Supporting Information

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1 Supporting Information Visible-Light-Enhanced Ring-Opening of Cycloalkanols Enabled by Brønsted Base-Tethered Acyloxy Radical Induced Hydrogen Atom Transfer-Electron Transfer Rong Zhao,,, Yuan Yao,, Dan Zhu,, Denghu Chang,, Yang Liu, and Lei Shi *,,, Shenzhen Graduate School, Harbin Institute of Technology, Shenzhen , P. R. China MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin , P. R. China State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin , P. R. China These authors contributed equally. 1

2 Table of Contents 1. General information S3 2. General procedure for the ring-opening reaction S4 3. Drugs and biologically active compounds bearing γ- halogenated ketones moiety S4 4. Summary of C C bond cleavage in cycloalkanols S5 5. Reaction conditions screening S6 6. Characterization of products S8 7. Mechanistic Studies S Radical inhibition experiment S Competitive experiment S Kinetic isotope effect experiment S UV/Vis Experiment S DFT calculation details and results S21 8. Gram-scale Synthesis S63 9. X-Ray Crystal Structure of by-product S References S H, 13 C, and 19 F NMR spectra of products S67 2

3 1. General information All reagents were purchased from Energy, Sigma-Aldrich, Alfa Aesar, or TCI, and used without further purification. The reaction solvent, 1,2-dichloroethane, was used without purification. Reactions were monitored by thin layer chromatography (TLC) and visualized by UV lamp (254 nm) or by staining with a solution of phosphomolybdic acid in EtOH followed by heating. Flash column chromatography was performed using mesh silica gel. Yields refer to purified compounds unless otherwise noted. 1 H NMR (400 MHz or 600 MHz), 13 C NMR (150 MHz), and 19 F NMR (376 MHz) spectra were obtained on Bruker 400M or 600M nuclear resonance spectrometers. 1 H NMR and 13 C NMR chemical shifts are referenced with respect to CDCl 3 ( 1 H NMR: residual CHCl 3 at δ 7.26, 13 C NMR: CDCl 3 triplet at δ 77.16). Data for 1 H NMR spectra were reported as chemical shifts (δ ppm), broad peak (b), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, h = hextet, m = multiplet), coupling constant (Hz) and integration; data for 13 C NMR were reported in terms of chemical shift (δ ppm) and no special nomenclature is used for equivalent carbons; and 19 F NMR data were reported as chemical shifts (δ ppm). HR-ESI-MS spectra were recorded on a Bruker Esquire LC mass spectrometer and Thermo Scientific LTQ Orbitrap XL using electrospray ionization. Tertiary cycloalkanols were prepared by the addition of Grignard reagents to the corresponding cyclic ketones following reported protocols. 6b, 6c, 8 Caution 9, 10 : We have examined the stability of phthaloyl peroxide and demonstrated that this compound is insensitive to direct heating, shock, crush and scrape. Thermogravimetric analysis (TGA) data has shown that phthaloyl peroxide is stable below 90 C. Rapid loss of mass occurs at 110 C, indicating an exothermic decomposition at that temperature. Differential scanning calorimetry (DSC) data for cyclopentyl malonoyl peroxide shows an onset temperature of 70 C. However, all peroxides might be dangerous under inappropriate conditions. The preparation and use of cyclic diacyl peroxides should be conducted by experienced practitioners of organic synthesis using appropriate safety equipment. 3

4 2. General procedure for the ring-opening reaction TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml) and cyclobutanol (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (PE/EA). 3. Drugs and biologically active compounds bearing γ-halogenated ketones moiety Figure S-1 Drugs and biologically active compounds 21 4

5 4. Summary of C C bond cleavage in cycloalkanols Scheme S-1 Summary of C C bond cleavage 5

6 5. Reaction conditions screening Table S-1 Optimization of the reaction conditions. a entry oxidant Br source light solvent time yield b [%] 1 PPO or none NBS - DCE PPO or none N-Bromophthalimide - DCE PPO TBAB - DCE overnight 59 4 PPO TBABr 3 - DCE overnight 96 5 PPO TBAB blue LEDs DCE 30 min 95 6 PPO TBAB blue LEDs MeCN 50 min 90 7 PPO TBAB blue LEDs THF 1 h 80 8 PPO TBAB blue LEDs toluene 50 min 89 9 PPO TBAB blue LEDs Et 2O 1 h PPO TBAB blue LEDs acetone 1 h PPO TBAB blue LEDs EtOH overnight 0 12 PPO TBAB blue LEDs H 2O overnight 0 13 PPO TBAB no hν DCE >24 h BPO TBAB blue LEDs DCE overnight MPO TBAB blue LEDs DCE 30 min PPO-2 TBAB blue LEDs DCE 1.5 h PPO-3 TBAB blue LEDs DCE overnight < 5 18 PPO-4 TBAB blue LEDs DCE 2 h 84 a Reaction conditions: 1a (0.30 mmol), oxidant (0.6 mmol, 2.0 equiv) and Br source (0.3 mmol, 1.0 equiv) in solvent (1 ml) under nitrogen with blue LEDs irradiation at room temperature. b Yields of isolated products. 6

7 Scheme S-2 Other exploration of ring-opening of cycloalkanols Unfortunately, the product of cyclopropanol 4 after ring-opening/bromination reaction continues to proceed elimination by basic byproduct carboxylate, and generates the α,βunsaturated ketone 5. On account of the unsuccessful combination of PPO and TBACl, Cl source was changed to alkali salt CsCl, and a low yield 22% was obtained from the same blue LEDs irradiation conditions. Efforts to reduce these constraints are ongoing. 7

8 6. Characterization of products 2a: Yellow oil, 65 mg (95% yield), 30 min; 1 H NMR (400 MHz, CDCl 3): δ 7.97 (d, J = 7.5 Hz, 2H; H Ar), 7.57 (t, J = 7.3 Hz, 1H; H Ar), 7.47 (t, J = 7.6 Hz, 2H; H Ar), 3.55 (t, J = 6.3 Hz, 2H; CH 2), 3.18 (t, J = 6.9 Hz, 2H; CH 2), 2.31 (p, J = 6.6 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 36.6 (CH 2), 33.8 (CH 2), 26.9 (CH 2); GC-MS (EI): m/z (%): 227, 146, 115, 105 (100), 77, 51, 28; HRMS (ES+) exact mass calculated for [M+H] + (C 10H 11BrO) requires m/z , found m/z b: Yellow oil, 54 mg (75% yield); 40 min, 1 H NMR (400 MHz, CDCl 3): δ 7.95 (d, J = 7.6 Hz, 2H; H Ar), 7.55 (t, J = 7.3 Hz, 1H; H Ar), 7.45 (t, J = 7.6 Hz, 2H; H Ar), 3.44 (t, J = 6.3 Hz, 2H; CH 2), 3.00 (t, J = 6.8 Hz, 2H; CH 2), (m, 4H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 37.5 (CH 2), 33.5 (CH 2), 32.3 (CH 2), 22.8 (CH 2); GC-MS (EI): m/z (%): 241, 160, 105 (100), 77, 51, 28; HRMS (ES+) exact mass calculated for [M+Na] + (C 11H 13BrO) requires m/z , found m/z c: Yellow solid, 56 mg (73% yield); 40 min, 1 H NMR (400 MHz, CDCl 3): δ 7.94 (d, J = 7.5 Hz, 2H; H Ar), 7.55 (t, J = 7.3 Hz, 1H; H Ar), 7.45 (t, J = 7.6 Hz, 2H; H Ar), 3.41 (t, J = 6.8 Hz, 2H; CH 2), 2.98 (t, J = 7.3 Hz, 2H; CH 2), (m, 2H; CH 2), 1.76 (dt, J = 15.1, 7.4 Hz, 2H; CH 2), (m, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 38.3 (CH 2), 33.7 (CH 2), 32.7 (CH 2), 27.9 (CH 2), 23.3 (CH 2); GC-MS (EI): m/z (%): 255, 120, 105 (100), 77, 51, 28; HRMS (ES+) exact mass calculated for [M+H] + (C 12H 15BrO) requires m/z , found m/z d: Pale yellow solid, 64 mg (79% yield); 1.5 h, 1 H NMR (400 MHz, CDCl 3): δ 7.94 (d, J = 7.4 Hz, 2H; H Ar), 7.54 (t, J = 7.3 Hz, 1H; H Ar), 7.44 (t, J = 7.6 Hz, 2H; H Ar), 3.39 (t, J = 6.8 Hz, 2H; CH 2), 2.96 (t, J = 7.3 Hz, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2), (m, 4H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 38.4 (CH 2), 33.9 (CH 2), 32.6 (CH 2), 28.4 (CH 2), 28.0 (CH 2), 24.0 (CH 2); GC-MS (EI): m/z (%): 269, 120 (100), 105, 77, 51, 28; HRMS (ES+) exact mass calculated for [M+H] + (C 13H 17BrO) requires m/z , found m/z e: Pale yellow oil, 32 mg (38% yield); 2 h, 1 H NMR (400 MHz, CDCl 3): δ (m, 2H; H Ar), 7.54 (t, J = 7.4 Hz, 1H; H Ar), 7.45 (t, J = 7.6 Hz, 2H; H Ar), 3.39 (t, J = 6.8 Hz, 2H; CH 2), 2.96 (t, J = 7.3 Hz, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2), (m, 6H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 38.6 (CH 2), 34.1 (CH 2), 32.8 (CH 2), 29.2 (CH 2), 28.7 (CH 2), 28.1 (CH 2), 24.2 (CH 2); GC-MS (EI): m/z (%): 283, 120, 105 (100), 77, 51, HRMS (ES+) exact mass calculated for [M+H] + (C 14H 19BrO) requires m/z , found m/z

9 3a: Brown oil, 55 mg (67% yield); 1 h, 1 H NMR (400 MHz, CDCl 3): δ 7.97 (d, J = 7,5 Hz, 2H; H Ar), 7.57 (t, J = 7.3 Hz, 1H; H Ar), 7.47 (t, J = 7.6 Hz, 2H; H Ar), 3.32 (t, J = 6.6 Hz, 2H; CH 2), 3.13 (t, J = 6.9 Hz, 2H; CH 2), 2.25 (p, J = 6.7 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 39.0 (CH 2), 27.6 (CH 2), 7.0 (CH 2); GC-MS (EI): m/z (%): 274, 147, 128, 115, 105 (100), 77, 51, 28; HRMS (ES+) exact mass calculated for [M+H] + (C 10H 11IO) requires m/z , found m/z b: Light yellow solid, 66 mg (76% yield); 1.5 h, 1 H NMR (400 MHz, CDCl 3): δ 7.94 (d, J = 7.9 Hz, 2H; H Ar), 7.55 (t, J = 7.3 Hz, 1H; H Ar), 7.45 (t, J = 7.6 Hz, 2H; H Ar), 3.21 (t, J = 6.6 Hz, 2H; CH 2), 2.99 (t, J = 6.8 Hz, 2H; CH 2), (m, 4H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 37.3 (CH 2), 33.0 (CH 2), 25.1 (CH 2), 6.4 (CH 2); GC-MS (EI): m/z (%): 288, 161, 105 (100), 77, 51; HRMS (ES+) exact mass calculated for [M+H] + (C 11H 13IO) requires m/z , found m/z c: Yellow oil, 70 mg (77% yield); 3 h, 1 H NMR (600 MHz, CDCl 3): δ 7.94 (d, J = 8.0 Hz, 2H; H Ar), 7.54 (t, J = 7.3 Hz, 1H; H Ar), 7.44 (t, J = 7.4 Hz, 2H; H Ar), 3.18 (t, J = 7.0 Hz, 2H; CH 2), 2.97 (t, J = 7.3 Hz, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 38.3 (CH 2), 33.4 (CH 2), 30.2 (CH 2), 23.1 (CH 2), 6.9 (CH 2); GC-MS (EI): m/z (%): 302, 175, 120, 105 (100), 77, 51; HRMS (ES+) exact mass calculated for [M+H] + (C 12H 15IO) requires m/z , found m/z d: Pale yellow solid, 31 mg (33% yield); 5 h, 1 H NMR (400 MHz, CDCl 3): δ 7.95 (d, J = 7.6 Hz, 2H; H Ar), 7.55 (t, J = 7.3 Hz, 1H; H Ar), 7.45 (t, J = 7.6 Hz, 2H; H Ar), 3.19 (t, J = 7.0 Hz, 2H; CH 2), 2.97 (t, J = 7.3 Hz, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2), (m, 4H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 38.5 (CH 2), 33.4 (CH 2), 30.4 (CH 2), 28.3 (CH 2), 24.1 (CH 2), 7.3 (CH 2); GC-MS (EI): m/z (%): 316, 189, 120 (100), 105, 77, 51, 41, 28; HRMS (ES+) exact mass calculated for [M+H] + (C 13H 17IO) requires m/z , found m/z e: Yellow solid, 30 mg (30% yield); 5 h, 1 H NMR (600 MHz, CDCl 3): δ 7.95 (d, J = 7.4 Hz, 2H; H Ar), 7.55 (t, J = 7.3 Hz, 1H; H Ar), 7.45 (t, J = 7.2 Hz, 2H; H Ar), 3.17 (t, J = 6.2 Hz, 2H; CH 2), 2.96 (t, J = 6.6 Hz, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2), 1.38 (m, 6H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 38.6 (CH 2), 33.5 (CH 2), 30.4 (CH 2), 29.2 (CH 2), 28.5 (CH 2), 24.3 (CH 2), 7.4 (CH 2); GC-MS (EI): m/z (%): 330, 203, 120, 105 (100), 77, 55; HRMS (ES+) exact mass calculated for [M+H] + (C 14H 19IO) requires m/z , found m/z f: Yellow oil, 53 mg (73% yield), 2 h; 1 H NMR (400 MHz, CDCl 3): δ 7.70 (d, J = 7.8 Hz, 1H; H Ar), 7.40 (td, J = 7.5, 1.2 Hz, 1H; H Ar), 7.29 (dd, J = 11.4, 7.8 Hz, 2H; H Ar), 3.56 (t, J = 6.4 Hz, 2H; CH 2), 3.12 (t, J = 6.9 Hz, 2H; CH 2), 2.52 (s, 3H; CH 3), 2.30 (p, J = 6.7 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar),

10 (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 39.5 (CH 2), 33.7 (CH 2), 27.1 (CH 2), 21.5 (CH 3); GC-MS (EI): m/z (%): 241, 160, 119, 91, 65, 51, 39 (100), 27. 2g: Yellow oil, 59 mg (82% yield), 30 min; 1 H NMR (400 MHz, CDCl 3): δ 7.77 (d, J = 8.1 Hz, 2H; H Ar), (m, 2H; H Ar), 3.54 (t, J = 6.3 Hz, 2H; CH 2), 3.16 (t, J = 6.9 Hz, 2H; CH 2), 2.41 (s, 3H; CH 3), 2.30 (p, J = 6.7 Hz; 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 36.7 (CH 2), 33.8 (CH 2), 27.0 (CH 2), 21.5 (CH 3); GC-MS (EI): m/z (%): 241, 160, 119, 91, 65, 51, 39 (100), 27. 2h 11 : Yellow solid, 61 mg (85% yield), 1.5 h; 1 H NMR (400 MHz, CDCl 3): δ 7.87 (d, J = 8.2 Hz, 2H; H Ar), (m, 2H; H Ar), 3.54 (t, J = 6.4 Hz, 2H; CH 2), 3.14 (t, J = 6.9 Hz, 2H; CH 2), 2.41 (s, 3H; CH 3), 2.29 (p, J = 6.7 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 36.5 (CH 2), 33.8 (CH 2), 27.0 (CH 2), 21.7 (CH 3); GC-MS (EI): m/z (%): 241, 161, 134, 119 (100), 91, 65, 39. 2i 12 : Yellow oil, 52 mg (71% yield); 20 min, 1 H NMR (600 MHz, CDCl 3): δ 7.99 (dd, J = 8.3, 5.6 Hz, 2H; H Ar), 7.12 (t, J = 8.5 Hz, 2H; H Ar), 3.53 (t, J = 6.3 Hz, 2H; CH 2), 3.14 (t, J =6.9 Hz, 2H; CH 2), 2.28 (p, J = 6.5 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (d, J = Hz; C Ar), (d, J = 3.0 Hz; C Ar), (d, J = 9.2 Hz; C Ar), (d, J = 21.9 Hz; C Ar), 36.5 (CH 2), 33.7 (CH 2), 26.8 (CH 2); 19 F NMR (376 MHz, CDCl 3): δ (s); GC-MS (EI): m/z (%): 245, 165, 138, 123 (100), 95, 75, 28. 2j: Pale yellow oil, 67 mg (85% yield); 20 min, 1 H NMR (400 MHz, CDCl 3): δ 7.89 (d, J = 8.5 Hz, 2H; H Ar), 7.42 (d, J = 8.4 Hz, 2H; H Ar), 3.52 (t, J = 6.3 Hz, 2H; CH 2), 3.13 (t, J = 6.9 Hz, 2H; CH 2), 2.28 (p, J = 6.6 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 36.6 (CH 2), 33.6 (CH 2), 26.8 (CH 2); GC-MS (EI): m/z (%): 261, 181, 154, 139 (100), 111, 75; HRMS (ES+) exact mass calculated for [M+Na] + (C 10H 10BrClO) requires m/z , found m/z k: Pale yellow oil, 66 mg (72% yield); 30 min, 1 H NMR (400 MHz, CDCl 3): δ 7.82 (d, J = 8.4 Hz, 2H; H Ar), 7.59 (d, J = 8.4 Hz, 2H; H Ar), 3.53 (t, J = 6.3 Hz, 2H; CH 2), 3.13 (t, J = 6.9 Hz, 2H; CH 2), 2.28 (p, J = 6.6 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 36.6 (CH 2), 33.6 (CH 2), 26.7 (CH 2); GC-MS (EI): m/z (%): 306, 225, 198, 183 (100), 155, 76, 50; HRMS (ES+) exact mass calculated for [M+H] + (C 10H 10Br 2O) requires m/z , found m/z l: Pale yellow oil, 75 mg (85% yield); 20 min, 1 H NMR (400 MHz, CDCl 3): δ 8.07 (d, J = 8.2 Hz, 2H; H Ar), 7.72 (d, J = 8.3 Hz, 2H; H Ar), 3.54 (t, J = 6.3 Hz, 2H; CH 2), 3.20 (t, J = 6.9 Hz, 2H; CH 2), 2.31 (p, J = 6.6 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (q, J = 32.8 Hz, C Ar), (C Ar), (q, J = 3.6 Hz, C Ar), (q, J = Hz, CF 3), 36.9 (CH 2), 33.4 (CH 2), 26.7 (CH 2); 19 F NMR (376 MHz, CDCl 3): δ (s); GC-MS (EI): m/z (%): 295, 215, 188, 173 (100), 145; HRMS (ES+) 10

11 exact mass calculated for [M+H] + (C 11H 10BrF 3O) requires m/z , found m/z m: Colorless oil, 64 mg (69% yield); 20 min, 1 H NMR (400 MHz, CDCl 3): δ (m, 2H; H Ar), 7.28 (d, J = 8.1 Hz, 2H; H Ar), 3.54 (t, J = 6.3 Hz, 2H; CH 2), 3.16 (t, J = 6.9 Hz, 2H; CH 2), 2.30 (p, J = 6.7 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (q, J = Hz; CF 3), 36.7 (CH 2), 33.6 (CH 2), 26.8 (CH 2); 19 F NMR (376 MHz, CDCl 3): δ (s); GC-MS (EI): m/z (%): 311, 231, 204, 189 (100), 161, 95, 28; HRMS (ES+) exact mass calculated for [M+H] + (C 11H 10BrF 3O 2) requires m/z , found m/z n: Yellow oil, 42 mg (55% yield); 30 min, 1 H NMR (400 MHz, CDCl 3): δ 7.95 (d, J = 8.8 Hz, 2H; H Ar), (m, 2H; H Ar), 3.86 (s, 3H; CH 3), 3.54 (t, J = 6.3 Hz, 2H; CH 2), 3.12 (t, J = 6.9 Hz, 2H; CH 2), 2.29 (p, J = 6.6 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 55.6 (CH 3), 36.2 (CH 2), 33.9 (CH 2), 27.1 (CH 2); GC-MS (EI): m/z (%): 257, 176, 135 (100), 77; HRMS (ES+) exact mass calculated for [M+Na] + (C 11H 13BrO 2) requires m/z , found m/z o: White solid, 67 mg (74% yield); 20 min, 1 H NMR (600 MHz, CDCl 3): δ 8.06 (d, J = 8.3 Hz, 2H; H Ar), 7.70 (d, J = 8.2 Hz, 2H; H Ar), 7.64 (d, J = 7.4 Hz, 2H; H Ar), 7.48 (t, J = 7.6 Hz, 2H; H Ar), 7.41 (t, J = 7.3 Hz, 1H; H Ar), 3.58 (t, J = 6.3 Hz, 2H; CH 2), 3.22 (t, J = 6.9 Hz, 2H; CH 2), 2.34 (p, J = 6.6 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 36.7 (CH 2), 33.8 (CH 2), 27.0 (CH 2); GC-MS (EI): m/z (%): 303, 222, 181 (100), 152; HRMS (ES+) exact mass calculated for [M+Na] + (C 16H 15BrO) requires m/z , found m/z p: Colorless oil, 27 mg (33% yield); 40 min, 1 H NMR (600 MHz, CDCl 3): δ 6.84 (s, 2H; H Ar), 3.56 (t, J = 6.3 Hz, 2H; CH 2), 2.90 (t, J = 6.9 Hz, 2H; CH 2), 2.28 (s, 5H; CH 2, CH 3), 2.20 (s, 6H; CH 3); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 42.7 (CH 2), 33.4 (CH 2), 26.4 (CH 2), 21.2 (CH 3), 19.2 (CH 3); GC-MS (EI): m/z (%): 269, 238, 188, 160 (100), 147, 128, 115, 91, 77, 39; HRMS (ES+) exact mass calculated for [M+Na] + (C 13H 17BrO) requires m/z , found m/z q: Yellow oil, 42 mg (58% yield); 20 min, 1 H NMR (600 MHz, CDCl 3): δ 7.34 (t, J = 7.5 Hz, 2H; H Ar), 7.28 (t, J = 7.3 Hz, 1H; H Ar), 7.21 (d, J = 7.4 Hz, 2H; H Ar), 3.71 (s, 2H; CH 2), 3.40 (t, J= 6.4 Hz, 2H; CH 2), 2.66 (t, J = 6.9 Hz, 2H; CH 2), 2.09 (p, J = 6.6 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 50.3 (CH 2), 39.9 (CH 2), 33.3 (CH 2), 26.4 (CH 2); GC-MS (EI): m/z (%): 241, 160, 118, 104, 90 (100), 63, 39; HRMS (ES+) exact mass calculated for [M+Na] + (C 11H 13BrO) requires m/z , found m/z

12 2r: Yellow oil, 43 mg (52% yield); 35 min, 1 H NMR (400 MHz, CDCl 3): δ 8.61 (d, J = 8.5 Hz, 1H; H Ar), 8.00 (d, J = 8.2 Hz, 1H; H Ar), 7.90 (dd, J = 12.0, 7.5 Hz, 2H; H Ar), 7.60 (ddd, J = 8.5, 6.9, 1.4 Hz, 1H; H Ar), (m, 2H; H Ar), 3.59 (t, J = 6.4 Hz, 2H; CH 2), 3.26 (t, J = 6.9 Hz, 2H; CH 2), 2.38 (p, J = 6.7 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 40.0 (CH 2), 33.7 (CH 2), 27.3 (CH 2); GC-MS (EI): m/z (%): 277, 196, 165, 155(100), 127; HRMS (ES+) exact mass calculated for [M+H] + (C 14H 13BrO) requires m/z , found m/z s: Yellow solid, 33 mg (40% yield); 2 h, 1 H NMR (400 MHz, CDCl 3): δ 8.50 (s, 1H; H Ar), 8.04 (dd, J = 8.6, 1.7 Hz, 1H; H Ar), 7.97 (d, J = 8.0 Hz, 1H; H Ar), 7.89 (t, J = 8.3 Hz, 2H; H Ar), (m, 2H; H Ar), 3.59 (t, J = 6.3 Hz, 2H; CH 2), 3.31 (t, J = 6.9 Hz, 2H; CH 2), 2.37 (p, J = 6.7 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 36.7 (CH 2), 33.9 (CH 2), 27.1 (CH 2); GC-MS (EI): m/z (%): 277, 196, 165, 155 (100), 127, 28; HRMS (ES+) exact mass calculated for [M+H] + (C 14H 13BrO) requires m/z , found m/z t: White solid, 8 mg (10% yield); 2 h, 1 H NMR (400 MHz, CDCl 3): δ 7.72 (d, J = 7.9 Hz, 1H; H Ar), 7.59 (d, J = 8.4 Hz, 1H; H Ar), 7.55 (s, 1H; H Ar), 7.49 (t, J = 7.7 Hz, 1H; H Ar), 7.32 (t, J = 7.5 Hz, 1H; H Ar), 3.56 (t, J = 6.3 Hz, 2H; CH 2), 3.19 (t, J = 7.0 Hz, 2H; CH 2), 2.34 (p, J = 6.7 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 37.0 (CH 2), 33.4 (CH 2), 26.8 (CH 2); GC-MS (EI): m/z (%): 267, 160 (100), 145, 89, 63, 39; HRMS (ES+) exact mass calculated for [M+Na] + (C 12H 11BrO 2) requires m/z , found m/z u: White solid, 16 mg (19 % yield); 3 h, 1 H NMR (400 MHz, CDCl 3): δ 8.01 (s, 1H; H Ar), (m, 2H; H Ar), 7.44 (dt, J = 22.7, 7.2 Hz, 2H; H Ar), 3.56 (t, J = 6.1 Hz, 2H; CH 2), 3.24 (t, J = 6.8 Hz, 2H; CH 2), (m, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 37.2 (CH 2), 33.5 (CH 2), 27.2 (CH 2); GC-MS (EI): m/z (%): 283, 238, 176, 161 (100), 133, 89; HRMS (ES+) exact mass calculated for [M+H] + (C 12H 11BrOS) requires m/z , found m/z v: Yellow oil, 50 mg (72% yield); 35 min, 1 H NMR (600 MHz, CDCl 3): δ 3.42 (t, J = 6.4 Hz, 2H; CH 2), 2.62 (t, J = 6.9 Hz, 2H; CH 2), 2.33 (tt, J = 11.3, 3.4 Hz, 1H; CH), 2.09 (p, J = 6.7 Hz, 2H; CH 2), 1.82 (d, J = 13.6 Hz, 2H; CH 2), (m, 2H; CH 2), 1.65 (ddd, J = 12.5, 4.7, 2.4 Hz, 1H; CH 2), (m, 5H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), 51.0 (CH), 38.4 (CH 2), 33.8 (CH 2), 28.6 (CH 2), 26.4 (CH 2), 25.9 (CH 2), 25.7 (CH 2); GC-MS (EI): m/z (%): 233, 152, 97, 55, 28 (100); HRMS (ES+) exact mass calculated for [M+H] + (C 10H 17BrO) requires m/z , found m/z

13 2w 13 : Yellow oil, 54 mg (77% yield); 40 min, 1 H NMR (400 MHz, CDCl 3): δ 3.44 (t, J = 6.4 Hz, 2H; CH 2), 2.60 (t, J = 6.9 Hz, 2H; CH 2), 2.41 (t, J = 7.5 Hz, 2H; CH 2), 2.11 (p, J = 6.7 Hz, 2H; CH 2), (m, 2H; CH 2), (m, 6H; CH 2), 0.87 (t, J = 6.8 Hz, 3H; CH 3); 13 C NMR (150 MHz, CDCl 3): δ (CO), 43.2 (CH 2), 40.6 (CH 2), 33.6 (CH 2), 31.7 (CH 2), 29.0 (CH 2), 26.5 (CH 2), 23.9 (CH 2), 22.6 (CH 2), 14.2 (CH 3); GC-MS (EI): m/z (%): 235, 164, 149, 121, 113, 85, 58, 41 (100), 27. 2x: Colorless oil, 75 mg (93% yield); 1 h 10 min, 1 H NMR (600 MHz, CDCl 3): δ 7.95 (d, J = 8.1 Hz, 2H; H Ar), 7.55 (t, J = 7.4 Hz, 1H; H Ar), 7.45 (t, J = 7.7 Hz, 2H; H Ar), (m, 1H; CH 2), 3.41 (dt, J = 9.9, 7.3 Hz, 1H; CH 2), (m, 2H; CH 2), (m, 1H; CH 2), (m, 3H; CH 2), (m, 1H; CH); 0.95 (d, J = 6.1 Hz, 3H; CH 3); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 39.9 (CH 2), 36.1 (CH 2), 31.9 (CH 2), 31.5 (CH 2), 30.6 (CH), 18.9 (CH 3); GC-MS (EI): m/z (%): 269, 120, 105 (100), 77, 51, 28; HRMS (ES+) exact mass calculated for [M+Na] + (C 13H 17BrO) requires m/z , found m/z y: Colorless oil, 76 mg (77% yield); 2 h, 1 H NMR (600 MHz, CDCl 3): δ (m, 2H; H Ar), 7.49 (t, J = 7.4 Hz, 1H; H Ar), 7.38 (t, J = 7.8 Hz, 2H; H Ar), 7.31 (t, J = 7.6 Hz, 2H; H Ar), 7.22 (t, J = 7.4 Hz, 1H; H Ar), (m, 2H; H Ar), 3.29 (ddd, J = 10.0, 7.1, 5.0 Hz, 1H; CH 2), 3.11 (ddd, J = 9.8, 8.6, 6.8 Hz, 1H; CH 2), (m, 2H; CH 2), 2.73 (ddd, J = 17.2, 9.5, 5.0 Hz, 1H; CH), (m, 1H; CH 2), (m, 2H; CH 2), (m, 1H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 43.7 (CH), 39.9 (CH 2), 36.5 (CH 2), 32.0 (CH 2), 30.5 (CH 2); GC-MS (EI): m/z (%): 331, 120 (100), 105, 91, 77, 51; HRMS (ES+) exact mass calculated for [M+Na] + (C 18H 19BrO) requires m/z , found m/z z: Colorless oil, 87 mg (93% yield); 1 h, 1 H NMR (600 MHz, CDCl 3): δ 7.93 (dd, J = 8.3, 1.1 Hz, 2H; H Ar), (m, 1H; H Ar), 7.44 (t, J = 7.8 Hz, 2H; H Ar), (m, 4H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C), 65.1 (CH 2), 41.1 (CH 2), 32.8 (CH 2), 31.3 (CH 2), 26.8 (CH 2); GC-MS (EI): m/z (%): 313, 157 (100), 128, 105, 77, 51, 28; HRMS (ES+) exact mass calculated for [M+Na] + (C 14H 17BrO 3) requires m/z , found m/z aa: White solid, 47 mg (51 % yield); 3h, 1 H NMR (400 MHz, CDCl 3): δ 7.92 (d, J = 7.5 Hz, 2H; H Ar), 7.57 (t, J = 7.1 Hz, 1H; H Ar), 7.49 (t, J = 7.4 Hz, 2H; H Ar), 4.94 (tt, J = 12.0, 6.0 Hz, 1H; CH), (m, 1H; CH), 2.45 (d, J = 8.3 Hz, 2H; CH 2), 2.26 (t, J = 13.0 Hz, 2H; CH 2), 2.18 (s, 1H; CH), (m, 4H; CH 2), (m, 3H; CH 2, CH); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 50.2 (CH), 44.0 (CH 2), 41.7 (CH), 33.4 (CH), 33.1 (CH 2), 31.4 (CH 2); GC-MS (EI): m/z (%): 307, 227, 105 (100), 77, 51; HRMS (ES+) exact mass calculated for [M+Na] + (C 16H 19BrO) requires m/z , found m/z

14 2ab 7d : Yellow solid, 23 mg (33% yield); 3 h, 1 H NMR (400 MHz, CDCl 3): δ 3.15 (d, J = 6.9 Hz, 2H; CH 2), 2.53 (s, 2H; CH 2), 2.43 (dd, J = 15.1, 5.3 Hz, 2H; CH 2), 2.27 (d, J = 14.9 Hz, 2H; CH 2), (m, 2H; CH 2), (m, 2H; CH), 1.63 (t, J = 10.9 Hz, 1H; CH), 0.96 (t, J = 12.5 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), 50.3 (CH 2), 39.5 (CH 2), 33.0 (CH 2), 32.1 (CH 2), 28.5 (CH), 28.5 (CH); GC-MS (EI): m/z (%): 231, 150 (100), 135, 121, 107, 95, 79, 66, 53, 39, 27. 2ac: Orange solid, 76 mg (30% yield); 1 h, 1 H NMR (400 MHz, CDCl 3): δ 7.93 (d, J = 8.7 Hz, 2H; H Ar); 6.96 (d, J = 8.7 Hz, 2H; H Ar), 4.18 (t, J = 4.8 Hz, 2H; CH 2), 3.74 (s, 2H; CH 2), 3.60 (s, 1H; CH), 3.53 (t, J = 6.3 Hz, 2H; CH 2), 3.11 (t, J = 6.9 Hz, 2H; CH 2), 2.28 (p, J = 6.6 Hz, 2H; CH 2), 1.93 (d, J = 12.3 Hz, 1H; CH), (m, 2H; CH 2), 1.61 (dd, J = 12.6, 2.8 Hz, 1H; CH), (m, 3H; CH 2), 1.45 (m, 3H; CH 2), 1.34 (m, 7H; CH 2), 1.23 (m, 1H; CH), (m, 4H; CH 2), (m, 3H; CH 2), 1.06 (s, 1H; CH), 0.97 (m, 5H; CH 2), 0.89 (d, J = 6.4 Hz, 3H; CH 3), 0.85 (d, J = 6.6 Hz, 6H; CH 3), 0.76 (s, 3H; CH 3), 0.62 (s, 3H; CH 3); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 74.7 (CH), 67.9 (CH 2), 66.2 (CH 2), 56.6 (CH), 56.3 (CH), 54.2 (CH), 42.7 (C), 40.1 (CH 2), 39.6 (CH), 39.4 (CH 2), 36.3 (CH 2), 36.3 (CH), 35.9 (CH), 35.5 (C), 33.9 (CH 2), 33.1 (CH 2), 32.6 (CH 2), 32.0 (CH 2), 28.7 (CH 2), 28.4 (CH 2), 28.1 (CH), 27.1 (CH 2), 25.8 (CH 2), 24.3 (CH 2), 23.9 (CH 3), 22.9 (CH 2), 22.7 (CH 2), 20.8 (CH 2), 18.8 (CH 3), 12.2 (CH 3), 11.5 (CH 3); HRMS (ES+) exact mass calculated for [M+H] + (C 39H 61BrO 3) requires m/z , found m/z : Yellow oil, 10 mg (25% yield); 4 h, 1 H NMR (400 MHz, CDCl 3): δ (m, 2H; H Ar), 7.58 (t, J = 7.3 Hz, 1H; H Ar), 7.48 (t, J = 7.6 Hz, 2H; H Ar), 7.16 (dd, 1H; CH), 6.44 (dd, J = 17.1, 1.1 Hz, 1H; =CH 2), 5.94 (dd, J = 10.6, 1.1 Hz, 1H; =CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (CH), (CH 2), (C Ar), (C Ar); GC-MS (EI): m/z (%): 132, 105, 77, 51, 28 (100). 6: Colorless oil, 12 mg (22% yield); 3 h, 1 H NMR (600 MHz, CDCl 3): δ 7.98 (d, J = 7.7 Hz, 2H; H Ar), 7.58 (t, J = 7.3 Hz, 1H; H Ar), 7.47 (t, J = 7.3 Hz, 2H; H Ar), 3.68 (t, J = 5.9 Hz, 2H; CH 2), 3.19 (t, J = 6.7 Hz, 2H; CH 2), 2.24 (p, J = 6.2 Hz, 2H; CH 2); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), (C Ar), 44.8 (CH 2), 35.4 (CH 2), 26.9 (CH 2); GC-MS (EI): m/z (%): 182, 146, 115, 105 (100), 77, 51, 39; HRMS (ES+) exact mass calculated for [M+Na] + (C 10H 11ClO) requires m/z , found m/z : 1 H NMR (400 MHz, CDCl 3): δ 8.30 (dd, J = 5.9, 3.5 Hz, 1H; H Ar), 7.97 (dd, J = 5.7, 3.0 Hz, 1H; H Ar), 7.89 (dd, J = 5.5, 3.1 Hz, 1H; H Ar), (m, 1H; H Ar), (m, 8H; CH 2), (m, 8H; CH 2), (m, 8H; CH 2), 0.91 (t, J = 7.3 Hz, 12H; CH 3); 13 C NMR (150 MHz, CDCl 3): δ (CO), (CO), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), (C Ar), 58.8 (CH 2), 23.9 (CH 2), 19.7 (CH 2), 13.6 (CH 3). 14

15 (CH 3). 8: 1 H NMR (400 MHz, CDCl 3): δ (s, 1H; COOH), (m, 2H; H Ar), (m, 2H; H Ar), (m, 8H; CH 2), (m, 8H; CH 2), (m, 8H; CH 2), 0.91 (t, J = 7.3 Hz, 12H; CH 3); 13 C NMR (150 MHz, CDCl 3): δ (CO), (C Ar), (C Ar), (C Ar), 58.8 (CH 2), 23.9 (CH 2), 19.7 (CH 2),

16 7. Mechanistic Studies 7.1 Radical inhibition experiment The radical inhibition experiments were carried out according to the general procedure: TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), additive (0.9 mmol, 3.0 equiv), and cyclobutanol 1a (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product 2a was purified by flash chromatography on silica gel (ethyl acetate/pe). Obviously, the reaction process was significantly suppressed by radical inhibitors, as 2,2,6,6- tetramethylpiperidin-1-yloxy (TEMPO) and 2,6-di-tert-butyl-4-methylphenol (BHT). 7.2 Competitive experiment The competitive experiments were carried out according to the general procedure: TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), 1n (0.3 mmol, 1 equiv), and 1l (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (ethyl acetate/pe). The product ratio (2n:2l) was calculated as 1.0:1.5. The competitive experiments were carried out according to the general procedure: 16

17 TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), 1n (0.3 mmol, 1 equiv), and 1a (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (ethyl acetate/pe). The product ratio (2n:2a) was calculated as 1.0:1.4. The competitive experiments were carried out according to the general procedure: TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), 1a (0.3 mmol, 1 equiv), and 1l (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (ethyl acetate/pe). The product ratio (2a:2l) was calculated as 1.0:1.2 by 1 H NMR. Above experimental results demonstrated that the more electron withdrawing group on arene the quicker reaction rate. 17

18 7.3 Kinetic isotope effect experiment The indirect kinetic isotope effect experiments were carried out according to the general procedure: TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), 2n (0.3 mmol, 1 equiv), and 2a (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (ethyl acetate/pe). The product ratio (2n:2a) was calculated as 1.0:1.4. The indirect kinetic isotope effect experiments were carried out according to the general procedure: TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), 1n (0.3 mmol, 1 equiv), and 1a' (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (ethyl acetate/pe). The product ratio (2n:2a) was calculated as 1.0:1.0. It can be assumed that the reaction rate of 1n is approximately as same as the reaction rate of 1a'. In the reaction of 1n, which on behalf of 1a', and 1a under standard conditions, KIE was roughly calculated as 1.4. The kinetic isotope effect experiments were carried out according to the general procedure: TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), 1a'' (0.3 mmol, 1 equiv), and 1a (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material 18

19 had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (ethyl acetate/pe). The KIE was calculated as 1.31 ± The kinetic isotope effect experiments were carried out according to the general procedure: TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), 1b'' (0.3 mmol, 1 equiv), and 1b (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (ethyl acetate/pe). The KIE was calculated as 1.15 ±

20 The kinetic isotope effect experiments were carried out according to the general procedure: TBAB (0.3 mmol, 1.0 equiv) and PPO (0.6 mmol, 2.0 equiv) were added to a 25 ml pressure tube under nitrogen atmosphere. DCE (1 ml), 1c'' (0.3 mmol, 1 equiv), and 1c (0.3 mmol, 1 equiv) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (ethyl acetate/pe). The KIE was calculated as 1.12 ± UV/Vis Experiment TU-1901 spectrophotometer was used for ultraviolet spectrum analysis (Beijing Purkinje General Co. Ltd., Beijing, P.R. China) PPO + TBAI PPO + TBAB PPO Absorbance (a. u.) Wavelength (nm) Figure S-2 UV/Vis Experiment of PPO with TBAB/TBAI 20

21 The absorbance of the combination of PPO with TBAB in DCE was measured at the concentration of 4.17 *10-5 M. It showed that addition of TBAB exhibited an intense and broad absorption and addition of TBAI induced an intense and a strong bathochromic shift (Figure S-2). 7.5 DFT calculation details and results Computational details The geometry optimizations of minima and transition states were carried out at the (U)B3LYP/6-31+G(d) level, 15 which has been used for this kind of reactions. 16 For Br atom, augcc-pvtz-pp basis set was used, in which the abbreviation PP means pseudopotential. 17,18 The vibrational frequencies of each stationary point were computed at the same level to check whether the optimized structure is an energy minimum or a transition state and to evaluate the zero-point vibration energy and thermal corrections at K. Intrinsic reaction coordinate calculations were performed to confirm that each transition state is connected with its corresponding minima. Solvent effects were also evaluated by a self-consistent reaction field (SCRF) using the SMD model 19 at the level for the geometry optimization, where 1,2-dichloroethane was used as the solvent and UFF radii were used. All calculations in the current study were performed with the Gaussian 09 program package. 20 Figure S-3 Energy profiles (in kcal mol 1 ) for the radical ring-openings of cyclic alcohols. For the reaction with PPO as the oxidant, one can see as shown in Figure S-3 that PPO undergoes two different pathways to generate radical/anion intermediate (INT4). In one pathway, PPO directly yields diradical molecule (INT1A) through O O bond homolysis, followed by single electron transfer (SET) from bromide anion to give both INT4 and bromide radical. In another one, PPO reacts with bromide anion to form O-Br bond in INT2B, which is subsequently homolyzed to generate both INT4 and bromide radical. Obviously, the activation free energy (18.0 kcal/mol) for the former pathway is much lower than 37.0 kcal/mol for the latter one, indicating that the former is more favorable in energy. Initiated by INT4, ring-openings of strained cycloalkanols assisted by the hydrogen bonds 21

22 between carboxylate groups and cycloalkanols occur. As shown in Figure S-3, one can see that the ring-opening reaction of 1a consists of hydrogen transfer from 1a to INT4 and C C bond cleavage of the ring. Both of them can be completed via only one transition state TS1C without alkoxy radical, obviously showing a concerted process. In TS1C (in Figure S-4), C C bonds in four-membered ring are elongated to be 1.60 and 1.61 Å in TS1C from 1.57 Å in INT5, respectively, becoming very weak and unstable. IRC analysis (in Figure S-4) clearly shows that C C bond cleavage occurs while hydrogen transfer. These results provide the evidence for the concerted process. In order to identify the nature of hydrogen transfer, hydrogen atom transfer (HAT) or proton coupled electron transfer (PCET), it is necessary to determine the route for electron transfer. We then analyzed the spin densities locating on some selected atoms (labeled in Figure S-3) and groups in both INT5 and TS1C. As shown in Table S-2, in the complex INT5 formed by 1a and INT4, the spin densities on 1a and INT4 parts are close to 0 and 1, respectively, showing that the single electron is locating on INT4, consistent with that INT4 is a radical anion. In TS1C, the spin density on INT4 part decreases to be and for 1a part, showing that an electron is also transferring from 1a to INT4 part while hydrogen nucleus transfer. Next, we need to know the destination of the transferred electron. As the calculated spin densities on O2 and O3 atoms in INT4 are the same so that we can t distinguish which one is the anion and which one is the radical. We then analyzed the total spin densities on both oxygen atoms in one carboxyl group. One can see that from INT5 to TS1C the total spin density on O1 and O2 atoms keeps almost unchanged, but the total spin density on O3 and O4 atoms decreases to be 0 from 0.446, showing that they are accepting the electron. Combined with that the change of the spin density on O3 atom is much bigger than that for O4 atom, it can be suggested that O3 atom accepts the electron from 1a. Therefore, O3 atom accepts both the hydrogen nucleus and the electron from 1a in the same time, clearly showing that it is a HAT process. This result is in good agreement with the result of KIE experiment. In sharp contrast, 1b-1e undergo sequential HAT and C C bond cleavage process to generate carbon radical INT6 via TS1D and TS2D, showing a stepwise reaction mechanism. It is obviously different from 1a. The calculated activation free energies for this process gradually increase from 1a to 1e, consistent with the reaction times shown in Table 2. This mechanism shows that several radical intermediates are involved in and play important role, consistent with the experimental observation that radical inhibitors as TEMPO and BHT under otherwise identical conditions can significantly suppress the reaction. In order to uncover the reason why the yield is very low for BPO as the oxidant in a very long reaction time, we also performed DFT calculation to explore the potential energy surface for the generation of benzoyloxy radical from BPO with bromide anion. Two possible pathways similar to those for PPO have been explored. Note that we can t successfully determine the transition state for O O bond hemolysis, so that a scan calculation was performed and the result in Figure S-5 shows that the barrier energy is much higher than 40 kcal/mol. The calculated barrier energy for another reaction pathway in Figure S-6 is 30.8 kcal/mol. It suggests that the reaction with BPO is very slow, consistent with the remaining of most starting material 1a in experiment. Table S-2 The spin densities locating on some atoms or groups in INT5 and TS1C for HAT from 1a to INT4. O1 O2 O1+O2 O3 O4 O3+O4 H1 O5 1a INT4 INT TS1C

23 Figure S-4 The optimized geometry of TS1C and IRC analysis. Figure S-5 Scanned potential energy profile for O O homolysis of BPO. Figure S-6 Potential energy profile for O O breaking of BPO with bromide anion. 23

24 Coordinates of the stationary points: PPO HF= TS1A HF= <S2>= INT1A 24

25 HF= <S2>= INT1B HF= TS1B HF=

26 INT2B HF= TS2B HF= <S2>=

27 INT3 HF= <S2>= INT4 HF= <S2>=

28 For 1a INT5 HF= <S2>=

29 TS1C HF= <S2>=

30 INT6 HF= <S2>=

31 2a HF= For 1b INT5 HF= <S2>=

32 TS1D HF= <S2>=

33 INT1D HF= <S2>=

34 INT2D HF= <S2>=

35 TS2D HF= <S2>=

36 INT6 HF= <S2>= b HF=

37 For 1c INT5 HF= <S2>=

38 TS1D HF= <S2>=

39 INT1D HF= <S2>=

40

41 INT2D HF= <S2>= TS2D HF= <S2>=

42 INT6 HF= <S2>=

43 c HF=

44 For 1d INT5 HF= <S2>=

45 TS1D HF= <S2>=

46 INT1D HF= <S2>=

47 INT2D HF= <S2>=

48 TS2D HF= <S2>=

49 INT6 HF= <S2>=

50 d HF=

51 For 1e INT5 HF= <S2>=

52 TS1D HF= <S2>=

53 INT1D HF= <S2>=

54 INT2D HF= <S2>=

55 TS2D HF= <S2>=

56 INT6 HF= <S2>=

57 e HF=

58 For 1a with BPO BPO HF=

59 INT1 HF= TS1 59

60 HF= INT2 HF=

61 TS2 HF= <S2>= INT4 61

62 HF= <S2>=

63 8. Gram-scale Synthesis According to the general procedure: TBAB (2.39 g, 7.43 mmol) and PPO (2.22 g, 13.5 mmol) were added to a 50 ml round bottom flask under nitrogen atmosphere. DCE (23 ml) and cyclobutanol 1a (1 g, 6.75 mmol) were added subsequently. The mixture was then stirred under blue LEDs until the starting material had been consumed as determined by TLC. After the reaction was finished, the crude product was purified by flash chromatography on silica gel (1.12 g, 73%). 9. X-Ray Crystal Structure of by-product 8 22 The data have been assigned to the following deposition numbers: CCDC Table S-3 Crystal data and structure refinement for Identification code Empirical formula C 24H 41NO 4 Formula weight Temperature/K 293(2) Crystal system monoclinic Space group P2 1/n a/å (9) b/å (6) c/å (10) α/ 90 β/ (5) γ/ 90 Volume/Å (3) Z 4 ρ calcg/cm μ/mm F(000) Crystal size/mm 3??? Radiation MoKα (λ = ) 2Θ range for data collection/ to 50.7 Index ranges -18 h 14, -11 k 11, -20 l 21 Reflections collected Independent reflections 4500 [R int = , R sigma = ] Data/restraints/parameters 4500/1/286 Goodness-of-fit on F Final R indexes [I>=2σ (I)] R 1 = , wr 2 =