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DOI: 10.1055/a-1702-4445
Cobalt–Tertiary Amine Mediated Peroxy-trifluoromethylation and -halodifluoromethylation of Alkenes with CF2XBr (X = F, Cl, Br) and tert-Butyl Hydroperoxide
We would like to thank the National Natural Science Foundation of China (Grant No. 22001008 to Q.L. and No. 21971260 to S.L.), Anhui Provincial Natural Science Foundation (Grant No. 2008085QB61), Anhui Agricultural University (Nos. RC381902 and 2019zd13) to Q.L., Natural Science Foundation of Guangdong Province for Distinguished Young Scholars (No. 2018B030306018), the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (No. 2017ZT07C069), the Pearl River Talent Recruitment Program ofGuangdong Province (No. 2019QN01L111), and the Open Fund of the Key Laboratory of Functional Molecular Engineering of Guangdong Province, South China University of Technology (No. 2018kf04) to S.L.
Abstract
An efficient cobalt-tertiary amine mediated peroxy-trifluoromethylation and -halodifluoromethylation of alkenes with simple and inexpensive CF2XBr (X = F, Cl, Br) has been described. This method demonstrated broad substrate scope and good to high yields with the tolerance of mono-, di-, and trisubstituted alkenes with both electron-donating and electron-withdrawing groups. The protocol provides an efficient access to various β-peroxyl trifluoromethyl/halodifluoromethyl derivatives. Further transformation of these type of compounds into other useful molecules, such as a ketene aminal, an α-trifluoromethyl ketone, and a gem-difluoroalkene, demonstrated the utility of this methodology.
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Key words
trifluoromethylation - chlorodifluoromethylation - bromodifluoromethylation - peroxyl - cobaltTrifluoromethyl and peroxy groups are of great interest and importance in the fields of chemical and biological science. CF3-Containing molecules have attracted considerable attention over the past decades from materials science and drug discovery due to their unique and preeminent properties.[1] Traditionally, the construction of CF3 moiety are mainly based on the substitution of trichloromethyl or carboxy groups by hazardous fluorinating agents such as HF, SF4, etc.[2] In recent years, various approaches to introduce the CF3 group into molecules have been developed employing trifluoroalkylation reagents, e.g., Togni reagents, Umemoto reagent, TMSCF3, and Langlois reagent (CF3SO2Na) etc.[3] However, despite extensive studies and the significance of the achievements, there still exists a strong interest to explore new methods that could make use of easily available and less expensive CF3 sources/reagents. Very recently, we[4g] developed a cobalt–tertiary amine mediated hydroxy-trifluoromethylation of alkenes under mild reaction conditions with simple, relatively inexpensive CF3Br,[4] which is the primary starting material for the preparation of several trifluoromethylation reagents, including TMSCF3, Togni’s, Umemoto’s, and Langlois reagent.[4a] [5]
Halodifluoromethylated (halo = Cl, Br) compounds are promising building blocks for the preparation of valuable fluorinated compounds[6] as well as candidates for investigating halogen bonding.[7] Despite these important applications, only a few methods are available for the synthesis of these compounds.[8] Among them, the radical halodifluoromethylation of alkenes represents an efficient pathway for incorporating halodifluoromethyl (halo = Cl, Br) moieties (Scheme [1a]). But to the best of our knowledge, an efficient approach regarding the peroxy-halodifluoromethylation (halo = Cl, Br) of alkenes introducing both peroxyl and halodifluoromethyl groups has not been explored (Scheme [1c]).
On the other hand, many natural peroxy products have shown very promising biological activity, such as artemisinin (qinghaosu), has already been clinically applied as antimalarial agent.[9] Organic peroxides are also well established synthetic agents that could be readily converted into ketone, alcohol, and epoxy compounds.[10] The difunctionalization of the alkenes is one of the most attractive strategies in organic chemistry.[11] Methodologies to introduce CF3 and peroxide groups by the difunctionalization of alkenes have been reported by Zhang and Duan employing CF3SO2Na and Togni reagent respectively (Scheme [1b]),[12] but halodifluoromethyl groups (halo = Cl, Br) were not tolerated due to the limitations of the corresponding reagents in these methods.
We have recently demonstrated an efficient cobalt–tertiary amine mediated single electron reduction (SET) of CF3Br to CF3 radical,[4g] thus we envisioned the cobalt–tertiary amine catalyst would be also a good candidate for the generation of CF2X (X = Cl, Br) radicals via the single electron reduction (SET) of simple and commercially available CF2XBr (X = Cl, Br). Inspired by previous work[12] and as part of our continued interest in the trifluoroalkylation of alkenes[4g], herein, we report an effective cobalt–tertiary amine mediated peroxy-trifluoromethylation and -halodifluoromethylation of alkenes with simple and inexpensive CF2XBr (X = F, Cl, Br) showing good functional group tolerance and a broad substrate scope including mono-, di-, and trisubstituted alkenes (Scheme [1c]).
We commenced our investigation by using styrene (1-1) as the model alkene substrate with CF3Br as the CF3 source, and tert-butyl hydroperoxide (TBHP, 70% solution in H2O) as the coupling partner in the presence of a series of metal salts (Table [1], entries 1–7) with DIPEA as the single electron transfer (SET) reductant at room temperature. The cobalt salts performed better compared to other metal salts such as Ag, Ni, and Cu. Full conversion of the styrene and 77% NMR yield of the target product 2-1 was observed when Co(OAc)2·4H2O was used (entry 7). Several other tertiary amines screened did not give better result (entries 8–10). Further studies showed that Co(acac)2 performed better and delivered the product in 74% isolated yield (entry 11). Increasing the temperature to 65 °C suppressed the formation of the alcohol byproduct 3-1 to 7% NMR yield and gave 2-1 in 83% isolated yield. Thus, we defined the reaction conditions in entry 13 of Table [1] as optimum for further study.
a Reaction conditions: 1-1 (1.0 mmol, 1.0 equiv), CF3Br (3.1 equiv), catalyst (10 mol%), TBHP (4.0 equiv, 70% solution in H2O), amine (4.0 equiv), CH3CN (4.0 mL), 50-mL Schlenk flask equipped with N2 balloon at r.t.
b The yield was determined by NMR analysis of the crude reaction mixture with mesitylene as the internal standard.
c Isolated yield.
d The reaction was conducted at 45 °C.
e The reaction was conducted at 65 °C.
f The reaction was conducted at 80 °C.
With the optimized reaction conditions in hand, the scope of this methodology was subsequently explored. Initial studies were focused on the monosubstituted alkene substrates, and most of the corresponding products 2-1–2-22 were obtained in good to high yields (Scheme [2]) including both electron-donating and electron-withdrawing groups. Disubstituted alkene substrates, including 1,1-disubstituted and 1,2-disubstituted alkenes, were also tolerated and gave the corresponding products 2-23–2-31 in moderate to good yields. Then trisubstituted alkene substrate was evaluated and gave the desired product 2-32 in practical yield.
The reaction also exhibits good functional group tolerance, such as ether (2-2, 2-31), ester (2-4, 2-10, 2-30), CF3 (2-11), fluoride (2-7), chloride (2-8), bromide (2-9), amide (2-5, 2-29), alkyne (2-27), and ketone (2-19) functionality. Alkenes bearing heteroaryl, such as pyridine (2-16, 2-25, 2-26), benzo[b]thiophene (2-17), and indole (2-18) were also applicable to the reaction and produced the corresponding products in good yields. Electron-deficient acrylamide 2-29 and acrylate 2-30 were also tolerated and afforded target alcohols in good yields. Internal alkenes were also tolerated well and gave the products 2-31, 2-32 in good to high yields. A conjugated diene was also found to be a good candidate for this protocol and delivered the target product 2-20 in moderate yield. Complex molecules with biology activities such as a modified estrone afforded the corresponding product 2-19 in 81% yield, demonstrating the utility of this protocol. The unactivated alkenes were also applicable and transformed into the trifluoromethyl peroxide products 2-21, 2-22 in moderate yields.
Having established the peroxy-trifluoromethylation of alkenes with CF3Br, we considered using commercially available starting materials: CF2ClBr and CF2Br2 as the precursors for the peroxy-chlorodifluoromethylation and -bromodifluoromethylation of alkenes. To our delight, the reaction also exhibits good reactivity with a broad substrate scope under the optimized reaction conditions and afford the desired products in high yields (Scheme [3]).
From the point of view of practical application, a gram scale reaction was conducted using 1-9 under the optimized conditions delivering the corresponding product 2-9 in 93% yield demonstrating the utilization of this method (Scheme [4]).
The synthetic potential of this method was next studied by further transformations of the synthetically useful peroxy moiety, CF3, and CF2Br groups. Ketene aminals are of highly important and frequently found in many pharmaceuticals and agrochemicals.[13] α-Oxoketene aminal 6 was obtained in high yield by the reaction of 2-9 with diethylamine in the presence of DABCO in CH3CN at 80 °C [Scheme [5], (1)].[14] Meanwhile, Kornblum–DeLaMare rearrangement of 2-9 gave the corresponding α-trifluoromethyl ketone 7 in 81% yield [Scheme [5], (2)].[10a] Modification of the CF2Br motif by treatment of 5-1 with NaOH in CH3CN led to a terminal gem-difluoroalkene 8 in 48% yield [Scheme [5], (3)]. These transformations demonstrate that our method provides an efficient strategy for the synthesis of molecules that containing both CF2X (X = F, Cl, Br) and peroxy groups, and thus offers a powerful method for drug discovery by further transformations.
Based on our previous report on the cobalt-catalyzed hydroxyl-trifluoromethylation of alkenes with CF3Br and atmospheric oxygen, a tentative mechanism is proposed in Scheme [6]. The single electron reduction (SET) of CF2XBr delivers the CF2X radical Int 3 via cobalt–tertiary amine catalysis (Cycle 1, Scheme [6], X = F, Cl, Br).[4g] Then benzyl radical intermediate Int 5 is afforded by the radical addition of CF2X radical to alkene. In addition, the Co-mediated decomposition of TBHP affords CoIII-OO t Bu according to the reported literature (Cycle 2, Scheme [6]).[15] The reaction of benzyl radical intermediate Int 5 and CoIII-OO t Bu delivers the final products and recycles Co(II) catalyst.
In conclusion, we have developed an efficient cobalt–tertiary amine mediated peroxy-trifluoromethylation and -halodifluoromethylation of alkenes with simple and inexpensive CF2XBr (X = F, Cl, Br) to afford various β-peroxyl trifluoromethyl and halodifluoromethyl derivatives. The reaction proceeds smoothly with broad substrate scope and good yields with only 10 mol% of earth abundant and inexpensive cobalt salt. Mono-, di-, and trisubstituted alkenes with both electron-donating and electron-withdrawing groups could be tolerated well. Furthermore, the β-peroxyl fluoroalkyl products could be transformed to other useful molecules, demonstrating the utility of this methodology.
All the reagents were used as received unless otherwise noted. Commercially available chemicals were purchased from Energy, Bidepharm, and Macklin. The CF3Br and CF2ClBr were purchased from Shangfluoro. The CF2Br2 was purchased from Energy. Visualization was accomplished with UV light (254 nm) or KMnO4 stain. Flash column chromatography was performed using silica gel (300–400 mesh). 1H NMR spectra were acquired on an Agilent DD2 (at 600 MHz) and are reported relative to TMS (δ = 0.00) or residual undeuterated solvent in the deuterated solvent. 13C NMR spectra were acquired on an Agilent DD2 (at 151 MHz) and are reported relative to CDCl3 (δ = 77.16) or the deuterated solvent. 19F NMR spectra were acquired on a Bruker AscendTM 400 (at 377 MHz) and are reported relative to CFCl3 (δ = 0.0). NMR acquisitions were performed at 295 K unless otherwise noted. High-resolution mass spectrometry data was acquired by Synapt G2-Si or Thermo Scientific Q Exactive GC. Petroleum ether = PE.
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3-(tert-Butylperoxy)-1,1,1-trifluoroalkanes 2 and 3-(tert-Butylperoxy)-1-chloro-1,1-difluoroalkanes 4; General Procedure
To a 50-mL Schlenk flask was added Co(acac)2 (0.1 mmol, 10 mol%). The flask was sealed and evacuated for 30 s and purged with N2 (3 ×). After further evacuating for 30 s, CF3Br (3.1 mmol in a 50-mL Schlenk flask based on our previous report[4g]) or CF2ClBr (4.1 mmol, see below) was backfilled. Then the flask was equipped with a N2 balloon and CH3CN (4 mL), alkene (1 mmol), amine (4 mmol, 4 equiv), and TBHP (4 mmol, 4 equiv, 70% solution in H2O) were added sequentially. After stirring for 4 h at 65 °C, the mixture was filtered through a pad of Celite. The filtrate was concentrated, and the residue was purified by chromatography (silica gel).
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Calculating the Amount of CF2ClBr in a 50-mL Schlenk Flask
A rubber stopper sealed 50-mL Schlenk flask was evacuated for 30 s then closed. The container was weighed in a balance. Then CF2ClBr was backfilled and the total weight was recorded on the same balance. This was reproduced three times and the average net weight of CF2ClBr in this 50-mL Schlenk flask was 679 mg (4.1 mmol).
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1-Bromo-3-(tert-butylperoxy)-1,1-difluoroalkanes 5; General Procedure
To a 50-mL Schlenk flask was added Co(acac)2 (0.1 mmol, 10 mol%). The flask was sealed and evacuated for 30 s and purged with N2 (3 ×). Then the flask was equipped with a N2 balloon and CH3CN (4 mL), alkene (1 mmol), CF2Br2 (3 mmol, 3 equiv), amine (4 mmol, 4 equiv), and TBHP (4 mmol, 4 equiv, 70% solution in H2O) were added sequentially. After stirring for 4 h at 65 °C, the mixture was filtered through a pad of Celite. The filtrate was concentrated, and the residue was purified by chromatography (silica gel).
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[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]benzene (2-1)
Purified by chromatography (silica gel, PE) to afford 2-1 [12b] (216.3 mg, 83%) as a colorless oil; Rf = 0.23 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.40–7.30 (m, 5 H), 5.16–5.14 (m, 1 H), 2.89–2.76 (m, 1 H), 2.53–2.41 (m, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 139.25, 128.67, 128.63, 127.04, 125.68 (q, J = 277.1 Hz), 80.94, 79.96, 39.33 (q, J = 28.1 Hz), 26.47.
19F NMR (377 MHz, CDCl3): δ = –63.80.
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1-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-4-methoxybenzene (2-2)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-2 [12b] (241.3 mg, 83%) as a colorless oil; Rf = 0.42 (PE/EtOAc 200:1).
1H NMR (600 MHz, CDCl3): δ = 7.26 (d, J = 8.4 Hz, 2 H), 6.89 (d, J = 8.4 Hz, 2 H), 5.09 (t, J = 6.3 Hz, 1 H), 3.80 (s, 3 H), 2.94–2.82 (m, 1 H), 2.53–2.41 (m, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 159.99, 131.06, 128.48, 125.79 (q, J = 277.0 Hz), 114.04, 80.73, 79.60 (q, J = 2.9 Hz), 55.19, 38.99 (q, J = 27.9 Hz), 26.40.
19F NMR (377 MHz, CDCl3): δ = –63.69.
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1-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-4-methylbenzene (2-3)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-3 [12b] (215.7 mg, 82%) as a colorless oil; Rf = 0.30 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.23 (d, J = 8.0 Hz, 2 H), 7.17 (d, J = 7.9 Hz, 2 H), 5.11 (t, J = 6.5 Hz, 1 H), 2.91–2.78 (m, 1 H), 2.52–2.41 (m, 1 H), 2.35 (s, 3 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 138.42, 136.20, 129.36, 127.07, 125.79 (q, J = 277.0 Hz), 80.81, 79.87 (q, J = 2.7 Hz), 39.22 (q, J = 28.0 Hz), 26.45, 21.24.
19F NMR (377 MHz, CDCl3): δ = –63.75.
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4-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]phenyl Acetate (2-4)
Purified by chromatography (silica gel, PE/EtOAc 30:1) to afford 2-4 (275.8 mg, 88%) as a colorless oil; Rf = 0.48 (PE/EtOAc 10:1).
1H NMR (600 MHz, CDCl3): δ = 7.35 (d, J = 8.5 Hz, 2 H), 7.10 (d, J = 8.5 Hz, 2 H), 5.16 (dd, J = 7.5, 5.5 Hz, 1 H), 2.84–2.72 (m, 1 H), 2.50–2.38 (m, 1 H), 2.29 (s, 3 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 169.20, 150.81, 136.80, 127.96, 125.55 (q, J = 277.1 Hz), 121.70, 80.87, 79.21 (q, J = 3.0 Hz), 39.27 (q, J = 28.3 Hz), 26.31, 21.00.
19F NMR (377 MHz, CDCl3): δ = –63.82.
HRMS (EI): m/z [M – t BuOO]+ calcd: 231.0627; found: 231.0628.
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N-{4-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]phenyl}acetamide (2-5)
Purified by chromatography (silica gel, PE/EtOAc 3:1) to afford 2-5 (264.4 mg, 83%) as a light yellow solid; Rf = 0.67 (PE/EtOAc 1:1).
1H NMR (600 MHz, CDCl3): δ = 7.75 (s, 1 H), 7.51 (d, J = 7.9 Hz, 2 H), 7.28 (d, J = 8.0 Hz, 2 H), 5.11 (t, J = 6.3 Hz, 1 H), 2.88–2.74 (m, 1 H), 2.51–2.38 (m, 1 H), 2.15 (s, 3 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 169.52, 138.58, 134.60, 127.53, 125.53 (q, J = 277.1 Hz), 120.25, 80.83, 79.43, 38.86 (q, J = 28.2 Hz), 26.25, 24.13.
19F NMR (377 MHz, CDCl3): δ = –63.71.
HRMS (APCI): m/z [M + H]+ calcd: 320.1468; found: 320.1467.
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4-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]biphenyl (2-6)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-6 [12b] (288.3 mg, 88%) as a colorless oil; Rf = 0.17 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.62–7.57 (m, 4 H), 7.46–7.40 (m, 4 H), 7.37–7.32 (m, 1 H), 5.21 (t, J = 6.5 Hz, 1 H), 2.93–2.80 (m, 1 H), 2.57–2.46 (m, 1 H), 1.24 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 141.55, 140.78, 138.27, 128.91, 127.56, 127.45, 127.39, 127.23, 125.76 (q, J = 277.1 Hz), 80.92, 79.70 (q, J = 2.7 Hz), 39.29 (q, J = 28.2 Hz), 26.44.
19F NMR (377 MHz, CDCl3): δ = –63.72.
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1-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-4-fluorobenzene (2-7)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-7 [12b] (197.4 mg, 74%) as a colorless oil; Rf = 0.33 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.32 (dd, J = 8.5, 5.4 Hz, 2 H), 7.05 (t, J = 8.6 Hz, 2 H), 5.13 (t, J = 6.5 Hz, 1 H), 2.88–2.75 (m, 1 H), 2.50–2.38 (m, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 162.97 (d, J = 246.8 Hz), 135.16 (d, J = 3.0 Hz), 128.84 (d, J = 8.2 Hz), 125.65 (q, J = 277.0 Hz), 115.62 (d, J = 21.6 Hz), 80.99, 79.27 (q, J = 2.9 Hz), 39.30 (q, J = 28.3 Hz), 26.40.
19F NMR (377 MHz, CDCl3): δ = –63.78, –114.00.
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1-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-4-chlorobenzene (2-8)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-8 [12b] (222.5 mg, 77%) as a colorless oil; Rf = 0.31 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.34 (d, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.4 Hz, 2 H), 5.15–5.10 (m, 1 H), 2.84–2.72 (m, 1 H), 2.47–2.36 (m, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 137.92, 134.44, 128.90, 128.38, 125.55 (q, 277.2 Hz), 81.04, 79.20 (q, J = 2.9 Hz), 39.27 (q, J = 28.4 Hz), 26.39.
19F NMR (377 MHz, CDCl3): δ = –63.80.
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1-Bromo-4-[1-(tert-butylperoxy)-3,3,3-trifluoropropyl]benzene (2-9)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-9 (290.5 mg, 87%) as a colorless oil; Rf = 0.43 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.50 (d, J = 8.4 Hz, 2 H), 7.22 (d, J = 8.4 Hz, 2 H), 5.14–5.09 (m, 1 H), 2.82–2.70 (m, 1 H), 2.47–2.36 (m, 1 H), 1.20 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 138.46, 131.86, 128.68, 125.51 (q, J = 277.2 Hz), 122.56, 81.04, 79.22 (q, J = 2.8 Hz), 39.25 (q, J = 28.5 Hz), 26.39.
19F NMR (377 MHz, CDCl3): δ = –63.79.
HRMS (EI): m/z [M(79Br) – t BuO]+ calcd: 266.9627; found: 266.9630.
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1-Bromo-4-[1-(tert-butylperoxy)-3,3,3-trifluoropropyl]benzene (2-9) Gram-Scale Reaction
Reaction was performed in a 250-mL three-necked flask and purified by chromatography (silica gel, PE) to afford 2-9 (1.4959 g, 93%) as a light yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.50 (d, J = 8.1 Hz, 2 H), 7.23 (d, J = 8.2 Hz, 2 H), 5.15–5.09 (m, 1 H), 2.84–2.71 (m, 1 H), 2.48–2.36 (m, 1 H), 1.21 (s, 9 H).
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Methyl 4-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]benzoate (2-10)
Purified by chromatography (silica gel, PE/EtOAc 50:1) to afford 2-10 (237.7 mg, 74%) as a colorless oil; Rf = 0.26 (PE/EtOAc 50:1).
1H NMR (600 MHz, CDCl3): δ = 8.05 (d, J = 8.2 Hz, 2 H), 7.43 (d, J = 8.2 Hz, 2 H), 5.21 (dd, J = 7.7, 5.3 Hz, 1 H), 3.92 (s, 3 H), 2.84–2.69 (m, 1 H), 2.50–2.38 (m, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 166.56, 144.38, 130.31, 129.85, 126.76, 125.40 (q, J = 277.1 Hz), 80.92, 79.22 (q, J = 2.9 Hz), 51.95, 39.10 (q, J = 28.7 Hz), 26.18.
19F NMR (377 MHz, CDCl3): δ = –63.82.
HRMS (EI): m/z [M – MeO]+ calcd: 289.1046; found: 289.1046.
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1-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-4-(trifluoromethyl)benzene (2-11)
Reaction time: 12 h. Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-11 (265.7 mg, 81%) as a colorless oil; Rf = 0.48 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.64 (d, J = 8.1 Hz, 2 H), 7.47 (d, J = 8.0 Hz, 2 H), 5.22 (dd, J = 7.6, 5.3 Hz, 1 H), 2.82–2.69 (m, 1 H), 2.50–2.37 (m, 1 H), 1.22 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 143.65, 130.90 (q, J = 32.4 Hz), 127.27, 125.74 (q, J = 3.6 Hz), 125.51 (q, J = 277.0 Hz), 124.27 (q, J = 272.0 Hz), 81.29, 79.27 (q, J = 2.9 Hz), 39.49 (q, J = 28.8 Hz), 26.38.
19F NMR (377 MHz, CDCl3): δ = –63.15, –63.87.
HRMS (APCI): m/z [M – H]– calcd: 329.0982; found: 329.0984.
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1-Bromo-2-[1-(tert-butylperoxy)-3,3,3-trifluoropropyl]benzene (2-12)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-12 (248.8 mg, 75%) as a colorless oil; Rf = 0.37 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.54 (d, J = 8.0 Hz, 2 H), 7.36 (t, J = 7.5 Hz, 1 H), 7.17 (td, J = 8.0, 1.5 Hz, 1 H), 5.63 (dd, J = 8.9, 3.8 Hz, 1 H), 2.58–2.42 (m, 2 H), 1.25 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 138.89, 133.04, 129.69, 128.22, 127.85, 125.50 (q, J = 277.5 Hz), 122.20, 81.24, 78.60 (q, J = 2.8 Hz), 38.55 (q, J = 29.0 Hz), 26.41.
19F NMR (377 MHz, CDCl3): δ = –63.92.
HRMS (EI): m/z [M(79Br)]+ calcd: 340.0280; found: 340.0279.
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1-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-2-methylbenzene (2-13)
Reaction time: 12 h. Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-13 [12b] (210.2 mg, 78%) as a colorless oil; Rf = 0.24 (PE/EtOAc 200:1).
1H NMR (600 MHz, CDCl3): δ = 7.38 (d, J = 7.0 Hz, 1 H), 7.26–7.19 (m, 2 H), 7.16 (d, J = 6.8 Hz, 1 H), 5.47–5.42 (m, 1 H), 2.84–2.72 (m, 1 H), 2.49–2.39 (m, 1 H), 2.37 (s, 3 H), 1.22 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 137.50, 135.36, 130.76, 128.27, 126.62, 126.40, 125.86 (q, J = 277.1 Hz), 80.75, 76.28 (q, J = 2.8 Hz), 38.72 (q, J = 28.1 Hz), 26.43, 19.02.
19F NMR (377 MHz, CDCl3): δ = –64.08.
HRMS (EI): m/z [M – t BuO]+ calcd: 203.0678; found: 203.0681.
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1-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-3-methylbenzene (2-14)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-14 (204.3 mg, 77%) as a colorless oil; Rf = 0.30 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.28–7.22 (m, 1 H), 7.17–7.10 (m, 3 H), 5.12 (t, J = 6.5 Hz, 1 H), 2.87–2.75 (m, 1 H), 2.52–2.40 (m, 1 H), 2.36 (s, 3 H), 1.22 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 139.24, 138.29, 129.41, 128.57, 127.69, 125.77 (q, J = 277.1 Hz), 124.15, 80.87, 80.04 (q, J = 2.9 Hz), 39.38 (q, J = 28.1 Hz), 26.45, 21.48.
19F NMR (377 MHz, CDCl3): δ = –63.80.
HRMS (EI): m/z [M – t BuO]+ calcd: 203.0678; found: 203.0678.
#
2-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]naphthalene (2-15)
Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-15 [12a] (163.2 mg, 54%) as a light yellow oil (17% recovery of starting material 1-15 was observed in the crude NMR prior to purification); Rf = 0.30 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.87–7.81 (m, 3 H), 7.80 (s, 1 H), 7.51–7.45 (m, 3 H), 5.35–5.31 (m, 1 H), 2.95–2.83 (m, 1 H), 2.61–2.49 (m, 1 H), 1.23 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 136.76, 133.60, 133.35, 128.59, 128.24, 127.88, 126.45, 126.41, 125.75 (q, J = 277.1 Hz), 124.41, 80.99, 80.08 (q, J = 2.8 Hz), 39.37 (q, J = 28.3 Hz), 26.47.
19F NMR (377 MHz, CDCl3): δ = –63.73.
#
3-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]pyridine (2-16)
Purified by chromatography (silica gel, PE/EtOAc 10:1) to afford 2-16 (131.5 mg, 51%) as a light yellow oil; Rf = 0.20 (PE/EtOAc 5:1).
1H NMR (600 MHz, CDCl3): δ = 8.62 (s, 2 H), 7.69 (d, J = 7.9 Hz, 1 H), 7.33 (dd, J = 7.6, 5.0 Hz, 1 H), 5.22–5.17 (m, 1 H), 2.91–2.78 (m, 1 H), 2.54–2.43 (m, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 149.86, 148.72, 134.74, 134.40, 125.29 (q, J = 277.1 Hz), 123.58, 81.08, 77.59 (q, J = 3.4 Hz), 38.80 (q, J = 28.6 Hz), 26.24.
19F NMR (377 MHz, CDCl3): δ = –63.76.
HRMS (APCI): m/z [M + H]+ calcd: 264.1206; found: 264.1205.
#
5-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]benzo[b]thiophene (2-17)
Purified by chromatography (silica gel, PE/EtOAc 75:1) to afford 2-17 (191.3 mg, 60%) as a colorless oil (13% recovery of starting material 1-17 was observed in the crude NMR prior to purification); Rf = 0.32 (PE/EtOAc 50:1).
1H NMR (600 MHz, CDCl3): δ = 7.87 (d, J = 8.3 Hz, 1 H), 7.80 (s, 1 H), 7.46 (d, J = 5.4 Hz, 1 H), 7.35–7.31 (m, 2 H), 5.28 (t, J = 6.5 Hz, 1 H), 2.94–2.83 (m, 1 H), 2.59–2.47 (m, 1 H), 1.23 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 140.01, 139.83, 135.54, 127.21, 125.71 (q, J = 277.2 Hz), 124.00, 123.10, 122.78, 122.23, 80.96, 80.10 (q, J = 2.8 Hz), 39.55 (q, J = 28.1 Hz), 26.44.
19F NMR (377 MHz, CDCl3): δ = –63.71.
HRMS (EI): m/z [M]+ calcd: 318.0896; found: 318.0895.
#
5-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-1H-indole (2-18)
Purified by chromatography (silica gel, PE/EtOAc 10:1) to afford 2-18 (123.4 mg, 41%) as a yellow solid; Rf = 0.40 (PE/EtOAc 10:1).
1H NMR (600 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.62 (s, 1 H), 7.36 (d, J = 8.4 Hz, 1 H), 7.22–7.14 (m, 2 H), 6.55 (s, 1 H), 5.25 (t, J = 6.5 Hz, 1 H), 3.04–2.89 (m, 1 H), 2.64–2.51 (m, 1 H), 1.23 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 136.02, 130.19, 127.87, 125.88 (q, J = 277.1 Hz), 125.09, 121.06, 119.78, 111.39, 102.78, 80.98, 80.92, 39.40 (q, J = 27.7 Hz), 26.50.
19F NMR (377 MHz, CDCl3): δ = –63.64.
HRMS (APCI): m/z [M + H]+ calcd: 302.1362; found: 302.1362.
#
(8R,9S,13S,14S)-3-[1-(tert-Butylperoxy)-3,3,3-trifluoropropyl]-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one (2-19)
Purified by chromatography (silica gel, PE/EtOAc 40:1) to afford 2-19 (355.5 mg, 81%) as a white solid; Rf = 0.21 (PE/EtOAc 20:1).
1H NMR (600 MHz, CDCl3): δ = 7.29 (d, J = 8.1 Hz, 1 H), 7.13 (d, J = 8.0 Hz, 1 H), 7.06 (s, 1 H), 5.10 (t, J = 6.4 Hz, 1 H), 2.93 (dd, J = 8.7, 3.8 Hz, 2 H), 2.89–2.78 (m, 1 H), 2.56–2.39 (m, 3 H), 2.35–2.27 (m, 1 H), 2.19–2.10 (m, 1 H), 2.10–2.00 (m, 2 H), 2.00–1.94 (m, 1 H), 1.68–1.58 (m, 2 H), 1.58–1.43 (m, 4 H), 1.24 (s, 9 H), 0.91 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 220.03, 139.96, 136.55, 136.36, 136.34, 127.36, 127.34, 125.56 (q, J = 277.1 Hz), 125.44, 124.22, 124.21, 80.62, 79.69–79.46 (m), 50.52, 47.81, 44.40, 39.03 (q, J = 27.9 Hz), 39.00 (q, J = 28.1 Hz), 38.02, 38.01, 35.67, 31.62, 29.34, 29.30, 26.85, 26.43, 26.41, 26.26, 25.60, 21.51, 13.73.
19F NMR (377 MHz, CDCl3): δ = –63.73.
HRMS (APCI): m/z [M + H]+ calcd: 439.2455; found: 439.2457.
#
(E)-[3-(tert-Butylperoxy)-5,5,5-trifluoropent-1-enyl]benzene (2-20a) and (E)-[1-(tert-Butylperoxy)-5,5,5-trifluoropent-2-enyl]benzene (2-20b)
Purified by chromatography (silica gel, 200:1 to PE/EtOAc 100:1) to afford 2-20 (137.8 mg, 48%, ratio 2-20a/2-20b = 1.8:1) as a light yellow oil; Rf = 0.23 (PE/EtOAc 100:1).
#
2-20a
1H NMR (600 MHz, CDCl3): δ = 7.40 (d, J = 7.4 Hz, 2 H), 7.38–7.30 (m, 2 H), 7.29–7.25 (m, 1 H), 6.66 (d, J = 15.9 Hz, 1 H), 6.14 (dd, J = 15.9, 7.9 Hz, 1 H), 4.77 (q, J = 6.6 Hz, 1 H), 2.80–2.68 (m, 1 H), 2.44–2.33 (m, 1 H), 1.26 (s, 9 H).
#
2-20b
1H NMR (600 MHz, CDCl3): δ = 7.38–7.29 (m, 5 H), 5.95 (dd, J = 15.5, 6.9 Hz, 1 H), 5.68 (dt, J = 14.5, 7.4 Hz, 1 H), 5.33 (d, J = 6.9 Hz, 1 H), 2.92–2.81 (m, 1 H), 1.24 (s, 9 H).
#
2-20a and 2-20b
13C NMR (151 MHz, CDCl3): δ = 141.93, 138.92, 136.46, 136.35, 134.36, 128.75, 128.57, 128.32, 127.62, 126.90, 126.31, 121.53, 125.95 (q, J = 276.6 Hz), 125.83 (q, J = 276.9 Hz), 85.71, 80.85, 80.67, 78.70 (q, J = 2.9 Hz), 37.93 (q, J = 27.9 Hz), 37.33 (q, J = 30.0 Hz), 26.60, 26.53.
19F NMR (377 MHz, CDCl3): δ = –63.33 (2-20a), –66.73 (2-20b).
HRMS (EI): m/z [M – t BuO]+ calcd: 215.0678; found: 215.0675 and 215.0677.
#
3-(tert-Butylperoxy)-1,1,1-trifluorotridecane (2-21)
Reaction temperature: r.t. Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-21 [12a] (175.3 mg, 57%) as a colorless oil; Rf = 0.39 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 4.21–4.12 (m, 1 H), 2.72–2.59 (m, 1 H), 2.27–2.11 (m, 1 H), 1.70–1.57 (m, 2 H), 1.33–1.25 (m, 16 H), 1.23 (s, 9 H), 0.88 (t, J = 6.9 Hz, 3 H).
13C NMR (151 MHz, CDCl3): δ = 126.39 (q, J = 276.8 Hz), 80.33, 77.69 (q, J = 2.6 Hz), 37.20 (q, J = 27.5 Hz), 33.07, 32.09, 29.77, 29.74, 29.70, 29.65, 29.50, 26.57, 25.37, 22.85, 14.23.
19F NMR (377 MHz, CDCl3): δ = –63.60.
#
[2-(tert-Butylperoxy)-4,4,4-trifluorobutyl]benzene (2-22)
Reaction temperature: r.t. Purified by chromatography (silica gel, PE/EtOAc 200:1) to afford 2-22 [12a] (129.1 mg, 47%) as a colorless oil; Rf = 0.78 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.30 (t, J = 7.3 Hz, 2 H), 7.27–7.19 (m, 3 H), 4.50–4.36 (m, 1 H), 3.11–2.88 (m, 2 H), 2.65–2.45 (m, 1 H), 2.29–2.14 (m, 1 H), 1.16 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 137.22, 129.82, 128.52, 126.77, 126.24 (q, J = 276.7 Hz), 80.76, 78.54 (q, J = 2.7 Hz), 39.13, 36.42 (q, J = 28.0 Hz), 26.45.
19F NMR (377 MHz, CDCl3): δ = –63.54.
#
[2-(tert-Butylperoxy)-4,4,4-trifluorobutan-2-yl]benzene (2-23)
Reaction time: 12 h. Purified by chromatography (silica gel, PE) to afford 2-23 [12b] (188.3 mg, 69%) as a colorless oil; Rf = 0.39 (PE/EtOAc 200:1).
1H NMR (600 MHz, CDCl3): δ = 7.43 (d, J = 7.9 Hz, 2 H), 7.34 (t, J = 7.6 Hz, 2 H), 7.28 (t, J = 7.2 Hz, 1 H), 2.88–2.77 (m, 1 H), 2.75–2.63 (m, 1 H), 1.77 (s, 3 H), 1.25 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 143.44, 128.23, 127.67, 125.87, 125.74 (q, J = 278.0 Hz), 80.63 (q, J = 1.8 Hz), 79.68, 43.32 (q, J = 27.1 Hz), 26.73, 23.52.
19F NMR (377 MHz, CDCl3): δ = –60.31.
#
[1-(tert-Butylperoxy)-3,3,3-trifluoropropane-1,1-diyl]dibenzene (2-24)
Purified by chromatography (silica gel, PE) to afford 2-24 [12a] (219.0 mg, 67%) as a colorless oil (3% recovery of starting material 1-24 was observed in the crude NMR prior to purification); Rf = 0.43 (PE/EtOAc 200:1).
1H NMR (600 MHz, CDCl3): δ = 7.30–7.26 (m, 8 H), 7.26–7.21 (m, 2 H), 3.40 (q, J = 10.3 Hz, 2 H), 1.14 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 143.29, 127.88, 127.48, 126.96, 125.96 (q, J = 278.4 Hz), 83.28, 80.03, 39.66 (q, J = 26.8 Hz), 26.70.
19F NMR (377 MHz, CDCl3): δ = –59.45.
#
4-[2-(tert-Butylperoxy)-4,4,4-trifluorobutan-2-yl]pyridine (2-25)
Purified by chromatography (silica gel, PE/EtOAc 10:1) followed by preparative TLC (PE/EtOAc/DCM 5:1:3) to afford 2-25 (144.0 mg, 51%) as a white solid; Rf = 0.23 (PE/EtOAc 5:1).
1H NMR (600 MHz, CDCl3): δ = 8.60 (s, 2 H), 7.33 (d, J = 4.8 Hz, 2 H), 2.82–2.59 (m, 2 H), 1.73 (s, 3 H), 1.25 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 152.37, 149.78, 125.23 (q, J = 278.0 Hz), 120.78, 80.08, 79.80, 42.48 (q, J = 27.9 Hz), 26.49, 23.29.
19F NMR (377 MHz, CDCl3): δ = –60.16.
HRMS (APCI): m/z [M + H]+ calcd: 278.1362; found: 278.1364.
#
2-[2-(tert-Butylperoxy)-4,4,4-trifluorobutan-2-yl]pyridine (2-26)
Reaction time: 12 h. Purified by chromatography (silica gel, PE/EtOAc 20:1) to afford 2-26 (165.3 mg, 59%) as a yellow oil; Rf = 0.72 (PE/EtOAc 8:1).
1H NMR (600 MHz, CDCl3): δ = 8.50–8.45 (m, 1 H), 7.72–7.58 (m, 2 H), 7.18–7.09 (m, 1 H), 3.19–3.07 (m, 1 H), 3.03–2.91 (m, 1 H), 1.67 (s, 3 H), 1.27 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 162.74, 148.27, 136.29, 126.27 (q, J = 277.9 Hz), 122.22, 120.62, 82.66, 79.90, 39.95 (q, J = 27.5 Hz), 26.66, 24.18.
19F NMR (377 MHz, CDCl3): δ = –60.19.
HRMS (APCI): m/z [M + H]+ calcd: 278.1362; found: 278.1367.
#
3-(tert-Butylperoxy)-1,1,1-trifluoro-3-methylundec-4-yne (2-27)
Purified by chromatography (silica gel, PE) to afford 2-27 (156.0 mg, 51%) as a colorless oil; Rf = 0.46 (PE).
1H NMR (600 MHz, CDCl3): δ = 2.83–2.67 (m, 1 H), 2.65–2.51 (m, 1 H), 2.20 (t, J = 7.0 Hz, 2 H), 1.56 (s, 3 H), 1.53–1.45 (m, 2 H), 1.42–1.19 (m, 15 H), 0.89 (t, J = 7.0 Hz, 3 H).
13C NMR (151 MHz, CDCl3): δ = 125.39 (q, J = 277.5 Hz), 86.16, 80.03, 79.94, 73.81 (q, J = 2.2 Hz), 42.87 (q, J = 27.4 Hz), 31.48, 28.55, 28.53, 26.74, 25.66, 22.70, 18.83, 14.13.
19F NMR (377 MHz, CDCl3): δ = –61.22.
HRMS (EI): m/z [M – t BuO]+ calcd: 235.1304; found: 235.1306.
#
tert-Butyl 4-(tert-Butylperoxy)-4-(2,2,2-trifluoroethyl)piperidine-1-carboxylate (2-28)
Reaction time: 12 h. Purified by chromatography (silica gel, PE/EtOAc 50:1) to afford 2-28 (174.0 mg, 52%) as a yellow oil; Rf = 0.49 (PE/EtOAc 10:1).
1H NMR (600 MHz, CDCl3): δ = 4.04–3.65 (m, 2 H), 3.06 (s, 2 H), 2.49 (s, 2 H), 2.05–1.90 (m, 2 H), 1.66–1.57 (m, 2 H), 1.46 (s, 9 H), 1.24 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 154.86, 125.95 (q, J = 277.7 Hz), 79.49, 79.35, 76.37, 40.48 (q, J = 26.9 Hz), 40.04–38.57 (m), 38.81, 32.48, 28.47, 26.65.
19F NMR (377 MHz, CDCl3): δ = –60.23.
HRMS (EI): m/z [M – t BuO]+ calcd: 282.1312; found: 282.1313.
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2-(tert-Butylperoxy)-4,4,4-trifluoro-N,2-dimethylbutanamide (2-29)
Purified by chromatography (silica gel, PE/EtOAc 10:1) to afford 2-29 (158.4 mg, 64%) as a light yellow oil; Rf = 0.40 (PE/EtOAc 5:1).
1H NMR (600 MHz, CDCl3): δ = 6.58 (s, 1 H), 2.85 (d, J = 5.0 Hz, 3 H), 2.84–2.71 (m, 2 H), 1.53 (s, 3 H), 1.28 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 172.81, 125.63 (q, J = 277.8 Hz), 82.60, 80.91, 38.14 (q, J = 28.0 Hz), 26.35, 26.12, 21.25.
19F NMR (377 MHz, CDCl3): δ = –60.67.
HRMS (APCI): m/z [M + H]+ calcd: 258.1312; found: 258.1312.
#
Benzyl 2-(tert-Butylperoxy)-4,4,4-trifluoro-2-methylbutanoate (2-30)
Purified by chromatography (silica gel, PE/EtOAc 80:1) to afford 2-30 (223.9 mg, 68%) as a light yellow oil; Rf = 0.23 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.39–7.30 (m, 5 H), 5.21 (d, J = 12.5 Hz, 1 H), 5.19 (d, J = 12.4 Hz, 1 H), 2.95–2.84 (m, 1 H), 2.82–2.72 (m, 1 H), 1.55 (s, 3 H), 1.16 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 171.18, 135.68, 128.58, 128.37, 128.30, 125.76 (q, J = 277.3 Hz), 80.67 (q, J = 2.1 Hz), 80.44, 67.19, 37.72 (q, J = 28.3 Hz), 26.36, 19.86 (App. d, J = 1.2 Hz).
19F NMR (377 MHz, CDCl3): δ = –60.52.
HRMS (EI): m/z [M – C4H8O2]+ calcd: 246.0862; found: 246.0864.
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1-[1-(tert-Butylperoxy)-3,3,3-trifluoro-2-methylpropyl]-4-methoxybenzene (2-31)
Purified by chromatography (silica gel, PE/EtOAc 100:1) to afford 2-31 (231.1 mg, 77%, 2.4:1 dr) as a colorless oil; Rf = 0.29 (PE/EtOAc 50:1).
1H NMR (600 MHz, CDCl3): δ = 7.25 (d, J = 8.6 Hz, 2 H), 7.20 (d, J = 8.5 Hz, 0.84 H), 6.89 (t, J = 8.9 Hz, 2.84 H), 5.20 (d, J = 3.5 Hz, 1 H), 4.99 (d, J = 7.0 Hz, 0.42 H), 3.81 (s, 4.26 H), 2.83–2.73 (m, 0.42 H), 2.52–2.40 (m, 1 H), 1.22 (s, 9 H), 1.20 (s, 3.78 H), 1.10 (d, J = 7.3 Hz, 3 H), 0.92 (d, J = 7.2 Hz, 1.26 H).
13C NMR (151 MHz, CDCl3): δ = 159.66, 159.29, 131.58, 129.93, 128.99, 127.85, 127.42 (q, J = 280.0 Hz), 127.33 (q, J = 280.3 Hz), 113.70, 113.65, 83.56, 81.42, 80.69, 80.64, 55.24, 55.21, 44.64 (q, J = 25.7 Hz), 41.62 (q, J = 25.3 Hz), 26.47, 9.76, 7.23.
19F NMR (377 MHz, CDCl3): δ = –69.02, –69.99.
HRMS (EI): m/z [M – t BuO]+ calcd: 233.0784; found: 233.0782.
#
[2-(tert-Butylperoxy)-4,4,4-trifluoro-3-methylbutan-2-yl]benzene (2-32)
Purified by chromatography (silica gel, PE) to afford 2-32 (210.9 mg, 73%, 5.5:1 dr) as a colorless oil (4% recovery of starting material 1-32 was observed in the crude NMR prior to purification); Rf = 0.39 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.46–7.38 (m, 2 H), 7.36–7.29 (m, 2 H), 7.28–7.22 (m, 1 H), 2.79–2.60 (m, 1 H), 1.79 (s, 0.46 H), 1.77 (s, 2.54 H), 1.22 (s, 9 H), 1.10 (d, J = 7.2 Hz, 2.54 H), 0.92 (d, J = 7.2 Hz, 0.46 H).
13C NMR (151 MHz, CDCl3): δ = 143.74, 142.92, 127.91, 127.83, 127.46, 127.38 (q, J = 281.5 Hz), 127.21, 126.76, 126.68, 83.50, 83.03, 79.62, 79.46, 47.44 (q, J = 24.5 Hz), 46.63 (q, J = 24.6 Hz), 26.77, 26.72, 21.85, 19.99, 10.39, 9.70 (q, J = 2.8 Hz).
19F NMR (377 MHz, CDCl3): δ = –64.42, –64.58.
HRMS (EI): m/z [M – t BuO]+ calcd: 217.0835; found: 217.0829.
#
[1-(tert-Butylperoxy)-3-chloro-3,3-difluoropropyl]benzene (4-1)
Purified by chromatography (silica gel, PE) to afford 4-1 (243.0 mg, 88%) as a light yellow oil; Rf = 0.54 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.39–7.29 (m, 5 H), 5.22 (dd, J = 6.7, 5.7 Hz, 1 H), 3.09–2.98 (m, 1 H), 2.74–2.63 (m, 1 H), 1.22 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 139.36, 128.65, 128.59, 128.01 (t, J = 293.0 Hz), 127.14, 80.91, 80.88, 46.98 (t, J = 23.7 Hz), 26.52.
19F NMR (377 MHz, CDCl3): δ = –48.64 (d, J = 161.0 Hz), –49.22 (d, J = 161.8 Hz).
HRMS (EI): m/z [M(35Cl) – t BuOO]+ calcd: 189.0277; found: 189.0275.
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4-[1-(tert-Butylperoxy)-3-chloro-3,3-difluoropropyl]phenyl Acetate (4-2)
Purified by chromatography (silica gel, PE/EtOAc 50:1) to afford 4-2 (301.2 mg, 91%) as a light yellow oil; Rf = 0.33 (PE/EtOAc 50:1).
1H NMR (600 MHz, CDCl3): δ = 7.36 (d, J = 8.5 Hz, 2 H), 7.09 (d, J = 8.5 Hz, 2 H), 5.22 (dd, J = 7.1, 5.2 Hz, 1 H), 3.06–2.94 (m, 1 H), 2.73–2.58 (m, 1 H), 2.29 (s, 3 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 169.35, 150.81, 136.96, 128.13, 127.89 (t, J = 293.1 Hz), 121.75, 80.97, 80.20 (t, J = 2.3 Hz), 47.03 (t, J = 23.8 Hz), 26.48, 21.22.
19F NMR (377 MHz, CDCl3): δ = –48.69 (d, J = 161.7 Hz), –49.37 (d, J = 161.9 Hz).
HRMS (EI): m/z [M(35Cl) – t BuOO]+ calcd: 247.0332; found: 247.0331.
#
4-[1-(tert-Butylperoxy)-3-chloro-3,3-difluoropropyl]biphenyl (4-3)
Purified by chromatography (silica gel, PE to PE/EtOAc 100:1) to afford 4-3 (299.5 mg, 86%) as a colorless oil; Rf = 0.54 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.61–7.54 (m, 4 H), 7.45–7.39 (m, 4 H), 7.34 (t, J = 7.4 Hz, 1 H), 5.30–5.25 (m, 1 H), 3.13–3.01 (m, 1 H), 2.78–2.66 (m, 1 H), 1.24 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 141.55, 140.83, 138.34, 128.92, 128.03 (t, J = 293.1 Hz), 127.56, 127.42, 127.27, 81.00, 80.65, 46.99 (t, J = 23.7 Hz), 26.56.
19F NMR (377 MHz, CDCl3): δ = –48.60 (d, J = 161.7 Hz), –49.19 (d, J = 160.9 Hz).
HRMS (EI): m/z [M(35Cl) – C4H8O]+ calcd: 282.0618; found: 282.0620.
#
1-Bromo-4-[1-(tert-butylperoxy)-3-chloro-3,3-difluoropropyl]benzene (4-4)
Purified by chromatography (silica gel, PE to PE/EtOAc 100:1) to afford 4-4 (268.4 mg, 79%) as a light yellow oil; Rf = 0.62 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.49 (d, J = 8.1 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 5.18 (t, J = 6.0 Hz, 1 H), 3.04–2.92 (m, 1 H), 2.63 (qd, J = 14.5, 5.1 Hz, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 138.52, 131.85, 128.78, 127.77 (t, J = 293.0 Hz), 122.55, 81.07, 80.17 (t, J = 2.4 Hz), 46.89 (t, J = 23.9 Hz), 26.49.
19F NMR (377 MHz, CDCl3): δ = –48.73 (d, J = 162.3 Hz), –49.34 (d, J = 162.2 Hz).
HRMS (EI): m/z [M(35Cl, 79Br) – t BuOO]+ calcd: 266.9382; found: 266.9383.
#
1-[1-(tert-Butylperoxy)-3-chloro-3,3-difluoropropyl]-4-methoxybenzene (4-5)
Purified by chromatography (silica gel, PE/EtOAc 100:1) to afford 4-5 (253.6 mg, 82%) as a light yellow oil; Rf = 0.30 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.26 (d, J = 8.4 Hz, 2 H), 6.89 (d, J = 8.5 Hz, 2 H), 5.16 (t, J = 6.2 Hz, 1 H), 3.80 (s, 3 H), 3.09 (ddd, J = 27.8, 13.7, 6.4 Hz, 1 H), 2.69 (ddd, J = 28.2, 13.6, 6.1 Hz, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 159.94, 131.15, 128.62, 128.09 (t, J = 293.0 Hz), 114.06, 80.81, 80.56 (t, J = 2.4 Hz), 55.37, 46.66 (t, J = 23.4 Hz), 26.53.
19F NMR (377 MHz, CDCl3): δ = –48.78.
HRMS (EI): m/z [M(35Cl) – t BuOO]+ calcd: 219.0383; found: 219.0383.
#
1-[1-(tert-Butylperoxy)-3-chloro-3,3-difluoropropyl]-4-methylbenzene (4-6)
Purified by chromatography (silica gel, PE to PE/EtOAc 100:1) to afford 4-6 (251.6 mg, 91%) as a light yellow oil; Rf = 0.49 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.23 (d, J = 7.8 Hz, 2 H), 7.17 (d, J = 7.7 Hz, 2 H), 5.18 (t, J = 6.2 Hz, 1 H), 3.06 (ddd, J = 27.5, 14.0, 6.7 Hz, 1 H), 2.68 (ddd, J = 28.3, 14.3, 5.7 Hz, 1 H), 2.34 (s, 3 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 138.42, 136.24, 129.35, 128.08 (t, J = 293.1 Hz), 127.17, 80.85, 80.80 (t, J = 2.4 Hz), 46.87 (t, J = 23.5 Hz), 26.54, 21.34.
19F NMR (377 MHz, CDCl3): δ = –48.82, –48.86.
HRMS (EI): m/z [M(35Cl) – t BuOO]+ calcd: 203.0434; found: 203.0432.
#
[2-(tert-Butylperoxy)-4-chloro-4,4-difluorobutan-2-yl]benzene (4-7)
Purified by chromatography (silica gel, PE) to afford 4-7 (270.5 mg, 93%) as a light yellow oil; Rf = 0.53 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.43 (d, J = 7.5 Hz, 2 H), 7.33 (t, J = 7.6 Hz, 2 H), 7.27 (t, J = 7.3 Hz, 1 H), 3.15–3.03 (m, 1 H), 3.02–2.90 (m, 1 H), 1.79 (s, 3 H), 1.25 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 143.41, 128.19, 128.04 (t, J = 295.3 Hz), 127.64, 125.98, 81.60, 79.68, 51.26 (t, J = 22.5 Hz), 26.79, 23.44.
19F NMR (377 MHz, CDCl3): δ = –46.97, –46.99.
HRMS (EI): m/z [M(35Cl) – t BuOO]+ calcd: 203.0434; found: 203.0432.
#
[1-(tert-Butylperoxy)-3-chloro-3,3-difluoropropane-1,1-diyl]dibenzene (4-8)
Purified by chromatography (silica gel, PE) to afford 4-8 (306.2 mg, 90%) as a light yellow oil; Rf = 0.61 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.32–7.20 (m, 10 H), 3.68 (t, J = 13.8 Hz, 2 H), 1.13 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 143.18, 128.39 (t, J = 297.0 Hz), 127.79, 127.46, 127.17, 84.10, 80.03, 47.14 (t, J = 21.8 Hz), 26.73.
19F NMR (377 MHz, CDCl3): δ = –46.29.
HRMS (EI): m/z [M(35Cl) – t BuO]+ calcd: 281.0539; found: 281.0540.
#
Benzyl 2-(tert-Butylperoxy)-4-chloro-4,4-difluoro-2-methylbutanoate (4-9)
Purified by chromatography (silica gel, PE/EtOAc 100:1) to afford 4-9 (281.4 mg, 81%) as a light yellow oil; Rf = 0.44 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.41–7.28 (m, 5 H), 5.21 (d, J = 12.4 Hz, 1 H), 5.18 (d, J = 12.4 Hz, 1 H), 3.19–3.02 (m, 2 H), 1.57 (s, 3 H), 1.16 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 171.14, 135.67, 128.62, 128.41, 128.35, 127.89 (t, J = 293.9 Hz), 81.52, 80.52, 67.28, 45.43 (t, J = 23.3 Hz), 26.49, 19.99 (t, J = 2.0 Hz).
19F NMR (377 MHz, CDCl3): δ = –46.70 (d, J = 160.9 Hz), –47.76 (d, J = 160.6 Hz).
HRMS (EI): m/z [M(35Cl) – C4H8O2]+ calcd: 262.0567; found: 262.0568.
#
[2-(tert-Butylperoxy)-4-chloro-4,4-difluoro-3-methylbutan-2-yl]benzene (4-10)
Purified by chromatography (silica gel, PE) to afford 4-10 (242.0 mg, 79%, 8.9:1 dr) as a light yellow oil; Rf = 0.69 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.43 (d, J = 7.1 Hz, 2 H), 7.32 (t, J = 7.4 Hz, 2 H), 7.27–7.22 (m, 1 H), 3.02–2.72 (m, 1 H), 1.79 (s, 3 H), 1.24–1.16 (m, 12 H).
13C NMR (151 MHz, CDCl3): δ = 143.68, 131.38 (dd, J = 300.0, 296.3 Hz), 127.57, 126.97, 126.55, 83.60, 79.42, 53.20 (t, J = 20.0 Hz), 26.59, 21.89, 11.36 (t, J = 3.4 Hz).
19F NMR (377 MHz, CDCl3): δ = –45.26 (d, J = 161.0 Hz), –51.54 (d, J = 160.5 Hz).
HRMS (EI): m/z [M(35Cl) – t BuOO]+ calcd: 217.0590; found: 217.0589.
#
[3-Bromo-1-(tert-butylperoxy)-3,3-difluoropropyl]benzene (5-1)
Purified by chromatography (silica gel, PE to PE/EtOAc 100:1) to afford 5-1 (288.4 mg, 90%) as a yellow oil; Rf = 0.53 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.39–7.29 (m, 5 H), 5.25–5.21 (m, 1 H), 3.17–3.06 (m, 1 H), 2.84–2.72 (m, 1 H), 1.22 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 139.29, 128.65, 128.59, 127.15, 120.44 (t, J = 306.7 Hz), 81.26 (t, J = 2.4 Hz), 80.91, 49.41 (t, J = 21.2 Hz), 26.53.
19F NMR (377 MHz, CDCl3): δ = –41.94 (d, J = 156.5 Hz), –42.73 (d, J = 156.4 Hz).
HRMS (EI): m/z [M(79Br) – t BuOO]+ calcd: 232.9772; found: 232.9770.
#
4-[3-Bromo-1-(tert-butylperoxy)-3,3-difluoropropyl]phenyl acetate (5-2)
Purified by chromatography (silica gel, PE/EtOAc 50:1) to afford 5-2 (333.6 mg, 89%) as a light yellow oil; Rf = 0.33 (PE/EtOAc 50:1).
1H NMR (600 MHz, CDCl3): δ = 7.36 (d, J = 8.5 Hz, 2 H), 7.09 (d, J = 8.5 Hz, 2 H), 5.23 (dd, J = 7.0, 5.2 Hz, 1 H), 3.14–3.03 (m, 1 H), 2.82–2.70 (m, 1 H), 2.29 (s, 3 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 169.36, 150.81, 136.88, 128.14, 121.76, 120.29 (t, J = 306.6 Hz), 80.99, 80.60, 49.43 (t, J = 21.3 Hz), 26.49, 21.22.
19F NMR (377 MHz, CDCl3): δ = –41.99 (d, J = 156.9 Hz), –42.96 (d, J = 156.6 Hz).
HRMS (EI): m/z [M(79Br) – t BuOO]+ calcd: 290.9827; found: 290.9826.
#
4-[3-Bromo-1-(tert-butylperoxy)-3,3-difluoropropyl]biphenyl (5-3)
Purified by chromatography (silica gel, PE/EtOAc 100:1) to afford 5-3 (359.7 mg, 92%) as a light yellow oil; Rf = 0.52 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.61–7.55 (m, 4 H), 7.42 (t, J = 7.9 Hz, 4 H), 7.33 (t, J = 7.4 Hz, 1 H), 5.30–5.26 (m, 1 H), 3.20–3.10 (m, 1 H), 2.87–2.77 (m, 1 H), 1.24 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 141.55, 140.81, 138.25, 128.92, 127.57, 127.42, 127.26, 120.43 (t, J = 306.7 Hz), 81.04, 81.02, 49.40 (t, J = 21.2 Hz), 26.57.
19F NMR (377 MHz, CDCl3): δ = –41.91 (d, J = 156.6 Hz), –42.73 (d, J = 155.9 Hz).
HRMS (EI): m/z [M(79Br) – C4H8O]+ calcd: 326.0112; found: 326.0113.
#
1-Bromo-4-[3-bromo-1-(tert-butylperoxy)-3,3-difluoropropyl]benzene (5-4)
Purified by chromatography (silica gel, PE to PE/EtOAc 100:1) to afford 5-4 (312.1 mg, 82%) as a light yellow oil; Rf = 0.65 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.49 (d, J = 8.2 Hz, 2 H), 7.23 (d, J = 8.1 Hz, 2 H), 5.23–5.16 (m, 1 H), 3.12–3.00 (m, 1 H), 2.80–2.65 (m, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 138.44, 131.86, 128.79, 122.56, 120.12 (t, J = 306.6 Hz), 81.09, 80.56 (t, J = 2.3 Hz), 49.28 (t, J = 21.4 Hz), 26.50.
19F NMR (377 MHz, CDCl3): δ = –42.09 (d, J = 157.3 Hz), –42.95 (d, J = 157.2 Hz).
HRMS (EI): m/z [M(79Br) – t BuOO]+ calcd: 310.8877; found: 310.8876.
#
1-[3-Bromo-1-(tert-butylperoxy)-3,3-difluoropropyl]-4-methoxybenzene (5-5)
Purified by chromatography (silica gel, PE to PE/EtOAc 100:1) to afford 5-5 (304.6 mg, 87%) as a light yellow oil; Rf = 0.35 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.27 (d, J = 8.6 Hz, 2 H), 6.89 (d, J = 8.7 Hz, 2 H), 5.17 (t, J = 6.2 Hz, 1 H), 3.80 (s, 3 H), 3.23–3.12 (m, 1 H), 2.84–2.73 (m, 1 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 159.94, 131.05, 128.64, 120.51 (t, J = 306.6 Hz), 114.06, 80.95 (t, J = 2.1 Hz), 80.84, 55.37, 49.05 (t, J = 20.9 Hz), 26.54.
19F NMR (377 MHz, CDCl3): δ = –41.92 (d, J = 155.5 Hz), –42.40 (d, J = 156.2 Hz).
HRMS (EI): m/z [M(79Br) – t BuOO]+ calcd: 262.9878; found: 262.9877.
#
1-[3-Bromo-1-(tert-butylperoxy)-3,3-difluoropropyl]-4-methylbenzene (5-6)
Purified by chromatography (silica gel, PE to PE/EtOAc 100:1) to afford 5-6 (273.6 mg, 86%) as a light yellow oil; Rf = 0.53 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.23 (d, J = 8.0 Hz, 2 H), 7.17 (d, J = 7.9 Hz, 2 H), 5.19 (t, J = 6.1 Hz, 1 H), 3.21–3.05 (m, 1 H), 2.84–2.72 (m, 1 H), 2.34 (s, 3 H), 1.21 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 138.42, 136.16, 129.36, 127.19, 120.52 (t, J = 306.7 Hz), 81.18 (t, J = 2.1 Hz), 80.86, 49.29 (t, J = 21.0 Hz), 26.55, 21.34.
19F NMR (377 MHz, CDCl3): δ = –41.92 (d, J = 156.3 Hz), –42.53 (d, J = 155.6 Hz).
HRMS (EI): m/z [M(79Br) – t BuOO]+ calcd: 246.9928; found: 246.9930.
#
[4-Bromo-2-(tert-butylperoxy)-4,4-difluorobutan-2-yl]benzene (5-7)
Purified by chromatography (silica gel, PE) to afford 5-7 (296.9 mg, 89%) as a light yellow oil; Rf = 0.66 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.43 (d, J = 7.3 Hz, 2 H), 7.34 (t, J = 7.6 Hz, 2 H), 7.27 (t, J = 7.3 Hz, 1 H), 3.24 (ddd, J = 22.0, 15.7, 10.4 Hz, 1 H), 3.12 (ddd, J = 22.5, 15.7, 10.5 Hz, 1 H), 1.78 (s, 3 H), 1.25 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 143.37, 128.21, 127.66, 125.94, 120.36 (t, J = 309.5 Hz), 82.14, 79.72, 54.04 (t, J = 20.1 Hz), 26.79, 23.57.
19F NMR (377 MHz, CDCl3): δ = –40.34 (d, J = 149.2 Hz), –40.80 (d, J = 149.3 Hz).
HRMS (EI): m/z [M(79Br) – t BuOO]+ calcd: 246.9928; found: 246.9931.
#
[3-Bromo-1-(tert-butylperoxy)-3,3-difluoropropane-1,1-diyl]dibenzene (5-8)
Purified by chromatography (silica gel, PE) to afford 5-8 (358.1 mg, 93%) as a light yellow oil; Rf = 0.60 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.34–7.19 (m, 10 H), 3.84 (t, J = 15.1 Hz, 2 H), 1.13 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 143.11, 127.81, 127.48, 127.14, 120.79 (t, J = 311.7 Hz), 84.61, 80.08, 50.00 (t, J = 19.2 Hz), 26.74.
19F NMR (377 MHz, CDCl3): δ = –39.62.
HRMS (EI): m/z [M(79Br) – t BuO]+ calcd: 325.0034; found: 325.0034.
#
Benzyl 4-Bromo-2-(tert-butylperoxy)-4,4-difluoro-2-methylbutanoate (5-9)
Purified by chromatography (silica gel, PE/EtOAc 100:1) to afford 5-9 (317.1 mg, 82%) as a yellow oil; Rf = 0.52 (PE/EtOAc 100:1).
1H NMR (600 MHz, CDCl3): δ = 7.43–7.27 (m, 5 H), 5.21 (d, J = 12.4 Hz, 1 H), 5.18 (d, J = 12.3 Hz, 1 H), 3.32–3.15 (m, 2 H), 1.57 (s, 3 H), 1.16 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 171.04, 135.64, 128.62, 128.42, 128.35, 119.87 (dd, J = 308.7, 307.2 Hz), 81.88, 80.55, 67.30, 48.02 (t, J = 20.7 Hz), 26.51, 20.12.
19F NMR (377 MHz, CDCl3): δ = –40.65 (d, J = 154.3 Hz), –41.82 (d, J = 154.3 Hz).
HRMS (EI): m/z [M(79Br) – C4H8O2]+ calcd: 306.0062; found: 306.0064.
#
[4-Bromo-2-(tert-butylperoxy)-4,4-difluoro-3-methylbutan-2-yl]benzene (5-10)
Purified by chromatography (silica gel, PE) to afford 5-10 (284.8 mg, 82%, 11.3:1 dr) as a light yellow oil; Rf = 0.68 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.42 (d, J = 7.5 Hz, 2 H), 7.32 (t, J = 7.6 Hz, 2 H), 7.25 (t, J = 7.3 Hz, 1 H), 3.04–2.79 (m, 1 H), 1.79 (s, 3 H), 1.25–1.18 (m, 12 H).
13C NMR (151 MHz, CDCl3): δ = 143.61, 127.58, 127.00, 126.52, 125.44 (dd, J = 315.0, 310.9 Hz), 83.78, 79.45, 54.96 (dd, J = 18.4, 16.9 Hz), 26.59, 22.07 (t, J = 2.7 Hz), 12.40 (t, J = 3.2 Hz).
19F NMR (377 MHz, CDCl3): δ = –37.61 (d, J = 153.4 Hz), –45.11 (d, J = 153.4 Hz).
HRMS (EI): m/z [M(79Br) – t BuOO]+ calcd: 261.0085; found: 261.0085.
#
1-(4-Bromophenyl)-3,3-bis(diethylamino)prop-2-en-1-one (6)
To a 25-mL Schlenk flask was added DABCO (279.4 mg, 2.49 mmol) and the flask was purged with N2 (3 ×). The flask was then equipped with a N2 balloon, CH3CN (2 mL), 2-9 (167.7 mg, 0.492 mmol), and Et2NH (155 μL, d = 0.707 g/mL, 1.50 mmol) were added sequentially, and the mixture was stirred at 80 °C in an oil bath. After 4 h, the mixture was cooled to r.t. and filtered through a pad of Celite eluting with DCM (15 mL). The filtrate was concentrated, and the residue was purified by chromatography (silica gel, PE/EtOAc 1:1) to afford 6 [14] (161.8 mg, 93%) as a yellow oil; Rf = 0.30 (PE/EtOAc 1:1).
1H NMR (600 MHz, CDCl3): δ = 7.74 (d, J = 8.3 Hz, 2 H), 7.48 (d, J = 8.3 Hz, 2 H), 5.15 (s, 1 H), 3.29 (q, J = 6.6 Hz, 8 H), 1.16 (t, J = 7.1 Hz, 12 H).
13C NMR (151 MHz, CDCl3): δ = 182.36, 167.28, 141.40, 130.74, 128.77, 123.79, 85.23, 43.90, 12.93.
#
1-(4-Bromophenyl)-3,3,3-trifluoropropan-1-one (7)
To a 25-mL Schlenk flask was added DABCO (12.1 mg, 0.108 mmol) and the flask was purged with N2 (3 ×). The flask was then equipped with a N2 balloon, CH3CN (2 mL) and 2-9 (171.0 mg, 0.501 mmol) were added sequentially, and the mixture was stirred at 60 °C in an oil bath. After 10 h, the mixture was cooled to r.t. and filtered through a pad of Celite eluting with DCM (15 mL). The filtrate was concentrated, and the residue was purified by chromatography (silica gel, PE/EtOAc 20:1) to afford 7 [16] (109.1 mg, 81%) as a colorless solid; Rf = 0.36 (PE/EtOAc 20:1).
1H NMR (600 MHz, CDCl3): δ = 7.79 (d, J = 8.6 Hz, 2 H), 7.65 (d, J = 8.7 Hz, 2 H), 3.77 (q, J = 9.9 Hz, 2 H).
13C NMR (151 MHz, CDCl3): δ = 188.88, 134.69, 132.44, 129.93, 129.77, 123.96 (q, J = 277.1 Hz), 42.26 (q, J = 28.5 Hz).
19F NMR (377 MHz, CDCl3): δ = –62.50.
#
[1-(tert-Butylperoxy)-3,3-difluoroallyl]benzene (8)
To a 25-mL Schlenk flask was added NaOH (66.0 mg, 1.65 mmol), CH3CN (5 mL), and 5-1 (161.1 mg, 0.499 mmol). The mixture was then stirred at 80 °C in an oil bath. After 36 h, the mixture was cooled to r.t., H2O (10 mL) was added, and the mixture was extracted with DCM (3 × 15 mL). The combined organic layers were evaporated under vacuum and the residue was purified by chromatography (silica gel, PE) to afford 8 (58.0 mg, 48%) as a light yellow oil; Rf = 0.22 (PE).
1H NMR (600 MHz, CDCl3): δ = 7.41–7.28 (m, 5 H), 5.57 (d, J = 9.7 Hz, 1 H), 4.62 (ddd, J = 24.0, 9.7, 1.8 Hz, 1 H), 1.25 (s, 9 H).
13C NMR (151 MHz, CDCl3): δ = 157.58 (t, J = 291.3 Hz), 138.41, 128.52, 128.37, 126.93, 80.67, 79.95 (dd, J = 22.0, 17.4 Hz), 78.61 (d, J = 8.2 Hz), 26.38.
19F NMR (377 MHz, CDCl3): δ = –84.97 (d, J = 33.7 Hz), –86.60 (d, J = 34.0 Hz).
HRMS (EI): m/z [M – t BuOO]+ calcd: 153.0510; found: 153.0509.
#
#
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-1702-4445.
- Supporting Information
-
References
- 1a Fluorine in Medicinal Chemistry and Chemical Biology. Ojima I. Blackwell; Chichester: 2009
- 1b Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, 2nd ed. Wiley-VCH; Weinheim: 2013
- 1c Smart BE. J. Fluorine Chem. 2001; 109: 3
- 1d Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
- 1e Hird M. Chem. Soc. Rev. 2007; 36: 2070
- 1f Inoue M, Sumii Y, Shibata N. ACS Omega 2020; 5: 10633
- 1g Ogawa Y, Tokunaga E, Kobayashi O, Hirai K, Shibata N. iScience 2020; 23: 101467
- 1h Han J, Kiss L, Mei H, Remete AM, Ponikvar-Svet M, Sedgwick DM, Roman R, Fustero S, Moriwaki H, Soloshonok VA. Chem. Rev. 2021; 121: 4678
- 2a Simons JH, Lewis CJ. J. Am. Chem. Soc. 1938; 60: 492
- 2b Yagupolskii LM, Fedyuk DV, Petko KI, Troitskaya VI, Rudyk VI, Rudyuk VV. J. Fluorine Chem. 2000; 106: 181
- 2c Hasek WR, Smith WC, Engelhardt VA. J. Am. Chem. Soc. 1960; 82: 543
- 3a Tomashenko OA, Grushin VV. Chem. Rev. 2011; 111: 4475
- 3b Chu L, Qing F.-L. Acc. Chem. Res. 2014; 47: 1513
- 3c Charpentier J, Früh N, Togni A. Chem. Rev. 2015; 115: 650
- 3d Liu X, Xu C, Wang M, Liu Q. Chem. Rev. 2015; 115: 683
- 3e Yang X, Wu T, Phipps RJ, Toste FD. Chem. Rev. 2015; 115: 826
- 3f Alonso C, Martínez de Marigorta E, Rubiales G, Palacios F. Chem. Rev. 2015; 115: 1847
- 3g Koike T, Akita M. Acc. Chem. Res. 2016; 49: 1937
- 4a Rozen, S.; Hagooly, A. Bromotrifluoromethane, In e-EROS Encyclopedia of Reagents for Organic Synthesis [Online]; Wiley & Sons, Posted October 15, 2005.
- 4b Qi Q, Shen Q, Lu L. J. Fluorine Chem. 2012; 133: 115
- 4c He L, Natte K, Rabeah J, Taeschler C, Neumann H, Brückner A, Beller M. Angew. Chem. Int. Ed. 2015; 54: 4320
- 4d Natte K, Jagadeesh RV, He L, Rabeah J, Chen J, Taeschler C, Ellinger S, Zaragoza F, Neumann H, Brückner A, Beller M. Angew. Chem. Int. Ed. 2016; 55: 2782
- 4e Ren Y.-Y, Zheng X, Zhang X. Synlett 2018; 29: 1028
- 4f Zhang K.-F, Bian K.-J, Li C, Sheng J, Li Y, Wang X.-S. Angew. Chem. Int. Ed. 2019; 58: 5069
- 4g Li Q, Fan W, Peng D, Meng B, Wang S, Huang R, Liu S, Li S. ACS Catal. 2020; 10: 4012
- 4h Peng D, Fan W, Zhao X, Chen W, Wen Y, Zhang L, Li S. Org. Chem. Front. 2021; 8: 6356
- 5a Beckers H, Bürger H, Bursch P, Ruppert I. J. Organomet. Chem. 1986; 316: 41
- 5b Tordeux M, Langlois B, Wakselman C. J. Org. Chem. 1989; 54: 2452
- 6a Xu B, Mashuta MS, Hammond GB. Angew. Chem. Int. Ed. 2006; 45: 7265
- 6b Lin J.-H, Xiao J.-C. Eur. J. Org. Chem. 2011; 4536
- 6c Nguyen JD, Tucker JW, Konieczynska MD, Stephenson CR. J. J. Am. Chem. Soc. 2011; 133: 4160
- 6d Min Q.-Q, Yin Z, Feng Z, Guo W.-H, Zhang X. J. Am. Chem. Soc. 2014; 136: 1230
- 6e Yue X, Zhang X, Qing F.-L. Org. Lett. 2009; 11: 73
- 6f Surmont R, Verniest G, De Kimpe N. Org. Lett. 2009; 11: 2920
- 7a Farina A, Meille SV, Messina MT, Metrangolo P, Resnati G, Vecchio G. Angew. Chem. Int. Ed. 1999; 38: 2433
- 7b Zhu S, Xing C, Xu W, Jin G, Li Z. Cryst. Growth Des. 2004; 4: 53
- 8a Tarrant P, Lovelace AM. J. Am. Chem. Soc. 1955; 77: 768
- 8b Molines H, Wakselman C. J. Fluorine Chem. 1987; 37: 183
- 8c Yoshida M, Morinaga Y, Iyoda M. J. Fluorine Chem. 1994; 68: 33
- 8d Salomon P, Zard SZ. Org. Lett. 2014; 16: 2926
- 8e Daniel M, Dagousset G, Diter P, Klein P.-A, Tuccio B, Goncalves A.-M, Masson G, Magnier E. Angew. Chem. Int. Ed. 2017; 56: 3997
- 8f McAtee RC, Beatty JW, McAtee CC, Stephenson CR. J. Org. Lett. 2018; 20: 3491
- 8g Kawamura S, Henderson CJ, Aoki Y, Sekine D, Kobayashi S, Sodeoka M. Chem. Commun. 2018; 54: 11276
- 8h Zhang J, Xu X.-H, Qing F.-L. Tetrahedron Lett. 2016; 57: 2462
- 8i Yu J, Wang D, Xu Y, Wu Z, Zhu C. Adv. Synth. Catal. 2018; 360: 744
- 8j Lin Q.-Y, Xu X.-H, Qing F.-L. Org. Biomol. Chem. 2015; 13: 8740
- 8k Dmitriev IA, Supranovich VI, Levin VV, Dilman AD. Eur. J. Org. Chem. 2019; 4119
- 8l Wallentin C.-J, Nguyen JD, Finkbeiner P, Stephenson CR. J. J. Am. Chem. Soc. 2012; 134: 8875
- 8m Zhao Y, Gao B, Hu J. J. Am. Chem. Soc. 2012; 134: 5790
- 9a The Chemistry of Peroxides, Parts 1 and 2. Rappoport Z. Wiley; Chichester: 2006
- 9b Dembitsky VM. Eur. J. Med. Chem. 2008; 43: 223
- 10a Kornblum N, DeLaMare HE. J. Am. Chem. Soc. 1951; 73: 880
- 10b Staben ST, Linghu X, Toste FD. J. Am. Chem. Soc. 2006; 128: 12658
- 10c Liu W, Li Y, Liu K, Li Z. J. Am. Chem. Soc. 2011; 133: 10756
- 10d Lv L, Shen B, Li Z. Angew. Chem. Int. Ed. 2014; 53: 4164
- 10e Chen Y, Li L, Ma Y, Li Z. J. Org. Chem. 2019; 84: 5328
- 10f Chen Y, Ma Y, Li L, Cui M, Li Z. Org. Chem. Front. 2020; 7: 1837
- 10g Wang L, Ma Y, Jiang Y, Lv L, Li Z. Chem. Commun. 2021; 57: 7846
- 10h Chen Y, Li L, He X, Li Z. ACS Catal. 2019; 9: 9098
- 10i Ma Y, Chen Y, Lv L, Li Z. Adv. Synth. Catal. 2021; 363: 3233
- 10j Ma Y, Chen Y, Lou C, Li Z. Asian J. Org. Chem. 2020; 9: 1018
- 11a Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483
- 11b Minatti A, Muñiz K. Chem. Soc. Rev. 2007; 36: 1142
- 11c Jensen KH, Sigman MS. Org. Biomol. Chem. 2008; 6: 4083
- 11d McDonald RI, Liu G, Stahl SS. Chem. Rev. 2011; 111: 2981
- 11e Wolfe JP. Angew. Chem. Int. Ed. 2012; 51: 10224
- 11f Yin G, Mu X, Liu G. Acc. Chem. Res. 2016; 49: 2413
- 11g Cao MY, Ren X, Lu Z. Tetrahedron Lett. 2015; 56: 3732
- 12a Zhang H.-Y, Ge C, Zhao J, Zhang Y. Org. Lett. 2017; 19: 5260
- 12b Qi B, Zhang T, Li M, He C, Duan C. Catal. Sci. Technol. 2017; 7: 5872
- 13a Shi Y, Sitkoff D, Zhang J, Klei HE, Kish K, Liu EC.-K, Hartl KS, Seiler SM, Chang M, Huang C, Youssef S, Steinbacher TE, Schumacher WA, Grazier N, Pudzianowski A, Apedo A, Discenza L, Yanchunas JJr, Stein PD, Atwal KS. J. Med. Chem. 2008; 51: 7541
- 13b Chen N, Meng X, Zhu F, Cheng J, Shao X, Li Z. J. Agric. Food Chem. 2015; 63: 1360
- 14 Wang L, Qi C, Guo T, Jiang H. Org. Lett. 2019; 21: 2223
- 15a Spier E, Neuenschwander U, Hermans I. Angew. Chem. Int. Ed. 2013; 52: 1581
- 15b Turrà N, Neuenschwander U, Baiker A, Peeters J, Hermans I. Chem. Eur. J. 2010; 16: 13226
- 16 Su X, Huang H, Yuan Y, Li Y. Angew. Chem. Int. Ed. 2017; 56: 1338
Corresponding Authors
Publication History
Received: 22 October 2021
Accepted after revision: 22 November 2021
Accepted Manuscript online:
22 November 2021
Article published online:
20 January 2022
© 2021. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1a Fluorine in Medicinal Chemistry and Chemical Biology. Ojima I. Blackwell; Chichester: 2009
- 1b Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, 2nd ed. Wiley-VCH; Weinheim: 2013
- 1c Smart BE. J. Fluorine Chem. 2001; 109: 3
- 1d Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
- 1e Hird M. Chem. Soc. Rev. 2007; 36: 2070
- 1f Inoue M, Sumii Y, Shibata N. ACS Omega 2020; 5: 10633
- 1g Ogawa Y, Tokunaga E, Kobayashi O, Hirai K, Shibata N. iScience 2020; 23: 101467
- 1h Han J, Kiss L, Mei H, Remete AM, Ponikvar-Svet M, Sedgwick DM, Roman R, Fustero S, Moriwaki H, Soloshonok VA. Chem. Rev. 2021; 121: 4678
- 2a Simons JH, Lewis CJ. J. Am. Chem. Soc. 1938; 60: 492
- 2b Yagupolskii LM, Fedyuk DV, Petko KI, Troitskaya VI, Rudyk VI, Rudyuk VV. J. Fluorine Chem. 2000; 106: 181
- 2c Hasek WR, Smith WC, Engelhardt VA. J. Am. Chem. Soc. 1960; 82: 543
- 3a Tomashenko OA, Grushin VV. Chem. Rev. 2011; 111: 4475
- 3b Chu L, Qing F.-L. Acc. Chem. Res. 2014; 47: 1513
- 3c Charpentier J, Früh N, Togni A. Chem. Rev. 2015; 115: 650
- 3d Liu X, Xu C, Wang M, Liu Q. Chem. Rev. 2015; 115: 683
- 3e Yang X, Wu T, Phipps RJ, Toste FD. Chem. Rev. 2015; 115: 826
- 3f Alonso C, Martínez de Marigorta E, Rubiales G, Palacios F. Chem. Rev. 2015; 115: 1847
- 3g Koike T, Akita M. Acc. Chem. Res. 2016; 49: 1937
- 4a Rozen, S.; Hagooly, A. Bromotrifluoromethane, In e-EROS Encyclopedia of Reagents for Organic Synthesis [Online]; Wiley & Sons, Posted October 15, 2005.
- 4b Qi Q, Shen Q, Lu L. J. Fluorine Chem. 2012; 133: 115
- 4c He L, Natte K, Rabeah J, Taeschler C, Neumann H, Brückner A, Beller M. Angew. Chem. Int. Ed. 2015; 54: 4320
- 4d Natte K, Jagadeesh RV, He L, Rabeah J, Chen J, Taeschler C, Ellinger S, Zaragoza F, Neumann H, Brückner A, Beller M. Angew. Chem. Int. Ed. 2016; 55: 2782
- 4e Ren Y.-Y, Zheng X, Zhang X. Synlett 2018; 29: 1028
- 4f Zhang K.-F, Bian K.-J, Li C, Sheng J, Li Y, Wang X.-S. Angew. Chem. Int. Ed. 2019; 58: 5069
- 4g Li Q, Fan W, Peng D, Meng B, Wang S, Huang R, Liu S, Li S. ACS Catal. 2020; 10: 4012
- 4h Peng D, Fan W, Zhao X, Chen W, Wen Y, Zhang L, Li S. Org. Chem. Front. 2021; 8: 6356
- 5a Beckers H, Bürger H, Bursch P, Ruppert I. J. Organomet. Chem. 1986; 316: 41
- 5b Tordeux M, Langlois B, Wakselman C. J. Org. Chem. 1989; 54: 2452
- 6a Xu B, Mashuta MS, Hammond GB. Angew. Chem. Int. Ed. 2006; 45: 7265
- 6b Lin J.-H, Xiao J.-C. Eur. J. Org. Chem. 2011; 4536
- 6c Nguyen JD, Tucker JW, Konieczynska MD, Stephenson CR. J. J. Am. Chem. Soc. 2011; 133: 4160
- 6d Min Q.-Q, Yin Z, Feng Z, Guo W.-H, Zhang X. J. Am. Chem. Soc. 2014; 136: 1230
- 6e Yue X, Zhang X, Qing F.-L. Org. Lett. 2009; 11: 73
- 6f Surmont R, Verniest G, De Kimpe N. Org. Lett. 2009; 11: 2920
- 7a Farina A, Meille SV, Messina MT, Metrangolo P, Resnati G, Vecchio G. Angew. Chem. Int. Ed. 1999; 38: 2433
- 7b Zhu S, Xing C, Xu W, Jin G, Li Z. Cryst. Growth Des. 2004; 4: 53
- 8a Tarrant P, Lovelace AM. J. Am. Chem. Soc. 1955; 77: 768
- 8b Molines H, Wakselman C. J. Fluorine Chem. 1987; 37: 183
- 8c Yoshida M, Morinaga Y, Iyoda M. J. Fluorine Chem. 1994; 68: 33
- 8d Salomon P, Zard SZ. Org. Lett. 2014; 16: 2926
- 8e Daniel M, Dagousset G, Diter P, Klein P.-A, Tuccio B, Goncalves A.-M, Masson G, Magnier E. Angew. Chem. Int. Ed. 2017; 56: 3997
- 8f McAtee RC, Beatty JW, McAtee CC, Stephenson CR. J. Org. Lett. 2018; 20: 3491
- 8g Kawamura S, Henderson CJ, Aoki Y, Sekine D, Kobayashi S, Sodeoka M. Chem. Commun. 2018; 54: 11276
- 8h Zhang J, Xu X.-H, Qing F.-L. Tetrahedron Lett. 2016; 57: 2462
- 8i Yu J, Wang D, Xu Y, Wu Z, Zhu C. Adv. Synth. Catal. 2018; 360: 744
- 8j Lin Q.-Y, Xu X.-H, Qing F.-L. Org. Biomol. Chem. 2015; 13: 8740
- 8k Dmitriev IA, Supranovich VI, Levin VV, Dilman AD. Eur. J. Org. Chem. 2019; 4119
- 8l Wallentin C.-J, Nguyen JD, Finkbeiner P, Stephenson CR. J. J. Am. Chem. Soc. 2012; 134: 8875
- 8m Zhao Y, Gao B, Hu J. J. Am. Chem. Soc. 2012; 134: 5790
- 9a The Chemistry of Peroxides, Parts 1 and 2. Rappoport Z. Wiley; Chichester: 2006
- 9b Dembitsky VM. Eur. J. Med. Chem. 2008; 43: 223
- 10a Kornblum N, DeLaMare HE. J. Am. Chem. Soc. 1951; 73: 880
- 10b Staben ST, Linghu X, Toste FD. J. Am. Chem. Soc. 2006; 128: 12658
- 10c Liu W, Li Y, Liu K, Li Z. J. Am. Chem. Soc. 2011; 133: 10756
- 10d Lv L, Shen B, Li Z. Angew. Chem. Int. Ed. 2014; 53: 4164
- 10e Chen Y, Li L, Ma Y, Li Z. J. Org. Chem. 2019; 84: 5328
- 10f Chen Y, Ma Y, Li L, Cui M, Li Z. Org. Chem. Front. 2020; 7: 1837
- 10g Wang L, Ma Y, Jiang Y, Lv L, Li Z. Chem. Commun. 2021; 57: 7846
- 10h Chen Y, Li L, He X, Li Z. ACS Catal. 2019; 9: 9098
- 10i Ma Y, Chen Y, Lv L, Li Z. Adv. Synth. Catal. 2021; 363: 3233
- 10j Ma Y, Chen Y, Lou C, Li Z. Asian J. Org. Chem. 2020; 9: 1018
- 11a Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483
- 11b Minatti A, Muñiz K. Chem. Soc. Rev. 2007; 36: 1142
- 11c Jensen KH, Sigman MS. Org. Biomol. Chem. 2008; 6: 4083
- 11d McDonald RI, Liu G, Stahl SS. Chem. Rev. 2011; 111: 2981
- 11e Wolfe JP. Angew. Chem. Int. Ed. 2012; 51: 10224
- 11f Yin G, Mu X, Liu G. Acc. Chem. Res. 2016; 49: 2413
- 11g Cao MY, Ren X, Lu Z. Tetrahedron Lett. 2015; 56: 3732
- 12a Zhang H.-Y, Ge C, Zhao J, Zhang Y. Org. Lett. 2017; 19: 5260
- 12b Qi B, Zhang T, Li M, He C, Duan C. Catal. Sci. Technol. 2017; 7: 5872
- 13a Shi Y, Sitkoff D, Zhang J, Klei HE, Kish K, Liu EC.-K, Hartl KS, Seiler SM, Chang M, Huang C, Youssef S, Steinbacher TE, Schumacher WA, Grazier N, Pudzianowski A, Apedo A, Discenza L, Yanchunas JJr, Stein PD, Atwal KS. J. Med. Chem. 2008; 51: 7541
- 13b Chen N, Meng X, Zhu F, Cheng J, Shao X, Li Z. J. Agric. Food Chem. 2015; 63: 1360
- 14 Wang L, Qi C, Guo T, Jiang H. Org. Lett. 2019; 21: 2223
- 15a Spier E, Neuenschwander U, Hermans I. Angew. Chem. Int. Ed. 2013; 52: 1581
- 15b Turrà N, Neuenschwander U, Baiker A, Peeters J, Hermans I. Chem. Eur. J. 2010; 16: 13226
- 16 Su X, Huang H, Yuan Y, Li Y. Angew. Chem. Int. Ed. 2017; 56: 1338
