduct 1 and one proton transferred to form adduct 2. Then the phenyl group migrated to oxygen to generate the adduct 3 with the removal of H + by H2O.Finally, phenol formed after the hydrolysis.Scheme 1. Plausible mechanism.

Conclusions
In conclusion, we have developed a catalyst-free system for the oxidative hydroxylation of aryl boronic acids into phenols at room temperature under mild condition.The oxidative hydroxylation reactions could proceed efficiently both solvent-free and green solvent condition, affording various phenols as products with excellent yields in a very short reaction time.

Experimental Section
General.Reactions were carried out using commercially available reagents in over-dried apparatus.H2O2 and ethanol was commercially available and used directly.All the products are known compounds and have been reported in previous work.The 1 H NMR of products was corresponding with the references: 2a, 2b, 2d, 2f, 2j, 2l, 2m, 2o, 8 2c, 2k, 2n, 9 2e, 2g, 20 2i, 12 2q, 21 2r, 14 2h, 2p. 22neral procedure for the oxidation using H2O2 A 25 ml flask was charged with phenylboronic acid (1 mmol).Then 1.6 mL H2O2 was added under stirring.The reaction was stirred for 1 min, then quenched by water (10 ml).The aqueous layer was extracted with 20 mL ethyl acetate for three times.The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure.The pure product was obtained without flash column chromatography and the purity was determine by TLC (thin layer chromatography).General procedure for the oxidation using H2O2 A 25 ml flask was charged with phenylboronic acid (1 mmol).Then 1.6 mL H2O2 and 1 mL EtOH were added under stirring.The reaction was stirred for 1 min, then quenched by water (10 ml).The aqueous layer was extracted with 20 mL ethyl acetate for three times.The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure.The pure product was obtained without flash column chromatography and the purity was determine by TLC.

Table 1 .
Oxidation of arylboronic acids a