Supporting Information. Difluorohomologation of ketones. Mikhail D. Kosobokov, Vitalij V. Levin, Marina I. Struchkova, Alexander D.

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1 S1 Supporting Information Difluorohomologation of ketones Mikhail D. Kosobokov, Vitalij V. Levin, Marina I. Struchkova, Alexander D. Dilman* N. D. Zelinsky Institute of rganic Chemistry, Moscow, Leninsky prosp. 47, Russian ederation Content General Methods Reactions of ketones 1a-r (General Procedure 1) Compounds 2a-p Synthesis of compounds 2s,t (General Procedure 2) Synthesis of compound 4o Synthesis of compound 6 Compound 7 Synthesis of compounds 11a,b (General Procedure 3) NMR spectra Page S2 S2 S3-S7 S8 S9 S10 S10 S11 S12-S78 Content of NMR spectra Spectrum Page Spectrum Page Spectrum Page Spectrum Page 2a ( 1 H NMR) S12 2g ( 1 H NMR) S29 2l ( 19 NMR) S46 2t ( 13 C NMR) S63 2a ( 19 NMR) S13 2g ( 13 C NMR) S30 2m ( 1 H NMR) S47 2t ( 19 NMR) S64 2b ( 1 H NMR) S14 2g ( 19 NMR) S31 2m ( 13 C NMR) S48 4n ( 1 H NMR) S65 2b ( 13 C NMR) S15 2h ( 1 H NMR) S32 2m ( 19 NMR) S49 4n ( 13 C NMR) S66 2b ( 19 NMR) S16 2h ( 13 C NMR) S33 2n ( 1 H NMR) S50 4n ( 19 NMR) S67 2c ( 1 H NMR) S17 2h ( 19 NMR) S34 2n ( 13 C NMR) S51 6 ( 1 H NMR) S68 2c ( 13 C NMR) S18 2i ( 1 H NMR) S35 2n ( 19 NMR) S52 6 ( 13 C NMR) S69 2c ( 19 NMR) S19 2i ( 13 C NMR) S35 2o ( 1 H NMR) S53 6 ( 19 NMR) S70 2d ( 1 H NMR) S20 2i ( 19 NMR) S37 2o ( 13 C NMR) S54 7 ( 1 H NMR) S71 2d ( 13 C NMR) S21 2j ( 1 H NMR) S38 2o ( 19 NMR) S55 7 ( 13 C NMR) S72 2d ( 19 NMR) S22 2j ( 13 C NMR) S39 2r ( 1 H NMR) S56 7 ( 19 NMR) S73 2e ( 1 H NMR) S23 2j ( 19 NMR) S40 2r ( 13 C NMR) S57 11a ( 1 H NMR) S74 2e ( 13 C NMR) S24 2k ( 1 H NMR) S41 2r ( 19 NMR) S58 11a ( 19 NMR) S75 2e ( 19 NMR) S25 2k ( 13 C NMR) S42 2s ( 1 H NMR) S59 11b ( 1 H NMR) S76 2f ( 1 H NMR) S26 2k ( 19 NMR) S43 2s ( 13 C NMR) S60 11b ( 13 C NMR) S77 2f ( 13 C NMR) S27 2l ( 1 H NMR) S44 2s ( 19 NMR) S61 11b ( 19 NMR) S78 2f ( 19 NMR) S28 2l ( 13 C NMR) S45 2t ( 1 H NMR) S62

2 General Methods. All reactions were performed under an argon atmosphere. Dioxane was distilled from sodium benzophenone ketyl prior to use. Hexamethylphosphoramide (HMPA) was distilled under vacuum from CaH 2 and stored over MS 4A. Column chromatography was carried out employing silica gel ( mesh). Precoated silica gel plates -254 were used for thin-layer analytical chromatography using UV and/or visualization reagents [reagent A: Ce(S 4 ) 2, 1 g; (NH 4 ) 6 Mo 7 24, 5 g; H 2, 100 ml; H 2 S 4, 10 ml; reagent B: p-anisaldehyde, 2 ml; H 2 S 4, 1 ml; EtH, 80 ml; reagent C: saturated aqueous KMn 4 ]. High resolution mass spectra (HRMS) were measured using electrospray ionization (ESI) and time-of-flight (T) mass analyzer. The measurements were done in a positive ion mode (interface capillary voltage 4500 V) or in a negative ion mode (3200 V); mass range from m/z 50 to m/z Reagents. (Bromodifluoromethyl)trimethylsilane (Me 3 SiC 2 Br) 1 and compounds 1f, 2 1n 3 and 1r 4 were prepared according to literature procedures. Reactions of ketones 1a-r (General Procedure 1). Me 3 SiTf (108 μl, 0.6 mmol, 1.2 equiv) was added to a solution of ketone 1 (0.5 mmol, 1 equiv) and Et 3 N (97 μl, 0.7 mmol, 1.4 equiv) in dioxane (1 ml) at 10 С. The cooling bath was removed and the solution was stirred for 40 min at room temperature. Then, the mixture was cooled to 10 C, Me 3 SiC 2 Br (355 mg, 1.75 mmol, 3.5 equiv) was added followed by HMPA (262 μl, 1.5 mmol, 3 equiv), and the mixture was stirred for 3 hours at room temperature (the reaction mixture becomes cloudy as reaction progresses, and finally becomes a two-phase mixture). or ketones 1a-d,h-r, volatile components were evaporated under vacuum (ca. 5 Torr, room temperature), then HBr (33% solution in acetic acid, 1 ml, 5.5 mmol, 11 equiv) was added in one portion followed by H 2 (100 μl, 5.5 mmol, 11 equiv). The reaction vessel was tightly closed and stirred for 1 hour at 80 С. Then, the mixture was cooled to room temperature and worked-up. or ketones 1e-g, HCl (1 ml, 4M in dioxane) was added followed by H 2 (100 μl, 5.5 mmol, 11 equiv). The reaction vessel was tightly closed and stirred for 1 hour at 65 С. Then, the mixture was cooled to room temperature and worked-up. Work-up: The mixture was quenched with saturated aqueous Na 2 C 3 (5mL), and diluted with water (5 ml). or volatile products (2a,b,d,l), aqueous phase was extracted with pentane/diethyl ether (1/1, 3 3 ml). The combined organic phases were filtered through Na 2 S 4, the solvent was evaporated under atmospheric pressure, and the residue was purified by column chromatography on silica. or non-volatile products (2c,e-k,m-r,7), aqueous phase was extracted with methyl tert-butyl ether (3 3 ml). The combined organic phases were filtered through Na 2 S 4, concentrated under vacuum, and the residue was purified by column chromatography on silica gel. S2 1 Kosobokov, M. D.; Dilman, A. D.; Levin, V. V.; Struchkova, M. I. J. rg. Chem. 2012, 77, (a) Yamaguchi, Y.; Koura, M.; Kurobuchi, S.; Matsuda, T.; kuda, A.; Sumida, H.; Watanabe, Y.; Enomoto, T.; Shibuya, K. US (A1). (b) Al-Smadi, M.; Hanold, N.; Kalbitz, H.; Meier, H. Synthesis 2009, Ranu, B. C.; Ghosh, K.; Jana, U. J. rg. Chem. 1996, 61, Takeuchi, J.; Inukai, T.; Sakai, M. W A1 (Chem. Abstr. 154:64832).

3 S3 2,2-Difluoro-1-phenylpropan-1-one (2a). 5 Yield 60 mg (71%). Colorless oil. Chromatography: pentane/et 2, 15/1. R f 0.41 (pentane/et 2, 15/1). Bp C (bath temp.)/138 Torr. 1 H NMR (300 MHz, ), δ: 1.89 (t, 3H, J = 19.4), 7.49 (t, 2H, J = 7.33), 7.63 (t, 1H, J = 7.3), 8.12 (d, 2H, J = 7.3). 19 NMR (282 MHz, ), δ: 93.6 (q, 2, J = 19.4). 1-(4-Bromophenyl)-2,2-difluoropropan-1-one (2b). Br Yield 111 mg (89%). Colorless crystals. Chromatography: hexane/ch 2 Cl 2, 4/1. R f 0.33 (hexane/ch 2 Cl 2, 4/1). Mp C. Bp C (bath temp.)/5 Torr. 1 H NMR (300 MHz, ), δ: 1.88 (t, 3H, J = 19.8), 7.64 (d, 2H, J = 7.3), 7.98 (d, 2H, J = 7.3). 13 C{ 1 H} NMR (75 MHz, ), δ: 20.7 (t, J = 24.7), (t, J = 250.1), 130.0, (t, J = 3.4), (t, J = 3.4), 132.2, (t, J = 32.7). 19 NMR (282 MHz, ), δ: 93.5 (q, 2, J = 19.8). Calcd for C 9 H 7 Br 2 (249.05): C, 43.40; H, ound: C, 43.25; H, ,2-Difluoro-1-(4-methoxyphenyl)propan-1-one (2c). 6 Me Yield 95 mg (95%). Colorless oil. Chromatography: hexane/ch 2 Cl 2, 1/1. R f 0.33 (hexane/ch 2 Cl 2, 1/1). Bp C (bath temp.)/0.26 Torr. 1 H NMR (300 MHz, ), δ: 1.87 (t, 3H, J = 19.8), 3.88 (s, 3H), 6.96 (d, 2H, J = 8.7), 8.11 (d, 2H, J = 8.7). 13 C{ 1 H} NMR (75 MHz, ), δ: 21.0 (t, J = 24.7), 55.6, 114.1, (t, J = 250.1), 124.7, (t, J = 3.4), 164.6, (t, J = 30.4). 19 NMR (282 MHz, ), δ: 93.1 (q, 2, J = 19.8). Calcd for C 10 H (200.18): C, 60.00; H, ound: C, 60.01; H, (2,4-Dimethylphenyl)-2,2-difluoropropan-1-one (2d). Yield 81 mg (82%). Colorless oil. Chromatography: pentane/et 2, 20/1. R f 0.53 (pentane/et 2, 20/1). Bp C (bath temp.)/5 Torr. 5 Bergeron, M.; Johnson, T.; Paquin, J.-. Angew. Chem. Int. Ed. 2011, 50, Aoyama, T.; Eguchi, T.; shima, T.; Kakinuma, K. J. Chem. Soc., Perkin Trans ,

4 1 H NMR (300 MHz, ), δ: 1.85 (t, 3H, J = 19.2), 2.37(s, 3H), 2.47 (s, 3H), (m, 2H), 7.85 (d, 1H, J = 8.2). 13 C{ 1 H} NMR (75 MHz, ), δ: 21.0 (t, J = 25.2), 21.57, 21.59, (t, J = 251.8), 126.3, (t, J = 5.7), 130.4, (t, J = 5.7), 133.1, 141.0, 143.4, (t, J = 31.0). 19 NMR (282 MHz, ), δ: 93.6 (q, 2, J = 19.2). Calcd for C 11 H 12 2 (198.21): C, 66.66; H, ound: C, 66.67; H, (2,4-Dimethoxyphenyl)-2,2-difluoropropan-1-one (2e). Me S4 Me Yield 104 mg (90%). Chromatography: hexane/ch 2 Cl 2, 2/1 1/2. R f 0.27 (hexane/ch 2 Cl 2, 1/2). Colorless oil. Bp C (bath temp.)/0.041 Torr. 1 H NMR (300 MHz, ), δ: 1.85 (t, 3H, J = 19.1), 3.85 (s, 3H), 3.86 (s, 3H), (m, 2H), 7.72 (d, 1H, J = 8.2). 13 C{ 1 H} NMR (75 MHz, ), δ: 20.9 (t, J = 25.2), 55.6, 55.8, 98.9, 105.1, (t, J = 2.3), (t, J = 250.7), (t, J = 4.0), 161.5, 165.0, (t, J = 31.0). 19 NMR (282 MHz, ), δ: 95.5 (q, 2, J = 19.1). HRMS (ESI): Calcd for C 11 H Na (M + Na): ound: [4-(Allyloxy)phenyl]-2,2-difluoropropan-1-one (2f). Yield 108 mg (95%). Chromatography: hexane/ch 2 Cl 2, 3/1. R f 0.17 (hexane/ch 2 Cl 2, 3/1). Colorless oil. 1 H NMR (300 MHz, ), δ: 1.88 (t, 3H, J = 19.4), 4.62 (ddd, 2H, J = 5.3, 1.4, 1.4), 5.33 (ddt, 1H, J = 10.6, 1.4, 1.4), 5.44 (ddt, 1H, J = 17.4, 1.4, 1,4), 6.05 (ddt, 1H, J = 17.4, 10.6, 5.3), 6.97 (d, 2H, J = 8.7), 8.11 (d, 2H, J = 8.7). 13 C{ 1 H} NMR (75 MHz, ), δ: 21.0 (t, J = 25.2), 69.1, 114.8, 118.4, (t, J = 250.5), (t, J = 2.8), 132.4, (t, J = 3.4), 163.6, (t, J = 31.7). 19 NMR (282 MHz, ), δ: 93.0 (q, J = 19.4). HRMS (ESI): Calcd for C 12 H (M + H): ound: errocenyl-2,2-difluoro-propan-1-one (2g). e Yield 102 mg (73%). Dark red crystals. Chromatography: hexane/etac, 20/1 10/1. R f 0.36 (hexane/etac, 10/1). Mp C (hexane). 1 H NMR (300 MHz, ), δ: 1.81 (t, 3H, J = 19.0), 4.25 (s, 5H), 4.64 (s, 2H), 4.97 (s, 2H). 13 C{ 1 H} NMR (75 MHz, ), δ: 21.1 (t, J = 25.5), 70.4, 71.0 (t, J = 3.2), 72.5 (t, J = 2.3), 73.5, (t, J = 250.1), (t, J = 31.0).

5 S5 19 NMR (282 MHz, ), δ: 94.1 (q, J = 19.0). Calcd for C 13 H 12 2 e (278.08): C, 56.15; H, ound: C, 56.31; H, ,2-Difluoro-1-(2-naphthyl)propan-1-one (2h). Yield 106 mg (96%). Colorless oil. Chromatography: hexane/ch 2 Cl 2, 4/1. R f 0.16 (hexane/ch 2 Cl 2, 4/1). Bp C (bath temp.)/0.21 Torr. 1 H NMR (300 MHz, ), δ: 1.96 (t, 3H, J = 19.2), (m, 2H), 7.90 (t, 2H, J = 9.2), 8.00 (d, 1H, J = 7.3), 8.11 (d, 1H, J = 9.2), 8.73 (s, 1H). 13 C{ 1 H} NMR (75 MHz, ), δ: 21.1 (t, J = 25.2), (t, J = 250.7), (t, J = 2.3), 127.1, 127.9, 128.6, (t, J = 2.3), 129.4, 130.2, 132.5, (t, J = 4.6), 136.1, (t, J = 31.6). 19 NMR (282 MHz, ), δ: 93.8 (q, 2, J = 19.2). Calcd for C 13 H 10 2 (220.21): C, 70.90; H, ound: C, 70.87; H, ,2-Difluoro-1-(1-naphthyl)propan-1-one (2i). Yield 74 mg (67%). Colorless oil. Chromatography: hexane/ch 2 Cl 2, 3/1. R f 0.33 (hexane/ch 2 Cl 2, 3/1). Bp C (bath temp.)/0.21 Torr. 1 H NMR (300 MHz, ), δ: 1.96 (t, 3H, J = 19.2), (m, 3H), 7.90 (d, 1H, J = 8.2), 8.06 (d, 1H, J = 8.2), 8.19 (d, 1H, J = 7.3), 8.49 (d, 1H, J = 8.2). 13 C{ 1 H} NMR (75 MHz, ), δ: 21.1 (t, J = 25.2), (t, J = 251.8), 124.3, 125.3, 126.7, 128.5, 128.9, (t, J = 5.7), 131.2, 134.0, 134.1, (t, J = 31.0). 19 NMR (282 MHz, ), δ: 93.3 (q, 2, J = 19.2). Calcd for C 13 H 10 2 (220.21): C, 70.90; H, ound: C, 70.69; H, (1E)-4,4-Difluoro-1-phenylpent-1-en-3-one (2j). Yield 84 mg (86%). Colorless oil. Chromatography: pentane/et 2, 20/1. R f 0.43 (pentane/et 2, 20/1). Bp C (bath temp.)/7 Torr. 1 H NMR (300 MHz, ), δ: 1.80 (t, 3H, J = 19.2), 7.16 (d, 1H, J = 16.5), (m, 3H), (m, 2H), 7.90 (d, 1H, J = 16.5). 13 C{ 1 H} NMR (75 MHz, ), δ: 19.9 (t, J = 23.0), 117.8, (t, J = 249.0), 129.0, 129.2, 131.6, 134.2, 147.7, (t, J = 31.6). 19 NMR (282 MHz, ), δ: (q, 2, J = 19.2). Calcd for C 11 H 10 2 (196.19): C, 67.34; H, ound: C, 67.18; H, 5.03.

6 S6 2,2-Difluoro-1-(4-methoxyphenyl)butan-1-one (2k). Me Yield 86 mg (80%). Colorless oil. Chromatography: hexane/ch 2 Cl 2, 3/1. R f 0.16 (hexane/ch 2 Cl 2, 3/1). Bp C (bath temp.)/0.17 Torr. 1 H NMR (300 MHz, ), δ: 1.09 (t, 3H, J = 7.3), 2.20 (tq, 2H, J = 17.7, 7.3), 3.88 (s, 3H), 6.95 (d, 2H, J = 8.7), 8.10 (d, 2H, J = 8.7). 13 C{ 1 H} NMR (75 MHz, ), δ: 5.9 (t, J = 5.7), 27.7 (t, J = 24.1), 55.6, 114.1, (t, J = 252.4), 125.3, (t, J = 4.0), 164.5, (t, J = 31.0). 19 NMR (282 MHz, ), δ: (t, 2, J = 17.7). Calcd for C 11 H (214.21): C, 61.68; H, ound: C, 61.62; H, ,2-Difluoro-1-phenylhexan-1-one (2l). Yield 69 mg (65%). Colorless oil. Chromatography: hexane/ch 2 Cl 2, 3/1. R f 0.33 (hexane/ch 2 Cl 2, 3/1). Bp C (bath temp.)/6 Torr. 1 H NMR (300 MHz, ), δ: 0.93 (t, 3H, J = 7.3), (m, 4H), 2.18 (tt, 2H, J = 17.7, 8.2), 7.49 (t, 2H, J = 7.3), 7.62 (t, 1H, J = 7.3), 8.1 (d, 2H, J = 7.3). 13 C{ 1 H} NMR (75 MHz, ), δ: 13.9, 22.6, 23.6 (t, J = 4.6), 33.9 (t, J = 23.0), (t, J = 252.4), 128.8, (t, J = 3.4), (t, J = 2.3), 134.3, (t, J = 31.6). 19 NMR (282 MHz, ), δ: (t, 2, J = 17.7). Calcd for C 12 H 14 2 (212.24): C, 67.91; H, ound: C, 67.90; H, ,4-Difluoro-1,6-diphenylhexan-3-one (2m). Yield 97 mg (67%). Colorless oil. Chromatography: hexane/ch 2 Cl 2, 3/1. R f 0.18 (hexane/ch 2 Cl 2, 3/1). Bp C (bath temp.)/0.07 Torr. 1 H NMR (300 MHz, ), δ: 2.30 (tt, 2H, J = 17.6, 8.2), 2.76 (t, 2H, J = 8.2), 2.94 (t, 2H, J = 6.4), 3.02 (t, 2H, J = 6.4), (m, 10H). 13 C{ 1 H} NMR (75 MHz, ), δ: 27.7 (t, J = 4.6), 28.8, 34.5 (t, J = 22.4), 38.1, (t, J = 252.4), , , , , 128.7, 140.0, 140.3, (t, J = 31.6). 19 NMR (282 MHz, ), δ: (t, 2, J = 17.6). Calcd for C 18 H 18 2 (288.33): C, 74.98; H, ound: C, 74.97; H, 6.38.

7 S7 2,2-Difluoro-1-(4-methoxyphenyl)-3-methylbutan-1-one (2n). Me Yield 84 mg (74%). Colorless oil. Chromatography: hexane/etac, 10/1. R f 0.34 (hexane/etac, 10/1). Bp C (bath temp.)/0.23 Torr. 1 H NMR (300 MHz, ), δ: 1.07 (d, 6H, J = 7.3), (m, 1H), 3.88 (s, 3H), 6.95 (d, 2H, J = 9.2), 8.08 (d, 2H, J = 9.2). 13 C{ 1 H} NMR (75 MHz, ), δ: 15.2 (t, J = 5.2), 33.0 (t, J = 22.4), 55.6, 114.1, (t, J = 254.7), 125.9, (t, J = 3.4), 164.5, (t, J = 29.8). 19 NMR (282 MHz, ), δ: (d, 2, J = 14.8). Calcd for C 12 H (228.24): C, 63.15; H, ound: C, 63.04; H, ,6-Difluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one (2o). 7 Yield 90 mg (92%). Colorless oil. Chromatography: hexane/ch 2 Cl 2, 3/1 1/1. R f 0.24 (hexane/ch 2 Cl 2, 3/1). Bp C (bath temp.)/0.30 Torr. 1 H NMR (300 MHz, ), δ: (m, 2H), 2.36 (tt, 2H, J = 16.0, 6.9), 3.02 (t, 2H, J = 5.5), 7.23 (d, 1H, J = 7.3), 7.32 (t, 1H, J = 7.3), 7.45 (t, 1H, J = 7.3), 7.69 (d, 1H, J = 7.3). 13 C{ 1 H} NMR (75 MHz, ), δ: 22.1 (t, J = 5.2), 33.6, 34.4 (t, J = 23.5), (t, J = 249.6), 127.0, 130.0, 130.2, 132.9, 134.9, 141.6, (t, J = 29.8). 19 NMR (282 MHz, ), δ: (t, 2, J = 16.0). Calcd for C 11 H 10 2 (196.19): C, 67.34; H, ound: C, 67.29; H, ,2-Difluorocyclotridecanone (2p). 8 Yield 81 mg (70%). Colorless crystals. Chromatography: hexane/ch 2 Cl 2, 5/1 3/1. R f 0.32 (hexane/ch 2 Cl 2, 3/1). Mp C. Bp C (bath temp.)/0.21 Torr. 1 H NMR (300 MHz, ), δ: (m, 16H), (m, 2H), (m, 2H), 2.73 (t, 2H, J = 6.0). 13 C{ 1 H} NMR (75 MHz, ), δ: 19.9 (t, J = 5.2), 21.4, 23.8, 24.4, 25.0, 25.4, 26.0, 26.2, 26.5, 33.5 (t, J = 23.0), 36.2, (t, J = 250.1), (t, J = 29.3). 19 NMR (282 MHz, ), δ: (t, 2, J = 14.8). Calcd for C 13 H 22 2 (232.31): C, 67.21; H, ound: C, 67.14; H, Pravst, I.; Zupan, M.; Stavber, S. Synthesis 2005, Kobayashi, Y.; Taguchi, T.; Mamada, M.; Shimizu, H.; Murohashi, H. Chem. Pharm. Bull. 1979, 27,

8 Synthesis of compounds 2s,t (General Procedure 2). To a stirred solution of n-buli (2.5M in hexane, 1 ml, 2.5 mmol) at 30 C was added TH (1.8 ml) and i-pr 2 NH (0.35 ml, 2.5 mmol). The mixture was cooled to 80 C, and a solution of ketone 1s,t (1.78 mmol) in TH (1 ml) was added dropwise. Then the temperature was allowed to rise up to 50 C during 15 min. Then, the mixture was cooled to 80 C, and Me 3 SiCl (3.21 mmol, 411 µl) wad added dropwise. The temperature was allowed to rise to 0 C during 1 hour. Volatile materials were evaporated under vacuum (ca. 7 Torr). Then, acetonitrile (1.5 ml) and Me 3 SiC 2 Br (723 mg, 3.56 mmol) were successively added, and the mixture was heated at 80 C (water bath) for 3 hours. Аcetonitrile was evaporated under vacuum, and HBr (33% solution in acetic acid, 3.5 ml) and water (0.35 ml) were added, and the mixture was heated at 80 C (water bath) for 1 hour. The mixture was diluted with water (5 ml), extracted with hexane (3 5 ml). Combined organic phases were filtered through Na 2 S 4, concentrated under vacuum, and the residue was purified by column chromatography on silica gel. S8 3,3-Difluoro-1,1-diphenylbutan-2-one (2s). Yield 371 mg (80%). Colorless crystals. Chromatography: hexane/ch 2 Cl 2, 2/1. R f 0.35 (hexane/ch 2 Cl 2, 2/1). Mp C. Bp C (bath temp.)/0.09 Torr. 1 H NMR (300 MHz, ), δ: 1.66 (t, 3H, J = 19.2), 5.69 (s, 1H), (m, 10H). 13 C{ 1 H} NMR (75 MHz, ), δ: 20.2 (t, J = 24.8), 56.9, (t, J = 250.7), 127.7, , , 137.3, (t, J = 31.6). 19 NMR (282 MHz, ), δ: 99.8 (q, 2, J = 19.2). Calcd for C 16 H 14 2 (260.28): C, 73.83; H, ound: C, 73.83; H, (1-Adamantyl)-2,2-difluoropropan-1-one (2t). Yield 358 mg (88%). Colorless oil. Chromatography: hexane/ch 2 Cl 2, 10/1. R f 0.26 (hexane/ch 2 Cl 2, 10/1). Bp C (bath temp.)/7 Torr. 1 H NMR (300 MHz, ), δ: 1.68 (t, 3H, J = 19.6), 1.74 (br, 6H), 1.99 (br, 6H), (br, 3H). 13 C{ 1 H} NMR (75 MHz, ), δ: 21.5 (t, J = 25.2), 28.0, 36.6, 37.6 (t, J = 2.3), 46.1 (t, J = 2.3), (t, J = 252.4), (t, J = 28.1). 19 NMR (282 MHz, ), δ: 96.1 (q, 2, J = 19.6). Calcd for C 13 H 18 2 (228.28): C, 68.40; H, ound: C, 68.24; H, 7.98.

9 [(1,1-Difluoro-1,1a,2,3-tetrahydro-7bH-cyclopropa[a]naphthalen-7b-yl)oxy](trimethyl)silane (4o). Method A. S9 (a) Me 3 SiTf, NEt (b) Me 3 SiC 2 Br, HMPA Me 3 Si 1o 4o, 43% Me 3 SiTf (108 μl, 0.6 mmol, 1.2 equiv) was added to a solution of tetralone 1o (73 mg, 0.5 mmol, 1 equiv) and Et 3 N (97 μl, 0.7 mmol, 1.4 equiv) in dioxane (1 ml) at 10 С. The cooling bath was removed, and the solution was stirred for 40 min at room temperature. Then, the mixture was cooled to 10 C, Me 3 SiC 2 Br (355 mg, 1.75 mmol, 3.5 equiv) was added followed by HMPA (262 μl, 1.5 mmol, 3 equiv), and the mixture was stirred for 3 hours at room temperature. or the work-up, the mixture was diluted with methyl tert-butyl ether (3 ml) followed by water (10 ml). Aqueous phase was extracted with methyl tert-butyl ether (3 3 ml). The combined organic phases were washed with water (5 ml), brine (5 ml), and concentrated under vacuum. Pale yellow residue was purified by column chromatography on silica affording 58 mg (43% yield ) of 4o as a colorless liquid. Chromatography: hexane/ch 2 Cl 2, 5/1 3/1. R f 0.26 (hexane/ch 2 Cl 2, 5/1). Method B. Me 3 Si Me 3 SiC 2 Br (1.5 equiv) Bu 4 NBr (0.2 equiv) Me 3 Si MeCN, Δ, 1 h 4o, 83% Me 3 SiC 2 Br (3.04 g, 15 mmol, 1.5 equiv) was added to solution of the silyl enol ether 9 (2.18 g, 10 mmol, 1 equiv) and Bu 4 NBr (644 mg, 3 mmol, 0.2 equiv) in acetonitrile (20 ml). Reaction was stirred under reflux for 1 hour. The solvent was evaporated under vacuum, and the residue was dissolved in CH 2 Cl 2 /hexane (1/3, 4 ml). The resulting solution was rapidly filtered through short pad of silica gel (ca. 3 cm) eluting with CH 2 Cl 2 /hexane (1/3, 15 ml). The solvent was evaporated under vacuum, and the crude product was fractionally distilled under vacuum affording 2.22 g (83%) of 4o as a colorless liquid. Bp C/0.365 Torr. 1 H NMR (300 MHz, ), δ: 0.15 (s, 9H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), 7.11 (d, 1H, J = 7.4), (m, 2H), 7.67 (d, 1H, J = 7.9). 13 C{ 1 H} NMR (75 MHz, ), δ: 1.1, 15.0, 26.7 (d, J = 6.3), 30.9 (dd, J = 10.9, 7.5), 59.4 (dd, J = 13.8, 10.9), (dd, J = 307.5, 298.9), 126.4, 126.9, 127.3, 128.5, (t, J = 2.5), (d, J = 1.5). 19 NMR (282 MHz, ), δ: (d, 1H, J = 155.7), (dd, 1, J = 155.7, 17.0). Calcd for C 14 H 18 2 Si (268.37): C, 62.65; H, ound: C, 62.61; H, Cazeau, P.; Duboudin,.; Moulines,.; Babot,.; Dunogues, J. Tetrahedron 1987, 43,

10 S10 2,2-Difluoro-1-(4-nitrophenyl)propan-1-ol (6). H 2 N Crude product obtained from p-nitroacetohenone 1q according to General Procedure 1 (after work-up and evaporation of solvent) was dissolved in ethanol (5 ml), and NaBH 4 (57 mg, 1.5mmol, 3 equiv) was added in one portion. Reaction mixture was stirred for 3 hours at room temperature, and quenched with saturated aqueous NH 4 Cl (5 ml). The was concentrated under vacuum to 1/3 of its volume and diluted with water (5 ml). Aqueous phase was extracted tert-butyl ether (3 3 ml). The combined organic phases were filtered through Na 2 S 4, concentrated under vacuum, and the residue was purified by column chromatography on silica gel. Yield 85 mg (78%). Pale yellow crystals. Chromatography: hexane/etac, 5/1 3/1. R f 0.24 (hexane/etac, 3/1). Mp C (hexane). 1 H NMR (300 MHz, ), δ: 1.51 (t, 3H, J = 19.0), 2.83 (d, 1H, J = 3.7), 4.98 (td, 1H, J = 9.4, 3.7), 7.65 (d, 2H, J = 9.2), 8.21 (d, 2H, J = 9.2). 13 C{ 1 H} NMR (75 MHz, ), δ: 18.8 (t, J = 26.4), 75.0 (t, J = 29.8), (t, J = 243.8), 123.5, 128.4, (d, J = 4.6), NMR (282 MHz, ), δ: (dqd, 1, J = 250.1, 19.0, 9.4), 99.6 (dqd, 1, J = 250.1, 19.0, 9.4). Calcd for C 9 H 9 2 N 3 (217.17): C, 49.78; H, 4.18; N, ound: C, 49.65; H, 4.19; N, ',2'-Difluoro-3H-spiro[2-benzofuran-1,1'-cyclopropan]-3-one (7). btained from o-(methoxycarbonyl)acetophenone 1r according to General Procedure 1. Yield 46 mg (47%). Colorless crystals. Chromatography: hexane/ch 2 Cl 2, 1/1 1/2. R f 0.36 (hexane/ch 2 Cl 2, 1/1). Mp C (hexane). 1 H NMR (300 MHz, ), δ: 2.25 (ddd, 1H, J = 16.9, 10.1, 6.9), 2.55 (ddd, 1H, J = 15.8, 10.1, 6.9), 7.32 (d, 1H, J = 7.8), 7.60 (t, 1H, J = 7.3), 7.73 (t, 1H, J = 7.3), 7.97 (d, 1H, J = 7.8). 13 C{ 1 H} NMR (75 MHz, ), δ: 23.5 (dd, J = 10.3, 9.2), 67.0 (dd, J = 14.3, 10.3), (dd, J = 300.0, 296.0), (d, J = 3.4), (d, J = 1.2), 126.2, 129.8, 134.8, (d, J = 1.9), NMR (282 MHz, ), δ: (ddd, 1, J = 165.3, 14.8, 6.9), (ddd, 1, J = 165.3, 14.8, 6.9) HRMS (ESI): Calcd for C 10 H (M + H): ound: Calcd for C 10 H (196.15): C, 61.23; H, ound: C, 61.27; H, 3.15.

11 Synthesis of compounds 11a,b (General Procedure 3). To a stirred solution of n-buli (2.5M in hexane, 1 ml, 2.5 mmol) at 30 C was added TH (1.8 ml) and i-pr 2 NH (0.35 ml, 2.5 mmol). The mixture was cooled to 80 C, and a solution of ester 8a,b (1.78 mmol) in TH (1 ml) was added dropwise. Then, the temperature was allowed to rise up to 50 C during 15 min. Then, the mixture was cooled to 80 C, and Me 3 SiCl (3.21 mmol, 411 µl) wad added dropwise. The temperature was allowed to rise to 0 C during 1 hour. Volatile materials were evaporated under vacuum (ca. 7 Torr). Then, acetonitrile (1.5 ml), Me 3 SiC 2 Br (723 mg, 3.56 mmol), and HMPA (620 µl, 3.56 mmol) were successively added. The mixture was stirred at room temperature for 3 hours. The mixture was diluted with water (5 ml), extracted with hexane (3 5 ml). Combined organic phases were filtered through Na 2 S 4, concentrated under vacuum, and the residue was purified by column chromatography on silica gel. Ethyl 2-benzyl-3,3-difluoro-3-(trimethylsilyl)propanoate (11a). 10 S11 Et SiMe 3 Yield 384 mg (75%). Colorless oil. Chromatography: hexane/etac, 20/1. R f 0.21 (hexane/etac, 20/1). 1 H NMR (300 MHz, ), δ: 0.01 (s, 9H), 1.26 (t, 3H, J = 7.1), 4.06 (dd, 1H, J = 23.8, 12.4), (m, 2H), (m, 3H), (m, 2H). 19 NMR (282 MHz, ), δ: (dd, 1, J = 322.1, 23.8), (dd, 1, J = 322.1, 12.4). Ethyl 2-[difluoro(trimethylsilyl)methyl]-4-phenylbutanoate (11b). Et SiMe 3 Yield 354 mg (66%). Colorless oil. R f = 0.26 (hexane/etac, 20:1). 1 H NMR (300 MHz, ), δ: 0.25 (s, 9H), 1.10 (t, 3H, J = 7.1), (m, 3H), (m, 2H), (m, 5H). 13 C{ 1 H} NMR (75 MHz, ), δ: 3.8 (t, J = 2.3), 14.0, 31.2 (t, J = 6.9), 55.4 (t, J = 20.6), 61.0, 126.7, (dd, J = 265.0, 269.0) 128.6, 129.0, 138.5, (dd, J = 10.9, 4.0). 19 NMR (282 MHz, ), δ: (dm, J = 323.2), (dm, J = 323.2). Calcd for C 15 H Si (300.42): C, 59.97; H, ound: C, 59.97; H, Hashimoto, R.; Iida, T.; Aikawa, K.; Ito, S.; Mikami, K. Chem. Eur. J. 2014, 20,

12 a 1 H NMR 300 MHz D-solv. residual peak S12

13 S13 19 NMR 282 MHz a

14 Br 1 H NMR 300 MHz b D-solv. residual peak S14

15 Br 13 C{ 1 H} NMR 75 MHz 2b S15

16 S16 Br 2b 19 NMR 282 MHz

17 S Me 1 H NMR 300 MHz 2c D-solv. residual peak

18 Me 2c C{ 1 H} NMR 75 MHz S18

19 S19 Me 2c 19 NMR 282 MHz

20 d 1 H NMR 300 MHz D-solv. residual peak S20

21 d 13 C{ 1 H} NMR 75 MHz S21

22 S22 19 NMR 282 MHz 2d

23 Me Me 2e 1 H NMR 300 MHz D-solv. residual peak S23

24 Me Me 2e C{ 1 H} NMR 75 MHz S24

25 S25 Me Me 2e 19 NMR 282 MHz

26 f H NMR 300 MHz 8.0 D-solv. residual peak S26

27 f 13 C{ 1 H} NMR 75 MHz S27

28 S28 2f 19 NMR 282 MHz

29 S29 e g D-solv. residual peak

30 e 2g C{ 1 H} NMR 75 MHz S30

31 S31 e 2g 19 NMR 282 MHz

32 S32 2h 1 H NMR 300 MHz D-solv. residual peak

33 h C{ 1 H} NMR 75 MHz S33

34 S34 2h 19 NMR 282 MHz

35 i 1 H NMR 300 MHz D-solv. residual peak S35

36 i C{ 1 H} NMR 75 MHz S36

37 S37 19 NMR 282 MHz 2i

38 j 1 H NMR 300 MHz D-solv. residual peak S38

39 j 13 C{ 1 H} NMR 75 MHz S39

40 S40 2j 19 NMR 282 MHz

41 Me 1 H NMR 300 MHz k D-solv. residual peak S41

42 Me 2k C{ 1 H} NMR 75 MHz S42

43 S43 Me 2k 19 NMR 282 MHz

44 H NMR 300 MHz 2l D-solv. residual peak S44

45 l C{ 1 H} NMR 75 MHz S45

46 S46 2l 19 NMR 282 MHz

47 H NMR 300 MHz m S47

48 m C{ 1 H} NMR 75 MHz S48

49 S49 2m 19 NMR 282 MHz

50 Me 1 H NMR 300 MHz n D-solv. residual peak S50

51 Me 2n C{ 1 H} NMR 75 MHz S51

52 S52 Me 2n 19 NMR 282 MHz

53 S53 1 H NMR 300 MHz 2o

54 o 13 C{ 1 H} NMR 75 MHz S54

55 S55 2o 19 NMR 282 MHz

56 p H NMR 300 MHz 8.0 D-solv. residual peak S56

57 p C{ 1 H} NMR 75 MHz S57

58 S58 2p 19 NMR 282 MHz

59 H NMR 300 MHz s S59

60 s C{ 1 H} NMR 75 MHz S60

61 S61 19 NMR 282 MHz 2s

62 S62 2t 1 H NMR 300 MHz D-solv. residual peak

63 t C{ 1 H} NMR 75 MHz S63

64 S64 2t 19 NMR 282 MHz

65 Me 3 Si 4o 1 H NMR 300 MHz S65

66 Me 3 Si 4o C{ 1 H} NMR 75 MHz S66

67 S67 Me 3 Si 4o 19 NMR 282 MHz

68 N 1 H NMR 300 MHz H D-solv. residual peak S68

69 N H C{ 1 H} NMR 75 MHz S69

70 N H 6 19 NMR 282 MHz S70

71 H NMR 300 MHz D-solv. residual peak S71

72 C{ 1 H} NMR 75 MHz S72

73 NMR 282 MHz S73

74 Et SiMe 3 11a 1 H NMR 300 MHz D-solv. residual peak S74

75 S75 11a Et SiMe 3 19 NMR 282 MHz

76 b 1 H NMR 300 MHz 10.0 Et SiMe S76

77 Et SiMe 3 11b 13 C{ 1 H} NMR 75 MHz S77

78 Et SiMe 3 11b 19 NMR 282 MHz S78