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Synthesis 2023; 55(18): 3040-3046
DOI: 10.1055/a-2025-1822
paper
Special Issue Electrochemical Organic Synthesis

Electrochemical Difunctionalization of Alkenes towards the Synthesis of β-Bromoethers under Metal-Free Conditions

Zhengjiang Fu∗
,
Feiwu Chen
,
Guangguo Hao
,
Xuezheng Yi
,
Junhua Zeng
,
Hu Cai∗

Financial supported by National Natural Science Foundation of China (NSFC) (22161028, 21861026 and 22075123) and Jiangxi Provincial Natural Science Foundation (20224BAB203012) is gratefully acknowledged.
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Abstract

A metal-free electrochemical method for vicinal difunctionalization of various alkenes with dibromomethane in alcohol as solvent has been well established to synthesize the corresponding β-bromo-α-alkyloxyalkanes with good functional group tolerance under ambient conditions. Preliminary mechanistic studies indicate the oxidation of bromine source occurs prior to that of alkene substrate with the involvement of bromine radical during electrolysis.


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Key words

difunctionalization - alkene - β-bromoethers - electrochemical transformation - metal-free conditions

Alkenes are not only prevalent structural constituents found in many natural and chemical products, but also are indispensable material resources for the development of social economy.[1] In view of the high reactivity for C=C bond in alkenes, alkenes can act as privileged building block in organic synthesis; thus, the difunctionalization of alkenes via introduction of two versatile functional groups provides an efficient strategy to alter their inherent properties and create complex molecules.[2] In this regard, intensive studies have been made in selective vicinal functionalization of alkenes to construct C–C and C–Het bonds with different catalytic system, such as 1,2-diamination,[3] aminooxygenation,[4] dicarbofunctionalization,[5] carboamination,[6] carboazidation,[7] carbochalcogenation,[8] carbohydrogenation,[9] carbooxygenation,[10] cyanophosphinoylation,[11] halosulfoximidation,[12] halophosphorylation,[13] hydroboration,[14] dioxygenation,[15] oxysulfonylation,[16] oxyhalogenation,[17] and oxyphosphorylation.[18)

It is noteworthy that green electrons for the oxidation or reduction of a desired substrate is superior to stoichiometric amounts of toxic and/or harsh chemical reagents. In this context, electro-organic synthesis is able to dramatically minimize waste and remarkably improve functional group tolerance using electrons as the ‘reagent’, which has attracted significant attention for efficient and environmentally benign synthetic strategy.[19] Furthermore, the development of electrochemical methods for incorporating two functional groups into alkenes has been a matter of great interest in organic synthesis community over the past decade,[20] especially selective electrochemical 1,2-difunctionalization of alkenes, such as diamination,[21] aminooxygenation,[22] aminotrifluoromethylation,[23] carboarylation,[24] carbohydroxylation,[25] carboselenation,[26] haloesterification,[27] halosulfuration,[28] hydroboration,[29] dioxygenation,[30] oxyazidation,[31] oxyphosphorylation,[32] oxyselenation,[33] oxysulfenylation,[34] and oxysulfonylation.[35] Because halo derivatives are widely used in the synthesis of natural products, bioactive molecules, pharmaceuticals and functional materials, alkoxyhalides (β-haloethers) are important building blocks in organic, medicinal and industrial chemistry.[36] Although the groups of Terent’ev[37] and Wirth[38] described electrochemical synthesis of bromohydrin ethers from alkoxybromination of alkenes with KBr or HBr as bromine source under acidic conditions, the employment of acid additives with constant current of more than 200 mA resulted into inferior functional group tolerance for the substrates, thereby reducing the green of the transformation and restraining the further application of the conversion. Recently, our group has gained considerable knowledge in electrochemical deborylative functionalization of arylborons[39] including­ halogenation,[39a] seleno/thiocyanation,[39b] selenylation[39c] and hydroxylation[39d] under metal-free conditions. As a part of our efforts to continuously develop cheap and eco-friendly methods under electrochemical conditions, herein, we first reveal an electrochemical method for vicinal halo-alkyloxylation of alkenes to synthesize β-bromoethers with dibromomethane (CH2Br2) as bromine source in alcohol solvent under metal-free conditions.

To this end, 1,2-difunctionalization of 1,1-diphenylethylene (1) with CH2Br2 in the presence of methanol was chosen as the model reaction in an undivided cell to probe various reaction parameters under electrolytic conditions (Table [1]).

Table 1 Optimization of the Reaction Conditionsa

Entry

Electrode

Electrolyte (equiv)

Solvent

Yield (%)b

 1

C(+)/Pt(–)

nBu4NBF4 (1)

MeCN/MeOH (7:1)

55

 2c

C(+)/Pt(–)

nBu4NBF4 (1)

MeCN/MeOH (7:1)

45

 3d

C(+)/Pt(–)

nBu4NBF4 (1)

MeCN/MeOH (7:1)

42

 4

C(+)/Pt(–)

nBu4NBF4 (1)

MeCN/MeOH (1:1)

61

 5

C(+)/Pt(–)

nBu4NBF4 (1)

MeOH

66

 6

Glassy C(+)/Pt(–)

nBu4NBF4 (1)

MeOH

91

 7

Glassy C(+)/Glassy C(–)

nBu4NBF4 (1)

MeOH

59

 8

Glassy C(+)/Pt(–)

nBu4NPF6 (1)

MeOH

70

 9

Glassy C(+)/Pt(–)

nBu4ClO4 (1)

MeOH

79

10

Glassy C(+)/Pt(–)

LiPF6 (1)

MeOH

51

11

Glassy C(+)/Pt(–)

nBu4NBF4 (2)

MeOH

84

12e

Glassy C(+)/Pt(–)

nBu4NBF4 (1)

MeOH

67

13f

Glassy C(+)/Pt(–)

nBu4NBF4 (1)

MeOH

54

14g

Glassy C(+)/Pt(–)

nBu4NBF4 (1)

MeOH

 0

a Conditions: 1 (0.2 mmol), CH2Br2 (2 equiv) and solvent (8 mL) in an undivided cell with electrodes, air, 50 °C, 15 mA, 5 h.

b Yield of isolated product.

c At 60 °C.

d At 40 °C.

e For 3 h.

f Current: 10 mA.

g No current.

Employing a two-electrode system with a carbon plate anode and platinum plate cathode, vicinal difunctionalization of 1,1-diphenylethylene (1) was performed with 2.0 equivalents of CH2Br2 under constant-current electrolysis (15 mA) in MeCN/MeOH (7:1, 8 mL) at 50 °C for 5 hours. The transformation afforded the desired 1,1-diphenyl-1-methoxy-2-bromoethane (1a) in an isolated yield of 55% (Table [1], entry 1). Unfortunately, an increase or decrease of reaction temperature failed to improve transformation efficiency (entries 2, 3). Screening of solvents clearly demonstrated that the model reaction was more efficient in MeOH alone than in MeCN/MeOH mixed solvents (entries 4, 5). To our delight, high yield (91%) was obtained for the 1,2-difunctionalization of alkene 1 with a glassy carbon (GC) anode and platinum plate cathode in methanol as solvent under otherwise equal solvent (entry 6). Nevertheless, the effect of the GC(+)/GC(–) electrode pair on the transformation was worse than that of a GC anode and Pt cathode under otherwise identical conditions (entry 7), which implied a significant influence of electrode material for the transformation. As for the choice of electrolyte, diminished yields were observed when other electrolytes instead of nBu4NBF4 for the model conversion (entries 8–10), however, increasing the amounts of nBu4NBF4 was not beneficial to improve the conversion efficiency (entry 11). Moreover, either shortening reaction time or operating current led to a reduced outcome; therefore, the reaction time of 5 h and operating current of 15 mA were the best for the transformation (entries 12, 13). Finally, control experiment demonstrated that no reaction took place without operating current under otherwise equal conditions (entry 14), implying the conversion was unambiguously controlled by switching the electric current on or off.

With the optimized reaction conditions in hand, the scope of alkenes substrates was investigated to evaluate generality of the protocol. As depicted in Scheme [1], in addition to 1-substituted styrenes 1–10 with a wide spectrum of substituents, the electrochemical vicinal difunctionalization of alkenes also worked well for styrenes 11–14, 2-substituted styrene 15, and enyne 16 containing multiple reactive sites. Although 1,2-difunctionalization of 1,1-diphenylethylene (1) afforded expected 1,1-diphenyl-1-methoxy-2-bromoethane (1a) with an isolated yield as high as 91%, good yield (85%) was also obtained for the substrate 1,2-difluoro-4-(1-phenylethenyl)benzene (2) bearing two fluoro functional groups. When one phenyl was replaced with methyl or cyclohexyl for 1,1-diphenylethylene, the substrates of 1-methyl-1-phenylethylene (3) and 1-cyclohexyl-1-phenylethene (10) afforded the corresponding vicinal difunctionalization products with CH2Br2 in MeOH under electrolytic conditions. Furthermore, introducing different types of substituents into the aromatic ring of the α-methylstyrene core at different positions, good reaction efficiencies were detected for α-methylstyrene with electron-donating groups 4–6 or electron-withdrawing groups 7, 8, thus, electronic properties of the substituents had almost no noticeable effect on the transformation efficiency. It is worth noting that aromatic ring-fused 2-isopropenylnaphthalene (9) was a suitable substrate to undergo electrochemical 1,2-difunctionalization transformation with moderated yield, furthermore, styrene (11) and 2-halostyrenes 12 and 13 as well as 4-fluorostyrene (14) smoothly furnished target products at synthetically useful levels. Albeit with moderate yields, β-methylstyrene 15 was an effective substrate to provide the hoped-for product. Interestingly, arylenyne 16 afforded anticipated product with good selectivity, while the C≡C bond was well tolerated under standard conditions. Remarkably, halo moieties of the products can be used for late-stage functionalization through classical C–Halo bond activation, which exhibits further application of this electrochemical methodology. Moreover, a 5-fold scale-up (1 mmol) electrochemical 1,2-difunctionalization of model substrate 1,1-diphenylethylene (1) was performed under otherwise identical conditions with the above electrosynthesis apparatus, and the desired product 1,1-diphenyl-1-methoxy-2-bromoethane (1a) was obtained in 92% isolated yield as an average of two runs under constant-current electrolysis for 60 hours, which was most nearly equal to the yields of the 0.2 mmol scale reaction without any reduction in efficiency.

Zoom Image
Scheme 1 Substrate scope of the alkenes. Reagents and conditions: alkene 1 (0.2 mmol), CH2Br2 (2 equiv.), nBu4NBF4 (1 equiv) and MeOH (8 mL) in an undivided cell with a GC anode and platinum plate cathode, air, 50 °C, 15 mA, 5 h. A 5-fold scale-up gave a 92% yield of 1a: alkene 1 (1 mmol) and MeOH (40 mL), 60 h.

Furthermore, the methanol substrate could be extended to other alcohols for this protocol, as shown in Scheme [2]. Employing alcohol as both the coupling partner and solvent under standard conditions, it was found that ethanol, n-propanol, and n-butyl alcohol straightforward underwent electrochemical 1,2-difunctionalization of 1,1-diphenylethylene (1) with CH2Br2 to afford corresponding β-bromoethers 1b–d in good yields. Unfortunately, the electrochemical vicinal difunctionalization of 1,1-diphenylethylene (1) with CH2Br2 was failed to provide desired product with iPrOH or tBuOH as coupling partner.

Several experiments were carried out to gain insight into the reaction mechanism. First, the fundamental importance of the electric current was confirmed by control experiment, which was necessary for this electrochemical vicinal difunctionalization transformation (Table [1], entry 14). Second, the drastically diminished yield suggested a possible radical process when 1 equivalent of 2,6-di-tert-butyl-4-methylphenol (BHT) was added as a radical scavenger into the model conversion under standard conditions, moreover, the detection of BHT-Br adduct exhibited the involvement of a free radical intermediate during electrolysis (Scheme [3]). Furthermore, the voltammogram properties of 1,1-diphenylethylene substrate (1), CH2Br2, and solvent MeOH provided key electrochemical parameters and information regarding the transformation pathway. As outlined in Figure [1], cyclic voltammetry (CV) of 1,1-diphenylethylene substrate (1) (curve b) showed an oxidation peak at 2.48 V (vs. Ag/AgCl), which was higher than that of CH2Br2 at 1.93 V (vs. Ag/AgCl) (curve c), so the comparison demonstrated that CH2Br2 could be oxidized more easily than alkene substrate in this galvanostatic mode. It is reported that halogen anion X– and +CH2X cation could be generated via C–X bond cleavage of the CH2X2,[40] thus the involvement of free radical intermediate probably corresponded to the oxidation of Br– to Br• intermediate in curve c (1.93 V) for this electrolysis process.

Zoom Image
Scheme 2 Substrate scope of the alcohols. Reagents and conditions: 1 (0.2 mmol), CH2Br2 (2 equiv), nBu4NBF4 (1 equiv) and alcohol (8 mL) in an undivided cell with a GC anode and platinum plate cathode, air, 50 °C, 15 mA, 5 h.
Zoom Image
Scheme 3 Radical trapping experiment
Zoom Image
Figure 1 Cyclic voltammograms of substrates in MeOH: (a) nBu4NBF4 (0.1 mol L–1); (b) 1,1-diphenylethylene (0.1 mol L–1) and nBu4NBF4 (0.1 mol L–1); (c) CH2Br2 (0.1 mol L–1) and nBu4NBF4 (0.1 mol L–1).

Based on preliminary mechanistic studies and literature reports,[27] [37] [38] [41] a plausible mechanism is proposed in Scheme [4]. Initially, bromine anion Br– and +CH2Br cation is gradually generated via C–X bond cleavage of the CH2Br2,[40] anodic oxidation of bromine anion Br– leads to the formation of bromine radical Br• intermediate, which undergoes radical addition process with alkene substrate I to afford carbon-centered radical intermediate II. After that, nucleophile attack of carbocation intermediate III from anodic oxidation of the resulting intermediate II by alcohol solvent gives the alkyl oxonium salt intermediate IV, which finally delivers the target product through deprotonation. Simultaneously, the cationic half-reaction leads to the electroreduction of proton H+ to hydrogen radical H•, which could undergo homocoupling to deliver hydrogen gas, and the observation of gas liberation at the cathode was confirmed with a gas chromatograph (GC) during electrolysis. Furthermore, the hydrogen radical H• could be subsequently reduced at the cathode and intercepted by the generated +CH2Br cation intermediate to provide CH3Br.

Zoom Image
Scheme 4 A proposed mechanism for the transformation

In summary, a protocol for electrochemical vicinal difunctionalization of various alkenes was well established in an undivided cell, which employed simple CH2Br2 and alcohol as bromine and alkoxy source without transition-metal mediator or exogenous oxidant. Therefore, it is a green and economical method to synthesize value-added β-bromoethers from cheap starting materials. Further exploration of the scope of halogen source and application of the protocol are underway in our laboratory, and the results will be reported in due course.


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Vicinal Difunctionlization of Alkenes; General Procedure

Alkene (0.2 mmol, 1.0 equiv), CH2Br2 (0.4 mmol, 2.0 equiv, 28 μL), nBu4NBF4 (0.2 mmol, 1 equiv, 65.9 mg), and MeOH (8 mL) were combined and added to an oven-dried three-necked flask with a stir bar. The flask was equipped with glassy carbon (d = 5 mm) as the anode and platinum electrode (1.0 × 1.0 cm2) as the cathode. The reaction mixture was stirred and electrolyzed at a constant current of 15 mA at 50 °C under air conditions for 5 h. After completion of the reaction, the mixture was evaporated under vacuum. The resulting residue was purified by flash chromatography on silica gel to provide the corresponding product.


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(2-Bromo-1-methoxyethane-1,1-diyl)dibenzene (1a)

Colorless liquid; yield: 53 mg (91%).

1H NMR (400 MHz, CDCl3): δ = 7.41–7.39 (m, 4 H), 7.34 (t, J = 7.20 Hz, 4 H), 7.30–7.24 (m, 2 H), 4.28 (s, 2 H), 3.20 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 142.8, 128.1, 127.5, 127.1, 81.2, 50.6, 38.7.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C15H15BrONa: 313.0204; found: 313.0198.


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4-(2-Bromo-1-methoxy-1-phenylethyl)-1,2-difluorobenzene (2a)

Colorless liquid; yield: 55.6 mg (85%).

1H NMR (400 MHz, CDCl3): δ = 7.34–7.24 (m, 6 H), 7.10–7.05 (m, 2 H), 4.24 (d, J = 10.80 Hz, 1 H), 4.16 (d, J = 11.20 Hz, 1 H), 3.17 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 151.3 (d, J = 12.5 Hz), 150.8 (d, J = 12.6 Hz), 141.7, 140.7 (dd, J = 5.6, 4.2 Hz), 131.7, 128.6, 128.2, 127.2, 123.0 (dd, J = 6.2, 3.6 Hz), 116.7 (dd, J = 24.1, 17.1 Hz), 80.7, 50.8, 38.1.

19F NMR (376 MHz, CDCl3): δ = –137.5, –139.6.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C15H13BrF2ONa: 349.0016; found: 349.0006.


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(1-Bromo-2-methoxypropan-2-yl)benzene (3a)

Colorless liquid; yield: 29.8 mg (65%).

1H NMR (400 MHz, CDCl3): δ = 7.42–7.36 (m, 4 H), 7.34–7.27 (m, 1 H), 3.63 (d, J = 10.80 Hz, 1 H), 3.51 (d, J = 10.80 Hz, 1 H), 3.15 (s, 3 H), 1.71 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 142.0, 128.7, 128.1, 126.6, 78.1, 51.3, 43.3, 22.0.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C10H13BrONa: 251.0047; found: 251.0042.


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(1-Bromo-2-methoxypropan-2-yl)-4-methylbenzene (4a)

Colorless liquid; yield: 36 mg (74%).

1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.00 Hz, 2 H), 7.17 (d, J = 8.00 Hz, 2 H), 3.61 (d, J = 10.40 Hz, 1 H), 3.47 (d, J = 10.40 Hz, 1 H), 3.11 (s, 3 H), 2.34 (s, 3 H), 1.68 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 138.9, 137.8, 129.4, 126.6, 78.0, 51.2, 43.4, 22.0, 21.2.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C11H15BrONa: 265.0204; found: 265.0197.


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1-(1-Bromo-2-methoxypropan-2-yl)-3-methylbenzene (5a)

Colorless liquid; yield: 35 mg (72%).

1H NMR (400 MHz, CDCl3): δ = 7.25–7.17 (m, 3 H), 7.11 (d, J = 7.60 Hz, 1 H), 3.62 (d, J = 10.40 Hz, 1 H), 3.48 (d, J = 10.80 Hz, 1 H), 3.13 (s, 3 H), 2.36 (s, 3 H), 1.68 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 141.2, 138.3, 128.8, 128.5, 127.3, 123.7, 78.0, 51.3, 43.3, 22.1, 21.8.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C11H15BrONa: 265.0204; found: 265.0199.


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1-(1-Bromo-2-methoxypropan-2-yl)-4-(tert-butyl)benzene (6a)

Colorless liquid; yield: 38.8 mg (68%).

1H NMR (400 MHz, CDCl3): δ = 7.39 (d, J = 8.40 Hz, 2 H), 7.32 (d, J = 8.80 Hz, 2 H), 3.64 (d, J = 10.40 Hz, 1 H), 3.50 (d, J = 10.80 Hz, 1 H), 3.14 (s, 3 H), 1.70 (s, 3 H), 1.33 (s, 9 H).

13C NMR (100 MHz, CDCl3): δ = 151.0, 138.8, 126.3, 125.6, 51.3, 43.6, 34.7, 31.5, 29.9, 22.1.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C14H21BrONa: 307.0673; found: 307.0671.


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1-(1-Bromo-2-methoxypropan-2-yl)-4-fluorobenzene (7a)

Colorless liquid; yield: 37.6 mg (76%).

1H NMR (400 MHz, CDCl3): δ = 7.46–7.31 (m, 2 H), 7.06 (t, J = 8.40 Hz, 2 H), 3.59 (d, J = 10.80 Hz, 1 H), 3.47 (d, J = 10.80 Hz, 1 H), 3.13 (s, 3 H), 1.70 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 163.8, 161.3, 137.8 (d, J = 3.2 Hz), 128.5 (d, J = 8.0 Hz), 115.5 (d, J = 21.3 Hz), 51.2, 43.1. 22.0.

19F NMR (376 MHz, CDCl3): δ = –114.6.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C10H12BrFONa: 268.9953; found: 268.9958.


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(1-Bromo-2-methoxypropan-2-yl)-4-(trifluoromethyl)benzene (8a)

Colorless liquid; yield: 50.5 mg (85%).

1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 7.60 Hz, 2 H), 7.53 (d, J = 8.00 Hz, 2 H), 3.59 (d, J = 10.80 Hz, 1 H), 3.52 (d, J = 10.80 Hz, 1 H), 3.17 (s, 3 H), 1.73 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 146.4, 130.3 (d, J = 32.4 Hz), 127.1, 125.6 (dd, J = 7.5, 3.7 Hz), 122.9, 78.0, 51.4, 42.2, 22.1.

19F NMR (376 MHz, CDCl3): δ = –62.7.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C11H12BrF3ONa: 318.9921; found: 318.9917.


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2-(1-Bromo-2-methoxypropan-2-yl)naphthalene (9a)

Colorless liquid; yield: 26.6 mg (45%).

1H NMR (400 MHz, CDCl3): δ = 7.90–7.80 (m, 4 H), 7.56 (dd, J = 8.40, 1.60 Hz, 1 H), 7.53–7.47 (m, 2 H), 3.74 (d, J = 10.40 Hz, 1 H), 3.61 (d, J = 10.80 Hz, 1 H), 3.19 (s, 3 H), 1.83 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 139.5, 133.3, 133.1, 128.6, 128.4, 127.8, 126.5, 126.5, 126.1, 124.4, 78.3, 51.5, 43.0, 22.1.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C14H15BrONa: 301.0204; found: 301.0199.


#

Bromo-1-cyclohexyl-1-methoxyethyl)benzene (10a)[42]

Colorless liquid; yield: 35.6 mg (60%).

1H NMR (400 MHz, CDCl3): δ = 7.36–7.22 (m, 5 H), 4.18 (d, J = 11.60 Hz, 1 H), 3.81 (d, J = 11.60 Hz, 1 H), 3.22 (s, 3 H), 2.07–1.96 (m, 2 H), 1.67 (d, J = 8.80 Hz, 3 H), 1.53 (d, J = 12.80 Hz, 1 H), 1.29–1.15 (m, 2 H), 0.88–0.78 (m, 1 H), 0.72–0.59 (m, 1 H), 0.53–0.40 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 138.3, 127.9, 127.7, 127.4, 82.1, 50.4, 44.6, 36.0, 28.0, 26.7, 26.7, 26.4, 26.4.


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Bromo-1-methoxyethyl)benzene (11a)[42]

Colorless liquid; yield: 36.1 mg (84%).

1H NMR (400 MHz, CDCl3): δ = 7.41–7.22 (m, 5 H), 4.41–4.37 (m, 1 H), 3.57–3.52 (m, 1 H), 3.50–3.45 (m, 1 H), 3.32 (d, J = 2.40 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 139.3, 128.9, 128.8, 127.0, 83.7, 57.5, 36.5.


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Bromo-2-(2-bromo-1-methoxyethyl)benzene (12a)

Colorless liquid; yield: 38.8 mg (66%).

1H NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 7.20 Hz, 1 H), 7.48 (d, J = 8.00 Hz, 1 H), 7.37 (t, J = 7.20 Hz, 1 H), 7.20 (t, J = 8.40 Hz, 1 H), 4.82 (d, J = 8.40 Hz, 1 H), 3.61 (d, J = 10.80 Hz, 1 H), 3.42 (t, J = 8.00 Hz, 1 H), 3.36 (d, J = 2.80 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 138.3, 133.2, 130.0, 128.1, 123.4, 82.0, 57.9, 35.2, 35.2.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C9H10Br2ONa: 316.8976; found: 316.8982.


#

(2-Bromo-1-methoxyethyl)-2-chlorobenzene (13a)

Colorless liquid; yield: 29.4 mg (59%).

1H NMR (400 MHz, CDCl3): δ = 7.50 (dd, J = 7.60, 2.00 Hz, 1 H), 7.38 (dd, J = 7.60, 1.20 Hz, 1 H), 7.35–7.31 (td, J = 7.20, 1.20 Hz 1 H), 7.28 (dd, J = 7.60, 2.00 Hz, 1 H), 4.87 (dd, J = 8.00, 3.20 Hz, 1 H), 3.62 (dd, J = 10.80, 3.20 Hz, 1 H), 3.44 (dd, J = 10.80, 8.00 Hz, 1 H), 3.36 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 136.7, 129.9, 129.7, 127.8, 127.4, 79.7, 35.1.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C9H10BrClONa: 270.9501; found: 270.9502.


#

1-(2-Bromo-1-methoxyethyl)-4-fluorobenzene (14a)[37]

Colorless liquid; yield: 39.9 mg (86%).

1H NMR (400 MHz, CDCl3): δ = 7.48–7.20 (m, 2 H), 7.08–7.04 (m, 2 H), 4.38–4.35 (m, 1 H), 3.53–3.49 (m, 1 H), 3.44–3.41 (m, 1 H), 3.29 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 162.7 (d, J = 245.4 Hz), 134.8 (d, J = 8.2 Hz), 128.5 (d, J = 8.2 Hz), 115.6 (d, J = 21.5 Hz), 82.7, 57.2, 36.1.

19F NMR (376 MHz, CDCl3): δ = –113.4.


#

(2-Bromo-1-methoxypropyl)-4-methoxybenzene (15a)

Colorless liquid; yield: 21.2 mg (41%).

1H NMR (400 MHz, CDCl3): δ = 7.24 (dd, J = 8.40, 2.00 Hz, 2 H), 6.90 (dd, J = 8.40, 1.60 Hz, 2 H), 4.27–4.25 (m, 1 H), 4.23–4.19 (m, 1 H), 3.81 (d, J = 1.60 Hz, 3 H), 3.28 (d, J = 1.60 Hz, 3 H), 1.63 (dd, J = 6.40, 1.60 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 159.7, 130.6, 128.9, 1139, 87.1, 57.7, 55.5, 53.0, 20.9.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C11H15BrO2Na: 281.0153; found: 281.0142.


#

Bromo-3-methoxy-3-methylbut-1-yn-1-yl)benzene (16a)

Colorless liquid; yield: 34.4 mg (68%).

1H NMR (400 MHz, CDCl3): δ = 7.90–7.83 (m, 3 H), 7.56 (d, J = 8.80 Hz, 1 H) 7.52–7.50 (m, 1 H), 3.75 (d, J = 10.80 Hz, 1 H), 3.61 (d, J = 10.80 Hz, 1 H), 3.19 (s, 3 H), 1.83 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 132.0, 128.9, 128.6, 122.3, 872, 72.8, 52.3, 39.4, 29.9, 25.5.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C12H13BrONa: 275.0047; found: 275.0044.


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(2-Bromo-1-ethoxyethane-1,1-diyl)dibenzene (1b)[43]

Colorless liquid; yield: 53.1 mg (87%).

1H NMR (400 MHz, CDCl3): δ = 7.43–7.34 (m, 4 H), 7.30 (t, J = 7.20 Hz, 4 H), 7.25–7.22 (m, 2 H), 4.25 (s, 2 H), 3.31–3.26 (m, 2 H), 1.25 (t, J = 6.80 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 143.5, 128.3, 127.5, 127.1, 81.0, 58.3, 39.5, 15.6.


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(2-Bromo-1-propoxyethane-1,1-diyl)dibenzene (1c)

Colorless liquid; yield: 52.3 mg (82%).

1H NMR (400 MHz, CDCl3): δ = 7.39–7.37 (m, 4 H), 7.31 (t, J = 7.20 Hz, 4 H), 7.26–7.23 (m, 2 H), 4.26 (s, 2 H), 3.19 (t, J = 6.80 Hz, 2 H), 1.70–1.65 (m, 2 H), 0.98 (t, J = 7.20 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 143.7, 128.2, 127.5, 127.2, 80.6, 64.1, 39.4, 23.4, 11.1.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C17H19BrONa: 341.0517; found: 341.0514.


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(2-Bromo-1-butoxyethane-1,1-diyl)dibenzene (1d)

Colorless liquid; yield: 44.7 mg (67%).

1H NMR (400 MHz, CDCl3): δ = 7.42–7.40 (m, 4 H), 7.34 (t, J = 8.00 Hz, 4 H), 7.31–7.27 (m, 2 H), 4.29 (s, 2 H), 3.27 (t, J = 6.40 Hz, 2 H), 1.72–1.61 (m, 2 H), 1.54–1.45 (m, 2 H), 0.96 (t, J = 7.20 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 143.7, 128.2, 127.5, 127.2, 80.6, 62.1, 39.4, 32.3, 19.7, 14.2.

HRMS (ESI-Orbitrap MS): m/z [M + Na]+ calcd for C18H21BrONa: 355.0673; found: 355.0669.


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Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2025-1822.
  • Supporting Information

Corresponding Authors

Zhengjiang Fu
School of Chemistry and Chemical Engineering, Nanchang University
Nanchang, Jiangxi 330031
P. R. of China   

Hu Cai
School of Chemistry and Chemical Engineering, Nanchang University
Nanchang, Jiangxi 330031
P. R. of China   

Publication History

Received: 16 December 2022

Accepted after revision: 02 February 2023

Accepted Manuscript online:
02 February 2023

Article published online:
09 March 2023

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Zoom Image
Scheme 1 Substrate scope of the alkenes. Reagents and conditions: alkene 1 (0.2 mmol), CH2Br2 (2 equiv.), nBu4NBF4 (1 equiv) and MeOH (8 mL) in an undivided cell with a GC anode and platinum plate cathode, air, 50 °C, 15 mA, 5 h. A 5-fold scale-up gave a 92% yield of 1a: alkene 1 (1 mmol) and MeOH (40 mL), 60 h.
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Scheme 2 Substrate scope of the alcohols. Reagents and conditions: 1 (0.2 mmol), CH2Br2 (2 equiv), nBu4NBF4 (1 equiv) and alcohol (8 mL) in an undivided cell with a GC anode and platinum plate cathode, air, 50 °C, 15 mA, 5 h.
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Scheme 3 Radical trapping experiment
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Figure 1 Cyclic voltammograms of substrates in MeOH: (a) nBu4NBF4 (0.1 mol L–1); (b) 1,1-diphenylethylene (0.1 mol L–1) and nBu4NBF4 (0.1 mol L–1); (c) CH2Br2 (0.1 mol L–1) and nBu4NBF4 (0.1 mol L–1).
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Scheme 4 A proposed mechanism for the transformation