Preparation of 2-(t-butyl)dimethylsilyl-3,3-difluoropropenones via acylation reactions of 1-(t-butyl)dimethylsilyl-2,2-difluoroethenylstannane

G Model

FLUOR-8611; No. of Pages 5 Journal of Fluorine Chemistry xxx (2015) xxx–xxx

Contents lists available at ScienceDirect

Journal of Fluorine Chemistry journal homepage: www.elsevier.com/locate/fluor

Preparation of 2-(t-butyl)dimethylsilyl-3,3-difluoropropenones via acylation reactions of 1-(t-butyl)dimethylsilyl-2, 2-difluoroethenylstannane Ye Rim Jeong, Hye Jin An, Sung Lan Jeon, In Howa Jeong * Department of Chemistry, Yonsei University, Wonju, 220-710, South Korea

A R T I C L E I N F O

A B S T R A C T

Article history: Received 29 April 2015 Received in revised form 7 July 2015 Accepted 9 July 2015 Available online xxx

Stannylation reaction of 1-(t-butyl)dimethylsilyl-2,2-difluoroethenyl p-toluenesulfonate 1b with hexabutylbistin in the presence of 3 mol% Pd2(dba)3, 6 mol% XPhos and 30 equiv LiBr in THF at reflux temperature for 8 h provided the corresponding 1-(t-butyl)dimethylsilyl-2,2-difluoroethenylstannane 2b in 70% yield. The acylation reactions of 2b with a variety of acyl chlorides in the presence of 5 mol% Pd(PPh3)4 and 10 mol% CuI in THF at reflux temperature for 2 h afforded the 2-(t-butyl)dimethylsilyl-3,3difluoropropenones 3b–3l in 45–86% yields. ß 2015 Elsevier B.V. All rights reserved.

Keywords: 1-(t-Butyl)dimethylsilyl-2, 2-difluoroethenylstannane Acylation reaction 2-(t-Butyl)dimethylsilyl-3, 3-difluoropropenones

1. Introduction The development of fluorine-containing synthons has received much attention because they played an important role in the preparation of organofluorine compounds. Among the fluorinecontaining synthons, fluorinated enones are valuable synthetic intermediates in the synthesis of biologically active compounds [1–3], cyclic and polycyclic molecules via Diels–Alder reactions [4–10] and substituted olefins via Michael type reactions [11,12]. Although methods for the preparation of fluorinated enones have been documented in the previous literatures, most of the preparations focused on 2-fluorinated or 1,2-difluorinated enones, and the preparation of 1,1-difluorinated enones has been quite rare and only a couple of examples has been reported so far. Especially, the preparation of 2-trialkylsilylated 3,3-difluoropropenones has not been reported previously. Non-fluorinated trialkylsilylated enones have also been useful reagents for a variety of transformations such as synthesis of natural products [13,14], cycloaddition reactions [15] and coupling reaction site [16]. Therefore, 2trialkylsilylated 3,3-difluoropropenones would also be remarkable synthons to provide the organofluorine compounds. Tomoda et al. prepared 2-fluorinated enones from the reaction of a-diazoketones

* Corresponding author. E-mail address: [email protected] (I.H. Jeong).

with phenylselenyl fluoride in moderate yields [17]. Nucleophilic addition–elimination reactions of 2,3-difluoro-4,4-dimethylbutyl2-enolide with Grignard reagents and copper bromide afforded 2-fluoro-4,4-dimethylbutyl-2-enolide in good yields [12]. Direct Stille cross-coupling reactions of 1-fluorovinylstannanes with acyl chlorides in the presence of Pd and CuI catalysts provided 2-fluorinated enones [18,19]. The 2-fluorinated enones were also prepared in a three-component assembly synthesis using HFC-134a as a starting material [20,21]. First stereospecifically synthesis of (E) or (Z)-2-fluoroenones was accomplished via a kinetically controlled Negishi coupling reaction of bromofluoroolefins with alkoxyvinylzinc reagents under controlled reaction temperature [10]. Zajc et al. [22] prepared 2-fluorinated enones from the Wittig reactions of fluoro Julia reagents with aldehydes in the presence of DBU in good yields. Preparation of 1,2-difluoroenones was also reported. Stilletype cross-coupling reactions of 1,2-difluoroethenylstannane with acyl chlorides in the presence of only CuI in DMF afforded the corresponding 1,2-difluoroenones in good yields [23]. Recently, Friedel–Craft’s acylation reaction between 1,2-difluorovinylsilane and acyl chlorides in the presence of AlCl3 provided the corresponding 1,2-difluoroenones [24]. In contrast to the preparation of 2fluorinated or 1,2-difluorinated enones, 1,1-difluoroenones were prepared using very limited methods. One-pot synthesis of 1,1difluoroenones was accomplished by the cross-coupling reactions of 2,2-difluorovinylcopper reagents, generated in situ from 2,2difluorovinylboranes, with acyl chlorides [25]. Similar reaction was

http://dx.doi.org/10.1016/j.jfluchem.2015.07.010 0022-1139/ß 2015 Elsevier B.V. All rights reserved.

Please cite this article in press as: Y.R. Jeong, et al., J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/j.jfluchem.2015.07.010

G Model

FLUOR-8611; No. of Pages 5 2

Y.R. Jeong et al. / Journal of Fluorine Chemistry xxx (2015) xxx–xxx

performed between 2,2-difluorovinylcopper reagent with acyl chlorides, in which 2,2-difluorovinylcopper reagent was prepared from the corresponding 2,2-difluororvinylstannane reagent [26]. Herein, we wish to report a general and straightforward preparation of unknown 2-(t-butyl)dimethylsilyl-3,3-difluoropropenones via the cross-coupling reaction of 1-(t-butyl)dimethylsilyl-2,2-difluoroethenylstannanes with acyl chlorides. 2. Results and discussion Recently, we reported that stable 2,2-difluoro-1-trimethylsilylethenylstannane 2a was prepared in 73% yield from the reaction of 2,2-difluoro-1-trimethylsilylethenyl tosylate 1a with hexabutylbistin in the presence of Pd catalyst and LiBr in THF at reflux temperature [27]. 1-(t-Butyl)dimethylsilyl-2,2-difluoroethenylstannane 2b was also prepared in 70% yield in a similar manner. First of all, we attempted the palladium-catalyzed crosscoupling reaction of 2a with benzoyl chloride in the presence of

F

SiMe2R +

OTs F 1a (R = Me) 1b (R = t-Bu)

(Bu3Sn)2

the desired product 3b in 22% yield (Entry 6). The addition of CuI (10 mol%) in this reaction caused to increase the yield of 3b up to 60% (Entry 7). The use of 5 mol% of Pd(PPh3)4 in the same reaction resulted in the formation of 3b in 75% yield (Entry 8). However, the use of only CuI in this reaction did not proceed at all (Entry 9). Although several Pd catalysts such as Pd2(dba)3, Pd(CH3CN)2Cl2, Pd(PPh3)2Cl2 or Pd(OAc)2 were examined in this reaction, the yield of 3b was decreased in all reaction conditions (Entry 10–13). The results of these reactions were summarized in Table 1. Optimized reaction condition was applied to prepare a variety of the 2-(t-butyl)dimethylsilyl-3,3-difluoropropenone derivatives 3. Therefore, treatment of 2b with benzoyl chlorides substituted with the fluoro, chloro, methoxy or trifluoromethyl group at metaor para-position of the benzene ring in the presence of 5 mol% Pd(PPh3)4 and 10 mol% CuI in THF at reflux temperature for 2 h resulted in the formation of 3b–3h in 45–86% yields. Similarly, the coupling reaction of 2b with 2-naphthoyl chloride, 2-benzofuranyl chloride, trans-3-phenylacryloyl chloride or phenylacetyl chloride

Pd2(dba)3 (3 mol%) / XPhos (6 mol%)

F

SiMe2R

LiBr (30 equiv), THF, reflux, 8 h

F

SnBu3

2a (R = Me, 73%) 2b (R = t-Bu, 70%)

catalyst such as Pd(PPh3)4, Pd2(dba)3, Pd(CH3CN)2Cl2, or CuI in several solvents at elevated temperature. However, the acylating product, 3,3-difluoro-2-trimethylsilyl-1-phenylpropenone 3a, was obtained in very low yield from the reaction of 2a with benzoyl chloride under the various conditions (Entry 1–5). The use of 2b instead of 2a in this reaction resulted in the formation of 3b in the much higher yield, in which product 3b presumably is the more stable than 3a during the column chromatography. Actually, we found that product 3a was decomposed to unidentified compounds after flowing the silica-gel column chromatography. Therefore, 2b was used to optimize the acylation reaction with acyl chloride. The coupling reaction of 2b with benzoyl chloride in the presence of Pd(PPh3)4 (10 mol%) in THF at reflux temperature for 2 h provided

under the same reaction condition afforded the corresponding 2-(tbutyl)dimethylsilyl-3,3-difluoropropenone derivatives 3i–3l in 49– 74% yields. However, the reaction of 2b with p-nitrobenzoyl chloride under the same reaction condition did not provide the desired product and all starting material was recovered. The reaction of 2b with ortho substituted 2-methylbenzoyl chloride under the same reaction condition resulted in the formation of a trace amount of product (<5%) which result indicates that the steric effect between (t-butyl)dimethylsilyl group and ortho methyl one interferes the formation of the desired product 3. The acylation of 2b with heptanoyl chloride under the same reaction condition provided a messy reaction mixture which does not include the desired product 3. The results of these reactions are summarized in Table 2.

Table 1 Optimization for the cross-coupling reaction of 2 with benzoyl chloride.

F

SiMe2R

F 2

O + PhCCl

SnBu3

Pd catalyst (X mol%) / CuI (Y mol%) THF, reflux, 2 h

F

SiMe2R

F

O

.

Ph 3

Entry

R

Pd catalyst

X (mol%)

Y (mol%)

Yield (%)a

1 2 3 4 5 6 7

Me Me Me Me Me t-Bu t-Bu

Pd(PPh3)4 Pd(PPh3)4 Pd(PPh3)4 Pd2(dba)3 Pd(CH3CN)2CI2 Pd(PPh3)4 Pd(PPh3)4

10 10 5 5 5 10 10

0 10 10 10 10 0 10

4 18 23 10 0 22 60

8 9 10 11 12 13

t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu

Pd(PPh3)4 Pd(PPh3)4 Pd2(dba)3 Pd(CH3CN)2CI2 Pd(PPh3)2CI2 Pd(OAc)2

5 0 5 5 5 5

10 10 10 10 10 10

75 0 50 0 0 0

a

Isolated yield.

Please cite this article in press as: Y.R. Jeong, et al., J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/j.jfluchem.2015.07.010

G Model

FLUOR-8611; No. of Pages 5 Y.R. Jeong et al. / Journal of Fluorine Chemistry xxx (2015) xxx–xxx

3

Table 2 Preparation of 2-(t-butyl)dimethylsilyl-3,3-difluoropropenone derivatives 3.

F

Si(t-Bu)Me2 SnBu3 2b

F

O + RCCl

Pd(PPh3)4 (5 mol%) / CuI (10 mol%) THF, reflux, 2 h

F F

Si(t-Bu)Me2 O

.

R 3

Compound no.

R

Yield (%)a

3b 3c 3d 3e 3f 3g 3h 3i

C6H5 p-FC6H4 p-CIC6H4 p-CF3C6H4 p-CH3OC6H4 m-CIC6H4 m-CF3C6H4

75 86 67 70 45 58 60 68

3j

65

3k 31 a

PhCH2 trans-C6H5CH5 5CH

49 74

Isolated yield.

3. Conclusion In summary, we have developed a general method for the preparation of unknown 2-(t-butyl)dimethylsilyl-3,3-difluoropropenone derivatives 3 via the cross-coupling acylation reaction between 1-(t-butyl)dimethylsilyl-2,2-difluoroethenylstannane 2b with a variety of acyl chlorides, in which 2b was prepared from the stannylation reaction of 1b with hexabutylbistin in the presence of 3 mol% Pd2(dba)3, 6 mol% XPhos and 30 equiv LiBr in THF at reflux temperature for 8 h. This method provided an efficient and straightforward preparation of 2-(t-butyl)dimethyl-3,3-difluoropropenone derivatives which are potentially reactive species toward the nucleophiles to give monofluorinated enones and ynones. The further synthetic utilities of 3 will be described in the future paper. 4. Experimental 1 H and 13C NMR spectra were recorded on a 400 MHz Bruker AVANCEII++ NMR spectrometer with tetramethylsilane (TMS) as an internal standard and 19F NMR spectra were also recorded on a 400 MHz Bruker AVANCEII++ NMR spectrometer with C6H5CF3 ( 63.72 ppm from CFCl3) as an internal standard and the upfield as negative. All chemical shifts (d) are expressed in parts per million and coupling constant (J) are given in Hertz. Mass spectra were obtained by using Agilent Technologies 6890N GC/5973 Network MSD (EI, 70 eV). Elemental analysis data were obtained by using EA1110 elemental analyzer. Melting points were determined in open capillary tubes and are uncorrected. Commercially available reagents were purchased from Aldrich, Lancaster, Tokyo Kasei and Fluorochem. All solvents were dried by general purification method. Flash chromatography was performed on 40–60 mm silica gel (230–400 mesh).

was charged with 2,2,2-trifluoroethyl p-toluenesulfonate (3.00 g, 11.8 mmol) and 120 mL of THF. After the reaction mixture was cooled down to 78 8C, LDA (2.0 M solution, 13.0 mL, 26.0 mmol) was added dropwise and then stirred at 78 8C for 30 min. Trialkylsilane (11.9 mmol) was added dropwise at 78 8C, followed by slowly warming to room temperature. The mixture was quenched with 50 mL of NH4Cl water solution, extracted with 100 mL of ether twice, dried over anhydrous MgSO4 and chromatographed on SiO2 column. Elution with n-hexane and ethyl acetate (10:1) provided 2,2-difluoro-1-trialkylsilylethenyl p-toluenesulfonates 1. 4.1.1. 2,2-Difluoro-1-(trimethylsilyl)ethenyl p-toluenesulfonates (1a) 1a was prepared in 95% yield (3.43 g) according to the general procedure. 1a: colorless oil; 1H NMR (CDCl3) d 7.82 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 2.47 (s, 3H) 0.29 (s, 9H); 19F NMR (CDCl3, internal standard C6H5CF3) d 75.69 (d, J = 33.9 Hz, 1F), 98.33 (d, J = 33.9 Hz, 1F); 13C NMR (CDCl3) d 161.7 (dd, J = 316, 283 Hz), 145.6, 132.8, 129.9, 128.6, 113.2 (dd, J = 61, 7 Hz), 21.8, 1.9; MS, m/z (relative intensity) 291 (M+-15, 30), 180 (7), 149 (56), 139 (17), 122 (14), 91 (100), 73 (88), 63 (42). Anal. Calcd for C12H16F2O3SSi: C, 47.04; H, 5.26. Found: C, 46.81; H, 5.19. 4.1.2. 1-(t-Butyl)dimethylsilyl-2,2-(difluoro)ethenyl ptoluenesulfonates (1b) 1b was prepared in 83% yield (3.41 g) according to the general procedure. 1b: light yellow oil; 1H NMR (CDCl3) d 7.79 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H), 0.91 (s, 9H), 0.19 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 73.07 (d, J = 33.8 Hz, 1F), 97.02 (d, J = 33.8 Hz, 1F); 13C NMR (CDCl3) d 162.7 (dd, J = 315, 284 Hz), 145.3, 133.9, 129.9, 128.3, 112.7 (dd, J = 63, 6 Hz), 26.7, 21.9, 17.8, 6.2; MS, m/z (relative intensity) 333 (M+-15, 1), 219 (100), 149 (97), 139 (7), 91 (32), 73 (43), 57 (6). Anal. Calcd for C15H22F2O3SSi: C, 51.70; H, 6.36. Found: C, 51.34; H, 6.32.

4.1. General procedure for the preparation of 2,2-difluoro-1(trialkylsilyl)ethenyl p-toluenesulfonates 1

4.2. General procedure for the preparation of 2,2-difluoro-1(trialkylsilyl)ethenyltributylstannane 2

A 250 mL two-neck round bottom flask equipped with a magnetic stirrer bar, a septum and nitrogen tee connected to an argon source

A 50 mL two-neck round bottom flask equipped with a magnetic stirrer bar, a septum and nitrogen tee connected to an

Please cite this article in press as: Y.R. Jeong, et al., J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/j.jfluchem.2015.07.010

G Model

FLUOR-8611; No. of Pages 5 4

Y.R. Jeong et al. / Journal of Fluorine Chemistry xxx (2015) xxx–xxx

argon source was charged with Pd2(dba)3 (3 mol%), X-Phos (6 mol%), LiBr (2.61 g, 30.0 mmol) and 10 mL of air bubbled THF containing 30 mg of water. The solution of 1 (1.0 mmol) and bis(tributylstannane) (1.0 mmol) dissolved in 3 mL of THF was added into the reaction mixture. After the reaction mixture was refluxed for 8 h and then cooled to room temperature, the mixture was quenched with water. The reaction mixture was extracted with 50 mL of ether twice, dried over anhydrous MgSO4 and chromatographed on SiO2 column. Elution with n-hexane provided 2,2-difluoro-1-(trialkylsilyl)ethenyl tributylstannane 2. 4.2.1. 2,2-Difluoro-1-(trimethylsilyl)ethenyltributylstannane (2a) 2a was prepared in 73% yield (0.31 g) according to the general procedure. 2a: colorless oil; 1H NMR (CDCl3) d 1.50–1.45 (m, 6H), 1.34–1.28 (m, 6H), 0.97 (t, J = 8.0 Hz, 6H), 0.88 (t, J = 7.2 Hz, 9H), 0.11 (s, 9H); 19F NMR (CDCl3, internal standard C6H5CF3) d 48.27 (d, J = 41.4 Hz, 1F), 51.64 (d, J = 41.4 Hz, 1F); 13C NMR (CDCl3) d 152.6 (dd, J = 305, 290 Hz), 69.3 (dd, J = 15, 5 Hz), 29.2, 27.5, 13.8, 11.4, 0.9; MS, m/z (relative intensity) 368 (M+-57, 7), 253 (100), 211 (17), 177 (19), 163 (9), 139 (6), 121 (5). Anal. Calcd for C17H36F2SiSn: C, 48.01; H, 8.53. Found: C, 47.77; H, 5.46. 4.2.2. 1-(t-Butyl)dimethylsilyl-2,2-(difluoro)ethenyltributylstannane (2b) 2b was prepared in 70% yield (0.33 g) according to the general procedure. 2b: colorless oil; 1H NMR (CDCl3) d 1.50–1.42 (m, 6H), 1.35–1.27 (m, 6H), 0.98–0.92 (m, 4H), 0.88–0.84 (m, 20H), 0.06 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 46.59 (d, J = 41.4 Hz, 1F), 48.19 (d, J = 41.4 Hz, 1F); 13C NMR (CDCl3) d 152.6 (dd, J = 307, 290 Hz), 67.1 (dd, J = 15, 6 Hz), 29.1, 27.5, 26.9, 18.2, 13.8, 11.8, 3.0; MS, m/z (relative intensity) 410 (M+-57, 4), 253 (100), 211 (17), 177 (24), 163 (7), 139 (7), 121 (7), 101 (7), 73 (6), 57 (8). Anal. Calcd for C20H42F2SiSn: C, 51.40; H, 9.06. Found: C, 51.18; H, 9.01. 4.3. General procedure for the preparation of 3,3-difluoro-2trialkylsilyl-1-(aryl or alkyl))prop-2-en-1-one 3 A 15 mL two-neck round bottom flask equipped with a magnetic stirrer bar, a septum and nitrogen tee connected to an argon source was charged with Pd(PPh3)4 (5 mol%), CuI (10 mol%) and 1 mL of THF. Then, 2 (1.0 mmol), acyl chloride (2.0 mmol) and 6 mL of THF was added into the reaction mixture. After the reaction mixture was refluxed for 2 h and then cooled to room temperature, the mixture was quenched with water. The reaction mixture was extracted with 20 mL of ether twice, dried over anhydrous MgSO4 and chromatographed on SiO2 column. Elution with n-hexane and dichloromethane (7:3) provided 3,3-difluoro-2-trialkylsilyl-1(phenyl)prop-2-en-1-one 3. 4.3.1. 3,3-Difluoro-2-trimethylsilyl-1-(phenyl)prop-2-en-1-one (3a) 3a was prepared in 23% yield (0.055 g) according to the general procedure. 3a: yellow liquid; 1H NMR (CDCl3) d 7.88 (d, J = 7.6 Hz, 2H), 7.58–7.47 (m, 1H), 7.43 (t, J = 7.6 Hz, 2H), 0.21 (s, 9H); 19F NMR (CDCl3, internal standard C6H5CF3) d 60.55 (d, J = 18.8 Hz, 1F), 74.36 (d, J = 18.8 Hz, 1F); 13C NMR (CDCl3) d 191.5 (d, J = 11 Hz), 156.2 (dd, J = 308, 291 Hz), 137.6, 133.8, 129.3, 128.9, 90.0 (dd, J = 27, 5 Hz), 1.0; MS, m/z (relative intensity) 240 (M+, 25), 225 (100), 151(14), 135 (17), 120 (7), 105 (90), 77 (36). Anal. Calcd for C12H14F2OSi: C, 59.97; H, 5.87. Found: C, 59.75; H, 5.84. 4.3.2. 2-(t-Butyl)dimethylsilyl-3,3-difluoro-1-(phenyl)prop-2-en-1one (3b) 3b was prepared in 75% yield (0.212 g) according to the general procedure. 3b: yellow oil; 1H NMR (CDCl3) d 7.88 (d, J = 7.6 Hz, 2H), 7.56–7.53 (m, 1H), 7.44 (t, J = 7.6 Hz, 2H), 0.96 (s, 9H), 0.12 (s, 6H);

19

F NMR (CDCl3, internal standard C6H5CF3) d 59.39 (d, J = 18.8 Hz, 1F), 71.42 (d, J = 18.8 Hz, 1F); 13C NMR (CDCl3) d 192.9 (d, J = 14 Hz), 156.8 (dd, J = 307, 292 Hz), 137.5, 133.7, 129.3, 128.9, 88.3 (dd, J = 28, 4 Hz), 26.7, 18.4, 5.3; MS, m/z (relative intensity) 267 (M+-15, 2), 225 (100), 151 (11), 135 (10), 105 (65), 77 (26), 51 (3). Anal. Calcd for C15H20F2OSi: C, 63.80; H, 7.14. Found: C, 63.52; H, 7.09. 4.3.3. 2-(t-Butyl)dimethylsilyl-3,3-difluoro-1-(4-fluorophenyl)prop2-en-1-one (3c) 3c was prepared in 86% yield (0.258 g) according to the general procedure. 3c: yellow oil; 1H NMR (CDCl3) d 7.95–7.91 (m, 2H), 7.17–7.13 (m, 2H), 0.98 (s, 9H), 0.15 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 59.22 (d, J = 18.8 Hz, 1F), 71.16 (d, J = 18.8 Hz, 1F), 105.41 (t, J = 7.5 Hz, 1F); 13C NMR (CDCl3) d 191.1 (d, J = 12 Hz), 167.3, 164.8, 156.6 (dd, J = 307, 294 Hz), 133.7, 131.8 (d, J = 10 Hz), 115.9 (d, J = 22 Hz), 88.3 (dd, J = 27, 4 Hz), 26.5, 18.2, 5.5; MS, m/z (relative intensity) 285 (M+-15, 3), 243 (100), 169 (14), 153 (13), 123 (69), 95 (14), 77 (13), 57 (3). Anal. Calcd for C15H19F3OSi: C, 59.98; H, 6.38. Found: C, 59.48; H, 6.34. 4.3.4. 2-(t-Butyl)dimethylsilyl-3,3-difluoro-1-(4-chlorophenyl)prop2-en-1-one (3d) 3d was prepared in 67% yield (0.212 g) according to the general procedure. 3d: yellow oil; 1H NMR (CDCl3) d 7.84 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 0.96 (s, 9H), 0.13 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 58.82 (d, J = 18.8 Hz, 1F), 70.86 (d, J = 18.8 Hz, 1F); 13C NMR (CDCl3) d 191.8 (d, J = 12 Hz), 156.9 (dd, J = 309, 294 Hz), 140.3, 135.9, 130.7, 129.3, 88.1 (dd, J = 28, 5 Hz), 26.7, 18.4, 5.2; MS, m/z (relative intensity) 303 (M+-15, 1), 301 (M+-15, 3), 261 (34), 259 (100), 187 (4), 185 (11), 171 (4), 169 (12), 141 (20), 139 (59), 113 (4), 111 (13), 77 (15), 57 (3). Anal. Calcd for C15H19ClF2OSi: C, 56.86; H, 6.04. Found: C, 56.61; H, 6.01. 4.3.5. 2-(t-Butyl)dimethylsilyl-3,3-difluoro-1-[4(trifluoromethyl)phenyl]prop-2-en-1-one (3e) 3e was prepared in 70% yield (0.245 g) according to the general procedure. 3e: yellow oil; 1H NMR (CDCl3) d 7.98 (d, J = 8.0 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H), 0.97 (s, 9H), 0.15 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 57.47 (d, J = 15.0 Hz, 1F), 64.17 (s, 3F), 69.89 (d, J = 15.0 Hz, 1F); 13C NMR (CDCl3) d 192.1 (d, J = 13 Hz), 157.4 (dd, J = 309, 295 Hz), 140.3, 136.1, 134.9 (q, J = 33 Hz), 129.6, 126.1, 122.4, 88.3 (dd, J = 28, 5 Hz), 29.5, 18.4, 5.2; MS, m/z (relative intensity) 331 (M+-19, 1), 293 (100), 219 (7), 197 (7), 173 (85), 145 (23), 77 (20), 57 (4). Anal. Calcd for C16H19F5OSi: C, 54.84; H, 5.47. Found: C, 54.51; H, 5.39. 4.3.6. 2-(t-Butyl)dimethylsilyl-3,3-difluoro-1(4methoxyphenyl)prop-2-en-1-one (3f) 3f was prepared in 45% yield (0.140 g) according to the general procedure. 3f: yellow oil; 1H NMR (CDCl3) d 7.86 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H), 3.85 (s, 3H), 0.97 (s, 9H), 0.11 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 60.72 (d, J = 18.8 Hz, 1F), 72.34 (d, J = 18.8 Hz, 1F); 13C NMR (CDCl3) d 191.4 (d, J = 12 Hz), 164.2, 156.4 (dd, J = 308, 293 Hz), 131.8, 130.6, 114.2, 88.6 (dd, J = 27, 5 Hz), 55.7, 26.8, 18.4, 5.2; MS, m/z (relative intensity) 297 (M+-15, 1), 255 (100), 181 (9), 165 (30), 135 (47), 107 (4). Anal. Calcd for C16H22F2O2Si: C, 61.51; H, 7.10. Found: C, 61.32; H, 7.05. 4.3.7. 2-(t-Butyl)dimethylsilyl-3,3-difluoro-1-(3-chlorophenyl)prop2-en-1-one (3g) 3g was prepared in 58% yield (0.184 g) according to the general procedure. 3g: yellow oil; 1H NMR (CDCl3) d 7.87 (s, 1H), 7.76 (m, 1H), 7.55 (m, 1H), 7.43 (m, 1H), 0.98 (s, 9H), 0.15 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 58.24 (d, J = 18.8 Hz, 1F),

Please cite this article in press as: Y.R. Jeong, et al., J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/j.jfluchem.2015.07.010

G Model

FLUOR-8611; No. of Pages 5 Y.R. Jeong et al. / Journal of Fluorine Chemistry xxx (2015) xxx–xxx

70.33 (d, J = 18.8 Hz, 1F); 13C NMR (CDCl3) d 191.7 (d, J = 10 Hz), 157.1 (dd, J = 309, 295 Hz), 139.1, 135.3, 133.7, 130.3, 129.2, 127.5, 88.2 (dd, J = 28, 5 Hz), 26.7, 18.4, 5.2; MS, m/z (relative intensity) 318 (M+, 1), 316 (M+, 3), 261 (34), 259 (100), 187 (4), 185 (12), 171 (3), 169 (10), 141 (27), 139 (80), 113 (6), 111 (18), 77 (25), 57 (5). Anal. Calcd for C15H19ClF2OSi: C, 56.86; H, 6.04. Found: C, 56.51; H, 5.99. 4.3.8. 2-(t-Butyl)dimethylsilyl-3,3-difluoro-1-[3(trifluoromethyl)phenyl]prop-2-en-1-one (3h) 3h was prepared in 60% yield (0.210 g) according to the general procedure. 3h: yellow oil; 1H NMR (CDCl3) d 8.16 (s, 1H), 8.07 (m, 1H), 7.86 (m, 1H), 7.63 (m, 1H), 0.99 (s, 9H), 0.16 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 57.77 (d, J = 15.0 Hz, 1F), 63.88 (s, 3F), 69.87 (d, J = 15.0 Hz, 1F); 13C NMR (CDCl3) d 191.7 (d, J = 13 Hz), 157.3 (dd, J = 309, 295 Hz), 138.1, 135.3, 134.9 (q, J = 33 Hz), 133.7, 130.3, 129.2, 127.5, 88.3 (dd, J = 28, 5 Hz), 26.7, 18.4, 5.2; MS, m/z (relative intensity) 331 (M+-19, 7), 293 (100), 219 (10), 197 (13), 173 (81), 145 (22), 77 (18), 57 (2). Anal. Calcd for C16H19F5OSi: C, 54.84; H, 5.47. Found: C, 54.58; H, 5.41. 4.3.9. 2-(t-Butyl)dimethylsilyl-3,3-difluoro-1-(naphthalene-2yl)prop-2-en-1-one (3i) 3i was prepared in 68% yield (0.226 g) according to the general procedure. 3i: yellow oil; 1H NMR (CDCl3) d 8.40 (s, 1H), 8.01–7.97 (m, 2H), 7.93–7.88 (m, 2H), 7.64–7.55 (m, 2H), 1.01 (s, 9H), 0.18 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 59.59 (d, J = 18.8 Hz, 1F), 71.39 (d, J = 18.8 Hz, 1F); 13C NMR (CDCl3) d 192.8 (d, J = 12 Hz), 168.6, 156.8 (dd, J = 309, 294 Hz), 136.1, 134.9, 132.8, 131.7, 130.1, 128.9, 128.1, 127.6, 127.1, 125.6, 124.5, 88.5 (dd, J = 27, 5 Hz), 26.8, 18.4, 5.2; MS, m/z (relative intensity) 317 (M+-19, 3), 275 (100), 201 (12), 185 (26), 155 (56), 127 (35), 77 (15). Anal. Calcd for C19H22F2OSi: C, 68.64; H, 6.67. Found: C, 68.52; H, 6.63. 4.3.10. 1-(Benzofuran-2-yl)-2-(t-butyl)dimethylsilyl-3,3difluoroprop-2-en-1-one (3j) 3j was prepared in 65% yield (0.209 g) according to the general procedure. 3j: yellow oil; 1H NMR (CDCl3) d 7.72 (d, J = 8.0 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.51–7.48 (m, 2H), 7.32 (t, J = 7. 6 Hz, 1H), 0.99 (s, 9H), 0.20 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 59.08 (d, J = 15.0 Hz, 1F), 69.48 (d, J = 15.0 Hz, 1F); 13 C NMR (CDCl3) d 193.8 (d, J = 12 Hz), 156.8 (dd, J = 308, 294 Hz), 156.3, 152.6, 128.8, 127.3, 124.2, 123.7, 115.2, 112.8, 88.2 (dd, J = 26, 5 Hz), 26.7, 18.3, 5.3; MS, m/z (relative intensity) 307 (M+15, 3), 265 (100), 191 (7), 175 (22), 145 (54), 89 (8), 77 (9). Anal. Calcd for C17H20F2O2Si: C, 63.33; H, 6.25. Found: C, 63.01; H, 6.28. 4.3.11. 3-(t-Butyl)dimethylsilyl-4,4-difluoro-1-phenylbut-3-en-2one (3k) 3k was prepared in 49% yield (0.145 g) according to the general procedure. 3k: colorless oil; 1H NMR (CDCl3) d 7.49–7.45 (m, 2H), 7.42–7.39 (m, 1H), 7.32 (d, J = 7.6 Hz, 2H), 4.01 (s, 2H), 1.05 (s, 9H), 0.15 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 57.57 (d, J = 16.9 Hz, 1F), 67.78 (d, J = 16.9 Hz, 1F); 13C NMR (CDCl3) d

5

199.1 (d, J = 13 Hz), 159.3 (dd, J = 311, 294 Hz), 133.9, 129.9, 128.8, 127.3, 91.0 (dd, J = 26, 7 Hz), 51.3, 26.8, 18.1, -5.2; MS, m/z (relative intensity) 296 (M+, 1), 281 (8), 239 (100), 205 (43), 115 (38), 105 (16), 91 (48), 77 (22), 73 (45). Anal. Calcd for C16H22F2OSi: C, 64.83; H, 7.48. Found: C, 64.51; H, 7.41. 4.3.12. (E)-2-(t-Butyl)dimethylsilyl-1,1-difluoro-5-phenylpenta-1,4dien-3-one (3l) 3l was prepared in 74% yield (0.228 g) according to the general procedure. 3l: yellow oil; 1H NMR (CDCl3) d 7.55–7.49 (m, 3H), 7.39–7.38 (m, 3H), 6.82 (d, J = 16.0 Hz, 1H), 0.97 (s, 9H), 0.17 (s, 6H); 19F NMR (CDCl3, internal standard C6H5CF3) d 59.76 (d, J = 18.8 Hz, 1F), 70.15 (d, J = 18.8 Hz, 1F); 13C NMR (CDCl3) d 191.8 (d, J = 13 Hz), 158.1 (dd, J = 309, 292 Hz), 145.0, 134.5, 130.9, 129.2, 128.7, 127.2, 89.7 (dd, J = 26, 7 Hz), 26.8, 18.2, 5.1; MS, m/z (relative intensity) 308 (M+, 1), 293 (5), 251 (100), 177 (5), 115 (38), 161 (13), 145 (6), 131 (25), 103 (13), 77 (19). Anal. Calcd for C17H22F2OSi: C, 66.20; H, 7.19. Found: C, 66.01; H, 7.17. Acknowledgment This work was supported by a Basic Research Grant (20110022295) funded by the National Research Foundation of Korea. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27]

F. Camps, J. Coll, G. Fabrias, A. Guerrero, Tetrahedron 40 (1984) 2871–2878. W.G. Dauber, B. Kohler, A. Roesle, J. Org. Chem. 50 (1985) 2007–2010. P.A. Grieco, T. Takigawa, T.R. Vedananda, J. Org. Chem. 50 (1985) 3111–3115. T. Ernet, G. Haufe, Tetrahedron Lett. 37 (1996) 7251–7254. P.J. Crowley, J.M. Percy, K. Stansfield, Chem. Commun. (1997) 2033–2034. M. Sridhar, K.L. Krishna, J.M. Rao, Tetrahedron 56 (2000) 3539–3545. M. Essers, C. Muck-Lichtenfeld, G. Haufe, J. Org. Chem. 67 (2002) 4715–4721. F. Chanteau, F. Essers, R. Plantier-Royon, G. Haufe, C. Portella, Tetrahedron Lett. 43 (2002) 1677–1680. M. Essers, T. Ernet, G. Haufe, J. Fluorine Chem. 121 (2003) 163–170. K. Shibatomi, K. Futasugi, F. Kobayashi, S. Iwasa, H. Yamamoto, J. Am. Chem. Soc. 132 (2010) 5625–5627. J. Ichikawa, M. Kobayashi, N. Yokota, Y. Noda, T. Minami, Tetrahedron 50 (1994) 11637–11646. O. Paleta, A. Pelter, J. Kebrle, Tetrahedron Lett. 35 (1994) 9259–9262. A.S. Kende, J. Chen, J. Am. Chem. Soc. 107 (1985) 7184–7186. A. Murai, N. Tanimoto, N. Sakamoto, T. Masamine, J. Am. Chem. Soc. 110 (1988) 1985–1986. C. Shih, E.L. Fritzen, J.S. Swenton, J. Org. Chem. 45 (1980) 4462–4471. N.T. Nicholas, D.A. Rooke, Z.A. Menard, E.M. Ferreira, Angew. Chem. Int. Ed. 52 (2014) 7579–7582. Y. Usuki, M. Iwaoka, J. Chem. Soc. Chem. Commun. (1992) 1148–1150. C. Chen, K. Wilcoxen, K.I. Kim, J.R. McCarthy, Tetrahedron Lett. 38 (1997) 7677–7680. Y. Shen, G. Wang, J. Fluorine Chem. 125 (2004) 91–94. J.M. Bainbridge, S. Corr, M. Kanai, J.M. Percy, Tetrahedron Lett. 41 (2000) 971–974. M. Kanai, J.M. Percy, Tetrahedron Lett. 41 (2000) 2453–2455. A.K. Ghosh, S. Banerjee, S. Sinha, S.S. Bang, B. Zajc, J. Org. Chem. 74 (2009) 3689–3697. Y. Wang, D.J. Burton, Org. Lett. 8 (2006) 1109–1111. Y.B. He, B.V. Nguyen, D.J. Burton, J. Fluorine Chem. 132 (2011) 940–944. J. Ichikawa, S. Hamada, T. Sonoda, H. Kobayashi, Tetrahedron Lett. 33 (1992) 337–340. P.J. Crowley, J.A. Howarth, W.M. Owton, J.M. Percy, K. Stansfield, Tetrahedron Lett. 37 (1996) 5975–5978. J.H. Jeon, J.H. Kim, Y.J. Jeong, I.H. Jeong, Tetrahedron Lett. 55 (2014) 1292–1295.

Please cite this article in press as: Y.R. Jeong, et al., J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/j.jfluchem.2015.07.010