Note Cite This: J. Org. Chem. 2019, 84, 423−434
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Copper-Catalyzed Perfluoroalkylation of Allyl Phosphates with Stable Perfluoroalkylzinc Reagents Lihua Liu,∥,⊥ Xifei Bao,†,⊥ Hua Xiao,∥ Junlan Li,† Feifan Ye,† Chaoqin Wang,† Qinhua Cai,† and Shilu Fan*,†,‡,§
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†
School of Chemistry and Chemical Engineering, Hefei University of Technology, 193 Tunxi Road, Anhui 230000, People’s Republic of China ‡ Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, People’s Republic of China § Anhui Province Key Laboratory of Advanced Catalytic Materials and Reaction Engineering, 193 Tunxi Road, Anhui 230000, People’s Republic of China ∥ School of Biological and Medical Engineering, Hefei University of Technology, 193 Tunxi Road, Anhui 230000, People’s Republic of China S Supporting Information *
ABSTRACT: A general and practical method for copper-catalyzed cross-coupling of allyl phosphates with stable perfluoroalkylzinc reagents has been developed. The reaction proceeds under mild reaction conditions with high efficiency, good functional group tolerance, and high regio- and stereoselectivities and provides general, straightforward, and useful access to allyl-perfluoroalkyl compounds. Preliminary mechanistic studies reveal that the allyl copper intermediate may be involved in the catalytic cycle.
T
considerable effort has been dedicated to the efficient introduction of perfluoroalkyl groups.8 The generation of allyl−RF bonds, however, remains synthetically challenging, particularly via transition metal catalysis. Matsubara described Pd-catalyzed coupling of allyl- and alkenylstannanes with perfluoroalkyl iodides,9 whereas Cu-mediated nucleophilic trifluoromethylation of allyl halides was also reported.10 In 2011, a copper-catalyzed Heck-type trifluoromethylation of terminal alkenes through allylic C−H bond activation was described by the group of Liu and Fu.11 Furthermore, Wang,12 Buchwald,13 Qing,14 and Sodeoka15 independently described the copper-catalyzed trifluoromethylation of alkenes using electrophilic or nucleophilic trifluoromethylating reagents and involving the addition of the CF3 radical to alkenes. Very recently, Sodeoka and co-workers realized a perfluoroalkylation of unactivated alkenes with acid anhydrides as the perfluoroalkyl source.16 Most of the reactions mentioned above focus on radical trifluoromethylation; perfluoroalkylation (C2F5, C3F7, C4F9, C6F13, etc.) via an allyl−M−RF intermediate reductive elimination remains a challenge.17 Moreover, it is hard to find an efficient perfluoroalkylating reagent. Only CF3SiR3, C2F5SiR3, C3F7SiR3, Togni, and Umemoto reagents are commercially available, yet they are very expensive. As
ransition metal-catalyzed allylation is one of the most frequently employed transformations in organic synthesis because of the presence of allyl moieties in many biologically active compounds.1 Moreover, the synthetical usefulness of allylic motifs is ascribed to the fact that the carbon−carbon double bond can transfer to a variety of structures after simple manipulations.2 The scenery is clearly dominated by Pd catalysts, but during the past decade, a range of other metals, especially late transition metals (Ru, Rh, Ir, etc.),3 made their way into the limelight. Inspired by the earlier studies of coppercatalyzed perfluoroalkylation of aryl boronic acids4 and aromatic halides,5 we hypothesized that the copper-catalyzed cross-coupling of allylic electrophilies with stable perfluoroalkylating reagents may be possible and would improve the preparation of allylated perfluoroalkyl compounds. Although Tsuji−Trost reaction involving addition of a nucleophile to a (π-allyl)palladium intermediate offers a powerful tool for the preparation of allyl-substituted compounds, the reaction of highly electron-deficient perfluoroalkyl groups through this strategy has rarely been studied.6 Consequently, developing new transition metal-catalyzed allylative cross-coupling reactions for widespread applications is still highly desirable. Organic compounds bearing a perfluoroalkyl group (RF) have been adopted in a wide range of applications such as agrochemicals, pharmaceuticals, and materials because of the unique properties of the fluorine atom.7 Over the past decade, © 2018 American Chemical Society
Received: October 15, 2018 Published: December 7, 2018 423
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
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The Journal of Organic Chemistry cheap and safe perfluoroalkyl sources, perfluoroalkyl halides18 and perfluoroalkanesulfonyl halides19 are prone to generation of perfluoroalkyl radicals. In 2011, Daugulis and co-workers synthesized (RF)2Zn from 1H-perfluoroalkane by deprotonative metalation with TMP2Zn and used it in copper-catalyzed perfluoroalkylation of aromatic iodides.20 These reagents are currently confined to the generation of C(sp2)−RF bonds,4,5 which creates the interesting challenge of establishing new transition metal-catalyzed perfluoroalkylation reactions to form C(sp3)−RF bonds (Scheme 1). Herein, we report a practical
examined a series of copper catalysts, such as CuSCN, Cu(OAc)2, and Cu(acac)2, employed in these reactions (Table 1, entries 2−4, respectively), and a higher yield was observed only with Cu(acac)2 (Table 1, entry 4, 80% yield). The nature of the solvent and ligand was critical to the reaction efficiency, and the use of ether solvent and L2 (4,7-diphenyl1,10-phenanthroline) was found to provide the most efficient reaction, providing 3ac in an 85% isolated yield (Table 1, entry 9). The control experiments revealed that a copper intermediate is involved in the reaction catalytic cycle (Table 1, entry 10). To our surprise, a 52% isolated yield was obtained without a ligand (Table 1, entry 11). DMPU dissociated from 2c, as a ligand, chelates with a copper center to stabilize the catalytic intermediate.5b An attempt to decrease the load of Cu(acac)2 to 5 mol % resulted in the yield dropping to 71% (Table 1, entry 12). Meanwhile, the choice of leaving group on the allyl substrate was crucial; the reaction of the corresponding acetate, halides, or carbonate instead of the phosphate resulted in low yields or no formation of the desired product. Under the optimum reaction conditions, a variety of allylated perfluoroalkyl compounds were generated by this method and good to high yields and regioselectivities were obtained (Scheme 2). Generally, alkyl-substituted allyl phosphates bearing functional groups apart from the carbon−carbon double bond coupled with 2c effectively (3a−f). It is noteworthy that many versatile functional groups, including base- and nucleophile-sensitive moieties, such as silyl ether, acetate, phosphate, halide, and hydroxyl, showed good tolerance toward the reaction conditions, providing opportunities for further functionalization without the need for protection/deprotection sequences. Importantly, product 3d also revealed an excellent chemical selectivity at allyl phosphate over alkyl phosphate. However, it should be mentioned that the reaction efficiency strongly depends on the nature of the steric hindrance on substrates. Substrates with bulky substituted groups near the reaction center (carbon−carbon double bond) gave the desired products with moderate yields (35−64%) and excellent regio- and stereoselectivities (3g−k). Furthermore, aromatic allyl phosphates were also suitable substrates, and reasonable yields with high stereoselectivities were still generated (3l−o). Notably, no branched product was observed with cinnamyl phosphates under this catalytic system. To prove the generality of these observations and evaluate the scope and limitations of this protocol, a wide range of other perfluoroalkylzinc reagents 2 were employed under optimized reaction conditions (Scheme 3). In a manner similar to that of perfluorobuthylation, allyl phosphates with versatile substituents gave moderate to good yields (49−77%) and high regioand steroselectivities (4a−6d). It should be noted that yields and selectivities are interrelated with the length of RF. The reaction with C2, C3 homologous perfluoroalkylzinc reagents afforded the desired products with yields and selectivities higher than those of C6 perfluoroalkylzinc reagents. In the catalytic process, the rate of transmetalation of the perfluoroalkyl group to the copper center from Zn(RF)2(DMPU)2 decreases due to the growing length of RF, which readily causes Schlenk equilibration of Zn(RF)2(DMPU)2 and ZnX2.21 For allyl phosphates with steric hindrance such as 1g, 1l, and 1m, the desired products were obtained with moderate yields and excellent regio- and stereoselectivities (4g−5n), thus suggesting that the steric effect still plays an important role in the yield and selectivity.
Scheme 1. Representative Approaches to the Preparation of Allyl−RF Compounds
example of copper-catalyzed perfluoroalkylation of allyl phosphates with a broad range of substrates in moderate to high yields and with moderate to high stereo- and regioselectivities. Initially, allyl phosphate (E)-1a and bis(perfluoroalkyl)zinc reagent 2c were chosen as model substrates to investigate this reaction (Table 1). To our delight, the treatment of (E)-1a and 2c in the presence of a catalytic amount of CuI/phen in 1,4dioxane at 100 °C afforded 3ac in a 77% isolated yield with high regio- and stereoselectivity [>99:1 linear:branched, 18:1 E:Z (Table 1, entry 1)]. Encouraged by this result, we Table 1. Representative Results for Optimization of Copper-Catalyzed Perfluoroalkylation of Phosphate (E)-1aa
entry
Cu source
ligand
solvent
yield (%)b
1 2 3 4 5 6 7 8 9 10 11 12
CuI CuSCN Cu(OAc)2 Cu(acac)2 Cu(acac)2 Cu(acac)2 Cu(acac)2 Cu(acac)2 Cu(acac)2 − Cu(acac)2 Cu(acac)2
phen phen phen phen phen phen phen L1 L2 L2 − L2
dioxane dioxane dioxane dioxane THF DME Diglyme dioxane dioxane dioxane dioxane dioxane
77 53 64 80 48 46 47 74 85 NR 52 71c
a Reaction conditions (unless otherwise specified): (E)-1a (0.2 mmol, 1.0 equiv), 2c (1.0 equiv), solvent (2 mL). bAll of the yields were isolated yields. NR, no reaction. cUsing 5 mol % CuI and 5 mol % phen. Abbreviations: phen, 1,10-phenanthroline; L1, 3,4,7,8-tetramethyl-1,10-phenanthroline; L2, 4,7-diphenyl-1,10-phenanthroline.
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DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
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The Journal of Organic Chemistry Scheme 2. Copper-Catalyzed Perfluoroalkylation of Allyl Phosphates (E)-1a,b
a
Reaction conditions (unless otherwise specified): (E)-1 (0.3 mmol, 1.0 equiv), 2c (1.0 equiv), Cu(acac)2 (10 mol %), L2 (10 mol %), dioxane (2 mL), 100 °C, 12 h. bThe yields are of isolated products, and the E:Z ratios were determined by 1H NMR spectroscopy. In all cases, the linear:branched ratios were >99:1. cUsing 2.0 equiv of 2c. Abbreviation: L2, 4,7-diphenyl-1,10-phenanthroline.
Scheme 3. Copper-Catalyzed Perfluoroalkylation of Allyl Phosphates (E)-1 with Various Perfluoroalkylzinc Reagents 2a,b
a
Reaction conditions (unless otherwise specified): (E)-1 (0.3 mmol, 1.0 equiv), 2 (1.0 equiv), Cu(acac)2 (10 mol %), L2 (10 mol %), dioxane (2 mL), 100 °C, 12 h. bThe yields are of isolated products and the E:Z ratios were determined by 1H NMR spectroscopy. In all cases, the linear:branched ratios were generally >99:1. cUsing 2.0 equiv of 2. Abbreviation: L2, 4,7-diphenyl-1,10-phenanthroline.
To investigate the regio- and stereoselectivity of the reaction, branched allyl phosphates 7 and 8 and (Z)-allyl phosphates (Z)-1p and (Z)-1l were also subjected to the standard reaction conditions (Scheme 4). In general, under the conditions described above, these substrates give the linear products predominantly as an E/Z mixture, with the (E)products as the major products, thus indicating that a π−allyl copper intermediate is involved in the catalytic process (eq 1). It should be noted that the stereochemical information about Z substrates was partially retained, which implies that the E/Z
mixtures were generated via at least two simultaneous pathways (eq 2). Although the exact mechanism of the reaction is still not clear, on the basis of the results reported by others,5,6 a plausible mechanism is proposed and shown in Scheme 5. The sequence begins with formation of copper catalyst I by in situ generation. Then, copper intermediate II is generated by transmetalation of the copper catalyst with zinc reagent 2. Subsequently, oxidative addition of (Z)- or (E)-1 with RFCu(I)Ln (II) would provide the key copper species (Z)or (E)-III, respectively. Finally, the reductive elimination 425
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
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The Journal of Organic Chemistry
Scheme 4. Copper-Catalyzed Perfluoroalkylation of Branched Allyl Phosphates 4 and 5 and Linear Phosphates (Z)-1 with Perfluoroalkylzinc Reagents 2a
a Standard condition: allyl phosphate (0.3 mmol, 1.0 equiv), 2 (1.0 equiv), Cu(acac)2 (10 mol %), L2 (10 mol %), dioxane (2 mL), 100 °C, 12 h. The yields are of isolated products, and the E:Z ratios were determined by 1H NMR spectroscopy. Abbreviation: L2, 4,7-diphenyl-1,10phenanthroline.
multiplicity, and coupling constant (hertz). High-resolution mass spectrometry (HRMS) analysis was performed by the analytical facility at the University of Science and Technology of China. Materials. All reagents were used as received from commercial sources, unless specified otherwise, or prepared as described in the literature. All reagents were weighed and handled in air, and the experimental space was refilled with an inert atmosphere of N2 at room temperature. DMF, DMSO, DMPU, NMP, and DCE were distilled under reduced pressure from CaH2. Toluene, 1,4-dioxane, THF, Diglyme, and DME were distilled from sodium and benzophenone immediately before use. Preparation of E Compounds 1a, 1g−j, and 1l−o. To a stirred solution of ethyl 2-(diethoxyphosphoryl)acetate (1.97 g, 8.8 mmol) in anhydrous THF (20 mL) was added MeMgBr (2.7 mL, 8 mmol) at room temperature, and the mixture was stirred for 15 min. Aldehyde (848 mg, 8 mol) dissolved in THF (5 mL) was added at room temperature, and the mixture stirred for 4 h under reflux. After the mixture had been cooled to room temperature, the reaction was quenched with distilled water and the aqueous phase was extracted with EA (2 × 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated in vacuo to give the crude product that was used in the next step. The crude product was dissolved in DCM (15 mL); DIBAL-H (10.7 mL, 16 mmol) was added at rt, and the mixture was stirred for 2 h (TLC monitoring). The reaction was quenched with a saturated NH4Cl solution, and the aqueous phase was extracted with EA (2 × 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated in vacuo to give the allyl alcohol that was used in the next step. The DMAP (244.4 mg, 2.0 mmol) were placed in a 20 mL twoneck reaction flask at 0 °C, which was filled with nitrogen by using the standard Schlenk technique. DCM (10 mL) was then added to the flask, and allyl alcohol (10 mmol) dissolved in DCM (5 mL) was added. Finally, Et3N (1.66 mL, 12 mmol) and diethyl phosphorochloridate (1.71 mL, 12 mmol) were added dropwise. The solution was stirred at 0 °C for 4 h, diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography to provide the pure product. (E)-Diethyl Tetradec-2-en-1-yl Phosphate [(E)-1a]. The product (2.10 g, 62% yield) as a colorless oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 5.77 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.56 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 4.44 (t, J = 8.4 Hz, 2 H), 4.07 (m, 4 H), 2.01 (m, 2 H), 1.31−1.22 (m, 24 H), 0.84 (m, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 136.6, 124.2 (d, J = 6.6 Hz), 68.2 (d, J = 5.7 Hz), 63.5 (d, J = 5.7 Hz), 32.1, 31.9, 29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 28.8, 22.6, 16.1 (d, J = 6.7 Hz), 14.1; IR (thin film) νmax 2925, 1269, 1033
Scheme 5. Proposed Reaction Mechanism
would lead to the desired allylated product (Z)- or (E)-3 and regenerate the Cu(I)Ln species (path A). Alternatively, a reversible pathway is used to form π−allyl copper complex IV from III by rapid σ−π conversion (path B), which would give (E)-3 as the major product, thus resulting in stereochemical inversion in Z substrates. In conclusion, we have demonstrated an efficient copper catalyst system for the perfluoroalkylation of phosphates with good to excellent yields and high regio- and stereoselectivities, which represents a useful, concise, and operationally simple method for preparing allyl−RF products. A preliminary study suggests that the reaction mechanism is complex and two main pathways leading to the desired allyl−RF products may be operating. Further studies to expand the substrate scope and its applications are now in progress in our laboratory.
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EXPERIMENTAL SECTION
General Information. 1H NMR and 13C NMR spectra were recorded on a Bruker 600 MHz spectrometer in CDCl3. Data for 1H NMR are reported as follows: chemical shift (parts per million, scale), multiplicity, coupling constant (hertz), and integration. Data for 13C NMR are reported as follows: chemical shift (parts per million, scale), 426
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
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The Journal of Organic Chemistry cm−1; LRMS (EI) m/z (%) 348 (M+), 207, 84 (100); HRMS (APCILTQ Orbitrap) m/z [M + H]+ calcd for C18H38O4P 349.2502, found 349.2496. (E)-Diethyl (4-Methylhept-2-en-1-yl) Phosphate [(E)-1g]. The product (1.98 g, 75% yield) as a colorless oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 5.57 (dd, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.77 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 4.39 (m, 2 H), 4.01 (m, 4 H), 2.07 (m, 1 H), 1.25−1.17 (m, 10 H), 0.89−0.77 (m, 6 H); 13C NMR (150.8 MHz, CDCl3) δ 142.1, 122.5 (d, J = 6.5 Hz), 68.2 (d, J = 5.7 Hz), 63.5 (d, J = 5.7 Hz), 38.7, 36.0, 20.2, 20.0, 16.0 (d, J = 6.7 Hz), 14.0; IR (thin film) νmax 2962, 1267, 1035 cm−1; LRMS (EI) m/z (%) 264 (M+), 95, 67 (100); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C12H26O4P 265.1563, found 265.1565. (E)-3-Cyclohexylallyl Diethyl Phosphate [(E)-1h]. The product (1.52 g, 55% yield) as a colorless oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 5.70 (dd, J = 15.6 Hz, J = 6.6 Hz, 1 H), 5.51 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 4.44 (t, J = 7.2 Hz, 2 H), 4.08 (m, 4 H), 1.95 (m, 1 H), 1.60−1.69 (m, 5 H), 1.03−1.31 (m, 11 H). This compound is known.22 (E)-Diethyl (4-Phenylbut-2-en-1-yl) Phosphate [(E)-1i]. The product (1.62 g, 57% yield) as a colorless oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 7.12 (t, J = 7.2 Hz, 2 H), 7.04 (d, J = 7.2 Hz, 1 H), 7.01 (d, J = 7.8 Hz, 2 H), 5.80 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.50 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 4.36 (t, J = 7.8 Hz, 2 H), 3.93 (m, 4 H), 3.32 (d, J = 6.6 Hz, 2 H), 1.16 (m, 6 H). This compound is known.23 (E)-Diethyl (5-Phenylpent-2-en-1-yl) Phosphate [(E)-1j]. The product (1.82 g, 61% yield) as a colorless oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 7.26 (t, J = 6.0 Hz, 2 H), 7.15 (m, 3 H), 5.81 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 5.61(dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 4.44 (t, J = 12.0 Hz, 2 H), 4.08 (m, 4 H), 2.68 (t, J = 6.0 Hz, 2 H), 2.37 (q, J = 7.8 Hz, 2 H), 1.31 (m, 6 H); 13C NMR (150.8 MHz, CDCl3) δ 141.4, 135.2, 128.4, 128.3 (d, J = 4.8 Hz), 125.9, 125.0 (d, J = 6.6 Hz), 68.0 (d, J = 6.7 Hz), 63.6 (d, J = 5.9 Hz), 35.2, 33.9, 16.1 (d, J = 6.7 Hz); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C15H24O4P 299.1047, found 299.1045. This compound is known.22 Cinnamyl Diethyl Phosphate [(E)-1l]. The product (2.61 g, 90% yield) as a colorless oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 7.37 (d, J = 7.2 Hz, 2 H), 7.30 (t, J = 7.2 Hz, 2 H), 7.24 (t, J = 7.2 Hz, 1 H), 6.66 (d, J = 15.6 Hz, 1 H), 6.30 (dt, J = 16.2 Hz, J = 6.0 Hz, 1 H), 4.67 (m, 2 H), 4.11 (m, 4 H), 1.32 (t, J = 17.8 Hz, 6 H). This compound is known.22 (E)-Diethyl [3-(p-Tolyl)allyl] Phosphate [(E)-1m]. The product (2.32 g, 82% yield) as a colorless oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 7.29 (d, 2 H, J = 8.2 Hz), 7.13 (d, 2 H, J = 8.2 Hz), 6.45 (d, 1 H, J = 15.9 Hz), 6.25 (dt, 1 H, J = 6.4 Hz, J = 15.9 Hz), 4.69 (dt, 2 H, J = 1.2 Hz, J = 6.4 Hz), 4.13 (dq, 4 H, J = 7.0 Hz, J = 7.0 Hz), 2.34 (s, 3 H), 1.34 (t, 6 H, J = 7.0 Hz). This compound is known.24 (E)-3-[4-(tert-Butyl)phenyl]allyl Diethyl Phosphate [(E)-1n]. The product (2.51 g, 77% yield) as a colorless oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 7.35 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.4 Hz, 2 H), 6.65 (d, J = 16.0 Hz, 1 H), 6.26 (dt, J = 16.0 Hz, J = 6.6 Hz, 1 H), 4.68 (t, J = 7.2 Hz, 2 H), 4.12 (m, 4 H), 1.34−1.28 (m, 15 H); 13C NMR (150.8 MHz, CDCl3) δ 151.3, 133.8, 133.2, 127.8, 126.4, 125.5, 122.7 (d, J = 6.5 Hz), 68.1 (d, J = 5.7 Hz), 63.7 (d, J = 5.7 Hz), 31.2, 16.1 (d, J = 6.8 Hz), 14.0; IR (thin film) νmax 2965, 1271, 1035 cm−1; LRMS (EI) m/z (%) 326 (M+), 207 (100); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C17H28O4P 327.1720, found 327.1721. (E)-Diethyl [3-(3-Methoxyphenyl)allyl] Phosphate (1o). The product (2.16 g, 72% yield) as a colorless oil was purified via silica
gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 7.25 (m, 2 H), 6.96 (m, 2 H), 6.82 (d, J = 7.8 Hz, 1 H), 6.65 (d, J = 16.2 Hz, 1 H), 6.30 (dt, J = 15.6 Hz, J = 6.0 Hz, 1 H), 4.70 (t, J = 7.2 Hz, 2 H), 4.13 (m, 4 H), 3.81 (s, 3 H), 1.32 (m, 6 H). This compound is known.22 Preparation of Compound (E)-1k. Ethyl 2(diethoxyphosphoryl)acetate (1.35 g, 6.0 mmol) was slowly added to a solution of NaH (60%, 240 mg, 6.0 mmol) in THF (20 mL) at 0 °C. After the mixture had been stirred for 1 h, a solution of undecan2-one (951 mg, 5.0 mmol) in THF (5 mL) was added dropwise to the solution of olefinating agent, and the resulting mixture was allowed to slowly warm to rt. After 12 h, H2O (20 mL) was added, and the solution diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography to provide pure ethyl ethyl (E)-3-methyldodec-2enoate (780 mg, 65%) as a pale yellow oil. The (E)-3-methyldodec-2-enoate (780 mg, 3.25 mmol) was dissolved in DCM (15 mL); DIBAL-H (4.4 mL, 6.5 mmol) was added at rt, and the mixture was stirred for 2 h (TLC monitoring). The reaction was quenched with a saturated NH4Cl solution, and the aqueous phase was extracted with EA (2 × 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated in vacuo to give the (E)-3-methyldodec-2-en-1-ol that was used in the next step. The DMAP (99 mg, 0.81 mmol) was placed in a 20 mL two-neck reaction flask at 0 °C that was filled with nitrogen by using the standard Schlenk technique. DCM (10 mL) was then added to the flask, and (E)-3-methyldodec-2-en-1-ol dissolved in DCM (5 mL) was added. Finally, Et3N (675.8 ul, 4.88 mmol) and diethyl phosphorochloridate (670.1 mL, 4.88 mmol) were added dropwise. The solution was stirred at 0 °C for 4 h, diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (petroleum ether/ ethyl ether = 3:1) to provide pure (E)-1k (750.0 mg, 69% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 5.80 (m, 1 H), 5.27 (d, J = 17.4 Hz, 1 H), 5.17 (d, J = 10.80 Hz, 1 H), 4.71 (m, 1 H), 4.05 (m, 4 H), 1.73−1.55 (m, 2 H), 1.33−1.22 (m, 24 H), 0.85 (t, J = 6.6 Hz, 2 H); 13C NMR (150.8 MHz, CDCl3) δ 143.0, 118.6 (d, J = 6.6 Hz), 64.1 (d, J = 5.7 Hz), 63.5 (d, J = 5.9 Hz), 39.5, 31.8, 29.5, 29.4, 29.3, 29.2, 27.5, 22.6, 16.3, 16.1 (d, J = 6.6 Hz), 14.1; IR (thin film) νmax 2927, 1267, 1040 cm−1; LRMS (EI) m/z (%) 334 (M+), 281, 207 (100); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C17H36O4P 335.2346, found 335.2344. Preparation of Compound B4. To a suspension of NaH (60%, 1.0 g, 25.0 mmol) and decane-1,10-diol (B1) (4.4 g, 25.0 mmol) in THF (30 mL) was slowly added TBSCl (3.8 g, 25.0 mmol) in THF (25 mL), and the resulting mixture was stirred at room temperature for 2 h. The reaction was quenched with saturated aqueous NaHCO3 and extracted with EA (2 × 30 mL). The organic layer was dried over Na2SO4 and evaporated. The residue was purified via column chromatography (petroleum ether/ethyl ether = 20:1) to afford alcohol B2 (5.76 g, 80%) as a pale yellow oil. To a stirred solution of oxalyl chloride (2.54 mL, 30 mmol) in anhydrous DCM (30 mL) at −78 °C was added DMSO (4.25 mL, 60.0 mmol) over 20 min, and the mixture was stirred for an additional 15 min. Alcohol B2 (5.77 mg, 20 mmol) dissolved in DCM (10 mL) was added, and the mixture was stirred for 30 min. Et3N (13.86 mL, 100 mmol) was added dropwise, and the mixture was stirred at rt for 1 h (TLC monitoring). The reaction was quenched with water, and the aqueous phase was extracted with EA (2 × 20 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated in vacuo to give aldehyde B3 that was used in the next step. To a stirred solution of ethyl 2-(diethoxyphosphoryl)acetate (4.93 g, 22.0 mmol) in anhydrous THF (30 mL) was added MeMgBr (2.7 mL, 8 mmol) at room temperature, and the mixture was stirred for 15 min. Aldehyde B3 dissolved in THF (100 mL) was added at room temperature, and the mixture stirred for 4 h under reflux. After the mixture had been cooled to room temperature, the reaction was quenched with distilled water, and the aqueous phase was extracted 427
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
Note
The Journal of Organic Chemistry with EA (2 × 30 mL). The combined organic layers were washed with brine and dried (Na2SO4), and the residue was purified via column chromatography (petroleum ether/ethyl ether = 20:1) to afford ethyl B4 (6.21 g, 86%) as a pale yellow oil. Preparation of Compound (E)-1b. To a stirred solution of ethyl B4 (3.57 g, 10 mmol) in anhydrous DCM (25 mL) at −78 °C was added 1.5 M DIBAL-H in toluene (13.4 mL, 20.0 mmol) slowly over 15 min. The mixture was stirred at this temperature for 2 h and cooled to 0 °C, the reaction quenched with saturated sodium potassium tartrate, and the mixture stirred for 2 h. The mixture was passed through a bed of Celite. The filtrate was extracted with EA (2 × 20 mL), and the combined organic extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo to give alcohol B6 that was used in the next step. The DMAP (305.4 mg, 2.5 mmol) was placed in a 50 mL two-neck reaction flask at 0 °C that was filled with nitrogen by using the standard Schlenk technique. DCM (25 mL) was then added to the flask, and alcohol B6 dissolved in DCM (10 mL) was added. Finally, Et3N (2.08 mL, 15 mmol) and diethyl phosphorochloridate (2.14 mL, 15 mmol) were added dropwise. The solution was stirred at 0 °C for 4 h, diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1) to provide (E)1b (3.65 g, 81% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 5.74 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.54 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 4.42 (t, J = 7.2 Hz, 2 H), 4.05 (m, 4 H), 3.54 (t, J = 6.6 Hz, 2 H), 2.00 (q, J = 7.2 Hz, 2 H), 1.44 (m, 2 H), 1.29 (m, 18 H), 0.84 (d, J = 1.2 Hz, 9 H), −0.01 (d, J = 1.8 Hz, 6 H); 13C NMR (150.8 MHz, CDCl3) δ 136.6, 124.3 (d, J = 6.5 Hz), 68.1 (d, J = 5.6 Hz), 63.6 (d, J = 5.9 Hz), 63.3, 32.8, 32.1, 29.5, 29.4, 29.3, 29.1, 28.8, 25.9, 25.7, 18.3, 16.1 (d, J = 6.6 Hz), −5.3; IR (thin film) νmax 2931, 2860, 1036 cm−1; LRMS (EI) m/z (%) 464 (M+), 281, 207 (100); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C23H50O5PSi 465.3160, found 465.3158. Preparation of Compound (E)-1c. To a stirred solution of acetic anhydride (216 μL, 2.1 mmol) was slowly added DMAP (122.2 mg, 1.0 mmol) in anhydrous DCM (5 mL) at rt (1f) (168.1 mg, 0.5 mmol). The mixture was stirred at room temperature until the starting material was consumed. The reaction mixture was poured into water (10 mL), and the mixture was stirred vigorously for 30 min. The aqueous phase was extracted with EA (2 × 20 mL). The combined organic phases were washed with 1 M aqueous HCl (15 mL), saturated aqueous NaHCO3 (20 mL), water (20 mL), and brine (2 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (petroleum ether/ ethyl ether = 3:1) to provide pure (E)-1c (159 mg, 89% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 5.70 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.55 (dt, J = 15.0 Hz, J = 6.0 Hz, 1 H), 4.39 (t, J = 7.2 Hz, 2 H), 4.02 (m, 4 H), 3.95 (t, J = 6.6 Hz, 2 H), 1.98− 1.95 (m, 5 H), 1.52 (m, 2 H), 1.17−1.29 (m, 18 H); 13C NMR (150.8 MHz, CDCl3) δ 171.2, 136.5, 124.2 (d, J = 6.6 Hz), 68.2 (d, J = 5.7 Hz), 64.6, 63.6 (d, J = 5.9 Hz), 32.1, 29.4, 29.3, 29.1, 29.0, 28.7, 28.5, 25.8, 21.0, 16.0 (d, J = 6.6 Hz); IR (thin film) νmax 2931, 1742, 1036 cm−1; LRMS (EI) m/z (%) 378 (M+), 281, 207 (100), 84; HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C18H36O6P, 379.2244, found 379.2239. Preparation of Compound (E)-1d. To a stirred solution of ethyl B4 (713 mg, 2 mmol) in anhydrous DCM (10 mL) at 40 °C was instantly added 1.5 M DIBAL-H in toluene (2.8 mL, 4.0 mmol). The mixture was stirred at this temperature for 2 h and cooled to rt, the reaction quenched with saturated sodium potassium tartrate, and the mixture stirred for 2 h. The mixture was passed through a bed of Celite. The filtrate was extracted with EA (2 × 20 mL), and the combined organic extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo to give alcohol B5 that was used in the next step. The DMAP (122.2 mg, 0.81 mmol) was placed in a 20 mL twoneck reaction flask at 0 °C that was filled with nitrogen by using the standard Schlenk technique. DCM (10 mL) was then added to the flask, and alcohol B5 dissolved in DCM (5 mL) was added. Finally,
Et3N (0.83 mL, 6.0 mmol) and diethyl phosphorochloridate (0.86 mL, 6 mmol) were added dropwise. The solution was stirred at 0 °C for 4 h, diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (petroleum ether/ethyl ether = 1:1) to provide (E)-1d (793.4 mg, 84% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 5.71 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 5.51 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 4.39 (t, J = 7.2 Hz, 2 H), 4.18 (m, 2 H), 4.03 (m, 8 H), 3.95 (q, J = 6.6 Hz, 2 H), 1.97 (q, J = 7.2 Hz, 2 H), 1.59 (m, 2 H), 1.20−1.32 (m, 22 H); 13C NMR (150.8 MHz, CDCl3) δ 136.5, 124.2 (d, J = 6.5 Hz), 68.1 (d, J = 5.6 Hz), 67.6 (d, J = 6.0 Hz), 63.6 (t, J = 5.1 Hz), 32.1, 30.2, 30.1, 29.4, 29.3, 29.1, 29.0, 28.7, 25.4, 16.1 (d, J = 6.6 Hz), 16.0 (d, J = 6.8 Hz); IR (thin film) νmax 2931, 1276, 1037 cm−1; LRMS (EI) m/z (%) 472 (M+), 281, 207 (100); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C20H43O8P2 473.2428, found 473.2423. Preparation of Compound (E)-1e. To a flask containing a stirring mixture of DDQ (136.2 mg, 1.2 mmol) and PPh3 (157.4 mg, 1.2 mmol) in dry DCM (5 mL) was added TBAB (199.5 mg, 1.2 mmol) at room temperature. 1f (168.16 mg, 0.5 mmol) was then added to this mixture. The yellow color of the reaction mixture immediately changed to deep red. GC analysis showed the immediate completion of the reaction. The solvent was diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (petroleum ether/ ethyl ether = 7:3) to provide pure (E)-1e (181.7 mg, 91% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 5.74 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.54 (dt, J = 15.6 Hz, J = 6.0 Hz, 1 H), 4.42 (t, J = 7.2 Hz, 2 H), 4.05 (m, 4 H), 3.35 (t, J = 6.6 Hz, 2 H), 1.99 (q, J = 7.2 Hz, 2 H), 1.79 (m, 2 H), 1.20−1.38 (m, 18 H); 13C NMR (150.8 MHz, CDCl3) δ 136.5, 124.2 (d, J = 6.6 Hz), 68.2 (d, J = 5.4 Hz), 63.6 (d, J = 5.9 Hz), 34.0, 32.8, 32.1, 29.7, 29.3 (d, J = 3.3 Hz), 29.0, 28.8, 28.7, 28.1, 16.1 (d, J = 6.7 Hz), 14.1; IR (thin film) νmax 2925, 1266, 1035 cm−1; LRMS (EI) m/z (%) 398 (M+), 343, 43 (100); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C16H33O4BrP 399.1294, found 399.1292. Preparation of Compound (E)-1f. 1b (2.70 g, 8 mmol) was dissolved in THF (8 mL) at 0 °C, and a solution of TBAF (1 M in THF, 19.2 mL, 19.2 mmol) was added over a period of 5 min. The mixture was stirred for 2 h at room temperature, and the reaction quenched by the addition of saturated aqueous NH4Cl. The mixture was extracted three times with ether; the combined organic layers were dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified via silica gel chromatography (petroleum ether/ethyl ether = 2:1) to provide (E)-1f (2.48 g, 89% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 5.73 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 5.53 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 4.42 (t, J = 7.2 Hz, 2 H), 4.05 (m, 4 H), 3.55 (t, J = 7.2 Hz, 2 H), 2.26 (s, 1 H), 1.99 (q, J = 6.6 Hz, 2 H), 1.50 (m, 2 H), 1.22−1.33 (m, 18 H); 13C NMR (150.8 MHz, CDCl3) δ 136.6, 124.2 (d, J = 6.5 Hz), 68.2 (d, J = 5.7 Hz), 63.6 (d, J = 5.9 Hz), 62.7, 32.7, 32.0, 29.4, 29.3, 29.2, 29.0, 28.7, 25.7, 16.0 (d, J = 6.6 Hz), 14.0; IR (thin film) νmax 3448, 2932, 1036 cm−1; LRMS (EI) m/z (%) 336 (M+), 281, 207 (100); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C16H34O5P 337.2138, found 337.2138. Preparation of Compounds (Z)-Diethyl (3-Phenylallyl) Phosphate (Z)-1l. To a solution of ethynylbenzene (1.07 mL, 10 mmol) in dried THF (10 mL) was added dropwise n-BuLi in nhexane (12 mL, 1.5 M, 12 mmol) over 10 min at 0 °C under an argon atmosphere. The reaction mixture was allowed to warm to rt and stirred for 1 h. Then the reaction mixture was cooled to 0 °C again, and paraformaldehyde (369 mg, 12 mmol) was added. After that, the reaction mixture was allowed to warm to room temperature and stirred for an additional 12 h. The reaction was quenched with saturated aqueous NH4Cl (15 mL), and the mixture was extracted with EA (3 × 20 mL). The combined organic phase was washed with brine (2 × 50 mL) and dried over anhydrous Na2SO4. After being filtered and concentrated under reduced pressure, the residue was purified via silica gel chromatography (petroleum ether/ethyl ether = 428
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
Note
The Journal of Organic Chemistry 10:1) to provide pure product 3-phenylprop-2-yn-1-ol (1.17 g, 89% yield). A mixture of 3-phenylprop-2-yn-1-ol (600 mg, 4.5 mmol), EA (8 mL), and Lindlar catalyst (40 mg) was stirred at room temperature under a hydrogen gas atmosphere for 1.5 h. After the reaction had reached completion (monitored by 1H NMR), the mixture was filtered to give (Z)-3-phenylprop-2-en-1-ol (573 mg, 95% yield) as a pale yellow oil. The DMAP (61 mg, 0.5 mmol) was placed in a 25 mL two-neck reaction flask at 0 °C that was filled with nitrogen by using the standard Schlenk technique. DCM (10 mL) was then added to the flask, and (Z)-3-phenylprop-2-en-1-ol (268 mg, 2 mmol) dissolved in DCM (5 mL) was added. Finally, Et3N (416 uL, 3 mmol) and diethyl phosphorochloridate (428 μL, 3 mmol) were added dropwise. The solution was stirred at 0 °C for 4 h, diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (petroleum ether/ethyl ether = 7:3) to provide pure (Z)-1l (491 mg, 91% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 7.34 (t, J = 7.2 Hz, 2 H), 7.26 (t, J = 7.8 Hz, 1 H), 7.19 (d, J = 7.2 Hz, 2 H), 6.66 (d, J = 11.4 Hz, 1 H), 5.81 (dt, J = 11.4 Hz, J = 6.6 Hz, 1 H), 4.80 (m, 2 H), 4.10 (m, 4 H), 1.31 (m, 6 H). This compound is known.22 Preparation of (Z)-Diethyl Tridec-2-en-1-yl Phosphate (Z)1p. To a solution of dodec-1-yne (998 mg, 6 mmol) in dried THF (10 mL) was added dropwise n-BuLi in n-hexane (3 mL, 2.4 M, 7.2 mmol) over 10 min at 0 °C under an argon atmosphere. The reaction mixture was allowed to warm to rt and stirred for 1 h. Then the reaction mixture was cooled to 0 °C again, and paraformaldehyde (216 mg, 7.2 mmol) was added. After that, the reaction mixture was allowed to warm to room temperature and stirred for an additional 12 h. The reaction was quenched with saturated aqueous NH4Cl (15 mL), and the mixture was extracted with diethyl ether (3 × 20 mL). The combined organic phase was washed with brine (2 × 50 mL) and dried over anhydrous Na2SO4. After being filtered and concentrated under reduced pressure, the residue was purified via silica gel chromatography (petroleum ether/ethyl ether = 10:1) to provide pure product tridec-2-yn-1-ol (0.94 g, 80% yield) as a pale yellow oil. A mixture of tridec-2-yn-1-ol (196.3 mg, 2.5 mmol), EtOH (8 mL), pyridine (1.5 mL), and Lindlar catalyst (21 mg) was stirred at room temperature under a hydrogen gas atmosphere for 1 h. The mixture was filtered to give (Z)-tridec-2-en-1-ol (470 mg, 98% yield) as a pale yellow oil. The DMAP (61 mg, 0.5 mmol) was placed in a 25 mL two-neck reaction flask at 0 °C, which was filled with nitrogen by using the standard Schlenk technique. DCM (10 mL) was then added to the flask, and (Z)-tridec-2-en-1-ol (397 mg, 2 mmol) dissolved in DCM (5 mL) was added. Finally, Et3N (416 uL, 3 mmol) and diethyl phosphorochloridate (428 μL, 3 mmol) was added dropwise. The solution was stirred at 0 °C for 4 h, diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (petroleum ether/ethyl ether = 7:3) to provide (Z)-1p (615 mg, 92% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 5.62 (dt, J = 10.8 Hz, J = 7.2 Hz, 1 H), 5.31 (dt, J = 10.8 Hz, J = 7.2 Hz, 1 H), 4.56 (t, J = 7.2 Hz, 2 H), 4.07 (m, 4 H), 2.04 (q, J = 7.2 Hz, 2 H), 1.38−1.22 (m, 22 H), 0.84 (t, J = 6.6 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 135.3, 123.8 (d, J = 6.9 Hz), 63.6 (d, J = 5.9 Hz), 63.0 (d, J = 5.6 Hz), 31.8, 29.5, 29.4, 29.3, 29.2, 29.1, 27.4, 22.6, 16.0 (d, J = 6.6 Hz), 14.0; IR (thin film) νmax 2921, 1264, 1034 cm−1; LRMS (EI) m/z (%) 348 (M+), 155, 67 (100); HRMS (APCI-LTQ Orbitrap) m/z [M + H]+ calcd for C18H38O4P 349.2502, found 349.2501. Preparation of Compounds 7 and 8. To a 1.0 M stirring solution in THF vinylmagnesium bromide (3.30 mL, 3.33 mmol) in THF (15 mL) at 0 °C was added aldehyde (3.0 mmol). After the mixture had been stirred for 1 h, the reaction was quenched with 1 M HCl, and the solvent was removed under reduced pressure. The resulting residue was then extracted with EA, and the organic layers were combined, washed with saturated NaHCO3, dried over Na2SO4, and concentrated in vacuo to give the alcohol (B7 and B8) that was used in the next step.
The DMAP (91.6 mg, 0.75 mmol) was placed in a 25 mL two-neck reaction flask at 0 °C, which was filled with nitrogen by using the standard Schlenk technique. DCM (10 mL) was then added to the flask, and alcohol B7 (3.1 mmol) dissolved in DCM (5 mL) was added. Finally, Et3N (623.7 μL, 4.5 mmol) and diethyl phosphorochloridate (642.7 μL, 4.5 mmol) were added dropwise. The solution was stirred at 0 °C for 4 h, diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1) to provide 7 (882 mg, 82% yield) as a clear, pale yellow oil: 1H NMR (600 MHz, CDCl3) δ 5.80 (m, 1 H), 5.27 (d, J = 17.4 Hz, 1 H), 5.17 (d, J = 10.8 Hz, 1 H), 4.71 (m, 1 H), 4.06 (m, 4 H), 1.73−1.55 (m, 2 H), 1.33−1.22 (m, 24 H), 0.85 (t, J = 6.6 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 137.02 (d, J = 3.8 Hz), 117.0, 79.8 (d, J = 6.0 Hz), 63.5 (dd, J = 5.7 Hz, J = 4.2 Hz), 35.8 (d, J = 5.7 Hz), 31.9, 29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 24.7, 22.6, 16.1 (dd, J = 6.9 Hz, J = 3.5 Hz), 14.1; IR (thin film) νmax 2922, 1265, 1033 cm−1; LRMS (EI) m/ z (%) 348 (M+), 207, 84 (100); HRMS (APCI-TOF) m/z [M + H]+ calcd for C18H38O4P 349.2502, found 349.2502. 1-Phenylprop-2-en-1-ol (B8) (0.5 mL, 3.79 mmol, 1.0 equiv) was dissolved in dry THF (6 mL), and n-BuLi (1.5 M in hexanes, 2.5 mL, 3.75 mmol) was added dropwise at 0 °C. The reaction mixture was stirred for 30 min at 0 °C, and diethyl chlorophosphate (0.55 mL, 3.8 mmol, 1.0 equiv) was added dropwise at 0 °C. The reaction mixture was allowed to warm to rt and stirred for 2 h at rt. The reaction was quenched by addition of saturated aqueous NH4Cl (10 mL), and then the mixture diluted with EtOAc (15 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (3 × 10 mL). The combined organic phases were washed with brine (10 mL), dried over MgSO4, filtered, and concentrated in vacuo. Compound 8 (0.56 g, 92% pure, 1.91 mmol, 50%) was obtained as a pale yellow oil and used without further purification: 1H NMR (600 MHz, CDCl3) δ 7.37−7.30 (m, 5 H), 6.02 (m, 1 H), 5.78 (m, 1 H), 5.36 (d, J = 17.4 Hz, 1 H), 5.24 (d, J = 10.2 Hz, 1 H), 4.07 (m, 2 H), 3.94 (m, 2 H), 1.26 (t, J = 7.2 Hz, 3 H), 1.17 (t, J = 7.2 Hz, 3 H). This compound is known.25 Preparation of Bis(pentafluoroethyl)zinc Reagent Zn(C2F5)2(DMPU)2. To an oven-dried 100 mL two-neck round-bottom flask equipped with a magnetic stir bar were added toluene (15 mL) and DMPU (2.4 mL, 20 mmol) under an argon atmosphere. Pentafluoroethyl iodide (3.0 mL, 25 mmol) was added to the solution. A diethylzinc solution (1.0 M in hexanes, 10 mL, 10 mmol) was then added dropwise at −35 °C. After the reaction mixture was stirred at −5 °C for 24 h, the precipitate was obtained. After the solution had been removed, the obtained precipitate was washed with hexane (50 mL) three times and dried under vacuum to give Zn(C2F5)2(DMPU)2 as a white powder (5.4 g, 95% yield). This compound is known.5b Preparation of Bis(heptafluoropropyl)zinc Reagent Zn(C3F7)2(DMPU)2. To an oven-dried 100 mL two-neck round-bottom flask equipped with a magnetic stir bar were added toluene (15 mL) and DMPU (2.4 mL, 20 mmol) under an argon atmosphere. Heptafluoropropyl iodide (3.6 mL, 25 mmol) was added to the solution. A diethylzinc solution (1.0 M in hexanes, 10 mL, 10 mmol) was then added dropwise at −35 °C. After the reaction mixture was stirred at −5 °C for 24 h, the precipitate was obtained. After the solution had been removed, the obtained precipitate was washed with hexane (50 mL) three times and dried under vacuum to give Zn(C3F7)2(DMPU)2 as a white powder (6.1 g, 93% yield). This compound is known.5b Preparation of Bis(perfluorobutyl)zinc Reagent Zn(C4F9)2(DMPU)2. To an oven-dried 100 mL two-neck round-bottom flask equipped with a magnetic stir bar were added toluene (15 mL) and DMPU (2.4 mL, 20 mmol) under an argon atmosphere. Perfluorobutyl iodide (4.3 mL, 25 mmol) was added to the solution. A diethylzinc solution (1.0 M in hexanes, 10 mL, 10 mmol) was then added dropwise at −35 °C. After the reaction mixture had been stirred at −5 °C for 24 h, the precipitate was obtained. After the solution had been removed, the obtained precipitate was washed with hexane (50 mL) three times and dried under vacuum to give 429
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
Note
The Journal of Organic Chemistry
(100); HRMS (ESI-TOF) m/z calcd for C18H25F9O2 444.1711, found 444.1712. (E)-Diethyl (13,13,14,14,15,15,16,16,16-Nonafluorohexadec-10en-1-yl) Phosphate (3d). The product [from (E)-1d, 97 mg, 60% yield] as a pale yellow oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 5.66 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 5.34 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 4.07 (m, 4 H), 3.99 (q, J = 6.6 Hz, 2 H), 2.74 (td, J = 18.0 Hz, J = 6.6 Hz, 2 H), 2.02 (q, J = 7.2 Hz, 2 H), 1.63 (m, 2 H), 1.34− 1.22 (m, 18 H); 13C NMR (150.8 MHz, CDCl3) δ 141.7, 121.2− 119.0 [m, -(CF2)CF3], 118.7 (t, J = 4.4 Hz, CH-CH2CF2), 118.1− 111.0 [m, -(CF2)CF3], 70.2 (d, J = 6.0 Hz), 66.2 (d, J = 6.0 Hz), 37.3 (t, J = 22.4 Hz, CH-CH2CF2), 35.1, 32.9, 32.8, 31.9, 31.6, 31.5, 31.4, 28.0, 18.7 (d, J = 6.8 Hz); 19F NMR (564 MHz, CDCl3) δ −81.3 (t, J = 9.6 Hz, 3 F), −113.8 (m, 2 F), −124.2 (m, 2 F), −126.3 (m, 2 F); IR (thin film) νmax 2926, 1237 cm−1; LRMS (EI) m/z (%) 538 (M+), 364, 155 (100); HRMS (ESI-TOF) m/z calcd for C20H32F9O4P 538.1894, found 538.1901. (E)-16-Bromo-1,1,1,2,2,3,3,4,4-nonafluorohexadec-6-ene (3e). The product [from (E)-1e, 94.5 mg, 65% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1 H NMR (600 MHz, CDCl3) δ 5.70 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 5.38 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 3.40 (t, J = 6.6 Hz, 2 H), 2.78 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.06 (q, J = 6.6 Hz, 2 H), 1.85 (m, 2 H), 1.43−1.36 (m, 4 H), 1.29−1.26 (m, 8 H); 13C NMR (150.8 MHz, CDCl3) δ 141.8, 123.3−119.1 [m, -(CF2)CF3], 118.8 (t, J = 4.2 Hz, CH-CH2CF2), 118.7−111.2 [m, -(CF2)CF3], 37.4 (t, J = 22.5 Hz, CH-CH2CF2), 36.5, 35.5, 35.1, 32.0, 31.9, 31.6, 31.5, 31.3, 30.8; 19F NMR (564 MHz, CDCl3) δ −81.2 (m, 3 F), −113.7 (m, 2 F), −124.2 (m, 2 F), −126.2 (m, 2 F); IR (thin film) νmax 2934, 1235 cm−1; LRMS (EI) m/z (%) 464 (M+), 420, 69 (100); HRMS (ESI-TOF) m/z calcd for C16H22F9Br 464.0761, found 464.0757. (E)-13,13,14,14,15,15,16,16,16-Nonafluorohexadec-10-en-1-ol (3f). The product [from (E)-1f, 76.0 mg, 63% yield] as a pale yellow oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 10:1): 1H NMR (600 MHz, CDCl3) δ 5.70 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.38 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 3.63 (t, J = 6.6 Hz, 2 H), 2.77 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.05 (q, J = 7.2 Hz, 2 H), 1.56 (m, 2 H), 1.38−1.28 (m, 13 H); 13C NMR (150.8 MHz, CDCl3) δ 141.8, 121.7−119.1 [m, -(CF2)CF3], 118.7 (t, J = 22.4 Hz, CH-CH2CF2), 118.0−111.2 [m, -(CF2)CF3], 65.7, 37.4 (t, J = 22.6 Hz, CH-CH2CF2), 35.4, 35.2, 32.1, 32.0, 32.0, 31.6, 31.5, 28.4; 19F NMR (564 MHz, CDCl3) δ −81.2 (t, J = 11.3 Hz, 3 F), −113.7 (m, 2 F), −124.2 (m, 2 F), −126.2 (m, 2 F); IR (thin film) νmax 3388, 2933, 1237 cm−1; LRMS (EI) m/z (%) 402 (M+), 401, 55 (100); HRMS (ESI-TOF) m/z calcd for C16H23F9O 402.1605, found 402.1594. (E)-8,8,9,9,10,10,11,11,11-Nonafluoro-4-methylundec-5-ene (3g). The product [from (E)-1g, 60.4 mg, 61% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.57 (dd, J = 15.6 Hz, J = 7.8 Hz, 1 H), 5.34 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 2.78 (td, J = 18.0 Hz, J = 6.6 Hz, 2 H), 2.17 (m, 1 H), 1.26 (m, 4 H), 0.98 (d, J = 6.6 Hz, 3 H), 0.88 (t, J = 6.6 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 147.6, 121.5−118.9 [m, -(CF2)CF3], 117.0 (t, J = 4.4 Hz, CHCH2CF2), 116.9−110.0 [m, -(CF2)CF3], 41.5, 39.3, 37.4 (t, J = 22.3 Hz, CH-CH2CF2), 32.3, 22.9 (d, J = 2.0 Hz), 16.7; 19F NMR (564 MHz, CDCl3) δ −81.2 (m, 3 F), −113.7 (m, 2 F), −124.2 (m, 2 F), −126.2 (m, 2 F); IR (thin film) νmax 2952, 1311, 514 cm−1; LRMS (EI) m/z (%) 330 (M+), 287, 69 (100); HRMS (ESI-TOF) m/z calcd for C12H15F9 330.1030, found 330.1028. (E)-(4,4,5,5,6,6,7,7,7-Nonafluorohept-1-en-1-yl)cyclohexane (3h). The product [from (E)-1h, 65.6 mg, 64% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.66 (dd, J = 16.0 Hz, J = 7.2 Hz, 1 H), 5.35 (dt, J = 16.0 Hz, J = 7.2 Hz, 1 H), 2.77 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.00 (m, 1 H), 1.72 (d, J = 10.2 Hz, 2 H), 1.30− 1.85 (m, 8 H); 13C NMR (150.8 MHz, CDCl3) δ 147.4, 121.0−117.2 [m, -(CF2)CF3], 116.4 (t, J = 4.4 Hz, CH-CH2CF2), 115.2−110.0 [m, -(CF2)CF3], 43.4, 37.5 (t, J = 22.5 Hz, CH-CH2CF2), 35.2, 32.4, 28.7, 28.5; 19F NMR (564 MHz, CDCl3) δ −81.3 (m, 3 F), −113.8 (m, 2
Zn(C4F9)2(DMPU)2 as a white powder (6.9 g, 89% yield). This compound is known.5b Preparation of Bis(tridecafluorohexyl)zinc Reagent Zn(C6F13)2(DMPU)2. To an oven-dried 100 mL two-neck round-bottom flask equipped with a magnetic stir bar were added toluene (15 mL) and DMPU (2.4 mL, 20 mmol) under an argon atmosphere. Tridecafluorohexyl iodide (5.4 mL, 25 mmol) was added to the solution. A diethylzinc solution (1.0 M in hexanes, 10 mL, 10 mmol) was then added dropwise at −35 °C. After the reaction mixture had been stirred at −5 °C for 24 h, the precipitate was obtained. After the solution had been removed, the obtained precipitate was washed with hexane (50 mL) three times and dried under vacuum to give Zn(C6F13)2(DMPU)2 as a white powder (8.4 g, 88% yield). This compound is known.5b General Procedure for Copper-Catalyzed Perfluoroalkylation of Allyl Phosphates. To a 25 mL septum-capped sealed tube were added Cu(acac) 2 (10 mol %), L2 (10 mol %), and Zn(RF)2(DMPU)2 (1.0 equiv) under N2, followed by dioxane (2.0 mL) with stirring. Allyl phosphates (E)-1 (0.3 mmol) were then added subsequently. The sealed tube was screw capped and heated to 100 °C (oil bath). After being stirred for 12 h, the reaction mixture was cooled to room temperature. The yield was determined by 19F NMR before workup. If necessary, the reaction mixture was diluted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography to provide a pure product. (E)-1,1,1,2,2,3,3,4,4-Nonafluorooctadec-6-ene (3a). The product [from (E)-1a, 105.6 mg, 85% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.71 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 5.38 (dt, J = 15.6 Hz, J = 7.2 Hz, 1 H), 2.78 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.06 (q, J = 7.2 Hz, 2 H), 1.37−1.26 (m, 18 H), 0.88 (t, J = 7.2 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 141.6, 124.9−120.6 [m, -(CF2) CF3], 118.2−115.4 [m, -(CF2)CF3)], 118.9 (t, J = 4.5 Hz, CHCH2CF2), 117.6 (m), 115.9 (m), 37.2 (t, J = 22.3 Hz, CH-CH2CF2), 35.2, 34.6, 32.29, 32.27, 32.2, 32.1, 32.0, 31.7, 31.6, 25.3, 16.7; 19F NMR (564 MHz, CDCl3) δ −81.2 (tt, J = 9.6 Hz, J = 2.3 Hz, 3 F), −113.8 (m, 2 F), −124.2 (m, 2 F), −126.3 (m, 2 F); IR (thin film) νmax 2924, 1224, 1133 cm−1; LRMS (EI) m/z (%) 414 (M+), 343, 43 (100); HRMS (ESI-TOF) m/z calcd for C18H27F9 414.1969, found 414.1963. (E)-tert-Butyldimethyl[(13,13,14,14,15,15,16,16,16-nonafluorohexadec-10-en-1-yl)oxy]silane (3b). The product [from (E)-1b, 108.4 mg, 70% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.71 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 5.38 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 3.60 (t, J = 6.6 Hz, 2 H), 2.78 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.06 (q, J = 7.2 Hz, 2 H), 1.51 (m, 2 H), 1.39−1.28 (m, 12 H), 0.90 (s, 9 H), 0.05 (s, 6 H); 13C NMR (150.8 MHz, CDCl3) δ 141.8, 121.0−119.1 [m, -(CF2)CF3], 118.7 (t, J = 4.5 Hz, CH-CH2CF2), 118.0−111.3 [m, -(CF2)CF3], 65.9, 37.4 (t, J = 22.5 Hz, CH-CH2CF2), 35.5, 35.2, 32.4, 32.2, 32.0, 32.0, 31.6, 31.5, 28.6, 28.4, −2.7; 19F NMR (564 MHz, CDCl3) δ −81.2 (s, 3 F), −113.8 (s, 2 F), −124.2 (s, 2 F), −126.2 (s, 2 F); IR (thin film) νmax 2933, 1237, 836 cm−1; LRMS (EI) m/z (%) 515 (M+), 323, 267 (100); HRMS (ESI-TOF) m/z calcd for C22H37F9OSi 516.2470, found 516.2467. (E)-13,13,14,14,15,15,16,16-Octafluorohexadec-10-en-1-yl Acetate (3c). The product [from (E)-1c, 77.0 mg, 62% yield] as a pale yellow oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 20:1): 1H NMR (600 MHz, CDCl3) δ 5.69 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.37 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 4.04 (t, J = 6.6 Hz, 2 H), 2.77 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.05 (m, 5 H), 1.60 (m, 2 H), 1.37−1.27 (m, 12 H); 13C NMR (150.8 MHz, CDCl3) δ 173.8, 141.8, 121.5−119.1 [m, -(CF2)CF3], 118.8 (t, J = 4.2 Hz, CH-CH2CF2), 118.0−111.0 [m, -(CF2)CF3], 67.2, 37.4 (t, J = 22.4 Hz, CH-CH2CF2), 35.1, 32.0, 31.9, 31.8, 31.6, 31.5, 31.2, 28.5, 23.55; 19F NMR (564 MHz, CDCl3) δ −81.3 (t, J = 9.6 Hz, 3 F), −113.8 (m, 2 F), −124.2 (m, 2 F), −126.3 (m, 2 F); IR (thin film) νmax 2934, 1748, 1232 cm−1; LRMS (EI) m/z (%) 384, 355, 43 430
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
Note
The Journal of Organic Chemistry F), −124.1 (m, 2 F), −126.2 (m, 2 F); IR (thin film) νmax 2917, 1232 cm−1; LRMS (EI) m/z (%) 342 (M+), 313, 81 (100); HRMS (ESITOF) m/z calcd for C13H15F9 342.1030, found 342.1032. (E)-(5,5,6,6,7,7,8,8,8-Nonafluorooct-2-en-1-yl)benzene (3i). The product [from (E)-1i, 53.5 mg, 51% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.37 (t, J = 7.2 Hz, 2 H), 7.28 (t, J = 7.8 Hz, 1 H), 7.25 (d, J = 7.2 Hz, 2 H), 5.94 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 5.57 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 3.48 (d, J = 7.2 Hz, 2 H), 2.89 (td, J = 29.4 Hz, J = 7.2 Hz, 2 H); 13C NMR (150.8 MHz, CDCl3) δ 142.1, 140.1, 131.2, 131.2, 130.0, 123.2−120.9 [m, -(CF2) CF3], 120.5 (t, J = 4.2 Hz, CH-CH2CF2), 120.0−117.1 [m, -(CF2) CF3], 41.6, 37.3 (t, J = 22.5 Hz, CH-CH2CF2); 19F NMR (564 MHz, CDCl3) δ −81.2 (m, 3 F), −113.5 (m, 2 F), −124.1 (m, 2 F), −126.2 (m, 2 F); IR (thin film) νmax 3030, 1243, 1130 cm−1; LRMS (EI) m/z (%) 350 (M+), 331, 117 (100); HRMS (ESI-TOF) m/z calcd for C14H11F9 350.0717, found 350.0711. (E)-(6,6,7,7,8,8,9,9,9-Nonafluoronon-3-en-1-yl)benzene (3j). The product [from (E)-1j, 60.1 mg, 55% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.31 (t, J = 7.2 Hz, 2 H), 7.21 (m, 3 H), 5.80 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 5.45 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 2.80 (td, J = 18.0 Hz, J = 7.2 Hz, 2 H), 2.73 (t, J = 7.2 Hz, 2 H), 2.42 (q, J = 7.2 Hz, 2 H); 13C NMR (150.8 MHz, CDCl3) δ 144.0, 140.7, 131.1, 131.0, 128.8, 123.1−119.8 [m, -(CF2)CF3], 119.7 (t, J = 4.2 Hz, CH-CH2CF2), 119.3−111.0 [m, -(CF2)CF3], 38.0, 37.4 (t, J = 22.5 Hz, CH-CH2CF2), 37.0; 19F NMR (564 MHz, CDCl3) δ −81.1 (m, 3 F), −113.6 (m, 2 F), −124.1 (m, 2 F), −126.1 (m, 2 F); IR (thin film) νmax 2929, 1236 cm−1; LRMS (EI) m/z (%) 364 (M+), 287, 91 (100); HRMS (ESI-TOF) m/z calcd for C15H13F9 364.0874, found 364.0872. (E)-1,1,1,2,2,3,3,4,4-Nonafluoro-7-methylhexadec-6-ene (3k). The product [from (E)-1k, 42.0 mg, 35% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1 H NMR (600 MHz, CDCl3) δ 5.17 (t, J = 7.2 Hz, 1 H), 2.81 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.05 (t, J = 7.2 Hz, 2 H), 1.64 (s, 3 H), 1.40 (m, 2 H), 1.31−1.26 (m, 12 H), 0.88 (t, J = 6.6 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 141.3, 118.2−108.3 [m, -(CF2)CF3], 108.0 (t, J = 4.2 Hz, CH-CH2CF2), 107.8−106.5 [m, -(CF2)CF3], 37.6, 29.8, 28.0 (t, J = 22.3 Hz, CH-CH2CF2), 27.6, 27.4, 27.2, 27.0, 25.5, 20.6, 14.1, 11.9; 19F NMR (564 MHz, CDCl3) δ −84.9 (m, 3 F), −117.2 (m, 2 F), −127.9 (m, 2 F), −129.9 (m, 2 F); IR (thin film) νmax 2938, 1745, 1233 cm−1; LRMS (EI) m/z (%) 400 (M+), 288, 69 (100); HRMS (ESI-TOF) m/z calcd for C17H25F9 400.1813, found 400.1806. (E)-(4,4,5,5,6,6,7,7,7-Nonafluorohept-1-en-1-yl)benzene (3l). The product [from (E)-1l, 40 mg, 40% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.40 (d, J = 7.2 Hz, 2 H), 7.35 (t, J = 7.2 Hz, 2 H), 7.28 (t, J = 7.2 Hz, 1 H), 6.63 (d, J = 16.2 Hz, 1 H), 6.15 (dt, J = 16.2 Hz, J = 7.2 Hz, 1 H), 3.01 (td, J = 18.0 Hz, J = 7.2 Hz, 2 H); 19F NMR (564 MHz, CDCl3) δ −80.0 (m, 3 F), −113.1 (m, 2 F), −124.0 (m, 2 F), −126.1 (m, 2 F). This compound is known.26 (E)-1-Methyl-4-(4,4,5,5,6,6,7,7,7-nonafluorohept-1-en-1-yl)benzene (3m). The product [from (E)-1m, 43 mg, 41% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.30 (d, J = 7.8 Hz, 2 H), 7.16 (d, J = 7.8 Hz, 2 H), 6.60 (d, J = 15.6 Hz, 1 H), 6.10 (dt, J = 15.6 Hz, J = 7.2 Hz, 1 H), 3.01 (td, J = 18.0 Hz, J = 7.2 Hz, 2 H), 2.36 (s, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 140.7, 139.8, 136.1, 132.0, 129.0, 123.2 [m, -(CF2)CF3], 117.5 (t, J = 4.5 Hz, CH-CH2CF2), 115.3−109.3 [m, -(CF2)CF3], 37.8 (t, J = 22.6 Hz, CH-CH2CF2), 23.8; 19F NMR (564 MHz, CDCl3) δ −81.1 (m, 3 F), −113.2 (m, 2 F), −124.0 (m, 2 F), −126.1 (m, 2 F); IR (thin film) νmax 2924, 1239 cm−1; LRMS (EI) m/z (%) 350 (M+), 311, 131 (100); HRMS (ESITOF) m/z calcd for C14H11F9 350.0717, found 350.0705. (E)-1-(tert-Butyl)-4-(4,4,5,5,6,6,7,7,7-nonafluorohept-1-en-1-yl)benzene (3n). The product [from (E)-1n, 53 mg, 45% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.37 (d, J = 8.4 Hz, 2 H),
7.34 (d, J = 8.4 Hz, 2 H), 6.61 (d, J = 16.0 Hz, 1 H), 6.10 (dt, J = 16.0 Hz, J = 7.2 Hz, 1 H), 3.01 (td, J = 18.0 Hz, J = 7.2 Hz, 2 H), 1.33 (s, 9 H); 13C NMR (150.8 MHz, CDCl3) δ 154.0, 139.7, 136.1, 128.8, 128.2, 121.6−117.7 [m, -(CF2)CF3], 117.8 (t, J = 4.4 Hz, CHCH2CF2), 113.5−111.2 [m, -(CF2)CF3], 37.8 (t, J = 22.8 Hz, CHCH2CF2), 37.3, 33.8; 19F NMR (564 MHz, CDCl3) δ −76.7 (s, 3 F), −108.8 (m, 2 F), −119.7 (s, 2 F), −121.7 (m, 2 F); IR (thin film) νmax 2958, 1230, 1132 cm−1; LRMS (EI) m/z (%) 392 (M+), 377 (100), 349; HRMS (ESI-TOF) m/z calcd for C17H17F9 392.1187, found 392.1183. (E)-1-Methoxy-3-(4,4,5,5,6,6,7,7,7-nonafluorohept-1-en-1-yl)benzene (3o). The product [from (E)-1o, 41.7 mg, 38% yield] as a pale yellow oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 20:1): 1H NMR (600 MHz, CDCl3) δ 7.26 (t, J = 7.8 Hz, 1 H), 6.99 (d, J = 7.8 Hz, 1 H), 6.93 (s, 1 H), 6.84 (dd, J = 8.4 Hz, J = 2.4 Hz, 1 H), 6.6 (d, J = 15.6 Hz, 1 H), 6.14 (dt, J = 15.6 Hz, J = 7.2 Hz, 1 H), 3.83 (s, 3 H), 3.01 (td, J = 18.0 Hz, J = 7.2 Hz, 2 H); 13 C NMR (150.8 MHz, CDCl3) δ 162.5, 140.3, 139.8, 132.3, 128.8, 121.7, 121.5−119.3 [m, -(CF2)CF3], 118.9 (t, J = 4.4 Hz, CHCH2CF2), 118.3−109.2 [m, -(CF2)CF3], 116.4, 114.5, 57.8, 37.7 (t, J = 22.8 Hz, CH-CH2CF2); 19F NMR (564 MHz, CDCl3) δ −81.1 (t, J = 9.6 Hz, 3 F), −113.2 (m, 2 F), −124.6 (m, 2 F), −126.1 (m, 2 F); IR (thin film) νmax 2988, 1230 cm−1; LRMS (EI) m/z (%) 366 (M+), 347, 147 (100); HRMS (ESI-TOF) m/z calcd for C14H11OF9 366.0666, found 366.0660. (E)-1,1,1,2,2-Pentafluorohexadec-4-ene (4a). The product [from (E)-1a, 69.7 mg, 74% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.70 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 5.37 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 2.74 (td, J = 17.4 Hz, J = 6.6 Hz, 2 H), 2.06 (m, 2 H), 1.37−1.26 (m, 18 H), 0.88 (m, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 141.6, 124.9−119.2 [m, -(CF2)CF3], 118.9 (t, J = 4.5 Hz, CH-CH2CF2), 118.7−111.1 [m, -(CF2)CF3], 37.3 (t, J = 22.3 Hz, CH-CH2CF2), 35.1, 34.6, 32.3, 32.3, 32.2, 32.1, 32.0, 31.7, 31.5, 25.3, 16.7; 19F NMR (564 MHz, CDCl3) δ −84.8 (m, 3 F), −117.4 (t, J = 17.0 Hz, 2 F); IR (thin film) νmax 2917, 1198 cm−1; LRMS (EI) m/z (%) 315 (M+ + H+), 314 (M+), 70 (100); HRMS (ESI-TOF) m/z calcd for C16H27F5 314.2033, found 314.2024. (E)-1,1,1,2,2,3,3-Heptafluoroheptadec-5-ene (5a). The product [from (E)-1a, 76.4 mg, 70% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.71 (dt, J = 18.2 Hz, J = 6.6 Hz, 1 H), 5.39 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 2.77 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.07 (q, J = 7.2 Hz, 2 H), 1.39−1.26 (m, 18 H), 0.88 (t, J = 6.6 Hz, 3 H); 13 C NMR (150.8 MHz, CDCl3) δ 141.6, 123.6−119.1 [m, -(CF2) CF3], 118.7 (t, J = 4.2 Hz, CH-CH2CF2), 117.9−109.5 [m, -(CF2) CF3], 37.2 (t, J = 22.6 Hz, CH-CH2CF2), 35.2, 34.6, 32.3, 32.3, 32.2, 32.1, 32.0, 31.7, 31.5, 25.3, 16.7; 19F NMR (564 MHz, CDCl3) δ −80.8 (s, 3 F), −114.5 (s, 2 F), −127.6 (s, 2 F); IR (thin film) νmax 2931, 1227 cm−1; LRMS (EI) m/z (%) 364 (M+), 308, 48 (100); HRMS (ESI-TOF) m/z calcd for C17H27F7 364.2001, found 364.2014. (E)-1,1,1,2,2,3,3,4,4,5,5,6,6-Tridecafluoroicos-8-ene (6a). The product [from (E)-1a, 94.1 mg, 61% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.71 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 5.39 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 2.78 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.07 (q, J = 7.2 Hz, 2 H), 1.39−1.27 (m, 18 H), 0.88 (t, J = 7.2 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 141.8, 123.2−119.2 [m, -(CF2)CF3], 118.7 (t, J = 4.2 Hz, CH-CH2CF2), 118.0−109.2 [m, -(CF2)CF3], 37.6 (t, J = 22.5 Hz, CH-CH2CF2), 35.2, 34.6, 32.3, 32.3, 32.2, 32.1, 32.0, 31.7, 31.5, 25.3, 16.7; 19F NMR (564 MHz, CDCl3) δ −80.1 (t, J = 10.8 Hz, 3 F), −113.5 (m, 2 F), −122.1 (s, 2 F), −123.0 (s, 2 F), −123.2 (s, 2 F), −127.6 (m, 2 F); IR (thin film) νmax 2930, 1239, cm−1; LRMS (EI) m/z (%) 514 (M+), 486, 43 (100); HRMS (ESI-TOF) m/z calcd for C20H27F13 514.1905, found 514.1910. (E)-tert-Butyl[(15,15,16,16,17,17,17-heptafluoroheptadec-12-en1-yl)oxy]dimethylsilane (5b). The product [from (E)-1b, 93.7 mg, 67% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, 431
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
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The Journal of Organic Chemistry
3 F), −119.8 (t, J = 17.5 Hz, 2 F); IR (thin film) νmax 2930, 1100, 463 cm−1; LRMS (EI) m/z (%) 230 (M+), 215, 69 (100); HRMS (ESITOF) m/z calcd for C10H15F5 230.1094, found 230.1095. (E)-1,1,1,2,2,3,3-Heptafluoro-7-methyldec-5-ene (5g). The product [from (E)-1g, 50.4 mg, 60% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.57 (dd, J = 15.0 Hz, J = 8.4 Hz, 1 H), 5.35 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 2.77 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.18 (m, 1 H), 1.27 (m, 4 H), 0.99 (d, J = 6.6 Hz, 3 H), 0.89 (t, J = 7.2 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 147.6, 121.7− 117.4 [m, -(CF2)CF3], 117.0 (t, J = 4.4 Hz, CH-CH2CF2), 114.0− 109.8 [m, -(CF2)CF3], 41.5, 39.3, 37.2 (t, J = 22.6 Hz, CH-CH2CF2), 22.9, 22.9, 16.6; 19F NMR (564 MHz, CDCl3) δ −83.4 (t, J = 9.6 Hz, 3 F), −117.0 (s, 2 F), −130.1 (m, 2 F); IR (thin film) νmax 2920, 1100, 474 cm−1; LRMS (EI) m/z (%) 280 (M+), 187, 69 (100); HRMS (ESI-TOF) m/z calcd for C11H15F7 280.1062, found 280.1069. (E)-(4,4,5,5,5-Pentafluoropent-1-en-1-yl)benzene (4l). The product [from (E)-1l, 31.8 mg, 45% yield] as a colorless oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.39 (d, J = 7.8 Hz, 2 H), 7.34 (t, J = 7.8 Hz, 2 H), 7.28 (t, J = 7.2 Hz, 1 H), 6.62 (d, J = 16.2 Hz, 1 H), 6.13 (dt, J = 16.2 Hz, J = 8.0 Hz, 1 H), 2.97 (td, J = 17.4 Hz, J = 7.2 Hz, 2 H); 19F NMR (564 MHz, CDCl3) δ −87.4 (m, 3 F), −119.5 (m, 2 F). This compound is known.27 (E)-(4,4,5,5,6,6,6-Heptafluorohex-1-en-1-yl)benzene (5l). The product [from (E)-1l, 236 mg, 42% yield] as a colorless oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.39 (d, J = 7.2 Hz, 2 H), 7.34 (t, J = 7.2 Hz, 2 H), 7.28 (t, J = 7.2 Hz, 1 H), 6.63 (d, J = 16.0 Hz, 1 H), 6.14 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 3.02 (td, J = 18.0 Hz, J = 7.2 Hz, 2 H); 19F NMR (564 MHz, CDCl3) δ −80.6 (t, J = 9.6 Hz, 3 F), −113.9 (m, 2 F), −127.4 (d, J = 3.4 Hz, 2 F). This compound is known.27 (E)-1-(tert-Butyl)-4-(4,4,5,5,5-pentafluoropent-1-en-1-yl)benzene (4n). The product [from (E)-1n, 41.2 mg, 47% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.38 (d, J = 8.4 Hz, 2 H), 7.35 (d, J = 8.4 Hz, 2 H), 6.62 (d, J = 16.0 Hz, 1 H), 6.12 (dt, J = 16.0 Hz, J = 7.2 Hz, 1 H), 2.97 (td, J = 17.4 Hz, J = 7.2 Hz, 2 H), 1.35 (s, 9 H); 13C NMR (150.8 MHz, CDCl3) δ 154.0, 139.5, 136.1, 128.9, 128.3, 131.1−115.9 (m, -CF2CF3), 117.9 (t, J = 4.4 Hz, CH-CH2CF2), 37.6 (t, J = 22.5 Hz, CH-CH2CF2), 37.3, 33.9; 19F NMR (564 MHz, CDCl3) δ −80.5 (s, 3 F), −112.7 (t, J = 17.5 Hz, 2 F); IR (thin film) νmax 2960, 1190 cm−1; LRMS (EI) m/z (%) 292 (M+), 277 (100), 249; HRMS (ESI-TOF) m/z calcd for C15H17F5 292.1250, found 292.1257. (E)-1-(tert-Butyl)-4-(4,4,5,5,6,6,6-heptafluorohex-1-en-1-yl)benzene (5n). The product [from (E)-1n, 45.2 mg, 44% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 7.38 (d, J = 8.4 Hz, 2 H), 7.34 (d, J = 8.4 Hz, 2 H), 6.61 (d, J = 16.0 Hz, 1 H), 6.10 (dt, J = 16.0 Hz, J = 7.2 Hz, 1 H), 3.00 (td, J = 16.8 Hz, J = 7.2 Hz, 2 H), 1.32 (s, 9 H); 13C NMR (150.8 MHz, CDCl3) δ 154.0, 139.6, 136.1, 128.8, 128.2, 128.8−117.7 [m, -(CF2)CF3], 117.8 (t, J = 4.4 Hz, CHCH2CF2), 37.6 (t, J = 22.6 Hz, CH-CH2CF2), 37.3, 33.9; 19F NMR (564 MHz, CDCl3) δ −80.6 (m, 3 F), −113.9 (m, 2 F), −127.4 (m, 2 F); IR (thin film) νmax 2960, 1220, 1110 cm−1; LRMS (EI) m/z (%) 342 (M+), 327 (100), 290; HRMS (ESI-TOF) m/z calcd for C16H17F7 342.1218, found 342.1213. (E)-1,1,1,2,2,3,3,4,4-Nonafluoroheptadec-6-ene (3p). The product [from (E)-1p, 105.7 mg, 88% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.71 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 5.37 (dt, J = 15.6 Hz, J = 7.2 Hz, 1 H), 2.78 (td, J = 6.6 Hz, J = 7.2 Hz, 2 H), 2.06 (m, 2 H), 1.39−1.27 (m, 16 H), 0.89 (t, J = 6.6 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 141.8, 123.2 [m, -(CF2)CF3], 118.7 (t, J = 4.2 Hz, CH-CH2CF2), 117.2−109.4 [m, -(CF2)CF3], 37.4 (t, J = 22.5 Hz, CH-CH2CF2), 35.2, 34.6, 32.4, 32.2, 32.1, 32.0, 31.7, 31.5, 25.3, 16.7; 19F NMR (564 MHz, CDCl3) δ −81.2 (td, J =
CDCl3) δ 5.70 (dt, J = 15.6 Hz, J = 6.6 Hz, 1 H), 5.38 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 3.60 (t, J = 6.6 Hz, 2 H), 2.76 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.06 (q, J = 6.6 Hz, 2 H), 1.51−1.26 (m, 14 H), 0.90 (s, 9 H), 0.05 (s, 6 H); 13C NMR (150.8 MHz, CDCl3) δ 141.8, 12123.6−119.1 [m, -(CF2)CF3], 118.7 (t, J = 4.2 Hz, CH-CH2CF2), 118.0−109.5 [m, -(CF2)CF3], 65.9, 37.2 (t, J = 22.5 Hz, CHCH2CF2), 35.5, 35.2, 32.3, 32.2, 32.0, 32.0, 31.6, 31.5, 28.6, 28.4, −2.7; 19F NMR (564 MHz, CDCl3) δ −80.7 (t, J = 10.8 Hz, 3 F), −114.4 (m, 2 F), −127.5 (m, 2 F); IR (thin film) νmax 2931, 1227 cm−1; LRMS (EI) m/z (%) 465, 409, 69 (100); HRMS (ESI-TOF) m/z calcd for C21H37F7OSi 466.2502, found 466.2503. (E)-tert-Butyldimethyl[(15,15,16,16,17,17,18,18,19,19,20,20,20tridecafluoroicos-12-en-1-yl)oxy]silane (6b). The product [from (E)-3b, 96.1 mg, 52% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.71 (dt, J = 16.0 Hz, J = 6.6 Hz, 1 H), 5.38 (dt, J = 15.0 Hz, J = 6.6 Hz, 1 H), 3.60 (t, J = 6.6 Hz, 2 H), 2.77 (td, J = 18.6 Hz, J = 6.6 Hz, 2 H), 2.06 (q, J = 7.2 Hz, 2 H), 1.52−1.26 (m, 14 H), 0.89 (s, 9 H), 0.05 (s, 6 H); 13C NMR (150.8 MHz, CDCl3) δ 139.1, 121.6−116.2 [m, -(CF2)CF3], 116.1 (t, J = 4.2 Hz, CH-CH2CF2), 116.0−108.1 [m, -(CF2)CF3], 63.2, 37.4 (t, J = 22.8 Hz, CHCH2CF2), 32.8, 32.5, 29.5, 29.4, 29.3, 29.0, 28.8, 25.9, 25.7, 18.3, −5.4; 19F NMR (564 MHz, CDCl3) δ −80.9 (m, 3 F), −113.5 (s, 2 F), −122.1 (s, 2 F), −123.0 (s, 2 F), −123.2 (m, 2 F), −126.2 (m, 2 F); IR (thin film) νmax 2934, 1240 cm−1; LRMS (EI) m/z (%) 615 (M+), 559, 83 (100); HRMS (ESI-TOF) m/z [M]+ calcd for C24H37F13OSi 616.2406, found 616.2415. (E)-Diethyl(13,13,14,14,15,15,15-heptafluoropentadec-10-en-1yl)phosphate (5d). The product [from (E)-1d, 93.7 mg, 64% yield] as a pale yellow oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 5.68 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 5.36 (dt, J = 16.0 Hz, J = 7.2 Hz, 1 H), 4.09 (m, 4 H), 4.00 (q, J = 6.6 Hz, 2 H), 2.75 (td, J = 18.6 Hz, J = 6.6 Hz, 2 H), 2.03 (q, J = 7.2 Hz, 2 H), 1.65 (m, 2 H), 1.35− 1.23 (m, 18 H); 13C NMR (150.8 MHz, CDCl3) δ 141.7, 123.5− 119.0 [m, -(CF2)CF3], 118.7 (t, J = 4.2 Hz, CH-CH2CF2), 118.0− 109.5 [m, -(CF2)CF3], 70.3 (d, J = 6.0 Hz), 66.2 (d, J = 5.7 Hz), 37.1 (t, J = 22.6 Hz, CH-CH2CF2), 35.1, 32.8, 32.0, 31.9, 31.7, 31.5, 31.5, 28.0, 18.7; 19F NMR (564 MHz, CDCl3) δ −80.7 (m, 3 F), −114.5 (m, 2 F), −127.6 (s, 2 F); IR (thin film) νmax 2934, 1228, 1038 cm−1; IR (thin film) νmax 2934, 1228, 1038 cm−1; LRMS (EI) m/z (%) 488 (M + ), 364, 155 (100); HRMS (ESI-TOF) m/z calcd for C19H32F7O4P 488.1926, found 488.1915. (E)-Diethyl(13,13,14,14,15,15,16,16,17,17,18,18,18-tridecafluorooctadec-10-en-1-yl)phosphate (6d). The product [from (E)-1d, 93.8 mg, 49% yield] as a pale yellow oil was purified via silica gel chromatography (petroleum ether/ethyl ether = 3:1): 1H NMR (600 MHz, CDCl3) δ 5.68 (dt, J = 16.0 Hz, J = 6.6 Hz, 1 H), 5.36 (dt, J = 16.0 Hz, J = 6.6 Hz, 1 H), 4.09 (m, 4 H), 4.00 (q, J = 6.6 Hz, 2 H), 2.74 (td, J = 18.0 Hz, J = 7.2 Hz, 2 H), 2.04 (q, J = 6.6 Hz, 2 H), 1.65 (m, 2 H), 1.36−1.23 (m, 18 H); 13C NMR (150.8 MHz, CDCl3) δ 141.8, 123.5−118.9 [m, -(CF2)CF3], 118.9 (t, J = 4.2 Hz, CHCH2CF2), 118.0−110.0 [m, -(CF2)CF3], 70.3 (d, J = 6.0 Hz), 66.2 (d, J = 5.9 Hz), 37.4 (t, J = 22.6 Hz, CH-CH2CF2), 35.1, 32.9, 32.8, 32.0, 31.9, 31.7, 31.6, 31.5, 28.0, 18.7; 19F NMR (564 MHz, CDCl3) δ −80.9 (m, 3 F), −113.5 (m, 2 F), −112.1 (s, 2 F) −123.0 (s, 2 F), −123.0 (m, 2 F), −126.3 (m, 2 F); IR (thin film) νmax 2941, 1245, 1030 cm−1; LRMS (EI) m/z (%) 639 (M+ + H+), 638 (M+), 155 (100); HRMS (ESI-TOF) m/z calcd for C22H32F13O4P 638.1831, found 638.1833. (E)-8,8,9,9,10,10,11,11,11-Nonafluoro-4-methylundec-5-ene (4g). The product [from (E)-1g, 40.7 mg, 59% yield] as a colorless oil was purified via silica gel chromatography [petroleum ether (100%)]: 1 H NMR (600 MHz, CDCl3) δ 5.57 (dd, J = 16.0 Hz, J = 8.4 Hz, 1 H), 5.35 (dt, J = 16.0 Hz, J = 7.2 Hz, 1 H), 2.77 (td, J = 18.6 Hz, J = 7.2 Hz, 2 H), 2.18 (m, 1 H), 1.31 (m, 4 H), 0.99 (d, J = 6.6 Hz, 3 H), 0.89 (t, J = 7.2 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 147.6, 122.7−117.2 (m, -CF2CF3), 117.0 (t, J = 4.4 Hz, CH-CH2CF2), 116.7−109.5 (m, -CF2CF3), 41.5, 39.3, 37.4 (t, J = 22.5 Hz, CHCH2CF2), 22.9, 22.9, 16.7; 19F NMR (564 MHz, CDCl3) δ −87.3 (s, 432
DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
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The Journal of Organic Chemistry 9.6 Hz, J = 2.3 Hz, 3 H), −113.8 (m, 2 F), −124.2 (m, 2 F), −126.2 (m, 2 F); IR (thin film) νmax 2938, 1239 cm−1; LRMS (EI) m/z (%) 400 (M+), 372, 48 (100); HRMS (ESI-TOF) m/z calcd for C17H25F9 400.1813, found 400.1811. (E)-1,1,1,2,2,3,3,4,4,5,5,6,6-Tridecafluorononadec-8-ene (6p). The product [from (E)-1p, 106.5 mg, 71% yield] as a pale yellow oil was purified via silica gel chromatography [petroleum ether (100%)]: 1H NMR (600 MHz, CDCl3) δ 5.70 (dt, J = 15.0 Hz, J = 7.2 Hz, 1 H), 5.37 (dt, J = 16.0 Hz, J = 7.2 Hz, 1 H), 2.78 (td, J = 19.0 Hz, J = 7.2 Hz, 2 H), 2.06 (m, 2 H), 1.39−1.27 (m, 16 H), 0.88 (t, J = 6.6 Hz, 3 H); 13C NMR (150.8 MHz, CDCl3) δ 141.8, 123.2 [m, -(CF2)CF3], 118.7 (t, J = 4.2 Hz, CH-CH2CF2), 117.0−109.0 [m, -(CF2)CF3], 37.4 (t, J = 22.6 Hz, CH-CH2CF2), 35.2, 34.5, 32.3, 32.2, 32.1, 32.0, 31.7, 31.5, 25.3, 16.6; 19F NMR (564 MHz, CDCl3) δ −81.0 (m, 3 H), −113.5 (m, 2 F), −122.1 (m, 2 F), −123.0 (s, 2 F), −123.2 (s, 2 F), −126.3 (s, 2 F); IR (thin film) νmax 2927, 1656, 1238 cm−1; LRMS (EI) m/z (%) 500 (M+), 472, 43 (100); HRMS (ESITOF) m/z calcd for C19H25F13 500.1749, found 500.1741.
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alpha(2A)-antagonism combination to prevent and contrast morphine tolerance and dependence. J. Med. Chem. 2010, 53, 7825. (2) For selected reviews, see: (a) Hollingworth, G. J. In Comprehensive Organic Functional Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Pattenden, G., Eds.; Elsevier Science: Oxford, 1995; Vol 5, p 4227. (b) Kevill, D. N. Choloroformate Esters and Related Compounds. In The Chemistry of the Functional Groups: The Chemistry of Acyl Halides; Patai, S., Ed. Wiley: New York, 1972, p 381. (c) Jacobsen, E. N.; Wu, M. H. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. Springer: New York, 1999, Chapter 18, p 2. (3) For selected examples, see: (a) Tsuji, J.; Minami, I.; Shimizu, I. Allyation of carbonucleophiles with allylic carbonates under neutral conditions catalyzed by rhodium complexes. Tetrahedron Lett. 1984, 25, 5157. (b) Kondo, T.; Ono, H.; Satake, N.; Mitsudo, T.-a.; Watanabe, Y. Nucleophilic and Electrophilic Allylation Reactions. Synthesis, Structure, and Ambiphilic Reactivity of (.eta.3-Allyl)ruthenium(II) Complexes. Organometallics 1995, 14, 1945. (c) Takeuchi, R.; Kitamura, N. Rhodium complex-catalysed allylic alkylation of allylic acetates. New J. Chem. 1998, 22, 659. (d) Evans, P. A.; Nelson, J. D. Regioselective rhodium-catalyzed allylic alkylation with a modified Wilkinson’s catalyst. Tetrahedron Lett. 1998, 39, 1725. (e) Morisaki, Y.; Kondo, T.; Mitsudo, T.-a. Ruthenium-Catalyzed Allylic Substitution of Cyclic Allyl Carbonates with Nucleophiles. Stereoselectivity and Scope of the Reaction. Organometallics 1999, 18, 4742. (f) Trost, B. M.; Fraisse, P. L.; Ball, Z. T. A Stereospecific Ruthenium-Catalyzed Allylic Alkylation. Angew. Chem., Int. Ed. 2002, 41, 1059. (g) Takeuchi, R. Iridium Complex-Catalyzed Highly Selective Organic Synthesis. Synlett 2002, 1954. (h) Hayashi, T.; Okada, A.; Suzuka, T.; Kawatsura, M. High enantioselectivity in rhodium-catalyzed allylic alkylation of 1-substituted 2-propenyl acetates. Org. Lett. 2003, 5, 1713. (4) Bao, X.; Liu, L.; Li, J.; Fan, S. Copper-Catalyzed Oxidative Perfluoroalkylation of Aryl Boronic Acids Using Perfluoroalkylzinc Reagents. J. Org. Chem. 2018, 83, 463. (5) (a) Kato, H.; Hirano, K.; Kurauchi, D.; Toriumi, N.; Uchiyama, M. Dialkylzinc-mediated cross-coupling reactions of perfluoroalkyl and perfluoroaryl halides with aryl halides. Chem. - Eur. J. 2015, 21, 3895. (b) Aikawa, K.; Nakamura, Y.; Yokota, Y.; Toya, W.; Mikami, K. Stable but reactive perfluoroalkylzinc reagents: application in ligand-free copper-catalyzed perfluoroalkylation of aryl iodides. Chem. - Eur. J. 2015, 21, 96. (6) (a) Yao, T.; Hirano, K.; Satoh, T.; Miura, M. Stereospecific copper-catalyzed C-H allylation of electron-deficient arenes with allyl phosphates. Angew. Chem., Int. Ed. 2011, 50, 2990. (b) Fan, S.; Chen, F.; Zhang, X. Direct palladium-catalyzed intermolecular allylation of highly electron-deficient polyfluoroarenes. Angew. Chem., Int. Ed. 2011, 50, 5918. (7) For selected reviews, see: (a) Fried, J.; Sabo, E. F. 9α-Fluoro Derivatives of Cortisone and Hydrocortisone. J. Am. Chem. Soc. 1954, 76, 1455. (b) Shimizu, M.; Hiyama, T. Modern synthetic methods for fluorine-substituted target molecules. Angew. Chem., Int. Ed. 2005, 44, 214. (c) Mullin, R. Insights. Chem. Eng. News 2006, 84, 15. (d) Muller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition. Science 2007, 317, 1881. (e) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in medicinal chemistry. Chem. Soc. Rev. 2008, 37, 320. (f) O’Hagan, D. Understanding organofluorine chemistry. An introduction to the CF bond. Chem. Soc. Rev. 2008, 37, 308. (g) Wang, J.; Sanchez-Rosello, M.; Acena, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001−2011). Chem. Rev. 2014, 114, 2432. (8) For selected reviews, see: (a) Zhang, C. Application of Langlois’ Reagent in Trifluoromethylation Reactions. Adv. Synth. Catal. 2014, 356, 2895. (b) Xu, J.; Liu, X.; Fu, Y. Recent advance in transitionmetal-mediated trifluoromethylation for the construction of C(sp3)− CF3 bonds. Tetrahedron Lett. 2014, 55, 585. (c) Merino, E.; Nevado, C. Addition of CF3 across unsaturated moieties: a powerful
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b02432. Preparation of allyl phosphates and copies of 1H, 19F, and 13C NMR spectra (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Shilu Fan: 0000-0003-0315-7874 Author Contributions ⊥
L.L. and X.B. contributed equally to this work.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was financially supported by the National Natural Science Foundation of China (Grant 21602041), the Natural Science Foundation of Anhui Province (Grant 1708085QB38), the Anhui Province Key Laboratory of Advanced Catalytic Materials and Reaction Engineering (Grant 45000-411104/ 007), and the Start-up Foundation of Hefei University of Technology. The authors thank Prof. Chun-Yang He and Dr. Ji-Wei Gu for helpful discussions.
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REFERENCES
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DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
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DOI: 10.1021/acs.joc.8b02432 J. Org. Chem. 2019, 84, 423−434
