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1 Supporting Information Iron-catalyzed three-component reaction: multiple C-C bond cleavages and reorganizations Peng Wang, Saihu Liao, Jian-Bo Zhu, Yong Tang* State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai , China 1. General Information...S2 2. General Procedure for Synthesis of Vinyl Phosphonium Salt 9...S3 3. General Procedure for 13 C-Labeled Experiments...S5 4. General Procedure for Capture of Cyclopropane Intermidates by Aldehyde...S7 5. Reaction Optimization...S8 6. General Procedure for Synthesis of Cyclopentadiene Derivatives...S9 7. General Procedure for Chemical Transformation...S17 8. NMR Spectra of the Compounds...S21 S1

2 General Information All reactions were carried out under N 2 unless otherwise noted. All carbonyl compounds and solvents were purified according to standard methods unless otherwise noted. 1 H NMR spectra were recorded on a VARIAN Mercury 300 MHz or VARIAN Mercury 400 MHz spectrometer in chloroform-d. All signals are reported in ppm with the internal TMS signal at 0.0 ppm or chloroform signal at 7.26 ppm as a standard. The data are reported as (s = singlet, d = doublet, t = triplet, q = quadruplet, m = multiplet or unresolved, coupling constant(s) in Hz, integration). 13 C NMR spectra were recorded on a VARIAN Mercury 75.5 MHz spectrometer in chloroform-d. All signals are reported in ppm with the internal chloroform signal at 77.0 ppm as a standard. IR spectra were recorded on a Perkin Elmer 983, Digital FT IR spectrometer or Bruker Tensor 27; frequencies are given in reciprocal centimeters (cm -1 ) and only selected absorbance is reported; Mass spectra were determined on an Agilent 5973N MSD (EI) and Shimadzu LCMS-2010EV (ESI) mass spectrometer or Agilent G6100 LC/MSD (ESI) single Quand mass spectrometer. High resolution mass spectra were recorded on Waters Micromass GCT Premier (EI) and Bruker Daltonics, Inc. APEXIII 7.0 TESLA FTMS (ESI) mass spectrometers. Fe(TCP)Cl was synthesized according to literature procedure 1. S2

3 2. General procedure for synthesis of vinyl phosphonium salt 9 To a stirred solution of phosphorus ylide 1 (259.2 mg, 0.72 mmol) in CH 2 Cl 2 (2.0 ml) under N 2 at room temperature was added Fe(TCP)Cl (1.7 mg, mmol) and MDA (84 L, 1.0 mmol) were added to the system respectively (Caution! N 2 release rapidly!), washed the Schlenk tube with dry CH 2 Cl 2 (1.0 ml), and the mixture stirred for another 20 min. ArCOCH 2 Br (0.4 mmol), Na 2 CO 3 (84.8 mg, 0.8 mmol) and CH 2 Cl 2 (1.0 ml) were added and the resulting mixture was stirred at room temperature for 24 h. The resulting mixture was filtered rapidly through a funnel with a thin layer of celite and eluted with CH 2 Cl 2. The filtrate was concentrated and the residue was purified by chromatography on silica gel to afford the desired products 9 as a white solid. 82% yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 8.51 (dd, J = 17.6, 21.2 Hz, 1H), 8.16 (d, J = 7.6 Hz, 2H), (m, 1H), (m, 3H), (m, 12H), 7.53 (t, J = 7.0 Hz, 1H), 7.43 (t, J = 7.0 Hz, 2H), 5.34 (d, J = 18.4 Hz, 1H), 4.06 (d, J = 16.4 Hz, 1H), 3.91 (d, J = 18.8 Hz, 1H), 3.67 (s, 3H), 3.59 (s, 3H), 3.21 (d, J = 16.4 Hz, 1H); 31 P NMR (CDCl 3, 162 MHz) δ IR (neat) ν 2951 (m), 1732 (s), 1676 (m), 1437 (m), 1210 (s), 1111 (m), 754 (m), 724 (s), 690 (s); HRMS (positive ESI) calcd for C 34 H 32 O 5 P + ([M-Br] + ): ; Found: This structure also determined by X-Ray analysis (CCDC ). 81% yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 8.56 (dd, J = 17.6, 21.2 Hz, 1H), 8.16 (d, J = 8.4 Hz, 2H), (m, 18H), 5.56 (d, J = 18.8 Hz, 1H), 3.93 (d, J = 17.6 Hz, 2H), 3.68 (s, 3H), 3.60 (s, 3H), 3.20 (d, J = 16.0 Hz, 1H); 31 P NMR (CDCl 3, 162 MHz) δ 21.4; 19 F NMR (CDCl 3, 376 MHz) δ -63.2; IR (neat) ν 2953 (m), 1736 (s), 1686 (m), 1437 (m), 1438 (m), 1323 (s), 1111 (s), 1065 (s), 997 (m), 723 (s), 689 (s); HRMS (positive ESI) calcd for C 35 H 31 F 3 O 5 P + ([M-Br] + ): ; Found: S3

4 X-Ray structure of 9a (CCDC ) Bond precision: C-C = A Wavelength= Cell: a= (9) b= (9) c= (14) alpha=83.565(2) beta=88.407(2) gamma=64.827(2) Temperature: 293 K Calculated Reported Volume (2) (2) Space group P -1 P-1 Hall group -P 1? Moiety formula C34 H32 O5 P, Br? Sum formula C34 H32 Br O5 P C34 H32 Br O5 P Mr Dx,g cm Z 2 2 Mu (mm-1) F F000' h,k,lmax 12,12,20 12,12,20 Nref Tmin,Tmax 0.706, ,1.000 Tmin' Correction method= EMPIRICAL Data completeness= Theta(max)= R(reflections)= ( 4777) wr2(reflections)= ( 6125) S = Npar= 372 S4

5 3. General procedure for 13 C-labeled experiments Sythesis of 13 C-labeled 2-bromo-1-phenylethanone 2 To a stirred suspension of AlCl 3 (2.2 g, 16.4 mmol) in dry benzene (5.0 ml) under nitrogen atmosphere was added acetyl-2-13 C chloride (1.0 g, 12.6 mmol) at 0, then benzene (6.0 ml) was added to wash the tube. After 10 min, the mixture was warmed up to room temperature for another 15 hours. After the reaction was completed, 5 ml of water were added dropwise to the reaction mixture until the reaction mixture turned white. HCl (10 ml, 2.0 M) was added then and the aqueous layer was extracted with Et 2 O (4 50 ml). The combined organic layers were washed with brine, dried over MgSO 4 and concentrated under reduced pressure. The crude product (1.39 g, 91% crude yield) was used for next step without further purification. To a solution of acetophenone-β- 13 C (1.39 g, mmol) in chloroform (100 ml) was added dropwise Br 2 (0.62 ml, 12.1 mmol) in chloroform (50 ml) in half an hour at 0. One hour later, the mixture was allowed to warm up to room temperature for another one hours. After the reaction was completed, the mixture was washed with saturated NaHCO 3 solution (3 30 ml) and brine (3 30 ml) and dried over MgSO 4. The filtrate was concentrated and the residue was purified by chromatography on silica gel to afford the desired 2-13 C-bromo-1-phenylethanone (1.66 g, 72% yield) as a white solid. 1 H NMR (CDCl 3, 400 MHz) δ (m, 2H), (m, 1H), 7.50 (t, J = 7.8 Hz, 2H), 4.46 (d, J = Hz, 2H); 13 C NMR (CDCl 3, 100 MHz) δ (d, J = 43.1 Hz, 1C), , (d, J = 16.6 Hz, 1C), , , According the same procedure, the 2-bromo-1-13 C phenylethanone was obtained as a white solid (1.4 g, 56% yield for two steps). 1 H NMR (CDCl 3, 400 MHz) δ (m, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 4.46 (d, J = 3.2 Hz, 2H); 13 C NMR (CDCl 3, 100 MHz) δ 191.2, (d, J = 0.7 Hz, 1C), (d, J = 56.0 Hz, 1C), (d, J = 2.9 Hz, 1C), (d, J = 4.2 Hz, 1C), 30.9 (d, J = 43.0 Hz, 1C). S5

6 To a stirred solution of phosphorus ylide 1 (259.2 mg, 0.72 mmol) in dry CH 2 Cl 2 (2.0 ml) under N 2 at room temperature was added Fe(TCP)Cl (1.7 mg, mmol) and MDA (67 μl, 0.8 mmol) respectively (Caution! N 2 Release!), then washed the Schlenk tube with dry CH 2 Cl 2 (1.0 ml). After 20 min, 13 C-labeled 2-bromo-1-phenylethanone (80.0 mg, 0.4 mmol), Cs 2 CO 3 (156.4 mg, 0.48 mmol) and dry CH 2 Cl 2 (1.0 ml) were added and the resulting mixture was stirred at room temperature. After the reaction was complete, the resulting mixture was filtered rapidly through a funnel with a thin layer of silica gel and eluted with CH 2 Cl 2. The filtrate was concentrated and the residue was purified by chromatography on silica gel to afford the desired products. 69% yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 4H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (s, 3H), (s, 3H), 3.37 (dd, J = 2.4, 16.2 Hz, 1H), 2.22 (dd, J = 2.0, 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ (d, J = 1.4 Hz, 1C), (d, J = 4.1 Hz, 1C), ( 13 C), (d, J = 6.5 Hz, 1C), (d, J = 60.4 Hz, 1C), (d, J = 3.1 Hz, 1C), (d, J = 69.3 Hz, 1C), (d, J = 5.0 Hz, 1C), (d, J = 2.1 Hz, 1C), (d, J = 1.5 Hz, 1C), 62.6 (d, J = 39.3 Hz, 1C), 52.8, 51.7, % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 4H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (s, 3H), (s, 3H), 3.37 (dd, J = 2.4, 16.2 Hz, 1H), 2.22 (dd, J = 2.0, 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ (d, J = 1.9 Hz, 1C), 171.3, (d, J = 7.3 Hz, 1C), ( 13 C), (d, J = 1.0 Hz, 1C), (d, J = 65.1 Hz, 1C), (d, J = 0.6 Hz, 1C), 128.7, 127.4, 125.9, 62.6 (d, J = 38.3 Hz, 1C), 52.8, 51.6, 37.8 (d, J = 1.3 Hz, 1C). S6

7 4. General procedure for capture of cyclopropane intermidates by aldehyde To a stirred solution of vinyl phosphonium salt 9a (347.3 mg, 0.55 mmol) and 4-nitrobenzaldehyde (75.6 mg, 0.5 mmol) in dry CH 2 Cl 2 (3.0 ml) under N 2 at room temperature was added Cs 2 CO 3 (195.5 mg, 0.6 mmol) and CH 2 Cl 2 (2.0 ml). After the reaction was complete, the resulting mixture was filtered rapidly through a funnel with a thin layer of celite and eluted with CH 2 Cl 2. The filtrate was concentrated and the residue was purified by chromatography on silica gel to afford the desired cyclopropane 15 (106.7 mg, 50% yield). The cyclopropane 15 is a mixture contained all isomers, and one isomer is full characterized without determining the absolute configuration. 1 H NMR (CDCl 3, 400 MHz) δ 8.21 (dt, J = 2.0, 8.8 Hz, 2H), (m, 2H), (m, 1H), (m, 4H), 6.65 (d, J = 11.6 Hz, 1H), 5.85 (dd, J = 9.0, 11.8 Hz, 1H), 3.90 (d, J = 6.8 Hz, 1H), 3.82 (s, 3H), 3.44 (s, 3H), 3.28 (d, J = 17.6 Hz, 1H), (m, 1H), 2.67 (d, J = 18.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 195.4, 171.1, 169.9, 146.6, 143.0, 137.4, 133.5, 131.2, , , , , 123.7, 53.0, 51.7, 38.8, 36.5, 32.6, 32.5; IR (neat) ν 2954 (m), 1730 (s), 1668 (m), 1516 (m), 1341 (s), 1217 (m), 1177 (m), 1143 (m), 856 (m), 733 (m), 716 (s), 688 (s); HRMS (positive ESI) calcd for C 23 H 22 NO + 7 ([M+H] + ): ; Found: S7

8 5. Reaction optimization 3 Entry a Base Solvent Yield (%) b 1 Cs 2 CO 3 THF 16 2 Cs 2 CO 3 DCM 68 3 Cs 2 CO 3 DCE 52 4 Cs 2 CO 3 PhCH 3 trace 5 Cs 2 CO 3 CH 3 CN 37 6 Cs 2 CO 3 DMF 42 7 Cs 2 CO 3 t-buoh 27 8 CH 3 ONa CH 2 Cl 2 trace 9 t-buok CH 2 Cl 2 trace 10 Na 2 CO 3 CH 2 Cl 2 trace 11 K 2 CO 3 CH 2 Cl NaOH CH 2 Cl c Cs 2 CO 3 CH 2 Cl d Cs 2 CO 3 CH 2 Cl 2 71 a Ylide (259.2 mg, 0.72 mmol), Fe(TCP)Cl (1.7 mg, mmol), MDA (84 μl, 1.0 mmol), PhCOCH 2 Br (79.6 mg, 0.4 mmol), base (2.0 mmol), solvent (4 ml), rt, 24 h. b Isolated yield. c MDA (67 μl, 0.8 mmol). d Ylide (259.2 mg, 0.72 mmol), Fe(TCP)Cl (1.7 mg, mmol), MDA (67 μl, 0.8 mmol), PhCOCH 2 Br (79.6 mg, 0.4 mmol), Cs 2 CO 3 (156 mg, 0.48 mmol), CH 2 Cl 2 (4.0 ml), rt, 24 h. S8

9 6. General procedure for synthesis of cyclopentadiene derivatives To a stirred solution of phosphorus ylide 1 (259.2 mg, 0.72 mmol) in dry CH 2 Cl 2 (2.0 ml) under N 2 at room temperature was added Fe(TCP)Cl (1.7 mg, mmol) and MDA (67 μl, 0.8 mmol) respectively (Caution! N 2 Release!), then washed the Schlenk tube with dry CH 2 Cl 2 (1.0 ml). After 20 min, ArCOCH 2 Br (0.4 mmol), Cs 2 CO 3 (156.4 mg, 0.48 mmol) and dry CH 2 Cl 2 (1.0 ml) were added and the resulting mixture was stirred at room temperature. After the reaction was complete, the resulting mixture was filtered rapidly through a funnel with a thin layer of silica gel and eluted with CH 2 Cl 2 or AcOEt. The filtrate was concentrated and the residue was purified by chromatography on silica gel to afford the desired products. 71% yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 4H), (m, 1H), 6.92 (dd, J = 1.2, 5.6 Hz, 1H), 6.89 (t, J = 2.0 Hz, 1H), 6.64 (dd, J = 2.6, 5.0 Hz, 1H), 3.66 (s, 3H), 3.65 (s, 3H), 3.37 (d, J = 16.0 Hz, 1H), 2.23 (d, J = 16.4 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.4, 171.3, 148.8, 139.2, 133.7, 133.4, 130.0, 128.7, 127.4, 125.9, 62.6, 52.8, 51.6, 37.8; IR (neat) ν 2952 (m), 1724 (s), 1434 (m), 1347 (m), 1228 (s), 1197 (s), 1175 (s), 1070 (m), 761 (s), 734 (m), 693 (m); MS (EI, m/z, rel. intensity) 272 (12.7, M + ), 240 (15.8), 230 (5.2), 212 (15.3), 197 (5.5), 181 (28.2), 171 (11.7), 153 (100), 141 (11.9), 128 (12.6), 115 (11.9), 102 (4.6), 91 (4.2), 77 (6.6), 59 (17.4), 51 (4.2), 43 (3.2); HRMS (EI) calcd for C 16 H 16 O 4 (M + ): ; Found: The DEPT-135, gcosy, ghmbc, ghmqc, NOSEY also are provided. 53% yield, colorless liquid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 2H), (m, 2H), 6.89 (dd, J = 1.2, 5.4 Hz, 1H), 6.80 (t, J = 1.8 Hz, 1H), 6.62 (dd, J = 2.6, 5.4 Hz, 1H), (s, 3H), (s, 3H), 3.33 (d, J = 16.0 Hz, 1H), 2.23 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.3, 171.1, (d, J = Hz, 1C), (d, J = 0.7 Hz, 1C), (d, J = 1.0 Hz, 1C), 133.2, (d, J = 3.3 Hz, 1C), (d, J = 2.2 Hz, 1C), (d, J = 7.5 Hz, 1C), (d, J = 21.7 Hz, 1C), 62.6, 52.8, 51.6, 37.7; 19 F NMR (CDCl 3, 376 MHz) δ (m, 1F); IR (neat) ν 2952 (m), 2845 (m), 1724 (s), 1503 (m), 1347 (m), 1227 (s), 1197 (s), 1162 (s), 1115 (m), 832 (m), 807 (m), 751 (m), 722 (m); MS S9

10 (EI, m/z, rel. intensity) 290 (18.2, M + ), 258 (19.6), 230 (95.6), 199 (31.4), 171 (100), 159 (12.5), 146 (11.2), 133 (11.8), 59 (16.5); HRMS (EI) calcd for C 16 H 15 FO 4 (M + ): ; Found: % yield, colorless liquid, 1 H NMR (CDCl 3, 400 MHz) δ 7.31 (m, 4H), 6.91 (dd, J = 1.2, 5.2 Hz, 1H), 6.87 (dd, J =1.6, 2.0 Hz, 1H), 6.63 (dd, J = 2.2, 5.4 Hz, 1H), (s, 3H), (s, 3H), 3.34 (d, J = 16.0 Hz, 1H), 2.24 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.2, 171.0, 147.4, 139.6, 133.2, 132.2, 130.6, 128.9, 127.1, 62.6, 52.8, 51.7, 37.6; IR (neat) ν 2951 (m), 1724 (s), 1489 (m), 1434 (m), 1346 (m), 1229 (s), 1197 (s), 1175 (s), 1094 (m), 1072 (m), 825 (s), 751 (m), 722 (m); MS (EI, m/z, rel. intensity) 306 (18.6, M + ), 290 (4.6), 274 (21.2), 246 (87.5), 211 (38.7), 183 (20.0), 152 (100), 139 (17.3), 127 (9.2), 115 (6.4), 101 (4.6), 87 (3.7), 76 (12.2), 59 (49.6), 51 (8.1), 43 (8.4); HRMS (EI) calcd for C 16 H 15 ClO 4 (M + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 7.46 (dt, J = 2.2, 8.8 Hz, 2H), 7.24 (dt, J = 2.2, 8.8 Hz, 2H), 6.92 (dd, J = 1.6, 5.6 Hz, 1H), 6.89 (t, J = 6.0 Hz, 1H), 6.63 (dd, J = 2.2, 5.4 Hz, 1H), (s, 3H), (s, 3H), 3.34 (d, J = 15.6 Hz, 1H), 2.24 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.2, 171.0, 147.3, 139.7, 133.3, 132.5, 131.8, 130.6, 127.3, 121.4, 62.5, 52.9, 51.7, 37.6; IR (neat) ν 2951 (m), 1724 (s), 1486 (m), 1434 (m), 1346 (m), 1229 (s), 1198 (s), 1175 (s), 1074 (m), 819 (s), 727 (m); MS (EI, m/z, rel. intensity) 350 (22.3, M + ), 320 (23.3), 292 (81.8), 261 (12.6), 249 (6.1), 211 (37.0), 183 (40.7), 152 (100), 139 (15.2), 127 (9.4), 113 (4.3), 101 (4.0), 87 (2.7), 76 (10.7), 59 (20.9), 51 (3.9), 43 (1.1); HRMS (EI) calcd for C 16 H 15 BrO 4 (M + ): ; Found: % yield, light yellow solid, 1 H NMR (CDCl 3, 400 MHz) δ 8.20 (dt, J = 2.4, 8.8 Hz, 2H), 7.55 (dt, J = 2.4, 9.2 Hz, 2H), 7.12 (dd, J = 1.6, 2.0 Hz, 1H), 7.02 (dd, J = 1.2, 5.6 Hz, 1H), 6.69 (dd, J = 2.2, 5.4 Hz, 1H), 3.67 (s, 3H), 3.65 (s, 3H), 3.39 (d, J = 16.0 Hz, 1H), 2.33 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 75 MHz) δ 171.7, 170.6, 146.4, 146.1, 141.8, 139.7, 134.4, 133.3, 126.1, 124.1, 62.7, 53.0, 51.8, 37.4; IR (neat) ν 2952 (m), 1724 (s), 1591 (m), 1510 (m), 1434 (m), 1334 (s), 1230 (m), 1198 (s), 1177 (s), 1071 (m), 849 (s), 726 (m), 694 (m); MS (EI, m/z, rel. intensity) 317 (22.0, M + ), 285 (25.1), 258 (100), S10

11 242 (5.7), 212 (5.4), 197 (8.1), 183 (22.2), 167 (9.8), 152 (66.6), 139 (11.3), 127 (7.1), 115 (8.3), 102 (2.7), 87 (1.6), 76 (3.4), 59 (21.6), 51 (2.3); HRMS (EI) calcd for C 16 H 15 NO 6 (M + ): ; Found: The structure also determined by X-Ray analysis (CCDC ). 88% yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 7.59 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 7.00 (t, J = 1.8 Hz, 1H), 6.96 (dd, J = 1.4, 5.4 Hz, 1H), 6.66 (dd, J = 2.2, 5.4 Hz, 1H), 3.66 (s, 3H), 3.65 (s, 3H), 3.36 (d, J = 16.0 Hz, 1H), 2.28 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.1, 171.0, 147.0, 140.6, (q, J = 1.4 Hz, 1C), 133.3, 132.3, (q, J = 32.4 Hz, 1C), 125.9, (q, J = 38.0 Hz, 1C), (q, J = Hz, 1C), 62.7, 53.0, 51.8, 37.5; 19 F NMR (CDCl 3, 376 MHz) δ -62.7; IR (neat) ν 2954 (m), 1727 (s), 1616 (m), 1324 (s), 1200 (s), 1113 (s), 1072 (m), 1012 (m), 838 (m); MS (EI, m/z, rel. intensity) 340 (20.6, M + ), 308 (26.0), 290 (7.4), 280 (100), 249 (34.6), 230 (28.3), 221 (43.9), 209 (8.0), 201 (18.6), 183 (9.6), 171 (26.0), 152 (46.3), 139 (6.8), 126 (2.8), 85 (1.9), 75 (3.6), 59 (29.0), 51 (2.8); HRMS (EI) calcd for C 17 H 15 F 3 O 4 (M + ): ; Found: The structure also determined by X-Ray analysis (CCDC ). 93% yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 7.63 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.8 Hz, 2H), 7.06 (t, J = 1.8 Hz, 1H), 7.00 (dd, J = 1.4, 5.4 Hz, 1H), 6.68 (dd, J = 2.4, 5.4 Hz, 1H), 3.66 (s, 3H), 3.65 (s, 3H), 3.36 (d, J = 16.4 Hz, 1H), 2.30 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 171.8, 170.7, 146.4, 141.3, 137.8, 133.5, 133.2, 132.5, 126.1, 118.7, 110.5, 62.6, 53.0, 51.8, 37.4; IR (neat) ν 2953 (m), 2225 (m), 1725 (s), 1603 (m), 1425 (m), 1230 (s), 1198 (s), 1177 (s), 1072 (m), 1006 (m), 835 (m), 732 (s); HRMS (positive ESI) calcd for C 17 H 16 NO + 4 ([M+H] + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 7.51 (d, J = 2.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.20 (dd, J = 2.4, 4.4 Hz, 1H), 6.92 (dd, J = 1.4, 5.4 Hz, 1H), 6.89 (dd, J = 1.4, 2.2 Hz, 1H), 6.63 (dd, J = 2.2, 5.4 Hz, 1H), 3.66 (s, 3H), 3.65 (s, 3H), 3.34 (d, J = 16.0 Hz, 1H), 2.28 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 171.8, 170.8, 146.0, 140.3, 133.7, 133.1, 132.8, 131.8, 131.3, 130.6, 127.7, S11

12 124.9, 62.6, 52.9, 51.7, 37.5; IR (neat) ν 2952 (m), 1725 (s), 1434 (m), 1229 (s), 1198 (s), 1176 (s), 1073 (m), 1007 (m), 818 (m), 763 (m), 735 (s); HRMS (positive ESI) calcd for C 16 H 15 Cl 2 O 4 + ([M+H] + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 4H), (m, 4H), (m, 1H), (m, 2H), (m, 1H), (s, 3H), (s, 3H), 3.43 (d, J = 16.0 Hz, 1H), 2.27 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.4, 171.3, 148.2, 140.3, 140.0, 139.3, 133.4, 132.6, 130.0, 128.7, 127.4, 127.3, 126.8, 126.1, 62.5, 52.8, 51.6, 37.8; IR (neat) ν 2951 (m), 1724 (s), 1434 (m), 1229 (s), 1198 (s), 1176 (s), 1072 (m), 1006 (m), 836 (m), 764 (s), 729 (s), 696 (s); HRMS (positive ESI) calcd for C 22 H 21 O + 4 ([M+H] + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 7.26 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 7.6 Hz, 2H), 6.89 (dd, J = 1.0, 5.4 Hz, 1H), 6.84 (s, 1H), 6.63 (dd, J = 2.4, 5.2 Hz, 1H), 3.66 (s, 3H), 3.64 (s, 3H), 3.37 (d, J = 16.0 Hz, 1H), 2.34 (s, 3H), 2.21 (d, J = 16.4 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.5, 171.3, 148.7, 138.7, 137.3, 133.3, 130.8, 129.4, 129.0, 125.7, 62.4, 52.7, 51.6, 37.8; IR (neat) ν 2951 (m), 1724 (s), 1434 (m), 1346 (s), 1229 (s), 1197 (s), 1174 (s), 1071 (m), 1006 (m), 814 (s), 748 (s); MS (EI, m/z, rel. intensity) 286 (15.1, M + ), 254 (15.1), 226 (100), 211 (7.2), 195 (40.9), 183 (14.4), 167 (92.5), 152 (60.9), 141 (9.7), 128 (9.6), 115 (11.7), 91 (5.4), 77 (3.3), 59 (15.2), 51 (1.7); HRMS (EI) calcd for C 17 H 18 O 4 (M + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 1H), (m, 1H), (m, 1H), 7.00 (dd, J = 1.8, 7.4 Hz, 1H), 6.92 (dd, J = 1.4, 5.4 Hz, 1H), (dd, J = 2.0, 5.6 Hz, 1H), (dd, J = 1.6, 6.0 Hz, 1H), 3.69 (s, 3H), 3.65 (s, 3H), 3.19 (d, J = 16.8 Hz, 1H), 2.34 (d, J = 16.8 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 171.7, 171.0, 146.0, 139.1, 135.7, 134.3, 133.0, 132.8, 130.5, 129.2, 126.8, 124.4, 65.4, 52.6, 51.7, 36.8; IR (neat) ν 2951 (m), 1726 (s), 1434 (m), 1342 (s), 1238 (m), 1199 (s), 1175 (s), 1076 (m), 1001 (m), 789 (s), 756 (m); MS (EI, m/z, rel. intensity) 350 (3.2, M + ), S12

13 320 (5.6), 290 (31.8), 258 (16.3), 230 (86.9), 211 (40.4), 199 (28.9), 183 (31.5), 171 (92.8), 152 (100), 139 (13.1), 133 (10.5), 127 (9.4), 115 (7.8), 101 (4.0), 91 (2.8), 75 (7.4), 59 (29.7), 51 (4.2), 43 (1.8); HRMS (EI) calcd for C 16 H 15 BrO 4 (M + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 7.56 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), (m, 2H), (m, 2H), 6.63 (dd, J = 2.0, 5.6 Hz, 1H), 3.66 (s, 3H), 3.65 (s, 3H), 3.35 (d, J = 15.6 Hz, 1H), 2.25 (d, J = 15.6 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.0, 171.0, 147.1, 140.0, 135.8, 133.2, 131.4, 130.3, 130.2, 129.0, 124.3, 122.9, 62.7, 52.9, 51.7, 37.6; IR (neat) ν 2951 (m), 1724 (s), 1434 (m), 1346 (s), 1229 (m), 1197 (s), 1175 (s), 1071 (m), 1006 (m), 869 (m), 752 (m), 709 (m), 688 (m); MS (EI, m/z, rel. intensity) 350 (2.9, M + ), 320 (16.7), 290 (62.0), 259 (12.6), 230 (30.6), 211 (41.8), 199 (8.0), 183 (34.6), 171 (22.1), 152 (100), 139 (14.9), 127 (9.0), 115 (5.1), 101 (3.6), 76 (10.3), 59 (23.4), 51 (4.4), 43 (1.3); HRMS (EI) calcd for C 16 H 15 BrO 4 (M + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 3H), 7.71 (d, J = 1.2 Hz, 1H), 7.60 (dd, J = 2.0, 8.8 Hz, 1H), (m, 2H), 7.04 (t, J = 1.8 Hz, 1H), 6.98 (dd, J = 1.2, 5.2 Hz, 1H), 6.70 (dd, J = 2.2, 5.6 Hz, 1H), 3.67 (s, 3H), 3.66 (s, 3H), 3.50 (d, J = 16.0 Hz, 1H), 2.31 (d, J = 16.4 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 172.5, 171.2, 148.4, 139.5, 133.4, 133.3, 132.4, 130.9, 130.5, , , 127.4, 126.3, 126.0, 124.2, 124.0, 62.5, 52.8, 51.6, 38.0; IR (neat) ν 2951 (m), 1724 (s), 1434 (m), 1349 (m), 1231 (m), 1200 (s), 1175 (s), 1072 (m), 1006 (m), 855 (m), 814 (m), 734 (s); MS (EI, m/z, rel. intensity) 322 (17.1, M + ), 290 (8.2), 262 (63.8), 231 (17.7), 203 (100), 189 (17.9), 178 (7.8), 165 (8.4), 152 (8.9), 139 (4.2), 127 (5.2), 115 (4.9), 101 (11.3), 77 (5.9), 59 (24.5), 51 (2.8), 43 (4.4); HRMS (EI) calcd for C 20 H 18 O 4 (M + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 7.53 (d, J = 7.6 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), (m, 1H), 7.19 (t, J = 7.4 Hz, 1H), 7.07 (s, 1H), 7.01 (dd, J = 1.4, 5.4 Hz, 1H), 6.80 (s, 1H), 6.66 (dd, J = 2.4, 5.6 Hz, 1H), 3.72 (s, 3H), 3.63 (s, 3H), 3.58 (d, J = 17.2 Hz, 1H), 2.22 (d, J S13

14 = 16.8 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 171.8, 171.5, 154.4, 150.5, 140.6, 138.0, 133.2, 130.9, 129.0, 124.8, 122.9, 121.1, 110.7, 103.2, 61.9, 52.8, 51.8, 38.9; IR (neat) ν 2952 (m), 1728 (s), 1435 (m), 1349 (m), 1239 (m), 1198 (s), 1175 (s), 1077 (m), 1005 (m), 871 (m), 806 (m), 738 (s); MS (EI, m/z, rel. intensity) 312 (10.6, M + ), 280 (4.0), 252 (100), 221 (24.9), 194 (29.1), 165 (56.2), 152 (7.6), 139 (8.0), 126 (2.7), 115 (3.5), 102 (1.1), 77 (1.6), 59 (9.5), 51 (1.0), 43 (1.4); HRMS (EI) calcd for C 18 H 16 O 5 (M + ): ; Found: % yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ 8.56 (d, J = 6.0 Hz, 2H), 7.28 (dd, J = 1.4, 4.6 Hz, 2H), 7.16 (dd, J = 1.6, 5.2 Hz, 1H), 7.04 (dd, J = 1.6, 5.2 Hz, 1H), 6.68 (dd, J = 2.0, 5.4 Hz, 1H), (s, 3H), (s, 3H), 3.41 (d, J = 16.0 Hz, 1H), 2.29 (d, J = 16.0 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 171.7, 170.8, 150.2, 145.6, 141.8, 140.3, 134.0, 133.0, 119.8, 62.4, 52.9, 51.7, 37.3; IR (neat) ν 2952 (m), 1724 (s), 1590 (m), 1435 (m), 1228 (s), 1198 (s), 1177 (s), 1071 (m), 1007 (m), 818 (m), 766 (m), 724 (s), 667 (m); HRMS (positive ESI) calcd for C 15 H 16 NO + 4 ([M+H] + ): ; Found: S14

15 X-Ray structure of 4e (CCDC ) Bond precision: C-C = A Wavelength= Cell: a= (13) b= (12) c=8.9203(9) alpha=90 beta=96.517(2) gamma=90 Temperature: 293 K Calculated Reported Volume (3) (3) Space group P 21/c P2(1)/c Hall group -P 2ybc? Moiety formula C16 H15 N O6? Sum formula C16 H15 N O6 C16 H15 N O6 Mr Dx,g cm Z 4 4 Mu (mm-1) F F000' h,k,lmax 16,15,11 16,15,11 Nref Tmin,Tmax 0.973, ,1.000 Tmin' Correction method= EMPIRICAL Data completeness= Theta(max)= R(reflections)= ( 2380) wr2(reflections)= ( 2982) S = Npar= 210 S15

16 X-Ray structure of 4f (CCDC ) Bond precision: C-C = A Wavelength= Cell: a= (12) b= (19) c=7.8459(8) alpha=90 beta= (2) gamma=90 Temperature: 293 K Calculated Reported Volume (3) (3) Space group P 21/c P2(1)/c Hall group -P 2ybc? Moiety formula C17 H15 F3 O4? Sum formula C17 H15 F3 O4 C17 H15 F3 O4 Mr Dx,g cm Z 4 4 Mu (mm-1) F F000' h,k,lmax 14,23,9 14,23,9 Nref Tmin,Tmax 0.970, ,1.000 Tmin' Correction method= EMPIRICAL Data completeness= Theta(max)= R(reflections)= ( 2266) wr2(reflections)= ( 3205) S = Npar= 255 S16

17 7. General procedure for chemical transformation Hydrogenation of cyclopentadiene 4a A mixture of cyclopentadiene (136.2 mg, 0.5 mmol) in methanol (30 ml) with 10% palladium on carbon (26.6 mg, mol) was rapidly stirred under H 2 (1 atm) at 25 C. After 18 hours, the solution was filtered through celite with methanol. The filtrate was concentrated and the residue was purified by chromatography on silica gel to afford the desired cyclopentane 16 (130.0 mg, 94% yield, dr = 80/20) as a colourless liquid. 94% yield, dr = 80/20, colorless liquid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 3H), (m, 2H), 3.71 (s, 0.6H), 3.62 (s, 2.4H), 3.52 (s, 0.6 H), (m, 0.2H), 3.26 (s, 2.4H), 3.1 (d, J = 16.8 Hz, 0.8H), 2.92 (dd, J = 6.8, 11.2 Hz, 0.8H), (m, 0.8H), (m, 0.2H), 2.42 (d, J = 17.2 Hz, 0.8H), 2.33 (d, J = 17.2 Hz, 0.2H), (m, 5.2H); 13 C NMR (CDCl 3, 100 MHz) minor isomer: δ 176.9, 172.1, 138.9, 128.6, 128.1, 126.8, 54.1, 53.3, 51.9, 51.3, 38.4, 36.1, 30.8, 23.5; major isomer: δ 174.6, 172.1, 139.6, , , 127.0, 56.6, 56.1, 51.4, 51.1, 42.2, 35.1, 30.8, 23.4; IR (neat) ν 2951 (m), 1728 (s), 1434 (m), 1201(s), 1168 (s), 701 (m); HRMS (positive ESI) calcd for C 16 H 21 O + 4 ([M+H] + ): ; Found: Reduction and lactonization of cyclopentadiene 4a 4 To a solution of cyclopentadiene 4a (76 mg, mmol) in dry THF (6 ml) at -78 under N 2 was added DIBAL-H (0.58 ml, 1.0 M in toluene, mmol) dropwise. After 30 min, The reaction mixture was stirred at 0 and warm to at room temperature for another 12 hours. Then the saturated solution of sodium potassium tartrate was added to the upper mixture slowly with gas release. The aqueous layer was extracted with CH 2 Cl 2 (3 50 ml). The combined organic layer S17

18 was dried over Mg 2 SO 4, filtered and concentrated. The residue was purified by chromatography on silica gel to afford the desired lactone 17 (34.3 mg, 59% yield) and cyclopentadiene 4a (28.7 mg, 38% yield SM recover). 59% yield (95% yield brsm), white solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 5H), 6.90 (s, 1H), 6.66 (d, J = 2.4 Hz, 1H), 6.58 (d, J = 4.8 Hz, 1H), 4.64 (t, J = 9.0 Hz, 1H), (m, 1H), 2.73 (q, J =10.8 Hz, 1H), 2.29 (q, J = 6.3 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 175.9, 148.4, 135.4, 133.9, 133.0, 131.0, 128.8, 127.6, 126.3, 66.5, 61.9, 30.4; IR (neat) ν 2920 (m), 1758 (s), 1368 (m), 1165 (m), 1132 (m), 1020 (s), 807 (m), 755 (s), 718 (s), 692 (s); MS (EI, m/z, rel. intensity) 212 (37.6, M + ), 167 (54.4), 153 (100), 139 (8.1), 128 (8.5), 115 (13.1), 102 (4.4), 89 (5.5), 76 (12.1), 51 (7.2), 43 (9.0); HRMS (EI) calcd for C 14 H 12 O 2 (M + ): ; Found: Saponification of cyclopentadiene 4a To a solution of cyclopentadiene 4a (551.3 mg, mmol) in methanol (20.0 ml) was added NaOH (2.8 ml, 1.0 M in water, 2.83 mmol), the resulting mixture was allowed to reflux for 7 hours. After the reaction was complete, the methanol was evaporated and the residue was diluted with water (20 ml). Then HCl (2.0 M) was added to adjust the ph = 2, the aqueous layer was extracted with CH 2 Cl 2 (5 50 ml). The combined organic layer was dried over Mg 2 SO 4, filtered and concentrated. The residue was purified by chromatography on silica gel to afford the desired acid 18 (435.5 mg, 83% yield) as a light yellow solid. 83% yield, light yellow solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 4H), (m, 1H), (m, 2H), 6.66 (dd, J = 2.4, 5.2 Hz, 1H), 3.66 (s, 3H), 3.41 (d, J =16.4 Hz, 1H), 2.22 (d, J = 16.4 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 177.1, 172.2, 148.4, 138.8, 133.5, 133.4, 129.9, 128.6, 127.4, 125.7, 62.1, 52.7, 37.7; IR (neat) ν 3057 (brs), 2951 (m), 1706 (s), 1434 (m), 1224 (s), 1071 (m), 762 (s), 693 (m); HRMS (positive ESI) calcd for C 15 H 15 O + 4 ([M+H] + ): ; Found: S18

19 Cu(OTf) 2 mediated cyclization of acid 18 A solution of acid 18 (51.6 mg, 0.2 mmol) and Cu(OTf) 2 (14.5 mg, 0.04 mmol) in DCE (2.0 ml) was stirred at room temperature under N 2. After the reaction was complete, the resulting mixture was concentrated and the residue was purified by chromatography on silica gel to afford the desired products 19 (41.1 mg, 80% yield) as a white solid. 80% yield, white solid, 1 H NMR (CDCl 3, 400 MHz) δ (m, 5H), (m, 1H), (m, 1H), (m, 2H), 3.17 (s, 3H), 2.67 (d, J = 18.0 Hz, 1H), 2.57 (dt, J = 2.0, 17.2 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz) δ 174.6, 171.5, 136.7, 134.6, 132.1, 128.5, 128.0, 125.3, 101.8, 60.1, 52.0, 41.2, 41.0; IR (neat) ν 2951 (m), 1792 (s), 1772 (s), 1735 (s), 1226 (s), 1201 (m), 1174 (m), 994 (s), 789 (m), 736 (m), 697 (m); HRMS (positive ESI) calcd for C 15 H 15 O + 4 ([M+H] + ): ; Found: The Dept-135, gcosy, ghmbc, NOSEY are provided. S19

20 Reference: 1 Borovkov, V. V.; Lintuluoto, J. M.; Inove, Y. Synlett. 1999, Bosson, J.; Poater, A.; Cavallo, L.; Nolan, S. P. J. Am. Chem. Soc. 2010, 132, Ouyang, K.; Xi, Z. Acta Chim. Sinica 2013, 71, Jankowska, R.; Han, Y.; Shia, K.-S. Angew. Chem. Int. Ed. 2003, 42, S20

21 8. NMR Spectra of the Compounds 1 H NMR (400 MHz in CDCl 3 ) S21

22 31 P NMR (162 MHz in CDCl 3 ) S22

23 1 H NMR (400 MHz in CDCl 3 ) S23

24 31 P NMR (162 MHz in CDCl 3 ) S24

25 19 F NMR (376 MHz in CDCl 3 ) S25

26 1 H NMR (400 MHz in CDCl 3 ) S26

27 13 C NMR (100 MHz in CDCl 3 ) S27

28 1 H NMR (400 MHz in CDCl 3 ) S28

29 13 C NMR (100 MHz in CDCl 3 ) S29

30 1 H NMR (400 MHz in CDCl 3 ) S30

31 13 C NMR (100 MHz in CDCl 3 ) S31

32 1 H NMR (400 MHz in CDCl 3 ) S32

33 13 C NMR (100 MHz in CDCl 3 ) S33

34 1 H NMR (400 MHz in CDCl 3 ) S34

35 13 C NMR (100 MHz in CDCl 3 ) S35

36 1 H NMR (400 MHz in CDCl 3 ) S36

37 13 C NMR (100 MHz in CDCl 3 ) S37

38 DEPT-135 (100 MHz in CDCl 3 ) S38

39 gcosy S39

40 ghmbc S40

41 ghmqc S41

42 NOESY S42

43 1 H NMR (400 MHz in CDCl 3 ) S43

44 13 C NMR (100 MHz in CDCl 3 ) S44

45 19 F NMR (376 MHz in CDCl 3 ) S45

46 1 H NMR (400 MHz in CDCl 3 ) S46

47 13 C NMR (100 MHz in CDCl 3 ) S47

48 1 H NMR (400 MHz in CDCl 3 ) S48

49 13 C NMR (100 MHz in CDCl 3 ) S49

50 1 H NMR (400 MHz in CDCl 3 ) S50

51 13 C NMR (75 MHz in CDCl 3 ) S51

52 1 H NMR (400 MHz in CDCl 3 ) S52

53 13 C NMR (100 MHz in CDCl 3 ) S53

54 19 F NMR (376 MHz in CDCl 3 ) S54

55 1 H NMR (400 MHz in CDCl 3 ) S55

56 13 C NMR (100 MHz in CDCl 3 ) S56

57 1 H NMR (400 MHz in CDCl 3 ) S57

58 13 C NMR (100 MHz in CDCl 3 ) S58

59 1 H NMR (400 MHz in CDCl 3 ) S59

60 13 C NMR (100 MHz in CDCl 3 ) S60

61 1 H NMR (400 MHz in CDCl 3 ) S61

62 13 C NMR (100 MHz in CDCl 3 ) S62

63 1 H NMR (400 MHz in CDCl 3 ) S63

64 13 C NMR (100 MHz in CDCl 3 ) S64

65 1 H NMR (400 MHz in CDCl 3 ) S65

66 13 C NMR (100 MHz in CDCl 3 ) S66

67 1 H NMR (400 MHz in CDCl 3 ) S67

68 13 C NMR (100 MHz in CDCl 3 ) S68

69 1 H NMR (400 MHz in CDCl 3 ) S69

70 13 C NMR (100 MHz in CDCl 3 ) S70

71 1 H NMR (400 MHz in CDCl 3 ) S71

72 13 C NMR (100 MHz in CDCl 3 ) S72

73 1 H NMR (400 MHz in CDCl 3 ), dr=80/20 S73

74 13 C NMR (100 MHz in CDCl 3 ) S74

75 1 H NMR (400 MHz in CDCl 3 ) S75

76 13 C NMR (100 MHz in CDCl 3 ) S76

77 1 H NMR (400 MHz in CDCl 3 ) S77

78 13 C NMR (100 MHz in CDCl 3 ) S78

79 1 H NMR (400 MHz in CDCl 3 ) S79

80 13 C NMR (100 MHz in CDCl 3 ) S80

81 DEPT-135 S81

82 gcosy S82

83 ghmbc S83

84 ghmqc S84

85 NOESY S85