English

• 1.   Introduction

  Introduction of a trifluoromethyl group to a molecule can modify its biological properties. This strategy has been used extensively in pharmaceutical research, ^[1] and syn-thetic protocols have been established for construction of C—CF₃ bonds.^[2] The analogous trichloromethyl group is present in various natural products^[3] and has also been applied in medicinal chemistry.^[4] However, methods for introduction of a trichloromethyl group have not been systematically explored. Photoredox catalysis is one pow-erful method for this transformation. For example, 1, 2-Kharasch addition of trichloromethyl radical to alkene under visible-light irradiation occurs in the presence or absence of a photoredox catalyst.^[5] In 2015, Meggers and co-workers^[6] reported catalytic enantioselective tri-chloromethylation of 2-acyl imidazoles with a chiral Ir catalyst via visible-light photoredox catalysis. In 2016, Li and co-workers^[7] reported a work on α-trichloromethylation of 2-acylpyridines with Ir-Co cap-sule as photocatalyst.

  The utilization of cyclopropyl group as radical clock was well-known for decades in mechanistic study to eluci-date a radical pathway. Despite extensive examples of cyclopropyl group as radical probe, its corresponding syn-thetic application was well explored. We recently reported that α-cyclopropyl styrenes underwent an photoredox Ir-catalyzed difluoroalkylation/C—H cascade to give par-tially hydrogenated naphthalene and quinoline derivatives (Scheme 1).^[8] In this reaction, α-cyclopropyl styrenes was a building block of five carbons with high reactivity in radical annulation reaction.^[9] We postulated that this an-nulation could be interrupted if the radical intermediate could be trapped and a chain product would be the desired product. Herein, we report a method for ring-opening 1, 5-bromotrichloromethylation of α-cyclopropyl styrene followed by E-Z isomerization via visible-light photoca-talysis with Ir catalyst, as well as extension of the method to trisubstituted styrenes.

  Scheme 1

  

  Scheme 1.  Application of α-cyclopropyl radical 1, 5-difunctiona- lizaton

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  2.   Results and discussion

  We began by carrying out reactions of α-cyclopropyl styrene (1a) with BrCCl₃ in the presence of various photo-catalysts under irradiation with blue LEDs at room tem-perature under argon (Table 1). With Ru or Ir complexes as catalysts, the desired ring-opening products were obtained in good to excellent yields (Entries 1~3), although the Z/E ratios of the products varied considerably. With Ru(bpy)₃-Cl₂ as the catalyst, the major product was a mixture of 2a (Z) and 2a' (E) (Z:E＝30:70, Entry 1). A similar Z/E ratio was achieved with 1 mol% fac-Ir(ppy)₃ as the catalyst (Entry 2). The Z/E selectivity changed to 60:40 in the presence of Ir(ppy)₂(dtbbpy)PF₆ (Entry 3). However, when Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆ was the catalyst, 2a became the predominant product, with a Z/E ratio of 96:4 (Entry 4). Experiments with various solvents, such as N, N-dimethylformamide (DMF), CH₂Cl₂, and EtOH, revealed that acetonitrile was optimal (Entries 5~8). The photocatalyst was essential (Entry 9). When white LEDs were used instead of blue LEDs, the Z/E ratio dropped to 75:25 (Entry 10). The reaction did not proceed in the absence of light (Entry 11). When the reaction was carried out under air, the yield and Z/E ratio dropped (Entry 12).

  Table 1

  

  Table 1.  Optimization of 1, 5-bromotrichloromethylation/iso- merization cascade reaction of α-cyclopropylstyrenea

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  Entry	Photocatalyst	Solvent	Yieldb/%	Z:Ec
  1	Ru(bpy)3Cl2	CH3CN	92	30:70
  2	fac-Ir(ppy)3	CH3CN	90	31:69
  3	Ir(ppy)2(dtbbpy)PF6	CH3CN	95	60:40
  4	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH3CN	95	96:4
  5	Ir[dF(CF3)ppy]2(dtbbpy)PF6	DMF	91	74:26
  6	Ir[dF(CF3)ppy]2(dtbbpy)PF6	DMSO	90	91:9
  7	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH2Cl2	89	73:27
  8	Ir[dF(CF3)ppy]2(dtbbpy)PF6	EtOH	94	94:6
  9	None	CH3CN	N.R.	—
  10d	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH3CN	93	75:25
  11e	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH3CN	N.R.	—
  12f	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH3CN	81	76:24
  a Reaction conditions: 1a (0.1 mmol), BrCCl3 (0.1 mmol), photocatalyst (0.001 mmol, 1.0 mol%), anhydrous solvent (1.0 mL), 24 W blue LEDs, 1.5 h, r.t., argon atmosphere. b Isolated yield of Z/E mixture. N.R.＝no reaction. c Determined by GC-MS. d White LEDs. e No light. f Under air.

  Using the optimized conditions, we explored the scope of the reaction with a series of α-cyclopropyl styrenes as substrates (Table 2). Our initial experiments revealed that para substitution on the phenyl ring did not affect the out-come of the reaction: products with either electron- withdrawing or electron-donating group could be prepared with high Z/E ratios and in excellent yields (2b~2h, the yields in Table 2 are for isolated Z isomers). Substrates with a meta substituent on the phenyl ring were tested as well, and desired Z products 2i and 2j could be achieved in good to excellent yields. Subsequently, we evaluated ortho-substituted substrates 1k and 1l and found that ortho substitution disturbed the conjugation between the phenyl ring and the double bond. Product 2k, which has an ortho methyl group, was obtained with a moderate Z/E ratio of 85:15 (as indicated by GC-MS), and was isolated in a good yield (82%). Substrates 1n and 1o, which have a naphthalene moiety, were synthesized and subjected to the standard reaction conditions to obtain α- and β-naphthalenyl products 2n and 2o in good yields. To our delight, the reaction of substrate 1p, which bears a pyridine ring, with BrCCl₃ in the presence of 1 mol% Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆ proceeded with excellent Z/E selectivity to afford 2p in 92% yield. α-Cyclopropyl vinyl thiophene 1q underwent the ring-opening reaction as well, offering 2q with moderate Z selectivity in 70% yield. We were interested to find that benzothiophene 2r could also be prepared with excellent Z selectivity and yield. A α-cyclpropyl-β-methyl styrene was also compatible with this conditions, and corresponding 2s was obtained in 89% yield with Z isomer as major product.

  Table 2

  

  Table 2.  Substrate scope of 1, 5-bromotrichloromethylation/isomerization cascade reaction^a

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  a Reaction conditions: 1 (0.1 mmol), BrCCl3 (0.1 mmol, 1 equiv.), and Ir[dF(CF3)ppy]2(dtbbpy)PF6 (0.001 mmol, 1 mol%) in anhydrous CH3CN (1.0 mL) with irradiation by blue LEDs for 1.5 h at room temperature under argon. b Isolated yield of Z product; ratio of 2 to 2' determined by GC-MS.

  Subsequently, we carried out several control reactions to track the steps of this process (Scheme 2). Ring-opening 1, 5-bromotrichloromethylation of 1a for 10 min using 1 mol% Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆ under irradiation with light gave 2a and 2a' with a conversion of 30% and a Z/E ratio of 30:70. This reaction reached full conversion after additional 1.5 h with Z/E ratio of 95:5 (Scheme 2a). On the other hand, under irradiation of LEDs, the isolated mixture of 2a and 2a', with a ratio of 30:70 reamained intact if catalyst was absent (Scheme 2b).

  Scheme 2

  

  Scheme 2.  Control experiments and proposed mechanism

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  With the other catalysts listed in Table 1, the ring- opening 1, 5-bromotrichloromethylation reaction occurred at a similar rate to that using Ir[dF(CF₃)-ppy]₂(dtbbpy)PF₆ within 10 min. In comparison, the redox radical annulation reaction of the radical intermediate with Z configuration deriving from α-cyclopropyl styrene takes more than 10 h.^[10] This difference suggested that the first step of the reaction might proceed via a chain pathway, a process much faster than the radical annulation pathway.^[11] Next, control experiment showed the subsequent Z-E isomerization took place only when the catalyst was Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆ (Scheme 2b). From these results, we postulated the mechanism shown in Scheme 2c. First, the excited photocatalyst donates an electron to BrCCl₃ (A), which then undergoes mesolysis to yield bromide anion and trichloromethyl radical B. Addition of this radical to the vinyl group of 1 leads to opening of the cyclopropyl ring. The resulting highly reactive intermediate C, which bears a terminal carbon radical, can react directly with BrCCl₃ to initiate another chain cycle and to afford a product with the E configuration (2') as the major product at this stage. In this innate chain reaction of 1b, a quantum yield of 1.4 was measured with a procedure reported by Yoon et al.^[12] Alternatively, the photocatalyst in the M⁺ state can oxidize intermediate C to produce carbocation D, which can combine with bromide anion to terminate the chain process. Subsequent E-Z isomerization can take place via energy transfer from excited-state Ir[dF(CF₃)-ppy]₂(dtbbpy)PF₆ to afford the Z product (2). E-Z isomeri-zation of double bond was achieved with UV light.^[13] Re-cently, E to Z isomerization of substituted styrenes, ^[14] stil-bene^[15] and α, β-unsaturated compounds^[16] were realized with visible-light-induced catalysis. However, to our knowledge, a cascade reaction involving bromotrichloro-methylation and E-Z isomerization to give trisubstituted styrenes has not previously been demonstrated.

  We further explored the E-Z isomerization of trisubsti-tuted styrenes 3 of E configuration that were readily avail-able from Horner-Wadsworth-Emmons reaction and fol-lowing reduction reaction (Table 3).^[17] With 1 mol% Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆ as catalyst under irradiation of blule LEDs for 1.5 h, Z-3a could be achieved in excellent yield with Z/E ratio of 99:1 observed on GC. Elec-tron-affacting groups in Z-3b and Z-3c did not impact this conversion of E-Z configuration, and corresponding Z-3b and Z-3c could be isolated in 95% and 96% yields, respec-tively. The size of substitution of alkene was changed in substrate E-3d and E-3e, and to our delight, Z-products could be generated with excellent yields as well.

  Table 3

  

  Table 3.  E-Z isomerization of trisubstituted styrenes

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  a Reaction conditions: E-3 (0.2 mmol) and Ir[dF(CF3)ppy]2(dtbbpy)PF6 (0.002 mmol, 1 mol%) in anhydrous CH3CN (2.0 mL) with irradiation by blue LEDs for 1.5 h at room temperature under argon. b Trace of E-3 was detected with GC-MS upon completion but could not be observed during the isolation of Z-3. Ratio of Z to E determined by GC-MS.

  Next, we demonstrated transformation of bromo atom in product 2b with nucleophilic substitution reaction (Scheme 3). Sodium azide reacted with 2b and gave rise to 4 in 91% yield. The basic hydrolysis of 2b in the presence of tri- chloromethyl group resulted in decomposition. A two-step procedure^[19] of esterification and acidic hydrolysis could prepare alcohol 5 in 63% yield.

  Scheme 3

  

  Scheme 3.  Transformation of bromo atom in product 2b

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  3.   Conclusions

  In summary, we developed a catalytic method for a 1, 5-bromotrichloromethylation/E-Z isomerization cascade reaction. Z products were generated in nearly quantitative yields via a radical chain/energy-transfer pathway. This method could also be used for E-Z isomerization of trisub-stituted styrenes with Z/E ratio up to 99:1 in excellent yields.

  4.   Experimental section

  4.1   General information

  All reactions that required anhydrous conditions were carried out with standard procedures under argon atmos-phere. Unless otherwise noted, materials were purchased from commercial suppliers and used without further puri-fication. The solvents were dried by distillation over the appropriate drying reagents. Column chromatography was generally performed on silica gel (300~400 mesh) and reactions were monitored by thin-layer chromatography (TLC) using 254 nm of UV light to visualize the progress. ¹H NMR (400 MHz), ¹³C NMR (100 MHz) and ¹⁹F NMR (376 MHz) were measured on 400M spectrometer. IR spectra were recorded as a thin film on a KBr disk (2 cm diameter) using an FT-IR spectrometer and reported in wavenumbers (cm^－1). A Hitachi F-4500 fluorescence spectrophotometer with a 150 W Xe lamp was used as the light source for the quantum yield measurements. High-resolution mass spectra (HRMS) were equipped with an EI source and a TOF detector mass spectrometer. The melting points were measured with digital melting point detector.

  4.2   Synthesis of substrates

  Substrates 1^[18] and E-3^[19] were synthesized according to the reported literature.

  Ethyl 4-(1-cyclopropylvinyl)benzoate (1h): 81% yield, chromatography on silica gel (petroleum ether/EtOAc, V:V＝98:2), colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 8.01 (d, J＝7.6 Hz, 2H), 7.64 (d, J＝7.7 Hz, 2H), 5.37 (s, 1H), 5.03 (s, 1H), 4.38 (q, J＝7.1 Hz, 2H), 1.68~1.68 (m, 1H), 1.40 (t, J＝7.1 Hz, 3H), 0.91~0.82 (m, 3H), 0.60~0.58 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 166.5, 148.6, 146.0, 129.4, 129.4 126.0, 111.0, 60.9, 15.5, 14.3, 6.7; IR (film) ν: 2983, 1770, 1759, 1716, 1368, 1276, 1247, 1108, 1020, 863, 781, 718 cm^－1; HRMS (EI) calcd for C₁₄H₁₆O₂ 216.1150, found 216.1153.

  1-Chloro-3-(1-cyclopropylvinyl)benzene (1i): 91% yield, chromatography on silica gel (petroleum ether), colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.61 (s, 1H), 7.50 (s, 1H), 7.29 (s, 2H), 5.32 (s, 1H), 5.01 (s, 1H), 1.70~1.59 (m, 1H), 0.89 (d, J＝7.2 Hz, 2H), 0.62 (d, J＝4.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 148.2, 143.5, 134.1, 129.3, 127.4, 126.3, 124.3, 110.2, 15.5, 6.7; IR (film) ν: 3085, 1594, 1563, 1475, 885, 787, 757 cm^－1; HRMS (EI) calcd for C₁₁H₁₁Cl 178.0549, found 178.0556.

  1-(1-Cyclopropylvinyl)-2-methylbenzene (1k): 92% yield, chromatography on silica gel (petroleum ether), col-orless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.23~7.10 (m, 3H), 7.06 (d, J＝7.0 Hz, 1H), 5.16~5.12 (m, 1H), 4.79 (d, J＝1.7 Hz, 1H), 2.32 (s, 3H), 1.59~1.66 (m, 1H), 0.76~0.68 (m, 2H), 0.45~0.38 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 151.2, 141.3, 135.4, 129.7, 128.9, 126.9, 125.1, 110.8, 19.9, 17.2, 6.4; IR (film) ν: 3083, 3015, 1627, 1488, 882, 761, 731 cm^－1; HRMS (EI) calcd for C₁₂H₁₄ 158.1096, found 158.1095.

  3-(1-Cyclopropylvinyl)benzo[b]thiophene (1r): 85% yield, chromatography on silica gel (petroleum ether/ EtOAc, V:V＝98:2), colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.99 (dt, J＝8.0, 1.1 Hz, 1H), 7.89~7.83 (m, 1H), 7.43~7.32 (m, 3H), 5.20 (dd, J＝3.4, 1.3 Hz, 2H), 1.79~1.69 (m, 1H), 0.85~0.79 (m, 2H), 0.66~0.60 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 145.1, 140.3, 138.3, 138.2, 124.2, 124.1, 123.4, 122.8, 122.7, 111.1, 17.1, 7.2; IR (film) ν: 3082, 3009, 1622, 1426, 1020, 762, 737 cm^－1; HRMS (EI) calcd for C₁₃H₁₂S 200.0660, found 200.0657.

  (1-Cyclopropylprop-1-en-1-yl)benzene (1s): 88% yield, chromatography on silica gel (petroleum ether), colorless oil. ¹H NMR (400 MHz, Chloroform-d) δ: 7.43~7.16 (m, 11H), 5.88~5.82 (m, 1H), 5.63~5.52 (m, 1H), 1.96 (dd, J＝6.9, 1.1 Hz, 3H), 1.80~1.72 (m, 1H), 1.67~1.59 (m, 1H), 1.59~1.54 (m, 4H), 0.88~0.82 (m, 2H), 0.69~0.63 (m, 2H), 0.50~0.44 (m, 2H), 0.39~0.31 (m, 2H); ¹³C NMR (100 MHz, Chloroform-d) δ: 142.7, 142.3, 141.2, 140.3, 128.8, 127.9, 127.7, 127.1, 126.4, 126.1, 125.7, 119.5, 18.4, 14.6, 14.2, 11.2, 6.5, 5.1; HRMS (EI) calcd for C₁₂H₁₄ 158.1096, found 158.1092.

  (E)-3-(4-Methoxyphenyl)pent-2-en-1-ol (E-3b): 85% yield, chromatography on silica gel (petroleum ether/ EtOAc, V:V＝5:1), colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.31 (d, J＝8.1 Hz, 2H), 6.86 (d, J＝8.1 Hz, 2H), 5.78 (t, J＝6.8 Hz, 1H), 4.33 (d, J＝6.7 Hz, 2H), 3.81 (s, 3H), 2.51 (q, J＝7.4 Hz, 2H), 1.84 (s, 1H), 0.98 (t, J＝7.5 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 158.8, 144.1, 134.2, 127.4, 124.7, 113.6, 59.5, 55.2, 23.1, 13.9; IR (film) ν: 3354, 2966, 2874, 2836, 1607, 1510, 1464, 1287, 1247, 1035, 828, 799 cm^－1; HRMS (EI) calcd for C₁₂H₁₆O₂ 192.1150, found 192.1154.

  (E)-3-(4-(Trifluoromethyl)phenyl)pent-2-en-1-ol (E-3c): 82% yield, chromatography on silica gel (petroleum ether/ EtOAc, V:V＝5:1), colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.56 (d, J＝8.1 Hz, 2H), 7.45 (d, J＝8.1 Hz, 2H), 5.87 (t, J＝6.6 Hz, 1H), 4.37 (d, J＝6.6 Hz, 2H), 2.53 (q, J＝7.5 Hz, 2H), 1.99 (s, 1H), 0.97 (t, J＝7.5 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 145.5, 143.4, 129.1 (q, J＝32.5 Hz), 128.1, 126.6, 125.2 (q, J＝3.8 Hz), 124.2 (q, J＝270 Hz), 59.4, 23.1, 13.6; IR (film) ν: 3332, 2972, 2937, 2878, 16151327, 1166, 1121, 1068, 1016, 835, 749 cm^－1; HRMS (EI) calcd for C₁₂H₁₃OF₃ 230.0918, found 230.0927.

  4.3   Synthesis of compound 2

  An oven-dried reaction vial was equipped with a mag-netic stir bar, compound 1 (0.1 mmol), Ir[dF(CF₃)ppy]₂-(dtbbpy)PF₆ (0.001 mmol), and bromotrichloromethane (0.1 mmol). The flask was evacuated and backfilled with argon for 3 times. Anhydrous CH₃CN (1 mL) was added with syringe. The vial was placed at a distance (app. 5 cm) from 24 W blue LED strip, and the resulting solution was stirred at ambient temperature for 1.5 h. The mixture was concentrated under reduced pressure. The residue was pu-rified by chromatography on silica gel to afford the desired product.

  (Z)-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)benzene (2a): chromatography on silica gel (petroleum ether), 91% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.38~7.32 (m, 2H), 7.32~.27 (m, 1H), 7.20~7.22 (m, 2H), 5.88 (t, J＝7.1 Hz, 1H), 3.78 (s, 2H), 3.38 (t, J＝6.8 Hz, 2H), 2.64 (q, J＝6.9 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 136.6, 133.8, 128.8, 128.2, 127.4, 98.4, 62.6, 32.2, 32.1. IR (film) ν: 3022, 2962, 2924, 1442, 1268, 964, 812, 701, 643 cm^－1; HRMS (EI) calcd for C₁₂H₁₂Cl₃Br 339.9188, found 339.9193.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-4-meth- oxybenzene (2b): chromatography on silica gel (petroleum ether/EtOAc, V:V＝99:1), 92% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.17~7.07 (m, 2H), 6.93~6.84 (m, 2H), 5.83 (t, J＝7.1 Hz, 1H), 3.82 (s, 3H), 3.74 (s, 2H), 3.37 (t, J＝6.8 Hz, 2H), 2.65 (q, J＝6.9 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 158.8, 136.3, 133.4, 131.1, 129.9, 113.6, 98.5, 62.6, 55.2, 32.3, 32.1; IR (film) ν: 2958, 2930, 2836, 1608, 1511, 1248, 1177, 1033, 839, 711 cm^－1; HRMS (EI) calcd for C₁₃H₁₄OCl₃Br 369.9294, found 369.9290.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-4-fluoro- benzene (2c): chromatography on silica gel (petroleum ether), 90% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.21~7.14 (m, 2H), 7.08~7.01 (m, 2H), 5.87 (t, J＝7.1 Hz, 1H), 3.74 (s, 2H), 3.38 (t, J＝6.7 Hz, 2H), 2.62 (q, J＝6.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 162.1 (d, J＝246.8 Hz), 135.7, 134.8 (d, J＝3.5 Hz), 134.3, 130.5 (d, J＝8.0 Hz), 115.4, 115.2, 98.2, 62.7, 32.1, 31.9. IR (film) ν: 2961, 2925, 2853, 1603, 1509, 1223, 844, 728, 712, 623 cm^－1; HRMS (EI) calcd for C₁₂H₁₁FCl₃Br 357.9094, found 357.9088.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-4-chloro- benzene (2d): chromatography on silica gel (petroleum ether), 91% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.37~7.30 (m, 2H), 7.18~7.12 (m, 2H), 5.89 (t, J＝7.2 Hz, 1H), 3.75 (s, 2H), 3.38 (t, J＝6.7 Hz, 2H), 2.62 (q, J＝6.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 137.3, 135.6, 134.6, 133.30, 130.2, 128.5, 98.2, 62.5, 32.1, 31.8; IR (film) ν: 2962, 2965, 1491, 1269, 1091, 1014, 841, 725, 710, 650 cm^－1; HRMS (EI) calcd for C₁₂H₁₁Cl₄Br 373.8798, found 373.8799.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-4-bromo- benzene (2e): chromatography on silica gel (petroleum ether), 93% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.54~7.45 (m, 2H), 7.14~7.04 (m, 2H), 5.89 (t, J＝7.2 Hz, 1H), 3.74 (s, 2H), 3.37 (t, J＝6.7 Hz, 2H), 2.62 (q, J＝6.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 137.8, 135.6, 134.6, 131.4, 130.5, 121.5, 98.2, 62.4, 32.1, 31.8; IR (film) ν: 2920, 2850, 1655, 1631, 1484, 1073, 1008, 837, 706 cm^－1; HRMS (EI) calcd for C₁₂H₁₁Cl₃Br₂ 417.8293, found 417.8289.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-4-methyl- benzene (2f): chromatography on silica gel (petroleum ether), 90% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.16 (d, J＝7.9 Hz, 2H), 7.11~7.05 (m, 2H), 5.85 (t, J＝7.1 Hz, 1H), 3.75 (s, 2H), 3.37 (t, J＝6.8 Hz, 2H), 2.64 (q, J＝6.9 Hz, 2H), 2.35 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 137.1, 136.6, 135.9, 133.5, 128.9, 128.7, 98.5, 62.6, 32.2, 32.1, 21.2; IR (film) ν: 2962, 2922, 1513, 1421, 1268, 832, 788, 711, 628 cm^－1; HRMS (EI) calcd for C₁₃H₁₄Cl₃Br 353.9344, found 353.9343.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-4-(trifluo-romethyl)benzene (2g): chromatography on silica gel (pe-troleum ether), 89% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.62 (d, J＝8.1 Hz, 2H), 7.34 (d, J＝8.0 Hz, 2H), 5.95 (t, J＝7.2 Hz, 1H), 3.79 (s, 2H), 3.39 (t, J＝6.6 Hz, 2H), 2.62 (q, J＝6.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 142.8, 135.5, 135.4, 129.6 (q, J＝32 Hz), 129.3, 125.3 (q, J＝3.7 Hz), 124.1 (q, J＝70 Hz), 98.0, 62.4, 32.1, 31.7; IR (film) ν: 2965, 2928, 1616, 1406, 1325, 1166, 1128, 1067, 1017, 852, 709 cm^－1; HRMS (EI) calcd for C₁₃H₁₁F₃Cl₃Br 407.9062, found 407.9057.

  (Z)-Ethyl 4-(6-bromo-1, 1, 1-trichlorohex-3-en-3-yl)- benzoate (2h): chromatography on silica gel (petroleum ether/EtOAc, V:V＝95:5), 93% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 8.03 (d, J＝8.3 Hz, 2H), 7.29 (d, J＝8.3 Hz, 2H), 5.93 (t, J＝7.2 Hz, 1H), 4.38 (q, J＝7.1 Hz, 2H), 3.79 (s, 2H), 3.38 (t, J＝6.7 Hz, 2H), 2.62 (q, J＝6.8 Hz, 2H), 1.40 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 166.3, 143.7, 135.9, 135.0, 129.6, 129.5, 128.9, 98.1 (s), 62.4, 61.0, 32.1, 31.7, 14.3; IR (film) ν: 2980, 29287, 1716, 1609, 1271, 1103, 1020, 865, 807, 710 cm^－1; HRMS (EI) calcd for C₁₅H₁₆O₂Cl₃Br 411.9399, found 411.9390.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-3-chloro- benzene (2i): chromatography on silica gel (petroleum ether), 89% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.27 (t, J＝5.9 Hz, 2H), 7.21 (s, 1H), 7.10 (d, J＝6.6 Hz, 1H), 5.91 (t, J＝7.1 Hz, 1H), 3.75 (s, 2H), 3.39 (t, J＝6.7 Hz, 2H), 2.63 (q, J＝6.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 140.8, 135.4, 135.0, 134.1, 129.5, 128.8, 127.6, 127.2, 98.1, 62.4, 32.1, 31.8; IR (film) ν: 2962, 2925, 2853, 1593, 1563, 1475, 1420, 1269, 965, 796, 703, 678, 648 cm^－1; HRMS (EI) calcd for C₁₂H₁₁Cl₄Br 373.8798, found 373.8802.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-3-meth- oxybenzene (2j): chromatography on silica gel (petroleum ether), 90% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.26 (t, J＝7.9 Hz, 1H), 6.85~6.73 (m, 3H), 5.87 (t, J＝7.1 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 2H), 3.38 (t, J＝6.8 Hz, 2H), 2.66 (q, J＝6.9 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 159.4, 140.4, 136.5, 133.9, 129.2, 121.3, 114.8, 112.5, 98.3, 77.3, 77.0, 76.7, 62.5, 55.3, 32.2, 32.1; IR (film) ν: 2957, 2928, 1599, 1577, 1488, 1286, 1257, 1045, 804, 705 cm^－1; HRMS (EI) calcd for C₁₃H₁₄OCl₃Br 369.9294, found 369.9293.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-2-methyl- benzene (2k): chromatography on silica gel (petroleum ether), 82% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.22~7.08 (m, 4H), 5.94 (t, J＝7.0 Hz, 1H), 3.72 (s, 2H), 3.34 (t, J＝6.7 Hz, 2H), 2.45 (q, J＝8 Hz, 2H), 2.27 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 138.1, 136.2, 135.6, 134.3, 130.2, 129.7, 127.5, 125.5, 98.2, 62.4, 32.3, 31.8, 19.7; IR (film) ν: 2961, 2924, 1489, 1419, 1268, 964, 800, 730, 713, 646, 601 cm^－1; HRMS (EI) calcd for C₁₃H₁₄Cl₃Br 353.9344, found 353.9341.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-2-metho- xybenzene (2l): chromatography on silica gel (petroleum ether/EtOAc, V:V＝95:5), 81% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.30~7.26 (m, 1H), 7.12 (dd, J＝7.4, 1.5 Hz, 1H), 6.97~6.86 (m, 2H), 5.89 (t, J＝7.1 Hz, 1H), 3.82 (s, 5H), 3.37 (t, J＝7.0 Hz, 2H), 2.56 (q, J＝7.0 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 156.6, 134.5, 134.3, 131.5, 129.0, 127.1, 120.3, 110.7, 98.8, 61.3, 55.4, 32.5, 32.0; IR (film) ν: 2959, 2931, 1599, 1489, 1461, 1435, 1244, 1027, 754, 714, 647 cm^－1; HRMS (EI) calcd for C₁₃H₁₄OCl₃Br 369.9294, found 369.9287.

  (Z)-4-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)-1, 2-dimeth- oxybenzene (2m): chromatography on silica gel (petrole-um ether/EtOAc, V:V＝95:5), 87% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 6.83 (d, J＝8.0 Hz, 1H), 6.74 (dd, J＝11.3, 1.8 Hz, 2H), 5.82 (t, J＝7.1 Hz, 1H), 3.87 (d, J＝1.6 Hz, 6H), 3.73 (s, 2H), 3.38 (t, J＝6.8 Hz, 2H), 2.65 (q, J＝6.9 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 148.6, 148.3, 136.4, 133.5, 131.4, 121.2, 112.2, 110.8, 98.4, 62.6, 56.0, 55.8, 32.2, 32.1; IR (film) ν: 2958, 2934, 2835, 1515, 1258, 1139, 1028, 817, 711 cm^－1; HRMS (EI) calcd for C₁₄H₁₆O₂Cl₃Br 399.9399, found 399.9398.

  (Z)-1-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)naphthalene (2n): chromatography on silica gel (petroleum ether), 77% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.90~7.83 (m, 2H), 7.81 (d, J＝8.2 Hz, 1H), 7.51~7.46 (m, 2H), 7.36 (dd, J＝7.0, 1.1 Hz, 1H), 6.20 (t, J＝7.0 Hz, 1H), 3.90 (s, 2H), 3.31 (t, J＝6.7 Hz, 2H), 2.51~2.33 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 136.4, 135.8, 134.9, 133.7, 131.1, 128.6, 128.0, 127.1, 126.3, 125.8, 125.4, 125.2, 98.2, 62.9, 32.5, 31.9; IR (film) ν: 2923, 2852, 1419, 1268, 965, 810, 775, 712 cm^－1; HRMS (EI) calcd for C₁₆H₁₄Cl₃Br 389.9344, found 389.9338.

  (Z)-2-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)naphthalene (2o): chromatography on silica gel (petroleum ether), 78% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.86 (d, J＝8.0 Hz, 3H), 7.69 (s, 1H), 7.57~7.47 (m, 2H), 7.37 (d, J＝8.4 Hz, 1H), 6.00 (t, J＝7.1 Hz, 1H), 3.90 (s, 2H), 3.42 (t, J＝6.7 Hz, 2H), 2.72 (q, J＝6.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 136.6, 136.5, 134.4, 133.1, 132.5, 128.0, 127.9, 127.7, 127.7, 126.9, 126.6, 126.1, 98.4, 62.6, 32.2, 32.0; IR (film) ν: 3055, 2925, 2853, 1597, 1504, 1421, 860, 823, 711, 683 cm^－1; HRMS (EI) calcd for C₁₆H₁₄Cl₃Br 389.9344, found 389.9346.

  (Z)-2-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)pyridine (2p): chromatography on silica gel (petroleum ether/ EtOAc, V:V＝7:3), 92% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 8.55 (d, J＝4.7 Hz, 1H), 7.67 (t, J＝7.7 Hz, 1H), 7.44 (d, J＝7.9 Hz, 1H), 7.17 (dd, J＝7.2, 5.1 Hz, 1H), 6.26 (t, J＝7.3 Hz, 1H), 4.29 (s, 2H), 3.51 (t, J＝6.8 Hz, 2H), 3.02 (q, J＝6.9 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 159.7, 148.5, 136.8, 136.7, 135.9, 122.2, 121.6, 98.8, 51.9, 33.2, 31.3; IR (film) ν: 2925, 2852, 1585, 1565, 1466, 1433, 1265, 1150, 1034, 828, 777, 744, 705, 640 cm^－1; HRMS (EI) calcd for C₁₁H₁₁NCl₃Br 340.9140, found 340.9135.

  (Z)-2-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)thiophene (2q): chromatography on silica gel (petroleum ether), 70% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.31 (dd, J＝5.1, 1.1 Hz, 1H), 7.02 (dd, J＝5.0, 3.6 Hz, 1H), 6.98 (dd, J＝3.5, 1.0 Hz, 1H), 5.97 (t, J＝7.1 Hz, 1H), 3.78 (s, 2H), 3.45 (t, J＝6.8 Hz, 2H), 2.87 (q, J＝6.9 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 140.5, 135.6, 129.2, 127.1, 127.0, 125.5), 98.2, 62.8, 32.6, 31.8; IR (film) ν: 2961, 2925, 2853, 1423, 1268, 1231, 963, 798, 703 cm^－1; HRMS (EI) calcd for C₁₀H₁₀SCl₃Br 345.8752, found 345.8745.

  (Z)-3-(6-Bromo-1, 1, 1-trichlorohex-3-en-3-yl)benzo[b]- thiophene (2r): chromatography on silica gel (petroleum ether/EtOAc, V:V＝95:5), 90% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.92~7.85 (m, 1H), 7.66~7.59 (m, 1H), 7.41~7.34 (m, 2H), 7.28 (s, 1H), 6.14 (t, J＝7.0 Hz, 1H), 3.83 (s, 2H), 3.35 (t, J＝6.6 Hz, 2H), 2.54 (q, J＝6.7 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 139.9, 138.1, 136.8, 134.3, 130.6, 124.7, 124.4, 124.3, 122.9, 122.8, 98.2, 62.1, 32.5, 31.93; HRMS (EI) calcd for C₁₄H₁₂SCl₃Br 395.8909, found 395.8899.

  (Z)-(6-Bromo-1, 1, 1-trichloro-2-methylhex-3-en-3-yl)- benzene (2s): chromatography on silica gel (petroleum ether), 89% yield, colorless oil. ¹H NMR (400 MHz, Chloroform-d) δ: 7.37~7.32 (m, 2H), 7.31~7.28 (m, 1H), 7.23~7.17 (m, 2H), 5.96 (t, J＝7.1 Hz, 1H), 3.62 (q, J＝6.9 Hz, 1H), 3.35 (t, J＝6.8 Hz, 2H), 2.50 (q, J＝7.0 Hz, 2H), 1.65 (d, J＝6.9 Hz, 3H); ¹³C NMR (100 MHz, Chlo-roform-d) δ: 142.0, 139.2, 130.8, 129.3, 128.0, 127.2, 103.9, 62.0, 321, 18.4; HRMS (EI) calcd for C₁₃H₁₄BrCl: 353.9344, found 353.9346.

  4.4   Synthesis of compound 3

  An oven-dried reaction vial was equipped with a mag-netic stir bar, compound E-3 (0.2 mmol), Ir[dF(CF₃)-ppy]₂(dtbbpy)PF₆ (0.002 mmol). The flask was evacuated and backfilled with argon for 3 times. Anhydrous CH₃CN (2 mL) was added with syringe. The vial was placed at a distance (app. 5 cm) from 24 W blue LEDs strip, and the resulting solution was stirred at ambient temperature for 1.5 h. The mixture was concentrated under reduced pres-sure. The residue was purified by chromatography on silica gel to afford the desired product.

  (Z)-3-Phenylpent-2-en-1-ol (Z-3a): chromatography on silica gel (petroleum ether/EtOAc, V:V＝5:1), 94% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.35~7.32 (m, 2H), 7.29~7.25 (m, 1H), 7.18~7.10 (m, 2H), 5.67 (t, J＝6.9 Hz, 1H), 4.04 (d, J＝6.9 Hz, 2H), 2.40 (q, J＝7.4 Hz, 2H), 1.55 (s, 1H), 1.00 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 146.2, 140.2, 128.1, 127.0, 124.3, 60.2, 31.7, 12.7. These data were identical to re-ported values.^[20]

  (Z)-3-(4-Methoxyphenyl)pent-2-en-1-ol (Z-3b): chro-matography on silica gel (petroleum ether/EtOAc, V:V＝5:1), 95% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.07 (d, J＝8.3 Hz, 2H), 6.87 (d, J＝8.3 Hz, 2H), 5.64 (t, J＝6.9 Hz, 1H), 4.06 (d, J＝6.7 Hz, 2H), 3.81 (s, 3H), 2.37 (q, J＝7.3 Hz, 2H), 1.27 (s, 1H), 0.99 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 58.6, 145.9, 132.4, 129.2, 124.0, 113.4, 60.4, 55.2, 31.8, 12.8; IR (film) ν: 3348, 2964, 2933, 1609, 1511, 1246, 1178, 1034, 834, 750 cm^－1; HRMS (EI) calcd for C₁₂H₁₆O₂ 192.1150, found 192.1143.

  (Z)-3-(4-(Trifluoromethyl)phenyl)pent-2-en-1-ol (Z-3c): chromatography on silica gel (petroleum ether/EtOAc, V:V＝5:1), 96% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.61 (d, J＝7.9 Hz, 2H), 7.27 (d, J＝8.0 Hz, 2H), 5.74 (t, J＝6.9 Hz, 1H), 4.01 (d, J＝6.9 Hz, 2H), 2.41 (q, J＝7.3 Hz, 2H), 1.90 (s, 1H), 1.01 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 144.9, 144.0, 129.2 (q, J＝32.4 Hz), 128.4, 125.4, 125.1 (q, J＝3.7 Hz), 124.1 (q, J＝271 Hz), 59.9, 31.5, 12.5; IR (film) ν: 3332, 2970, 2936, 2879, 1616, 1325, 1166, 1127, 1066, 1018, 848 cm^－1; HRMS (EI) calcd for C₁₂H₁₃OF₃ 230.0918, found 230.0923.

  (Z)-3-phenylbut-2-en-1-ol (Z-3d): chromatography on silica gel (petroleum ether/EtOAc, V:V＝5:1), 93% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.37~7.35 (m, 2H), 7.31~7.24 (m, 1H), 7.18 (d, J＝7.1 Hz, 2H), 5.71 (t, J＝6.9 Hz, 1H), 4.07 (d, J＝7.0 Hz, 2H), 2.09 (s, 3H), 1.73 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 140.7, 140.0, 128.1, 127.7, 127.1, 126.1, 60.1, 25.3. The data were identical to reported values.^[21]

  (Z)-4-Methyl-3-phenylpent-2-en-1-ol (Z-3e): chroma-tography on silica gel (petroleum ether/EtOAc, V:V＝5:1), 95% yield, colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.36~7.21 (m, 3H), 7.10 (d, J＝7.0 Hz, 2H), 5.66 (t, J＝6.7 Hz, 1H), 3.97 (d, J＝6.8 Hz, 2H), 2.56~2.66 (m, 1H), 1.68 (s, 1H), 1.07 (s, 3H), 1.05 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 150.8, 140.1, 128.4, 127.9, 126.8, 123.1, 60.4, 35.6, 21.5. These data were identical to reported val-ues.^[22]

  4.5   Synthesis of (Z)-1-(6-azido-1, 1, 1-trichlorohex-3- en-3-yl)-4-methoxybenzene (4)

  To a solution of 2b (74 mg, 0.2 mmol) in anhydrous DMF (2 mL) was added sodium azide (65 mg, 0.3 mmol) at room temperature. The reaction was covered with Al foil and stirred for 12 h. The mixture then was diluted with EtOAc, cautiously washed with water and brine, dried with anhydrous Na₂SO₄, and concentrated. The residue was purified by chromatography on silica gel (petroleumether/ EtOAc, V:V＝95:5) to provide the desired product 4^[23] as colorless oil, 60 mg, 91% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.12 (d, J＝8.5 Hz, 2H), 6.88 (d, J＝8.5 Hz, 2H), 5.81 (t, J＝7.1 Hz, 1H), 3.82 (s, 3H), 3.73 (s, 2H), 3.30 (t, J＝6.6 Hz, 2H), 2.38 (q, J＝6.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 158.8, 136.5, 132.4, 131.1, 129.9, 113.6, 98.5, 62.6, 55.2, 50.9, 28.94; IR (film) ν: 2956, 2933, 2837, 2097, 1609, 1511, 1290, 1248, 1177, 1033, 840, 712 cm^－1; HRMS (EI) calcd for C₁₃H₁₄N₃OCl₃ 333.0202, found 333.0199.

  4.6   Synthesis of (Z)-6, 6, 6-Trichloro-4-(4-methoxy- phenyl)hex-3-en-1-ol (5)

  To a solution of (Z)-2b (74 mg, 0.2 mmol) and HCOOH (0.46 mmol) in anhydrous CH₃CN (2 mL) was added tri-methylamine (0.4 mmol) dropwise at 0 ℃, then the reac-tion mixture was reflux for 12 h. After addition of brine (5 mL), the reaction mixture was extracted with EtOA. The organic layer was washed with H₂O, 1 mol•L^－1 HCl and NaHCO₃ solution in turn. The organic layer was dried with anhydrous Na₂SO₄ and concentrated under reduced pres-sure. Then to the residue dissolved in 2 mL of MeOH was added 2 drop of 12 mol•L^－1 HCl at room temperature. The solution was stirred for 2 h and then diluted with EtOAc, The mixture was cautiously washed with NaHCO₃ solution, H²O and brine, dried with anhydrous Na₂SO₄, and concentrated. The residue was purified by chromatography on silica gel (petroleumether/EtOAc, V:V＝4:1) to provide the desired product 5^[17] as colorless oil, 39 mg, 63% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.14 (d, J＝8.3 Hz, 2H), 6.87 (d, J＝8.3 Hz, 2H), 5.85 (t, J＝7.3 Hz, 1H), 3.81 (s, 3H), 3.74 (s, 2H), 3.68 (t, J＝5.7 Hz, 2H), 2.37 (q, J＝6.6 Hz, 2H), 1.31 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 158.6, 136.1, 133.0, 131.3, 130.1, 113.5, 98.7, 62.7, 62.2, 55.2, 32.6; IR (film) ν: 3362, 2955, 2933, 2837, 1609, 1512, 1247, 1177, 1034, 840, 711 cm^－1; HRMS (EI) calcd for C₁₃H₁₅O₂Cl₃ 308.0138, found 308.0131.

  Supporting Information  Control experiments, ¹H NMR and ¹³C NMR spectra for all new compounds. The Sup-porting Information is available free of charge via the In-ternet at http://sioc-journal.cn.

• 1. [1]

     (a) Yale, H. L. J. Med. Chem. 1959, 1, 121.
     (b) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359.
     (c) Tomashenko, O. A. ; Grushin, V. V. Chem. Rev. 2011, 111, 4475.
     (d) Mullard, A. Nat. Rev. Drug. Discovery 2013, 12, 87.

  2. [2]

     (a) Ma, J. -A. ; Cahard, D. Chem. Rev. 2008, 108, PR1.
     (b) Chen, P. ; Liu, G. Synthesis 2013, 45, 2919.
     (c) Liu, H. ; Gu, Z. ; Jiang, X. Adv. Synth. Catal. 2013, 355, 617.
     (d) Chu, L. ; Qing, F. -L. Acc. Chem. Res. 2014, 47, 15132.
     (e) Zhang, C. Org. Biomol. Chem. 2014, 12, 6580.
     (f) Alonso, C. ; Martínez de Marigorta, E. ; Rubiales, G. ; Palacios, F. Chem. Rev. 2015, 115, 1847.
     (g) Liu, X. ; Xu, C. ; Wang, M. ; Liu, Q. Chem. Rev. 2015, 115, 683.

  3. [3]

     (a) Hofheinz, W. ; Oberhänsli, W. E. Helv. Chim. Acta 1977, 60, 660.
     (b) Unson, M. D. ; Rose, C. B. ; Faulkner, D. J. ; Brinen, L. S. ; Steiner, J. R. ; Clardy, J. J. Org. Chem. 1993, 58, 6336.
     (c) Orjala, J. ; Gerwick, W. H. J. Nat. Prod. 1996, 59, 427.
     (d) Fu, X. ; Zeng, L. -M. ; Su, J. -Y. ; Pais, M. J. Nat. Prod. 1997, 60, 695.
     (e) MacMillan, J. B. ; Trousdale, E. K. ; Molinski, T. F. Org. Lett. 2000, 2, 2721.
     (f) Orsini, M. A. ; Pannell, L. K. ; Erickson, K. L. J. Nat. Prod. 2001, 64, 572.

  4. [4]

     (a) Hutt, M. P. ; Elslager, E. F. ; Werbel, L. M. J. Heterocycl. Chem. 1970, 7, 511.
     (b) Werbel, L. M. ; Elslager, E. F. ; Hess, C. ; Hutt, M. P. J. Med. Chem. 1987, 30, 1943.
     (c) Fujisawa, T. ; Ito, T. ; Fujimoto, K. ; Shimizu, M. ; Wynberg, H. ; Staring, E. G. J. Tetrahedron Lett. 1997, 38, 1593.
     (d) Huffman, M. A. ; Reider, P. J. Tetrahedron Lett. 1999, 40, 831.
     (e) Bringmann, G. ; Feineis, D. ; God, R. ; Peters, K. ; Peters, E. -M. ; Scholz, J. ; Riederer, F. ; Moser, A. Biorg. Med. Chem. 2002, 10, 2207.

  5. [5]

     Wallentin, C. -J. ; Nguyen, J. D. ; Finkbeiner, P. ; Stephenson, C. R. J. J. Am. Chem. Soc. 2012, 134, 8875.
     (b) Arceo, E. ; Montroni, E. ; Melchiorre, P. Angew. Chem., Int. Ed. 2014, 53, 12064.
     (c) Liu, Y. ; Zhang, J. -L. ; Song, R. -J. ; Li, J. -H. Eur. J. Org. Chem. 2014, 6, 1177.
     (d) Franz, J. F. ; Kraus, W. B. ; Zeitler, K. Chem. Commun. 2015, 51, 8280.

  6. [6]

     Huo, H.; Wang, C.; Harms, K.; Meggers, E. J. Am.Chem.Soc. 2015, 137, 9551. doi: 10.1021/jacs.5b06010

  7. [7]

     Li, X.; Wu, J.; Chen, L.; Zhong, X.; He, C.; Zhang, R.; Duan, C. Chem.Commun. 2016, 52, 9628. doi: 10.1039/C6CC04647A

  8. [8]

     Li, J.; Chen, J.; Jiao, W.; Wang, G.; Li, Y.; Cheng, X.; Li, G. J.Org.Chem. 2016, 81, 9992. doi: 10.1021/acs.joc.6b01825

  9. [9]

     For some examples of radical annulation of α-cyclopropylstyrene:
     (a) Zhang, F. ; Min, Q. -Q. ; Zhang, X. Synthesis 2015, 47, 2912.
     (b) Prieto, A. ; Melot, R. ; Bouyssi, D. ; Monteiro, N. ACS Catal. 2016, 6, 1093.
     (c) Prieto, A. ; Melot, R. ; Bouyssi, D. ; Monteiro, N. Angew. Chem., Int. Ed. 2016, 55, 1885.

  10. [10]

      (a) Feng, Z. ; Xiao, Y. -L. ; Zhang, X. Org. Chem. Front. 2016, 3, 466.
      (b) Ke, M. ; Song, Q. Adv. Synth. Catal. 2017, 359, 384.
      (c) Nie, X. ; Cheng, C. ; Zhu, G. Angew. Chem., Int. Ed. 2017, 56, 1898.

  11. [11]

      (a) Kimura, T. ; Fujita, M. ; Sohmiya, H. ; Ando, T. J. Org. Chem. 1998, 63, 6719.
      (b) Freeman, D. B. ; Furst, L. ; Condie, A. G. ; Stephenson, C. R. J. Org. Lett. 2012, 14, 94.

  12. [12]

      Cismesia, M. A.; Yoon, T. P. Chem.Sci. 2015, 6, 5426. doi: 10.1039/C5SC02185E

  13. [13]

      (a) Hammond, G. S. ; Saltiel, J. J. Am. Chem. Soc. 1962, 84, 4983.
      (b) Saltiel, J. ; Hammond, G. S. J. Am. Chem. Soc. 1963, 85, 2515.
      (c) Hammond, G. S. ; Saltiel, J. ; Lamola, A. A. ; Turro, N. J. ; Bradshaw, J. S. ; Cowan, D. O. ; Counsell, R. C. ; Vogt, V. ; Dalton, C. J. Am. Chem. Soc. 1964, 86, 3197.
      (d) Tatsuo, A. ; Hirochika, S. ; Katsumi, T. Chem. Lett. 1980, 9, 261.
      (e) Arai, T. ; Sakuragi, H. ; Tokumaru, K. Bull. Chem. Soc. Jpn. 1982, 55, 2204.
      (f) Sakaki, S. ; Okitaka, I. ; Ohkubo, K. Inorg. Chem. 1984, 23, 198.
      (g) Osawa, M. ; Hoshino, M. ; Wakatsuki, Y. Angew. Chem., Int. Ed. 2001, 40, 3472.

  14. [14]

      (a) Singh, K. ; Staig, S. J. ; Weaver, J. D. J. Am. Chem. Soc. 2014, 136, 5275.
      (b) Singh, A. ; Fennell, C. J. ; Weaver, J. D. Chem. Sci. 2016, 7, 6796.

  15. [15]

      (a) Fabry, D. C. ; Ronge, M. A. ; Rueping, M. Chem. -Eur. J. 2015, 21, 5350.
      For selected examples involving energy transfer, see: (b) Chen, Y. ; Kamlet, A. S. ; Steinman, J. B. ; Liu, D. R. Nat. Chem. 2011, 3, 146.
      (c) Lu, Z. ; Yoon, T. P. Angew. Chem., Int. Ed. 2012, 51, 10329.
      (d) Zou, Y. -Q. ; Duan, S. -W. ; Meng, X. -G. ; Hu, X. -Q. ; Gao, S. ; Chen, J. -R. ; Xiao, W. -J. Tetrahedron 2012, 68, 6914.
      (e) Alonso, R. ; Bach, T. Angew. Chem., Int. Ed. 2014, 53, 4368.
      (f) Farney, E. P. ; Yoon, T. P. Angew. Chem., Int. Ed. 2014, 53, 793.
      (g) Kumarasamy, E. ; Raghunathan, R. ; Jockusch, S. ; Ugrinov, A. ; Sivaguru, J. J. Am. Chem. Soc. 2014, 136, 8729.

  16. [16]

      Metternich, J. B.; Gilmour, R. J.Am.Chem.Soc. 2015, 137, 11254. doi: 10.1021/jacs.5b07136

  17. [17]

      Alexander, J.; Renyer, M. L.; Veerapanane, H. Synth.Commun. 1995, 25, 3875. doi: 10.1080/00397919508011463

  18. [18]

      Jiang, G.-J.; Fu, X-F.; Li, Q.; Yu, Z.-X. Org.Lett. 2012, 14, 692. doi: 10.1021/ol2031526

  19. [19]

      Li, J.-Q.; Liu, J.-G.; Krajangsri, S.; Chumnanvej, N.; Singh, T.; Andersson, P. G. ACS Catal. 2016, 6, 8342. doi: 10.1021/acscatal.6b02456

  20. [20]

      Abascal, N. C.; Lichtor, P. A.; Giuliano, M. W.; Miller, S. J. Chem. Sci. 2014, 5, 45041. https://millerlab.yale.edu/publications

  21. [21]

      Miller, D. J.; Yu, F.; Young, N. J.; Allemann, R. K. Org.Biomol. Chem. 2007, 5, 3287. doi: 10.1039/b713301b

  22. [22]

      Ren, K.; Hu, B.; Zhao, M.-M.; Tu, Y.-H.; Xie, X.-M.; Zhang, Z.-G. J. Org.Chem. 2014, 79, 2170. doi: 10.1021/jo500042h

  23. [23]

      Skapos, H.; Osipov, S. N.; Vorob'eva, D. V.; Odinets, I. L.; Lork, E.; Roeschenthaler, G. Org.Biomol.Chem. 2007, 5, 2361. doi: 10.1039/B705510B

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  Scheme 1  Application of α-cyclopropyl radical 1, 5-difunctiona- lizaton

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  Scheme 2  Control experiments and proposed mechanism

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  Scheme 3  Transformation of bromo atom in product 2b

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  Table 1.  Optimization of 1, 5-bromotrichloromethylation/iso- merization cascade reaction of α-cyclopropylstyrenea

  Entry	Photocatalyst	Solvent	Yieldb/%	Z:Ec
  1	Ru(bpy)3Cl2	CH3CN	92	30:70
  2	fac-Ir(ppy)3	CH3CN	90	31:69
  3	Ir(ppy)2(dtbbpy)PF6	CH3CN	95	60:40
  4	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH3CN	95	96:4
  5	Ir[dF(CF3)ppy]2(dtbbpy)PF6	DMF	91	74:26
  6	Ir[dF(CF3)ppy]2(dtbbpy)PF6	DMSO	90	91:9
  7	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH2Cl2	89	73:27
  8	Ir[dF(CF3)ppy]2(dtbbpy)PF6	EtOH	94	94:6
  9	None	CH3CN	N.R.	—
  10d	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH3CN	93	75:25
  11e	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH3CN	N.R.	—
  12f	Ir[dF(CF3)ppy]2(dtbbpy)PF6	CH3CN	81	76:24
  a Reaction conditions: 1a (0.1 mmol), BrCCl3 (0.1 mmol), photocatalyst (0.001 mmol, 1.0 mol%), anhydrous solvent (1.0 mL), 24 W blue LEDs, 1.5 h, r.t., argon atmosphere. b Isolated yield of Z/E mixture. N.R.＝no reaction. c Determined by GC-MS. d White LEDs. e No light. f Under air.

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  Table 2.  Substrate scope of 1, 5-bromotrichloromethylation/isomerization cascade reaction^a

  a Reaction conditions: 1 (0.1 mmol), BrCCl3 (0.1 mmol, 1 equiv.), and Ir[dF(CF3)ppy]2(dtbbpy)PF6 (0.001 mmol, 1 mol%) in anhydrous CH3CN (1.0 mL) with irradiation by blue LEDs for 1.5 h at room temperature under argon. b Isolated yield of Z product; ratio of 2 to 2' determined by GC-MS.

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  Table 3.  E-Z isomerization of trisubstituted styrenes

  a Reaction conditions: E-3 (0.2 mmol) and Ir[dF(CF3)ppy]2(dtbbpy)PF6 (0.002 mmol, 1 mol%) in anhydrous CH3CN (2.0 mL) with irradiation by blue LEDs for 1.5 h at room temperature under argon. b Trace of E-3 was detected with GC-MS upon completion but could not be observed during the isolation of Z-3. Ratio of Z to E determined by GC-MS.

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