Protected Hexafluoroacetone As an Air&#X02010

DOI: 10.1002/ejoc.201600711 Full Paper

Trifluoromethylation Cyclic-Protected Hexafluoroacetone as an Air-Stable Liquid Reagent for Trifluoromethylations Kazuyuki Negishi,[a] Kohsuke Aikawa,[a] and Koichi Mikami*[a]

Abstract: An air-stable liquid trifluoromethylating reagent is CuCF3 reagent prepared in situ by our method can be used for readily synthesized from gaseous hexafluoroacetone and 2- the trifluoromethylation of aryl iodides, arylboronic acids, and methylproline on a gram scale. The reaction of the trifluoro- terminal alkynes in good to excellent yields, even on a gram methylating reagent with tert-butoxy cuprate K[Cu(OtBu)2] scale. Furthermore, the CuC2F5 reagent can be prepared in the leads to the CuCF3 in high yield. This species is directly formed same way, and this can be used in the pentafluoroethylation of from the tetrahedral cuprate intermediate through intramolec- arylboronic acids or aryl bromides in good to excellent yields. ular migration of the trifluoromethyl group to copper. The

Introduction point: –28 °C), with a carbonyl group activated by two electron- withdrawing trifluoromethyl groups. This makes it difficult to Organic compounds bearing fluoroalkyl groups have received a handle in typical academic laboratories. To the best of our great deal of attention due to the unique properties of fluor- knowledge, only one example of the use of 1 as a trifluoro- ine.[1] Trifluoromethylated aromatic compounds in particular methylating reagent has been reported, by Colby and cowork- play important roles at the forefront of the development of new ers.[12] The amidinate salt prepared from hexafluoroacetone pharmaceuticals and agrochemicals as a result of their in- hydrate and DBU is a solid air-stable reagent that can efficiently creased lipophilicity and metabolic resistance.[2] Therefore, vari- release fluoroform under the basic conditions, and can be used ous methods for the synthesis of these compounds have been in the trifluoromethylation of aldehydes, ketones, and disulfides developed.[3,4] Considerable progress has been made in recent (Scheme 1, a). However, its use with aryl halides to give aro- years with copper-catalyzed and copper-mediated aromatic tri- matic derivatives has not been reported. Therefore, the devel- fluoromethylation reactions using the Ruppert–Prakash reagent opment of a stable trifluoromethylating reagent prepared from (Me SiCF )[5] as a trifluoromethylating reagent, because of the 3 3 hexafluoroacetone 1 that can be used for the trifluoromethyl- reliability of this approach.[2,6] However, this method is still ation reactions of aromatic compounds poses a challenge. In costly for large-scale operations. As a result, much effort has this communication, we report the preparation of a stable liq- been put into the development of aromatic trifluoromethyl- [7] uid trifluoromethylating reagent 2 derived from unstable gase- ation reactions using fluoroform (CF3H) as an alternative to [8] ous 1, and its application to copper-mediated aromatic tri- Me3SiCF3. In 2000, Normant and coworkers reported the prep- I fluoromethylations (Scheme 1, a). The noteworthy features of aration of CuCF3 by combination of a Cu salt and trifluorometh- – ylated hemiaminolate [CF3CH(O)NMe2] (DMF adduct), which can be prepared by deprotonation of fluoroform using dimsyl- K, followed by addition to dimethyformamide (DMF). The yield [9] of CuCF3 was moderate (up to 47 %). Furthermore, Grushin and coworkers have reported the direct cupration of fluoroform and its application to a variety of copper-mediated trifluoromethylations.[2,10] Hexafluoroacetone (1), which is manufactured using per- chloroacetone or hexafluoropropene, is also an attractive trifluoromethylating reagent.[11] However, the fundamental draw- back is that hexafluoroacetone is highly reactive gas (boiling

[a] Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8552, Japan E-mail: [email protected] www.apc.titech.ac.jp/~mikami/index-e.html Supporting information and ORCID(s) from the author(s) for this article are Scheme 1. a) Trifluoromethylating reagents prepared from hexafluoro-

available on the WWW under http://dx.doi.org/10.1002/ejoc.201600711. acetone; b) Preparation of CuCF3 from reagent 2.

Eur. J. Org. Chem. 2016, 4099–4104 4099 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Full Paper reagent 2 are that i) it is easy to handle as it is an air-stable acetylated 2-methyl proline ester 3 was also observed in 19F liquid; ii) it can be synthesized on a gram scale from readily NMR spectra, and was then isolated in 65 % yield. available starting materials; iii) it can be used for the direct preparation of the CuCF3 reagent and subsequent trifluoromethylations of aryl iodides, arylboronic acids, and terminal alkynes. Indeed, the carbonyl group of 2 reacts with K[Cu(OtBu)2], generating CuCF3 via a tetrahedral intermediate that is the ana- log of the DMF adduct[9] (Scheme 1, b). Scheme 3. The use of reagents 2 as CuCF3 source, yield was determined by 19F NMR spectroscopic analysis using benzotrifluoride (BTF) as an internal standard. Results and Discussion To gain insight into the generation of CuCF3 from cyclic-pro- Initially, we tried to prepare simple hemiaminal derivatives of tected hexafluoroacetone 2b, we carried out 19F NMR analysis hexafluoroacetone [(CF3)2C(OH)NR2], which would generate (Figure 1). At –20 °C, the reaction almost did not take place, CuCF3 by deprotonation of the hydroxyl group followed by ad- and so two peaks (δ = –73.2 and –82.5 ppm) corresponding to dition of a CuI salt. Unfortunately, the desired hemiaminals the trifluoromethyl group of 2b were mainly observed. After could not be isolated due to their instability.[13] Hence, we fo- the reaction temperature was warmed up to 10 °C, the genera- cused on cyclic protection of hexafluoroacetone so that the tion of CuCF3 (δ = –25.2 ppm) and 3 (δ = –74.1 ppm) was hemiaminal skeleton could be isolated as a 5-oxazolidinone de- observed. Finally, we found that 2b could be completely trans- [14] rivative (Scheme 2). Cyclic-protected hexafluoroacetone 2a formed into CuCF3 and 3 at 20 °C after 30 min; the formation was synthesized by cyclocondensation of hexafluoroacetone 1 of a small amount of fluoroform was also observed. However, and L-proline (Scheme 2, a).[15] The acidic α position of the carb- in this case, the tetrahedral intermediate was not detected. This onyl group of 2a was alkylated through a deprotonation–addi- result implies that tetrahedral cuprate intermediate A is not sta- tion sequence using LDA (lithium diisopropylamide) and alkyl ble in the range of –20–10 °C, and that it instantly forms CuCF3 halides, giving the corresponding products 2b–2d. Additionally, after the addition of the cuprate to the carbonyl group has cyclic-protected hexafluoroacetone 2b was prepared on a gram taken place. scale in 86 % yield (4.7 g) through the reaction between 2- methylproline[16] (scale: 3.5 g, 20 mmol) and hexafluoroacetone 1 (Scheme 2, b). Reagent 2b was easily purified by chromatography on a short column, and could be kept for at least one month in air at room temperature.

Figure 1. Variable temperature 19F NMR experiments for the generation of CuCF . Reaction conditions: 2b (0.3 mmol) was added to a DMF solution of Scheme 2. Synthesis of trifluoromethylating reagent 2. 3 K[Cu(OtBu)2] (0.3 mmol) at –20 °C. The generation of CuCF3 and 3 was moni- tored by 19F NMR spectroscopic analysis using benzotrifluoride (BTF) as an The reactivity of cyclic-protected hexafluoroacetones 2a–2d internal standard. a) Reaction temperature –20 °C; b) 10 °C; c) 20 °C. with cuprate was investigated for preparation of the CuCF3 reagent through a ring-opening reaction (Scheme 3).[17] We found In sharp contrast, the use of KOtBu (1.0 equiv.), a more that 2a, 2c, and 2d, which all have either an acidic proton or a nucleophilic reagent than K[Cu(OtBu)2], led to the direct detec- bulky substituent at the α position, gave almost no CuCF3, be- tion of tetrahedral intermediate A′ (δ = –78.9 and 75.6 ppm), cause of protonation of the cuprate or obstruction of the nu- even at –40 °C (Scheme 4).[18] The addition of TESCl (TES = cleophilic addition, respectively. Significantly, the combination triethylsilyl) to A′ provided O-silylated hemiaminal 4 in 80 % of K[Cu(OtBu)2] and 2b, without an acidic α-proton and with yield. Importantly, the reaction of A′ with CuOtBu (1.0 equiv.) less steric hindrance around the carbonyl group, generated was found to give CuCF3 in 51 % yield when the reaction mix- 19 CuCF3 in 87 % yield. The F NMR spectroscopic data of CuCF3 ture was warmed up to room temperature. Under the reaction [10] matched well with the data for CuCF3 reported by Grushin conditions, the DMF adduct formed by the nucleophilic addi- [17] – and with our previous results. In this reaction, N-trifluoro- tion of free CF3 to a DMF solvent molecule, as reported by

19 Scheme 4. Production of CuCF3 through intramolecular migration. [a] Isolated yield. [b] Yield was determined by F NMR spectroscopic analysis using benzotrifluoride (BTF) as an internal standard.

Normant,[9] was not detected. Moreover, gem-difluorocyclopro- Aromatic substrates with electron-withdrawing substituents pane could not be produced even in the presence of the elec- (5a–5d) and pyridine derivatives (5h and 5i) underwent the tron-rich alkene α-methylstyrene, even though generation of trifluoromethylation reaction to give the corresponding prod- – difluorocarbene through the decomposition of free CF3 is well ucts in good to high yields, even with only a slight excess of [17,19] known. These results strongly indicate that CuCF3 is di- the CuCF3 reagent (6a–6d, 6h, and 6i). In contrast, lower yields rectly formed from tetrahedral cuprate intermediate A through were obtained for substrates bearing electron-donating groups the intramolecular migration of the trifluoromethyl group to (5e and 5f), 1-iodonaphthalene (5g), 2-iodothiophene (5j), and copper. a uracil derivative (5k). However, the addition of 1,10-phen-

The CuCF3 reagent prepared from cyclic-protected hexa- anthroline as a ligand improved the yields to good to high lev- fluoroacetone 2b was successfully applied to the aromatic tri- els (6e–6g, 6j, and 6k). It is important that the reaction can be fluoromethylation of aryl iodides (Scheme 5).[2,3] When using carried out on a gram scale, and indeed, the reaction of 5b the CuCF3 reagent prepared from K[Cu(OtBu)2] and 2b in DMF, (scale: 1.95 g, 7.07 mmol) proceeded smoothly in 97 % yield it was necessary to neutralize the remaining KOtBu by the addi- (1.49 g). [10,17] tion of Et3N·3HF before it could be used in the reaction. The CuCF3 reagent was also used in the oxidative trifluoromethylation reactions of arylboronic acid 7 and terminal alkyne 9 to give the corresponding products 8 and 10, respectively [6h,17,20] [21] (Scheme 6). Furthermore, the CuC2F5 reagent was prepared from cyclic-protected decafluoropentanone 11 in 67 % yield, along with proline ester 12 in 85 % yield (Scheme 7,

a). The combination of the CuC2F5 reagent and arylboronic acid 7 or 2-bromobenzoate 14 led to the respective aromatic pentafluoroethylation products (Scheme 7, b).

Scheme 6. Trifluoromethylation reactions of an arylboronic acid and a termi- Scheme 5. Trifluoromethylation of aryl iodides. [a] Yields were determined by nal alkyne, yields were determined by 19F NMR spectroscopic analysis using 19 F NMR spectroscopic analysis using (trifluoromethoxy)benzene as an inter- benzotrifluoride (BTF) as an internal standard. CuCF3 was neutralized by nal standard. CuCF3 was neutralized by Et3N·3HF before being used in the Et3N·3HF before being used in the reaction. Conditions [Equation (1)]: 7 and reaction. [b] Conditions: 5 and CuCF3 (1.1 equiv.) in DMF at 50 °C for 24 h. CuCF3 (2.0 equiv.) in air (1 atm). Conditions [Equation (2)]: 9, CuCF3 [c] Gram-scale operation, and isolated yield. [d] Conditions: 5, CuCF3 (2.0 equiv.), and TMEDA (tetramethylethylenediamine; 2.0 equiv.) in air (1.5 equiv.), and 1,10-phenanthroline (1.5 equiv.) in DMF at 50 °C for 24 h. (1 atm). Alkyne 9 in DMF was added over a period of1hbysyringe pump.

using 2-methylproline. The cyclic-protected hexafluoroacetone

was allowed to react with tert-butoxy cuprate K[Cu(OtBu)2]in DMF to provide the CuCF3 reagent in high yield. This was then used in subsequent trifluoromethylation reactions of aryl iodides, an arylboronic acid, and a terminal alkyne in good to high yields under mild conditions. The reaction could also be carried out on a large scale. This reaction system was also applicable

to the preparation of the CuC2F5 reagent and its use in aromatic pentafluoroethylations. The development of asymmetric reactions based on our reagent is now underway in our laboratory.

Experimental Section General Remarks: 1H, 13C, and 19F NMR spectra were measured with a Bruker AV300M (300 MHz) spectrometer. 1H NMR spectra

were calibrated using the singlet (δ = 7.26 ppm) for CDCl3,and 13 Scheme 7. Application to pentafluoroethylation, yield was determined by 19F chemical shifts are expressed in parts per million. C NMR spectra NMR spectroscopic analysis using benzotrifluoride (BTF) as an internal stan- were calibrated using the central line of the triplet (δ = 77.0 ppm) 19 dard. The CuC2F5 reagent was neutralized by Et3N·3HF before being used in for CDCl3, and chemical shifts are expressed in parts per million. F the reaction. Conditions [Equation (1)]: 7 and CuC2F5 (2.0 equiv.) in air (1 atm). NMR were calibrated using the singlet (δ = –63.24) for BTF (benzo- Conditions [Equation (2)]: 14 and CuC2F5 (2.0 equiv.), which was prepared trifluoride), used as an internal standard, and chemical shifts are from Na[Cu(OtBu)2] instead of K[Cu(OtBu)2]. expressed in parts per million. Important NMR spectroscopic data are tabulated in the following order: multiplicity (s: singlet, d: dou- Our approach also gave new insight into the elimination of blet, t: triplet, q: quartet, sep: septet, m: multiplet) and coupling constant [J (Hz)]. Mass spectra were measured with a JEOL JMS- fluoroalkyl groups from tetrahedral intermediates (Scheme 8). T100CS (Accu-TOF) spectrometer. IR spectra were measured with a Interestingly, the reaction of cyclic-protected 16 bearing CF 3 JASCO FTIR-4200 spectrometer. Column chromatography was car- and C2F5 groups with K[Cu(OtBu)2]gaveCuC2F5 in 61 % yield, ried out on KANTO Silica Gel 60N (spherical, neutral). Potassium along with CuCF3 in 4 % yield [Scheme 8, Equation (1)]. Further- tert-butoxide (sublimed grade, 99.99 % trace-metals basis) and L- more, cyclic-protected 17 bearing CF3 and CF2H groups led only proline were purchased from TCI. Copper(I) chloride (anhydrous, to CuCF3 under the same reaction conditions [Scheme 8, Equa- beads, ≥99.99 % trace basis) was purchased from Aldrich. Substrates tion (2)]. In these reactions, it was demonstrated that the dia- 5a, 5g, 5h,and5i were purchased from TCI. Substrates 5c, 5d, 5e, stereomeric ratio of 16 and 17 did not affect the ratio of the 5f, 5j, 5k, 7, 9,and14 were purchased from Aldrich. Substrate 5b fluoroalkylated copper species obtained. These results show was purchased from Wako Pure Chemical Industries, Ltd. 2-Methyl- that the migration aptitude of fluoroalkyl groups from the cu- L-proline was synthesized from L-proline according to the published procedure.[16] prate tetrahedral intermediates is in the following order: Synthesis of Cyclic-Protected Hexafluoroacetone (2b): An oven- C2F5 >CF3 >CF2H. dried two-necked round-bottomed flask (50 mL) containing concd.

H2SO4 (12.2 mL) and equipped with a magnetic stirrer bar was at- tached to a distillation head and condenser, leading to a second two-necked round bottomed flask (30 mL) containing 2-methyl-L- proline (contains 1 equiv. of NaCl; 3.47 g, 20 mmol) and DMSO (30.4 mL), also equipped with a magnetic stirrer bar. Hexafluoroace- tone hydrate (9.76 mL, 70.0 mmol) was added dropwise to the

concd. H2SO4 over 4 h at 90 °C, and the evolution of gaseous hexafluoroacetone (1) was observed (caution). The reaction mixture (in the flask containing the 2-methyl-L-proline) was vigorously stirred under the hexafluoroacetone atmosphere at room temperature for

12 h. The reaction mixture was then diluted with H2O (30 mL), and the mixture was extracted with CH2Cl2 (3 × 60 mL). The combined organic extracts were then washed with brine (60 mL), dried with

MgSO4, filtered, and concentrated. The remaining DMSO was re- moved by silica-gel flash chromatography (CH Cl only) to give cy- Scheme 8. Competition experiment for elimination, yield was determined by 2 2 19 clic-protected hexafluoroacetone 2b (4.7 g, 86 %) as a pale yellow F NMR spectroscopic analysis using benzotrifluoride (BTF) as an internal 1 standard. liquid. H NMR (300 MHz, CDCl3): δ = 3.43–3.39 (m, 1 H): δ = 3.32– 3.24 (m, 1 H), 2.16–1.87 (m, 4 H), 1.45 (s, 3 H) ppm. 13C NMR

(75 MHz, CDCl3): δ = 173.2, 120.6 (q, JC,F = 284.8 Hz), 120.5 (q, JC,F = 290.0 Hz), 90.5 (qq, JC,F = 32.1, 31.9 Hz), 68.4, 48.1 (q, JC,H = 2.5 Hz), 19 Conclusions 35.8, 25.9, 25.1 ppm. F NMR (282 MHz, CDCl3): δ = –72.0 (q, JF,F = 8.9 Hz, 3 F), –81.1 (q, JF,F = 10.1 Hz, 3 F) ppm. HRMS (APCI-TOF): +· In summary, we have developed an air-stable liquid trifluoro- calcd. for C9H9F6NO2 [M] 277.0538; found 277.0524. FTIR (neat): methylating reagent by cyclic protection of hexafluoroacetone ν˜ = 719, 746, 967, 1194, 1228, 2923, 2990 cm–1.

Preparation of the CuCF3 Reagent from Cyclic-Protected Hexa- Acknowledgments fluoroacetone 2b: CuCl (29.7 mg, 0.30 mmol), KOtBu (67.3 mg, 0.6 mmol) and DMF (0.6 mL) were added to a test tube equipped This research was supported by the Japan Science and Technol- with a magnetic stirrer bar. The mixture was stirred for 30 min at ogy Agency (JST), grant “Advanced Catalytic Transformation room temperature. Then, cyclic-protected hexafafluoroacetone 2b program for Carbon utilization (ACT-C)”. The authors thank Cen- (83.1 mg, 0.30 mmol) was added dropwise to the mixture at room tral Glass Co., Ltd. for a gift of hexafluoroacetone hydrate. temperature. The mixture was stirred for 30 min at room temperature, then the yield of the CuCF species (87 % yield) was deter- 3 Keywords: Synthetic methods · Reagent design · Fluorine · mined by 19F NMR spectroscopic analysis using benzotrifluoride (10 μL, 0.0814 mmol) as an internal standard, and using a sealed Fluorinated compounds · Cuprates 19 capillary filled with [D6]benzene for signal lock. F NMR (282 MHz, [10a,17] DMF): δ = –25.2 (s, 3 F) ppm. [1] a) P. Kirsch, Modern Fluoroorganic Chemistry: Synthesis Reactivity, Applica- Typical Procedure for the Trifluoromethylation of Aryl Iodides tions, 2nd ed., Wiley-VCH, Weinheim, Germany, 2013; b) I. Ojima, Fluorine in Medicinal Chemistry and Chemical Biology, Wiley–Blackwell, Chichester, Using the CuCF3 Reagent: CuCl (29.7 mg, 0.30 mmol), KOtBu (67.3 mg, 0.6 mmol) and DMF (0.6 mL) were added to a test tube UK, 2009;c)V.A.Petrov,Fluorinated Heterocyclic Compounds: Synthesis Chemistry and Applications, Wiley, Hoboken, NJ, 2009; d) K. Uneyama, equipped with a magnetic stirrer bar. The mixture was stirred for Organofluorine Chemistry, Blackwell, Oxford, UK, 2006; e) T. Hiyama, Or- 30 min at room temperature. Compound 2b (0.30 mmol) was then ganofluorine Compounds: Chemistry and Applications, Springer, Berlin, added dropwise to the mixture at room temperature. The reaction 2000. mixture was stirred for 30 min, then it was cooled to 0 °C, and [2] For a review, see: O. A. Tomashenko, V. V. Grushin, Chem. Rev. 2011, 111, Et3N·3HF (0.1 mmol) was added for protonation of the remaining 4475. KOtBu. The concentration of the CuCF3 species in DMF (0.33–0.43 M) [3] For selected reviews, see: a) H. Amii, J. Synth. Org. Chem. Jpn. 2011, 69, was measured by 19F NMR spectroscopic analysis using benzotriflu- 752; b) S. Roy, B. T. Gregg, G. W. Gribble, V.-D. Le, S. Roy, Tetrahedron 2011, 67, 2161; c) T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. oride (10 μL, 0.0814 mmol) as an internal standard in CuCF3 solution in DMF (500 μL sample), and using a sealed capillary filled with Ed. 2013, 52, 8214; Angew. Chem. 2013, 125, 8372; d) G. Landelle, A. Panossian, S. Pazenok, J.-P. Vors, F. R. Leroux, Beilstein J. Org. Chem. 2013, [D ]benzene for signal lock. 6 9, 2476; e) T. Sugiishi, H. Amii, K. Aikawa, K. Mikami, Beilstein J. Org. Chem.

Aryl iodide (5; 0.050 mmol) and the solution of CuCF3 in DMF (0.33– 2015, 11, 2661. 0.43 M; 127–167 μL, 0.055 mmol) were added to a test tube [4] For selected excellent reports, see: a) E. J. Cho, T. D. Senecal, T. Kinzel, Y. equipped with a magnetic stirrer bar. The test tube was sealed with Zhang, D. A. Watson, S. L. Buchwald, Science 2010, 328, 1679; b) D. A. a screw cap, and the reaction mixture was stirred at 50 °C (oil bath) Nagib, D. W. C. MacMillan, Nature 2011, 480, 224; c) Y. Fujiwara, J. A. Dixon, F. O'Hara, E. D. Funder, D. D. Dixon, R. A. Rodriguez, R. D. Baxter, for 24 h. After this time, the reaction mixture was cooled down to B. Herlé, N. Sach, M. R. Collins, Y. Ishihara, P. S. Baran, Nature 2012, 492, room temperature, and (trifluoromethoxy)benzene (10 μL, 95. 0.0756 mmol) was added. The yield of the product was determined [5] a) G. K. S. Prakash, A. K. Yudin, Chem. Rev. 1997, 97, 757; b) G. K. 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Kovacs, C. Weber, T. Gati, A. Meszaros, A. mixture at room temperature. The reaction mixture was stirred at Kotschy, Z. Novak, Org. Lett. 2014, 16, 4268. [7] For a review, see: W. Han, Y. Li, H. Tang, H. Liu, J. Fluorine Chem. 2012, 50 °C for 24 h, then the reaction was quenched with HCl (1 M aq.; 140,7. 20 mL). The organic layer was separated, and the aqueous layer was [8] For examples of other reactions with fluoroform, see: a) T. Shono, M. extracted with Et2O (3 × 20 mL). The combined organic layers were Ishifune, T. Okada, S. Kashimura, J. Org. Chem. 1991, 56, 2; b) R. Barhdadi, washed with brine (40 mL), and dried with MgSO4, and the solvent M. Troupel, J. Périchon, Chem. Commun. 1998, 1251; c) J. Russell, N. was evaporated under reduced pressure. The resulting crude prod- Roques, Tetrahedron 1998, 54, 13771; d) S. Large, N. Roques, B. R. Lan- uct was purified by silica-gel column chromatography (pentane/ glois, J. Org. Chem. 2000, 65, 8848; e) T. Billard, S. Bruns, B. R. Langlois, ether, 10:1) to give ethyl 2-(trifluoromethyl)benzoate (6b; 1.49 g, Org. Lett. 2000, 2, 2101; f) B. R. Langlois, T. Billard, Synthesis 2003, 185; 97 %) as a pale yellow liquid. This product is a known compound, g) B. R. Langlois, T. Billard, ACS Symp., Ser. 2005, 911, 57; h) I. Popov, S. and the following data are identical to those reported in the litera- Lindeman, O. Daugulis, J. Am. Chem. Soc. 2011, 133, 9286; i) G. K. S. ture.[17] 1H NMR (300 MHz, CDCl ): δ = 7.71–7.78 (m, 2 H), 7.55–7.59 Prakash, P. V. Jog, P. T. D. Batamack, G. A. Olah, Science 2012, 338, 1324; 3 j) T. Iida, R. Hashimoto, K. Aikawa, S. Ito, K. Mikami, Angew. Chem. Int. Ed. (m, 2 H), 4.39 (q, J = 7.1 Hz, 2 H), 1.38 (t, J = 7.1 Hz, 3 H) ppm. 13C 2012, 51, 9535; Angew. Chem. 2012, 124, 9673; k) H. Kawai, Z. Yuan, E. NMR (75 MHz, CDCl3): δ = 166.6, 131.5, 131.4 (q, JC,F = 2.0 Hz), 130.9, Tokunaga, N. Shibata, Org. Biomol. Chem. 2013, 11, 1446; l) C. S. 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J. Am. Chem. Soc. 2011, 133, 20901; b) P. Novák, A. Lishchynskyi, V. V. [18] When K[Cu(OEt)2] was used instead of K[Cu(OtBu)2], the tetrahedral inter- Grushin, Angew. Chem. Int. Ed. 2012, 51, 7767; Angew. Chem. 2012, 124, mediate could be detected directly at –40 °C. After the reaction mixture

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