Electrochemical Radical Borylation of Aryl Iodides

中文 / Bilingual · English version

Accepted Article

Title: Electrochemical Radical Borylation of Aryl lodides

Authors: Junting Hong, Qianyi Liu, Feng Li, Guangcan Bai, Guoquan Liu, Man Li, Onkar S. Nayal, Xuefeng Fu and Fanyang Mo*

This manuscript has been accepted and appears as an Accepted Article online.

This work may now be cited as: Chin. J. Chem. 2019, 37, 10.1002/cjoc.201900001.

The final Version of Record (VoR) of it with formal page numbers will soon be published online in Early View: http://dx.doi.org/10.1002/cjoc.201900001.

WILEY-VCH SIOC CCS

Electrochemical Radical Borylation of Aryl Iodides†

Junting Hong, ${}^{\ddagger a}$ Qianyi Liu, ${}^{\ddagger a}$ Feng Li, ${}^{b}$ Guangcan Bai, ${}^{b}$ Guoquan Liu, ${}^{b}$ Man Li, ${}^{a}$ Onkar S. Nayal ${}^{a}$ , Xuefeng Fu ${}^{c}$ and Fanyang Mo**, a

Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing 100871, China

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China

${}^{c}$ Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China

’ Jiangsu Weiming Environmental Protection S&T Co., Itd

ite this paper: Chin. J. Chem. 2019, 37, XXX-XXX. DOI: 10.1002/cjoc.201900XXX

Summary of main observation and conclusion Herein, we report the first electrochemical strategy for the borylation of aryl iodides via a radical pathway using current as a driving force. A mild reaction condition allows an assorted range of readily available aryl iodides to be proficiently converted into synthetically valuable arylboronic esters under transition metal catalyst-free conditions. Moreover, this method also shows good functional group tolerance. Initial control mechanistic experiments reveal the formation of aryl radical as a key intermediate and the current plays important role in the generation of radical intermediate.

Packground and Originality Content

Arylboronic acids and their derivatives have found widespread applications in organic synthesis. ${}^{1 - 3}$ Consequently, the methods of ti eir preparation have been intensively developed in the past decades. Conventional approaches to the synthesis of arylboronic acids or esters from aryl halides require either prior preparation of ghly reactive organometallic reagents, ${}^{4 - 5}$ or the procedures ${}^{6}$ required transition-metal such as Pd, ${}^{7 - {10}}\mathrm{\;{Ni}}{,}^{{11} - {13}}\mathrm{{Cu}},{}^{{14} - {16}}{\mathrm{{Zn}}}^{17}$ and - ${\mathrm{e}}^{18}$ as a catalyst. These methods are widely used in laboratories and pharmaceutical companies. However, the limited functional c oup compatibility and the use of expensive metals and/or ligands or strong bases are the obvious drawbacks in these methods. Nevertheless, there is a strong need to the development of efficient, mild, and transition-metal-free synthetic approach for the borylation of aryl halides.

In this context, Organic electrochemistry offers a green and custainable alternative tool to conventional chemical approaches for organic transformations. ${}^{{19} - {35}}$ Various versatile reactive intermediate (e. g., radical cation, radical anion, and radical) can efficiently generated by anodic oxidation, cathodic reduction, as well as paired electrolysis. Our laboratory has been engaged in the development of organic electrochemistry to overcome unmet nthetic challenges. ${}^{{36} - {38}}$ With this background, we thought to the synthesis of aryl boronates from aryl halides through e’ectrochemical transformation (Scheme 1c).

In the context of electro-reduction of aryl halides, it’s well known that aryl halide easily transforms to aryl radical via a versible, dissociative electron transfer (DET) process. Ensuing, this radical is widely used in various organic transformations (Scheme 1a). ${}^{39}$ Except this strategy, transition-metal-free borylation approaches are also well known for the synthesis of a diverse range of organoboron compounds via radical pathway. ${}^{{40} - {42}}$ Since the pioneering work of the Wang group in 2010, ${}^{{43} - {45}}$ numerous transition-metal-free aromatic borylation protocols have been developed using anilines, ${}^{{46} - {49}}$ aryl (pseudo)halides, ${}^{{50} - {56}}$ and aryl carboxylates ${}^{57}$ as the coupling substrates (Scheme 1b). Inspired from these strategies, we thought to develop an electrochemical radical borylation of aryl halides via cathodic reduction under transition-metal-free condition (Scheme 1c).

We present herein mild radical borylation of aryl halides with commercially available bis(pinacolato)diboron $\left( {{\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}}\right)$ , as the boron source. After the comparison of the present study with the known borylation methods, we found that the electrochemical radical borylation reaction has many advantages over the known protocols. Primarily, the overall process is sustainable in which electron serves as the reductant with solvents being oxidized at the anode, therefore no sacrificing anode is needed. Furthermore, this reaction can be performed under air atmosphere. Moreover, this electrochemical radical borylation of aryl iodides approach got remarkable increase in reaction rate over the reported work on borylation of aryl iodides by Zhang’s group under the similar reaction conditions. ${}^{54}$

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/cjoc.201900001

Concise Report

Scheme 1 Electrochemical borylation of aryl halides

(c) Electrochemical radical borylation of aryl iodides (this work)

• Sustainable process (no sacrificing anode, no electrolyte)

• Soft conditions (not sensitive to air or moisture)

• Simple operation (undivided cell)

Desults and Discussion

Results (sample title, optional)

this investigation, we chose phenyl iodide 1a as model substrate and pinacol diboron $\left( {{\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}}\right)$ 2 as a borylating agent ${}^{\prime - }$ able 1). Interestingly, ${54}\%$ yield of 3a was obtained using platinum meshes as the electrodes with ${13}\mathrm{{mA}}$ constant current in the presence of cesium carbonate (entry 1). Notably, either increasing or decreasing the current resulted in lower yields (entries 2 and 3). After that, other bases such as CsF, CsOAc, $t$ -BuOK and MeONa were also investigated under similar reaction conditions. However, all these bases were less effective. (entries 4-5 and 7-8). To our delight, the significant change was observed in the yield of the desired product after the elevation of reaction temperature in 2h (entry 6). Moreover, other solvents, such as EtOH, THF and MeCN were also tested to optimize the best reaction solvent. Regrettably, no better yields of 3a were obtained (entries 9-11). In the cases of THF and MeCN solvents, the reaction media became less conductive (30 V, 1-3 mA). Therefore, electrolyte ${\mathrm{{Bu}}}_{4}{\mathrm{{NClO}}}_{4}$ was added in the reaction media to succeed the reaction (entries 10-11). After the screening of additional reaction times, it is revealed that $3\mathrm{\;h}$ is the optimum time for the completion of the reaction (entry 12). Moreover, drastically changes were observed in the yield of the desired product after increasing the amount of ${\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}$ from 3.0 and 4.0 equivalent (entry 1 and entries 12-13). Finally, in the absence of current, deleterious impact was observed in the yield of 3a (entry 14), which clearly indicates the significant role of current in the generation of aryl radical. Moreover, the “on and off” experiment also indicated the requirement of continuous current (entry 15). constant current. ${}^{b}$ Determined by GC-FID with $n$ -decane as an internal standard. ${}^{c}{\mathrm{{Bu}}}_{4}{\mathrm{{NClO}}}_{4}$ as the electrolyte was added. ${}^{d}$ “On and off” control experiment. During a total time of 3 hours, the current continued for 3 min and then interrupted for 27 min, cycled for 6 times.

${}^{\sigma }$ Reaction conditions: Platinum mesh electrodes (1 cm $\times 1$ cm),1a (0.5 mmol),2, base (2.0 equiv.), solvent (5 mL), heating, undivided cell, sealed tube. cc,

With the optimal reaction conditions in hand, we explored the substrate scope of aryl iodide (Table 2). Notably, a wide range of aryl iodide derivatives bearing both electron-withdrawing and electron-donating groups could be borylated in moderate to good yields. Aryl iodides with an electron-donating group furnished the corresponding borylation product in good yields (3a-3e). A sterically hindered aryl iodide such as 2e and 2f smoothly engaged ir the reaction and afforded a moderate yield of the respective product. In addition, aryl iodides with an electron-withdrawing group, such as an amide and an ester, produced borylation products in moderate yields (3g-j). Notably, for substrate 1j’, the ester group was converted to phenolic hydroxyl and furnished r oduct 3j in 60% yield.

To study the mechanism, we designed a series of electron paramagnetic resonance (EPR) experiments. In this context, dimethylpyridine N-oxide (DMPO) was introduced as a spin trapping agent to convert the short-living active radical into EPR uetectable nitroxide radicals. ${}^{58}$ The EPR spectra were simulated using the least-squares fitting method with EasySpin’s function garlic (for details, see Supporting Information). The parameters, isotropic $g$ values and hyperfine constants $A$ were carefully compared with literature data and used as the unique fingerprint of the trapped radicals.

Interestingly, when the current is passed through in a reaction medium for 5 minutes at room temperature, the strong EPR signal is appeared (see Figure 1a). Besides, in the absence of current, the intensity of EPR signal is decreased under similar conditions. This FPR signal is generally assigned to be DMPO-Ph, which is already Known in various reported literature. ${}^{{59} - {60}}$ However, on the basis of evious reports, we found that the signals of some other species such as DMPO-CH3, ${}^{{60} - {61}}$ DMPO-CH2, OH, ${}^{{61} - {62}}$ appear very close or similar to the EPR signal of DMPO-Ph. To verify an ectrochemically generating radical species by the reduction of halides on cathode process, we carried out the reaction with ${}^{n}{\mathrm{C}}_{4}{\mathrm{\;F}}_{9}\mathrm{I}$ in the presence of ${45}\mathrm{\;{mA}}$ current. As expected, a very special “quasi-quartet” signal of DMPO $\cdot {\mathrm{C}}_{4}{\mathrm{\;F}}_{9}{}^{61}$ appears within 30 minutes shown in Figure 1b due to the inductive effect caused by the adjacent fluorine substituents. On the basis of results of ol experiments presented in Supporting Information, the mentioned literatures and the cyclic voltammetry studies (vide ir fra), we concluded that the strong EPR signal appears due to the ormation of DMPO-Ph species in Figure 1a. Thus, these results indicate toward the generation of aryl radicals and current enhance the rate of formation of aryl radical.

able 2 Substrate scope ${}^{a}$ through intermediate E and F. Meanwhile, the reaction becomes redox neutral due to the anodic oxidation of the solvent to give oxides which balance the overall transformation. Consequently, intermediate G quenched by solvent, oxides or other aryl iodides via SET to afford E. However, the possibility of the formation of desired product 3 via the generation of boron-centered radical I cannot be ruled out at this stage.

${}^{a}$ Reaction conditions: 1 (0.5 mmol),2 (2.0 mmol,4.0 equiv.), ${\mathrm{{Cs}}}_{2}{\mathrm{{CO}}}_{3}$ (1.0 mmol,2.0 equiv), $\mathrm{{MeOH}}$ (5 mL), platinum mesh electrodes $\left( {1\mathrm{\;{cm}} \times 1\mathrm{\;{cm}}}\right)$ , constant current ${13}\mathrm{\;{mA}},{65}^{ \circ }\mathrm{C},3\mathrm{\;h}$ , undivided cell, sealed tube. ${}^{b}$ Using reticulated vitreous carbon (RVC) electrodes. ${}^{c}$ From $1{j}^{\prime }$ .

To further clarify the reduction process of iodides, we designed cyclic voltammetry (CV) measurements. Initially, when we mixed phenyl iodide 1a with ${\mathrm{{LiClO}}}_{4}$ solution, a single reduction peak was appeared which is shown in Figure 2a. Noteworthy, after the adding of ${\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}$ and base ${\mathrm{{Cs}}}_{2}{\mathrm{{CO}}}_{3}$ in the model reaction, the single reduction peak appeared with a sharp band. While this peak was completely disappeared in the absence of phenyl iodide 1a as shown in Figure 2b. Thus, these results indicate towards the single electron reduction process of aryl iodides on the cathode. In addition, we conducted differential pulsed voltammetry (DPV) experiments to further indicate toward the single electron reduction of aryl iodide shown in Supporting Information.

According to our mechanistic investigations and recent relevant literatures, ${}^{{63} - {64}}$ a plausible mechanism for this electrochemical borylation of aryl iodides is proposed (Scheme 2). Initially, at the cathode, aryl iodide 1 undergoes reduction to afford the corresponding radical anion C, which is further transformed into the aryl radical D via carbon-halogen bond cleavage. Further, aryl radical $D$ interacts with ${B}_{2}{\text{ pin }}_{2}$ in the presence of a base $\left( {\mathrm{{RO}}}^{ - }\right)$ to generate the desired product 3 along with the formation of G

Figure 1 EPR experiments. Reaction conditions: iodides (0.3 mmol), ${\mathrm{B}}_{2}{\mathrm{{Pin}}}_{2}$ (1.2 mmol,4.0 equiv.), ${\mathrm{{Cs}}}_{2}{\mathrm{{CO}}}_{3}$ (0.6 mmol,2.0 equiv), DMPO (0.3 mmol, ${30\mu }\mathrm{L}$ ), MeOH (3 mL), platinum mesh electrodes (1 cm × 1 cm), stirred at room temperature with given current and time.

Vithout ${\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}$ and base

(b) With ${\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}$ and base

Figure 2 Cyclic voltammetry (CV) experiments. Reaction conditions: 1a (3 mmol), ${\mathrm{{LiClO}}}_{4}$ (3 mmol), ${\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}$ (6 mmol), ${\mathrm{{Cs}}}_{2}{\mathrm{{CO}}}_{3}$ (3 mmol), MeOH (30 mL), 20 ${}^{ \circ }\mathrm{C}$ . L-type glassy carbon as working electrode, Pt wire as counter electrode and saturated calomel electrode (SCE) as reference. Scan rate: 0.02 V/s.

Scheme 2 Proposed mechanism

Conclusions

In summary, we have developed a sustainable and practical electrochemical borylation of aryl iodides, providing a very useful approach to arylboronic esters. EPR, CV and PVD experiments verified the formation of aryl radicals in this electrochemical borylation reaction, which supports a radical borylation mechanism. This electrochemical borylation reaction is complementary to other borylation methods and might inspire further investigations in the radical borylation strategy.

Experimental

An undivided cell was equipped with two platinum mesh electrodes and connected to a DC regulated power supply. Aryl iodide 1 (0.5 mmol), ${\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}$ (2 mmol,508 mg,4 equiv), ${\mathrm{{Cs}}}_{2}{\mathrm{{CO}}}_{3}$ (1.0 mmol, 326 mg, 2 equiv) and 5 mL of anhydrous MeOH was added to the cell. The mixture was electrolyzed using constant current conditions (13 mA) at ${65}^{ \circ }\mathrm{C}$ under magnetic stirring. After almost 3 hours, the TLC analysis indicated that the electrolysis was complete (witnessed by the disappearance of the aryl iodide). Upon cooling to room temperature, the reaction mixture was transferred to a 100 mL flask by methanol, and then a little silica gel was added into it. After removal of the solvent in vacuo, the residue was poured onto a silica gel column and purified by c lumn chromatography to give the desired product 3.

cupporting Information

The supporting information for this article is available on the WW under https://doi.org/10.1002/cjoc.2018xxxxx.

^cknowledgement (optional)

The project was supported by the Natural Science Foundation f China (Grant 21772003). We also thank the “1000-Youth Talents Plan” and Peking University for start-up funds. This work was also partially funded by the Peking University carbon capture, u.ilization and storage project supported by BHP Billiton.

The project was supported by the Natural Science Foundation f China (Grant 21772003). We also thank the “1000-Youth Talents Plan” and Peking University for start-up funds. This work was also partially funded by the Peking University carbon capture, u.ilization and storage project supported by BHP Billiton.

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Manuscript received: XXXX, 2019

Manuscript revised: XXXX, 2019

Manuscript accepted: XXXX, 2019

Accepted manuscript online: XXXX, 2019

Version of record online: XXXX, 2019

Entry for the Table of Contents

Page No.

Electrochemical Radical Borylation of Aryl Iodides

Junting Hong, Qianyi Liu, Feng Li, Guangcan Bai, uoquan Liu, Man Li, Onkar S. Nayal and Fanyang Mo*

The first electrochemical strategy for the radical borylation of aryl iodides is reported in this paper. The significant promoting effect of current in the aryl radical generation revealed by EPR studies.