SUPPORTING INFORMATION

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1 SUPPORTING INFORMATION For Synthesis of Fluorenone Derivatives through Palladium-Catalyzed Dehydrogenative Cyclization Hu Li, Ru-Yi Zhu, Wen-Juan Shi, Ke-Han He, and Zhang-Jie Shi* Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Green Chemistry Center, Peking University, Beijing , China State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai , China S1

2 General Experimental Section Analytic Methods. 1 H NMR and 13 C NMR data were obtained on Bruker 400M nuclear resonance spectrometers unless otherwise specified. CDCl 3 and CD 3 OD as solvent and tetramethylsilane (TMS) as the internal standard were employed. Chemical shifts were reported in units (ppm) by assigning TMS resonance in the 1 H NMR spectrum as 0.00 ppm. The data of 1 H NMR was reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet and br = broad), coupling constant (J values) in Hz and integration. Chemical shifts for 13 C NMR spectra were recorded in ppm from TMS using the central peak of CDCl 3 (77.0 ppm) as the internal standard. Flash chromatography was performed using mesh silica gel with the indicated solvent system according to standard techniques. Analytical thin layer chromatography (TLC) was performed on pre coated, glass backed silica gel plates. HRMS (ESI and EI) analyses were performed by Analytical Instrumentation Center, Peking University, and Institute of Chemistry, Chinese Academy of Sciences, respectively. General preparation for chemicals. Palladium(II) acetate were purchased from Sinocompand Technology Co., Ltd. Silver(I) oxide, 99+ % (metals basis) was purchased from Alfa Aesar, benzophenones were from Sinopharm Chemical Reagent Co., Ltd. Potassium carbonate was domestic reagent, and was grinded into power before used. Trifluoroacetic acid (TFA), 4,4 - difluorobenzophenone were from J&K Chemical Ltd. Other reagents were from Alfa Aesar. All reagents were directly used from purchased without any further purification unless otherwise specified. S2

3 General Experimental Procedures General procedures for preparation of substrates 1 (eq S1). The subtrates 1f, 1l, 1m were synthesized by oxidation of corresponding alcohols A. The corresponding phenyl magnesium bromide (1.3 eq) prepared in situ was added dropwisely to the corresponding benzaldehyde in anhydrous THF in N 2 atmosphere at 0, and stirred at room temperature overnight. Then the reaction was quenched by saturated NH 4 Cl (aq), extracted by EtOAc, dried over Na 2 SO 4, and evaporated in vacuum, further purified by flash chromatography on silica gel with petroleum ether/etoac (10:1) to afford the corresponding alcohols. And these alcohols were dissolved in CH 2 Cl 2, then PCC (1.5 eq) was added. The reaction was monitored by TLC for full conversion, then was quenched by saturated NH 4 Cl (aq), extracted by EtOAc, dried over Na 2 SO 4, and evaporated in vacuum, further purified by flash chromatography on silica gel with petroleum ether/etoac (15:1) to afford the products 1. The deuterium-labeled substrates 1x and 1y were prepared as shown in eq S2. The preparation of the corresponding brominated alcohols B was similar to alcohols A in eq S1. Then to a dried and degassed bottle, B was added and dissolved in anhydrous THF at 78, nbuli (4 eq) was added dropwisely in 0.5 h, then stirred for another 1.0 h. The reaction was quenched by D 2 O (40 eq) at 78, and stirred for another 0.5 h, and then warmed to room temperature, extracted by EtOAc for three times, dried over Na 2 SO 4, and evaporated in vacuum, further purified by flash chromatography on silica gel with petroleum ether/etoac (30:1) to afford the deuterium-labeled alcohols, which were oxidized into the ketones 1 by PCC and further purified by flash chromatography on silica gel with petroleum ether/etoac (20:1). The white solid 1x was obtained in 76 % yield, and the white solid 1y was in 65 % yield. S3

4 The deuterium-labeled substrate 1z was prepared as shown in eq S3. To a solution of conc. H 2 SO 4 (143 ml) and H 2 O (40 ml) at 0, d6 - benzene (1.0 eq, 19.5 ml) was added, then NaBrO 3 (1.1 eq, 36.8 g) was added in four portions in 1 h. The mixture was stirred for 10 h at 0 and diluted by water and extracted by n-hexane, washed by water and the organic layers were evaporated at 10 in water bath. The residue was distilled under reduced pressure (40, 20 mbar) to afford light yellow oil with the yield of 50%, which was confirmed by GC-MS. The corresponding alcohol C and product 1z were synthesized similarly to eq S1. And the white solid 1z was obtained in 46 % yield. S4

5 General procedures for Pd(II)-catalyzed dehydrogenative cyclization. Under air atmosphere, Pd(OAc) 2 (0.01 mmol, 2.2 mg), Ag 2 CO 3 (0.30 mmol, 69.5 mg), K 2 CO 3 (0.50 mmol, 69.1 mg) and the benzophenone (1a)(0.20 mmol, 36.4 mg) were added into a Schlenk tube dried by hot-gun. The tube was stopped and degassed with N 2 for three times. Then trifluoroacetic acid (TFA) (0.50 ml) was added by syringe. The mixture was stirred under N 2 atmosphere at 140 for 24 h. Then the mixture was cooled down to room temperature and evaporated in vacuum and further purified by flash chromatography on silica gel with petroleum ether/ethyl acetate (15:1) to give the product 2a (30.6 mg, 85%) as a yellow solid. Table S1. Base Screening for Pd(II)-Catalyzed Dehydrogenative Cyclization a a Reactions were conducted with 0.20 mmol of 1a, 0.01 mmol of Pd(OAc) 2, 0.30 mmol of Ag 2 O, and 0.5 ml of TFA, 140, 24 h, N 2 atmosphere. b GC yields were given using dodecane as the internal standard. And isolated yields were shown in the parentheses. Procedure for the deuterium labeling experiments. According to eqs S4 and S5, under air atmosphere, Pd(OAc) 2 (0.01 mmol, 2.2 mg), Ag 2 CO 3 (0.30 mmol, 69.5 mg), K 2 CO 3 (0.50 mmol, 69.1 mg) and the 84% deuteriumed benzophenone (1x) (0.20 mmol, 43.0 mg) [or 87% deuteriumed benzophenone (1y)(0.20 mmol, 43.0 mg)] were added into a Schlenk tube dried by hot-gun. The tube was stopped and degassed with N 2 for three times. Then trifluoroacetic acid (TFA) (0.50 ml) was added by syringe. The mixture was stirred under N 2 atmosphere at 140 for 4 h. Then the mixture was cooled down to room temperature and evaporated in vacuum and further puried by flash chromatography on silica gel with petroleum ether/ethyl acetate (30:1) to give the product 2x or 2y as a yellow solid. For 2x, 1 H NMR (400 MHz, CDCl 3 ): δ = 2.44 (s, 3H), (m, 1H), (m, 2H), 7.30 (s, 1H), 7.55 (d, J = 8 Hz, 1H), 7.64 (q, J = 4 Hz, 0.39H). For 2y, 1 H NMR (400 MHz, CDCl 3 ): δ = 2.43 (s, 3H), (m, 1H), (m, 2H), 7.29 (s, 1H), 7.54 (d, J = 8 Hz, 0.44H), 7.62 (q, J = 4 Hz, 1H). According to eq S6, under air atmosphere, Pd(OAc) 2 (0.01 mmol, 2.2 mg), Ag 2 CO 3 (0.30 mmol, 69.5 mg), K 2 CO 3 (0.50 mmol, 69.1 mg), 4-methylbenzophenone (1b) (0.10 mmol, 19.6 mg) and full deuteriumed benzophenone (1z) (0.10 mmol, 20.1 mg) were added into a Schlenk tube dried by hot-gun. The tube was stopped and degassed with N 2 for three times. Then trifluoroacetic acid (TFA) (0.50 ml) was added by syringe. The mixture was stirred under N 2 atmosphere at 140 for 4 h. Then the mixture was cooled down to room temperature and S5

6 evaporated in vacuum and further purified by flash chromatography on silica gel with petroleum ether/ethyl acetate (30:1) to give the product 2z as a yellow solid. 1 H NMR (400 MHz, CDCl 3 ): δ = 2.42 (s, 3H), 7.08 (d, J = 8Hz, 0.96H), (m, 0.89H), 7.32 (s, 0.99H), (m, 1.11H), 7.54 (d, J = 8Hz, 0.87H), 7.63 (d, J = 8Hz, 0.67H). S6

7 Characterization of Substrates in Details 4-Fluoro-4'-methylbenzophenone-2-d (1x). White solid. 1 H NMR (400 MHz, CDCl 3 ): δ = 2.44 (s, 3H), (m, 2H), 7.29 (d, J = 8 Hz, 2H), 7.69 (d, J = 8 Hz, 2H), 7.82 (q, J = 4 Hz, 1.16 H). 4-Methyl-4'-fluorobenzophenone-2-d (1y). White solid. 1 H NMR (400 MHz, CDCl 3 ): δ = 2.43 (s, 3H), 7.14 (t, J = 8 Hz, 2H), (m, 2H), 7.68 (d, J = 8 Hz, 1.13H), (m, 2 H). 4 -Methylbenzophenone-2,3,4,5,6-d (1z). White solid. 1 H NMR (400 MHz, CDCl 3 ): δ = 2.43 (s, 3H), 7.27 (d, J = 12 Hz, 2H), 7.72 (d, J = 8 Hz, 2H). S7

8 Characterization of Products in Details 9H-Fluoren-9-one (2a). Yellow solid (30.6 mg, 85%). NMR spectral data of the compound are in accordance with previous report. 1 2-Methyl-9H-fluoren-9-one (2b). Yellow solid (34.9 mg, 90%). NMR spectral data of the compound are in accordance with previous report. 1 2-Methyl-9H-fluoren-9-one (2c). Yellow solid (33.0 mg, 85%). NMR spectral data of the compound are in accordance with previous report. 2 2,3-Dimethyl-9H-fluoren-9-one (2d). Yellow solid (37.9 mg, 91%). NMR spectral data of the compound are in accordance with previous report. 3 3,6-Dimethyl-9H-fluoren-9-one (2e). Yellow solid (39.1 mg, 94%). 1 H NMR (400 MHz, CDCl 3 ): δ=7.0 (d, J = 8 Hz, 1H), 7.20 (s, 1H), 7.45 (d, J = 8 Hz, 1H), 2.30 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ = 22.12, , , , , , , HRMS (ESI): found: , calcd. for C 15 H 13 O ([M+H] + ): S8

9 2,3,6-Trimethyl-9H-fluoren-9-one (2f). Yellow solid (41.8 mg, 94%). 1 H NMR (400 MHz, CDCl 3 ): δ = 2.26, 2.31, 2.40 (s, each 3H), 7.02 (d, J = 4 Hz, 1H), 7.24 (s, 2H), 7.39 (s, 1H), 7.49 (d, J= 8 Hz); 13 C NMR (100 MHz, CDCl 3 ): δ = 19.90, 20.70, 22.14, , , , , , , , , , , , , HRMS (ESI): found: , calcd. for C 16 H 15 O ([M+H] + ): ,6-Diphenyl-9H-fluoren-9-one (2g). Yellow solid (30.6 mg, 46%). 1 H NMR (400 MHz, CDCl 3 ): δ = (m, 2H), (m, 6H), (m, 4H), (m, 2H), 7.76 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = , , , , , , , , , , HRMS (ESI): found: , calcd. for C 25 H 17 O ([M+H] + ): tert-Butyl-9H-fluoren-9-one (2h). Yellow solid (39.7 mg, 84%). NMR spectral data of the compound are in accordance with previous report. 4 1-Methyl-9H-fluoren-9-one (2i). Yellow solid (14.0 mg, 36%). NMR spectral data of the compound are in accordance with previous report. 7 3-Methoxy-9H-fluoren-9-one (2j). Yellow solid (30.3 mg, 72%). NMR spectral data of the compound are in accordance with previous report. 8 S9

10 3,6-Dimethoxy-9H-fluoren-9-one(2k). Yellow solid (35.1 mg, 73%). NMR spectral data of the compound are in accordance with previous report. 5 3-Fluoro-2-methyl-9H-fluoren-9-one (2l). Yellow solid (36.5 mg, 86%). 1 H NMR (400 MHz, CDCl 3 ): δ = 2.23 (s, 3H), 7.06 (d, J = 8 Hz, 1H), (m, 1H), (m, 1H), (m, 2H), 7.58 (d, J = 8 Hz); 13 C NMR (100 MHz, CDCl 3 ): δ = (d, J = 3 Hz), (d, J = 26 Hz), , (d, J = 18 Hz), (d, J = 7 Hz), , (d, J = 3 Hz), , , (d, J = 3 Hz), (d, J = 10 Hz), , , HRMS (ESI): found: , calcd. for C 14 H 10 FO ([M+H] + ): Fluoro-6-methyl-9H-fluoren-9-one (2m). Yellow solid (38.6 mg, 91%). 1 H NMR (400 MHz, CDCl 3 ): δ = 2.32 (s, 3H), (m, 1H), (m, 2H), 7.16 (s, 1H), 7.42 (d, J = 8 Hz, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ = 22.10, (d, J = 24 Hz), (d, J = 23 Hz), , , (d, J = 10 Hz), , , (d, J = 2 Hz), , (d, J = 10 Hz), (d, J = 253 Hz), HRMS (ESI): found: , calcd. for C 14 H 10 FO ([M+H] + ): Hydroxy-9H-fluoren-9-one (2n). Yellow solid (32.9 mg, 84%). NMR spectral data of the compound are in accordance with previous report. 8 S10

11 1-Fluoro-6-methoxy-9H-fluoren-9-one (2o). Yellow solid (9.1 mg, 20%). NMR spectral data of the compound are in accordance with previous report. 8 1-Hydroxy-3-methoxy-9H-fluoren-9-one (2p). Yellow solid (12.7 mg, 28% Yield). 1 H NMR (400 MHz, CDCl 3 ): δ = 3.87 (s, 3H), 6.19 (d, J = 4 Hz, 1H), 6.62 (d, J = 4 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), 8.52 (brs, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ = 56.01, 99.96, , , , , , , , , , , , HRMS (ESI): found: , calcd. for C 14 H 11 O 3 ([M+H] + ): Fluoro-9H-fluoren-9-one (2q). Yellow solid (25.7 mg, 65%). NMR spectral data of the compound are in accordance with previous report. 2 3-Chloro-9H-fluoren-9-one (2r). Yellow solid (29.1 mg, 68%). NMR spectral data of the compound are in accordance with previous report. 2 3,6-Difluoro-9H-fluoren-9-one (2s). Yellow solid (26.4 mg, 61%). 1 H NMR (400 MHz, CDCl 3 ): δ = (m, 2H), (m, 2H), (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ = (d, J = 24 Hz), (d, J = 23 Hz), (d, J = 10 Hz), , , (d, J = 254 Hz), HRMS (ESI): found: , calcd. for C 13 H 7 F 2 O ([M+H] + ): S11

12 3-(Trifluoromethyl)-9H-fluoren-9-one (2t). Yellow solid (23.8 mg, 48%). NMR spectral data of the compound are in accordance with previous report. 5 7H-Benzo[c]fluoren-7-one (2u). Yellow solid (22.1 mg, 48%). NMR spectral data of the compound are in accordance with previous report. 2, 4 S12

13 References [1] Zhao, J.; Yue, D.-W.; Campo, M. A.; Larock, R. C. J. Am. Chem. Soc. 2007, 129, [2] Thirunavukkarasu, V. S.; Parthasarathy, K.; Cheng, C.-H. Angew. Chem., Int. Ed. 2008, 47, [3] Zhang, X.-X.; Larock, R. C. Org. Lett. 2005, 7, *4+ Crawford, J. J.; Fleming, B. J.; Kennedy, A. R.; Klett, J.; O Hara, C. T.; Orr, S. A. Chem. Commun. 2011, 47, [5] Moorthy, J. N.; Samanta, S. J. Org. Chem. 2007, 72, [6] Rodríguez, D.; Martínez-Esperoón, M. F.; Navarro-Vázquez, A.; Castedo, L.; Domínguez, D.; Saá, C. J. Org. Chem. 2004, 69, [7] Liu, T.-P.; Liao, Y.-X.; Xing, C.-H.; Hu, Q.-S. Org. Lett. 2011, 13, [8] Coelho, P. J.; Carvalho, L. M.; Rodrigues, S.; Oliveira-Campos, A. M. F.; Dubest, R.; Aubard, J.; Samat, A.; Guglielmetti, R. Tetrahedron. 2002, 58, 925. S13

14 NMR Spectra of Mechanistic Study Experiments 3-Fluoro-6-methyl-9H-fluoren-9-one-2-d (2x) 3-Fluoro-6-methyl-9H-fluoren-9-one-8-d (2y) S14

15 3-Methyl-9H-fluoren-9-one-5,6,7,8-d (2z) S15

16 NMR Spectral of Substrates 4-Fluoro-4'-methylbenzophenone-2-d (1x) 4-Methyl -4'-fluorobenzophenone-2-d (1y) S16

17 4 -Methylbenzophenone-2,3,4,5,6-d (1z) S17

18 NMR Spectral of Products 9H-Fluoren-9-one (2a) S18

19 3-Methyl-9H-fluoren-9-one (2b) S19

20 2-Methyl-9H-fluoren-9-one (2c) S20

21 2,3-Dimethyl-9H-fluoren-9-one (2d) S21

22 3,6-Dimethyl-9H-fluoren-9-one (2e) S22

23 2,3,6-Trimethyl-9H-fluoren-9-one (2f) S23

24 3,6-Diphenyl-9H-fluoren-9-one(2g) S24

25 3-tert-Butyl-9H-fluoren-9-one (2h) S25

26 1-Methyl-9H-fluoren-9-one (2i) S26

27 3-Methoxy-9H-fluoren-9-one (2j) S27

28 3,6-Dimethoxy-9H-fluoren-9-one (2k) S28

29 3-Fluoro-2-methyl-9H-fluoren-9-one (2l) S29

30 3-Fluoro-6-methyl-9H-fluoren-9-one (2m) S30

31 3-Hydroxy-9H-fluoren-9-one (2n) S31

32 1-Fluoro-6-methoxy-9H-fluoren-9-one (2o) S32

33 1-Hydroxy-3-methoxy-9H-fluoren-9-one (2p) S33

34 3-Fluoro-9H-fluoren-9-one (2q) S34

35 3-Chloro-9H-fluoren-9-one (2r) S35

36 3,6-Difluoro-9H-fluoren-9-one(2s) S36

37 3-Trifluoromethyl-9H-fluoren-9-one (2t) S37

38 7H-Benzo[c]fluoren-7-one (2u) S38