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

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, 119991 Moscow, Leninsky prosp. 47, Russian ederation adil25@mail.ru 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

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 (230-400 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 3000. 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, 5850 5855. 2 (a) Yamaguchi, Y.; Koura, M.; Kurobuchi, S.; Matsuda, T.; kuda, A.; Sumida, H.; Watanabe, Y.; Enomoto, T.; Shibuya, K. US2010048610 (A1). (b) Al-Smadi, M.; Hanold, N.; Kalbitz, H.; Meier, H. Synthesis 2009, 2539 2546. 3 Ranu, B. C.; Ghosh, K.; Jana, U. J. rg. Chem. 1996, 61, 9546 9547. 4 Takeuchi, J.; Inukai, T.; Sakai, M. W2010147133A1 (Chem. Abstr. 154:64832).

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 124 126 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 48 50 C. Bp 112 116 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), 119.5 (t, J = 250.1), 130.0, 130.5 (t, J = 3.4), 131.8 (t, J = 3.4), 132.2, 188.3 (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, 2.83. ound: C, 43.25; H, 2.89. 2,2-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 74 78 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, 119.8 (t, J = 250.1), 124.7, 132.9 (t, J = 3.4), 164.6, 187.7 (t, J = 30.4). 19 NMR (282 MHz, ), δ: 93.1 (q, 2, J = 19.8). Calcd for C 10 H 10 2 2 (200.18): C, 60.00; H, 5.04. ound: C, 60.01; H, 5.07. 1-(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 104 110 C (bath temp.)/5 Torr. 5 Bergeron, M.; Johnson, T.; Paquin, J.-. Angew. Chem. Int. Ed. 2011, 50, 11112 11116. 6 Aoyama, T.; Eguchi, T.; shima, T.; Kakinuma, K. J. Chem. Soc., Perkin Trans. 1 1995, 1905 1912.

1 H NMR (300 MHz, ), δ: 1.85 (t, 3H, J = 19.2), 2.37(s, 3H), 2.47 (s, 3H), 7.06 7.16 (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, 119.4 (t, J = 251.8), 126.3, 129.2 (t, J = 5.7), 130.4, (t, J = 5.7), 133.1, 141.0, 143.4, 192.1 (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, 6.10. ound: C, 66.67; H, 6.02. 1-(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 95 98 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), 6.46 6.55 (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, 116.8 (t, J = 2.3), 119.1 (t, J = 250.7), 133.2 (t, J = 4.0), 161.5, 165.0, 191.0 (t, J = 31.0). 19 NMR (282 MHz, ), δ: 95.5 (q, 2, J = 19.1). HRMS (ESI): Calcd for C 11 H 12 2 3 Na (M + Na): 253.0643. ound: 253.0647. 1-[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, 119.8 (t, J = 250.5), 124.7 (t, J = 2.8), 132.4, 132.8 (t, J = 3.4), 163.6, 187.7 (t, J = 31.7). 19 NMR (282 MHz, ), δ: 93.0 (q, J = 19.4). HRMS (ESI): Calcd for C 12 H 13 2 2 (M + H): 227.0878. ound: 227.0880. 1-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 46 48 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, 119.0 (t, J = 250.1), 195.7 (t, J = 31.0).

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, 4.35. ound: C, 56.31; H, 4.19. 2,2-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 90 94 C (bath temp.)/0.21 Torr. 1 H NMR (300 MHz, ), δ: 1.96 (t, 3H, J = 19.2), 7.53 7.68 (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), 119.8 (t, J = 250.7), 125.0 (t, J = 2.3), 127.1, 127.9, 128.6, 129.0 (t, J = 2.3), 129.4, 130.2, 132.5, 133.0 (t, J = 4.6), 136.1, 189.2 (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, 4.58. ound: C, 70.87; H, 4.61. 2,2-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 90 94 C (bath temp.)/0.21 Torr. 1 H NMR (300 MHz, ), δ: 1.96 (t, 3H, J = 19.2), 7.48 7.67 (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), 119.4 (t, J = 251.8), 124.3, 125.3, 126.7, 128.5, 128.9, 129.8 (t, J = 5.7), 131.2, 134.0, 134.1, 192.8 (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, 4.58. ound: C, 70.69; H, 4.61. (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 126 130 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), 7.36 7.54 (m, 3H), 7.56 7.72 (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, 118.3 (t, J = 249.0), 129.0, 129.2, 131.6, 134.2, 147.7, 188.9 (t, J = 31.6). 19 NMR (282 MHz, ), δ: 100.7 (q, 2, J = 19.2). Calcd for C 11 H 10 2 (196.19): C, 67.34; H, 5.14. ound: C, 67.18; H, 5.03.

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 112 116 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, 120.4 (t, J = 252.4), 125.3, 132.8 (t, J = 4.0), 164.5, 188.1 (t, J = 31.0). 19 NMR (282 MHz, ), δ: 102.5 (t, 2, J = 17.7). Calcd for C 11 H 12 2 2 (214.21): C, 61.68; H, 5.65. ound: C, 61.62; H, 5.42. 2,2-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 122 128 C (bath temp.)/6 Torr. 1 H NMR (300 MHz, ), δ: 0.93 (t, 3H, J = 7.3), 1.32 1.60 (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), 120.1 (t, J = 252.4), 128.8, 130.2 (t, J = 3.4), 132.4 (t, J = 2.3), 134.3, 189.9 (t, J = 31.6). 19 NMR (282 MHz, ), δ: 101.0 (t, 2, J = 17.7). Calcd for C 12 H 14 2 (212.24): C, 67.91; H, 6.65. ound: C, 67.90; H, 6.47. 4,4-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 133 140 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), 7.15 7.37 (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, 117.9 (t, J = 252.4), 126.51, 126.54, 128.41, 128.44, 128.7, 140.0, 140.3, 200.2 (t, J = 31.6). 19 NMR (282 MHz, ), δ: 108.2 (t, 2, J = 17.6). Calcd for C 18 H 18 2 (288.33): C, 74.98; H, 6.29. ound: C, 74.97; H, 6.38.

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 87 94 C (bath temp.)/0.23 Torr. 1 H NMR (300 MHz, ), δ: 1.07 (d, 6H, J = 7.3), 2.43 2.66 (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, 121.1 (t, J = 254.7), 125.9, 132.7 (t, J = 3.4), 164.5, 188.6 (t, J = 29.8). 19 NMR (282 MHz, ), δ: 109.9 (d, 2, J = 14.8). Calcd for C 12 H 14 2 2 (228.24): C, 63.15; H, 6.18. ound: C, 63.04; H, 6.11. 6,6-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 92 96 C (bath temp.)/0.30 Torr. 1 H NMR (300 MHz, ), δ: 1.96 2.07 (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), 119.0 (t, J = 249.6), 127.0, 130.0, 130.2, 132.9, 134.9, 141.6, 194.1 (t, J = 29.8). 19 NMR (282 MHz, ), δ: 101.1 (t, 2, J = 16.0). Calcd for C 11 H 10 2 (196.19): C, 67.34; H, 5.14. ound: C, 67.29; H, 5.19. 2,2-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 34 36 C. Bp 78 88 C (bath temp.)/0.21 Torr. 1 H NMR (300 MHz, ), δ: 1.18 1.39 (m, 16H), 1.69 1.80 (m, 2H), 1.96 2.13 (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, 119.4 (t, J = 250.1), 202.9 (t, J = 29.3). 19 NMR (282 MHz, ), δ: 106.8 (t, 2, J = 14.8). Calcd for C 13 H 22 2 (232.31): C, 67.21; H, 9.55. ound: C, 67.14; H, 9.56. 7 Pravst, I.; Zupan, M.; Stavber, S. Synthesis 2005, 3140 3146. 8 Kobayashi, Y.; Taguchi, T.; Mamada, M.; Shimizu, H.; Murohashi, H. Chem. Pharm. Bull. 1979, 27, 3123 3129.

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 45 47 C. Bp 108 112 C (bath temp.)/0.09 Torr. 1 H NMR (300 MHz, ), δ: 1.66 (t, 3H, J = 19.2), 5.69 (s, 1H), 7.22 7.42 (m, 10H). 13 C{ 1 H} NMR (75 MHz, ), δ: 20.2 (t, J = 24.8), 56.9, 118.3 (t, J = 250.7), 127.7, 128.95, 129.04, 137.3, 198.8 (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, 5.42. ound: C, 73.83; H, 5.37. 1-(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 122 127 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), 2.02 2.10 (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), 120.3 (t, J = 252.4), 204.1 (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, 7.95. ound: C, 68.24; H, 7.98.

[(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 73 75 C/0.365 Torr. 1 H NMR (300 MHz, ), δ: 0.15 (s, 9H), 1.73 1.91 (m, 1H), 2.01-2.13 (m, 1H), 2.13 2.26 (m, 1H), 2.57 2.84 (m, 2H), 7.11 (d, 1H, J = 7.4), 7.18 7.32 (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), 113.3 (dd, J = 307.5, 298.9), 126.4, 126.9, 127.3, 128.5, 132.4 (t, J = 2.5), 134.6 (d, J = 1.5). 19 NMR (282 MHz, ), δ: 143.4 (d, 1H, J = 155.7), 130.4 (dd, 1, J = 155.7, 17.0). Calcd for C 14 H 18 2 Si (268.37): C, 62.65; H, 6.76. ound: C, 62.61; H, 6.94. 9 Cazeau, P.; Duboudin,.; Moulines,.; Babot,.; Dunogues, J. Tetrahedron 1987, 43, 2075 2088.

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 83 85 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), 122.9 (t, J = 243.8), 123.5, 128.4, 143.8 (d, J = 4.6), 148.2. 19 NMR (282 MHz, ), δ: 101.9 (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, 6.45. ound: C, 49.65; H, 4.19; N, 6.44. 2',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 94 96 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), 109.4 (dd, J = 300.0, 296.0), 120.7 (d, J = 3.4), 126.1 (d, J = 1.2), 126.2, 129.8, 134.8, 143.8 (d, J = 1.9), 168.2. 19 NMR (282 MHz, ), δ: 137.9 (ddd, 1, J = 165.3, 14.8, 6.9), 135.7 (ddd, 1, J = 165.3, 14.8, 6.9) HRMS (ESI): Calcd for C 10 H 7 2 2 (M + H): 197.0413. ound:197.0409. Calcd for C 10 H 6 2 2 (196.15): C, 61.23; H, 3.08. ound: C, 61.27; H, 3.15.

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), 4.09 4.29 (m, 2H), 7.28 7.40 (m, 3H), 7.44 7.54 (m, 2H). 19 NMR (282 MHz, ), δ: 118.2 (dd, 1, J = 322.1, 23.8), 110.9 (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), 3.00 3.26 (m, 3H), 3.94 4.12 (m, 2H), 7.14 7.33 (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, 127.4 (dd, J = 265.0, 269.0) 128.6, 129.0, 138.5, 169.9 (dd, J = 10.9, 4.0). 19 NMR (282 MHz, ), δ: 117.0 (dm, J = 323.2), 112.2 (dm, J = 323.2). Calcd for C 15 H 22 2 2 Si (300.42): C, 59.97; H, 7.38. ound: C, 59.97; H, 7.41. 10 Hashimoto, R.; Iida, T.; Aikawa, K.; Ito, S.; Mikami, K. Chem. Eur. J. 2014, 20, 2750 2754.

8.1363 8.1103 7.6528 7.6497 7.6284 7.6040 7.5170 7.4926 7.4667 1.9561 1.8920 1.8264 2a 1 H NMR 300 MHz 10.0 9.0 D-solv. residual peak 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S12

S13 19 NMR 282 MHz -93.4661-93.5337-93.6012-93.6687 2a -93.2-93.6-94.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

7.9929 7.9670 7.6574 7.6513 7.6284 7.6238 1.9469 1.9424 1.8829 1.8768 1.8173 1.8127 Br 1 H NMR 300 MHz 10.0 2b 9.0 8.0 D-solv. residual peak 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S14

188.7443 188.3111 187.8778 132.2149 131.8500 131.8044 131.7588 130.4894 129.9801 122.8427 119.5286 116.2069 77.5857 77.1600 76.7343 20.9954 20.6609 20.3341 Br 13 C{ 1 H} NMR 75 MHz 2b 200 180 160 140 120 100 80 60 40 20 0 S15

S16 Br 2b 19 NMR 282 MHz -93.3986-93.4736-93.5412-93.6087-93.0-93.5-94.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

S17 8.1286 8.0981 6.9710 6.9405 3.8824 1.9347 1.8707 1.8051 Me 1 H NMR 300 MHz 2c D-solv. residual peak 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0

188.1514 187.7334 187.3305 164.5728 132.8762 124.6746 123.1163 119.7946 116.4806 114.0862 77.5857 77.1600 76.7343 55.6185 21.3374 21.0030 20.6686 Me 2c 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S18

S19 Me 2c 19 NMR 282 MHz -92.9408-93.0084-93.0834-93.1509-92.8-93.2-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

7.8587 7.8328 7.1067 7.0762 2.4716 2.3679 1.9180 1.8539 1.7898 2d 1 H NMR 300 MHz 10.0 9.0 D-solv. residual peak 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S20

192.5069 192.1040 191.7012 143.4493 140.9789 133.0890 130.5198 130.4362 130.3526 129.2124 126.3316 122.7439 119.4070 116.0701 77.5781 77.1600 76.7343 21.5807 21.3603 21.0258 20.6838 2d 13 C{ 1 H} NMR 75 MHz 200 180 160 140 120 100 80 60 40 20 0 S21

S22 19 NMR 282 MHz 2d -93.4436-93.5111-93.5787-93.6462-93.0-93.5-94.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

7.7305 7.7016 6.5363 6.5287 6.5073 6.4997 6.4783 6.4707 3.8550 3.8473 1.9134 1.8493 1.7852 Me Me 2e 1 H NMR 300 MHz 10.0 9.0 8.0 D-solv. residual peak 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S23

191.4351 191.0246 190.6142 165.0288 161.5095 133.2182 133.1726 133.1270 122.4702 119.1409 116.7542 115.8193 105.1473 98.9068 77.5781 77.1600 76.7343 55.7933 55.5881 21.2690 20.9270 20.5849 Me Me 2e 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S24

S25 Me Me 2e 19 NMR 282 MHz -95.4173-95.4848-95.5523-95.6199-95.2-95.6-96.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

8.1285 8.0995 6.9877 6.9587 6.0802 6.0634 6.0405 6.0237 6.0054 4.6358 4.6312 4.6266 4.6190 4.6129 1.9438 1.8797 1.8141 10.0 2f 9.0 1 H NMR 300 MHz 8.0 D-solv. residual peak 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S26

188.0906 187.6726 187.2621 163.5466 132.8838 132.8381 132.8001 132.4125 124.7202 123.0935 119.7718 118.3808 116.4578 114.7551 77.5781 77.1600 76.7343 69.0572 21.3146 20.9802 20.6533 200 2f 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S27

S28 2f 19 NMR 282 MHz -92.9408-93.0084-93.0759-93.1434-92.0-93.0-94.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

S29 e 4.9729 4.6389 4.2485 1.8767 1.8142 1.7502 2g D-solv. residual peak 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0

196.0718 195.6613 195.2509 122.3258 119.0117 115.6976 77.5857 77.1600 76.7419 73.5039 72.4777 71.0031 70.9651 70.9195 70.4026 21.4059 21.0714 20.7370 e 2g 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S30

S31 e 2g 19 NMR 282 MHz -93.9764-94.0440-94.1115-94.1790-93.5-94.0-94.5-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

S32 2h 1 H NMR 300 MHz D-solv. residual peak 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0

189.6413 189.2232 188.7975 136.1370 133.0890 133.0358 132.9750 132.4657 130.2082 129.3796 129.0072 128.8628 128.6195 127.8746 127.0537 125.0470 123.1087 119.7946 116.4730 77.5857 77.1600 76.7419 21.3983 21.0638 20.7294 2h 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S33

S34 2h 19 NMR 282 MHz -92.7082-92.7757-92.8433-92.9108-92.0-93.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

8.5008 8.4733 8.1973 8.1744 8.0722 8.0448 7.9151 7.8877 7.6467 7.6238 7.5994 7.5948 7.5811 7.5597 7.5338 7.5079 2.0278 1.9637 1.8997 10.0 2i 1 H NMR 300 MHz D-solv. residual peak 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S35

192.8489 192.4461 134.0315 131.2343 129.8661 129.7901 129.7141 128.8780 128.5283 126.7421 125.3435 124.2793 122.7211 119.3842 116.0473 77.5857 77.1600 76.7419 21.4591 21.1246 20.7902 2i 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S36

S37 19 NMR 282 MHz 2i -93.1584-93.2260-93.2935-93.3611-92.8-93.6-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

7.9266 7.8728 7.6504 7.6321 7.6259 7.4500 7.4292 7.1872 7.1334 7.1310 1.8660 1.8013 1.7988 1.7377 1.7353 2j 1 H NMR 300 MHz 10.0 9.0 8.0 7.0 D-solv. residual peak 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S38

189.3600 188.9419 188.5239 147.7439 134.1531 131.5536 129.1516 128.9920 121.6417 118.3428 117.7955 115.0439 77.5781 77.1600 76.7343 20.1897 19.8552 19.5208 2j 13 C{ 1 H} NMR 75 MHz 200 180 160 140 120 100 80 60 40 20 0 S39

S40 2j 19 NMR 282 MHz -100.5880-100.6555-100.7231-100.7906-100.0-101.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

8.1164 8.0875 6.9680 6.9375 3.8824 2.2672 2.2413 2.2337 2.2077 2.1833 2.1574 2.1498 2.1239 1.1096 1.0852 1.0608 Me 1 H NMR 300 MHz 10.0 2k 9.0 8.0 D-solv. residual peak 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S41

188.5391 188.1362 187.7258 164.5348 132.7849 125.2598 123.7168 120.3723 117.0202 114.0862 77.5857 77.1600 76.7343 55.6413 28.0112 27.6996 27.3803 5.9680 5.8920 5.8160 Me 2k 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S42

S43 Me 2k 19 NMR 282 MHz -102.4414-102.5089-102.5690-102.0-102.5-103.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

8.1119 8.0859 7.6207 7.5963 7.5125 7.4865 7.4606 2.2077 2.2032 2.1772 2.1483 1.5275 1.4085 1.3857 0.9510 0.9266 0.9022 1 H NMR 300 MHz 2l 10.0 9.0 8.0 D-solv. residual peak 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S44

190.2645 189.8541 189.4360 134.2748 132.4277 130.3146 130.2690 130.2234 128.7943 123.4280 120.0835 116.7390 77.5857 77.1600 76.7343 34.2441 33.9401 33.6360 23.6710 23.6102 23.5570 22.6144 13.8731 2l 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S45

S46 2l 19 NMR 282 MHz -100.9405-101.0005-101.0681-100.8-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140

7.3096 7.2852 7.2242 7.1922 3.0222 3.0009 2.9627 2.9414 2.7889 2.7614 2.7492 2.7324 2.3237 2.2947 2.2672 1 H NMR 300 MHz 10.0 2m 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S47

200.5944 200.1764 199.7583 140.3176 139.9528 128.7107 128.5663 128.4295 126.5368 126.4988 121.2540 117.9096 114.5727 77.5781 77.1600 76.7343 38.1131 34.8066 34.5026 34.1985 28.7789 27.7148 27.6540 27.5856 2m 200 180 13 C{ 1 H} NMR 75 MHz 160 140 120 100 80 60 40 20 0 S48

S49 2m 19 NMR 282 MHz -108.1297-108.1897-108.2573-108.0-108.4-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

8.0951 8.0661 6.9603 6.9359 6.9298 3.8763 2.6119 2.5890 2.5845 2.5646 2.5601 2.5372 2.5143 2.5097 2.4914 2.4868 2.4640 1.0821 1.0592 Me 1 H NMR 300 MHz 10.0 2n 9.0 8.0 D-solv. residual peak 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S50

189.0408 188.6455 188.2427 164.4512 132.7469 132.6937 132.6481 125.8755 124.4617 121.0868 117.7119 114.0710 77.5857 77.1600 76.7419 55.6489 33.2636 32.9595 32.6631 15.2262 15.1577 15.0969 Me 2n 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S51

S52 Me 2n 19 NMR 282 MHz -109.8482-109.9007-109.8-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

S53 1 H NMR 300 MHz 2o 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0

194.5060 194.1183 193.7231 141.6478 134.9209 132.9218 130.2462 129.9573 126.9701 122.2650 118.9509 115.6368 77.5857 77.1600 76.7420 34.7610 34.4494 34.1301 33.6360 22.1280 22.0596 21.9835 2o 13 C{ 1 H} NMR 75 MHz 200 180 160 140 120 100 80 60 40 20 0 S54

S55 2o 19 NMR 282 MHz -101.0681-101.1206-101.1806-100.8-101.2-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

2.7507 2.7309 2.7111 2.0674 2.0415 2.0171 1.7654 1.7456 1.7273 1.3185 1.2606 10.0 2p 9.0 1 H NMR 300 MHz 8.0 D-solv. residual peak 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S56

203.3157 202.9204 202.5327 122.7135 119.3614 116.0093 77.5857 77.1600 76.7419 36.2204 33.7729 33.4688 33.1572 26.4986 26.1793 26.0197 25.4268 24.9556 24.4007 23.8078 21.4287 19.9312 19.8628 19.7944 2p 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S57

S58 2p 19 NMR 282 MHz -106.6889-106.7414-106.7939-106.4-107.2-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

7.3416 7.3340 7.3188 7.3005 7.2974 7.2821 7.2547 5.6883 1.7273 1.6632 1.5992 1 H NMR 300 MHz 10.0 2s 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0-1.0 S59

199.2491 198.8310 198.4129 137.2924 129.0376 128.9616 127.7454 121.6113 118.2896 114.9679 77.5857 77.1600 76.7419 56.9258 20.5241 20.1973 19.8628 2s 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S60

S61 19 NMR 282 MHz 2s -99.6798-99.7473-99.8148-99.8824-99.0-100.5-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

S62 2t 1 H NMR 300 MHz 2.0543 1.9920 1.7439 1.6779 1.6131 D-solv. residual peak 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0

204.4710 204.0834 203.7033 123.6028 120.2583 116.9138 77.5781 77.1600 76.7343 46.1551 46.1247 46.0943 37.6494 36.6005 27.9656 21.8315 21.4895 21.1550 2t 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S63

S64 2t 19 NMR 282 MHz -96.0103-96.0854-96.1529-96.2204-95.0-96.0-97.0-50 -55-60 -65-70 -75-80 -85-90 -95-100 -105-110 -115-120 -125-130 -135-140 -145-150

7.6802 7.6543 7.2791 7.2562 7.2440 7.2379 7.2181 7.2150 7.1235 7.0991 2.7339 2.7217 2.6775 2.2291 2.2184 2.2077 2.1955 2.1833 2.1726 2.1620 2.1513 2.1101 2.1010 2.0400 1.8524 1.8310 1.8142 1.8081 0.1441 Me 3 Si 4o 1 H NMR 300 MHz 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S65

134.5712 132.4353 128.5435 127.2893 126.9397 126.4076 117.3243 113.3641 113.2501 109.2899 77.5857 77.1600 76.7419 59.5862 59.4494 59.2670 31.0441 30.9452 30.8996 30.8008 26.7038 26.6202 14.9677 1.0805 Me 3 Si 4o 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S66

S67 Me 3 Si 4o 19 NMR 282 MHz -130.1026-130.1626-130.6504-130.7104-143.1677-143.7156-130 -132-134 -136-138 -140-142 -50-55 -60-65 -70-75 -80-85 -90-95 -100-105 -110-115 -120-125 -130-135 -140-145 -150

8.2278 8.2217 8.1988 7.6619 7.6329 5.0172 5.0035 4.9867 4.9745 4.9562 4.9440 2.8392 2.8270 1.5732 1.5107 1.4482 2 N 1 H NMR 300 MHz 10.0 6 H 9.0 8.0 D-solv. residual peak 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S68

148.2456 143.8750 143.8142 128.3763 126.1644 123.5116 122.9339 119.7034 77.5857 77.1600 76.7420 75.3433 74.9481 74.5528 19.1255 18.7759 18.4262 2 N H 6 200 13 C{ 1 H} NMR 75 MHz 180 160 140 120 100 80 60 40 20 0 S69

-99.1094-99.1394-99.1695-99.2070-99.2370-99.8974-99.9274-99.9574-99.9949-100.0250-100.0625-100.0925-100.1225-101.3007-101.3382-101.3682-101.3983-101.4358-101.4658-101.5033-101.5333-102.1862-102.2238-102.2538-102.2913-102.3213-102.3513-102.3888-102.4189-102.0-101.0-100.0-99.0-150 -145-140 -135-130 -125-120 -115-110 -105-100 -95-90 -85-80 -75-70 -65-60 -55-50 2 N H 6 19 NMR 282 MHz S70

7.9792 7.9532 7.7534 7.7290 7.7031 7.6207 7.5963 7.5704 7.3370 7.3126 7.2547 2.6073 2.5845 2.5738 2.5509 2.5341 2.5219 2.5006 2.3053 2.2825 2.2718 2.2550 2.2489 2.2321 2.2215 2.1986 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 7 1 H NMR 300 MHz D-solv. residual peak S71

168.2213 143.8446 134.7764 129.7977 126.1872 120.7144 120.6764 113.3717 109.4343 109.3887 105.4589 77.5781 77.1600 76.7343 67.1493 67.0125 66.9593 66.8225 23.6254 23.4962 23.3669 7 13 C{ 1 H} NMR 75 MHz 200 180 160 140 120 100 80 60 40 20 0 S72

-135.2881-135.3106-135.3407-135.3632-135.8735-135.8960-135.9260-135.9485-137.5845-137.6070-137.6370-137.6595-138.1698-138.1998-138.2299-138.2524-138.0-137.0-136.0-135.0-150 -145-140 -135-130 -125-120 -115-110 -105-100 -95-90 -85-80 -75-70 -65-60 -55-50 7 19 NMR 282 MHz S73

7.4972 7.4819 7.3462 7.3431 7.3355 7.3279 4.2393 4.2286 4.2164 4.2088 4.1920 4.1844 4.1676 4.1600 4.1478 4.1371 4.1188 4.0776 4.0395 3.9983 1.2850 1.2606 1.2377-0.0054 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 Et SiMe 3 11a 1 H NMR 300 MHz D-solv. residual peak S74

S75 11a Et SiMe 3 19 NMR 282 MHz -110.2234-110.2685-111.3641-111.4091-117.6078-117.6903-118.7484-118.8310-110 -112-114 -116-118 -50-55 -60-65 -70-75 -80-85 -90-95 -100-105 -110-115 -120-125 -130-135 -140-145 -150

7.2776 7.2547 7.2043 7.1784 4.0548 4.0365 4.0304 4.0121 3.1366 3.1259 3.1168 3.1091 1.1233 1.1004 1.0760 0.2463 11b 1 H NMR 300 MHz 10.0 Et SiMe 3 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 S76

169.9696 169.9164 169.8252 169.7719 138.4934 130.9607 129.2048 129.0072 128.5891 127.4566 127.4034 126.6736 123.8992 77.5857 77.1600 76.7419 60.9848 55.6337 55.3600 55.0788 31.3025 31.2113 31.1125 14.0100-3.7994-3.8298 Et SiMe 3 11b 13 C{ 1 H} NMR 75 MHz 200 180 160 140 120 100 80 60 40 20 0 S77

-111.5967-111.6343-112.7149-112.7449-112.7599-112.7824-112.8125-116.3170-116.3545-116.3921-116.4146-117.4952-117.5252-117.5402-117.5627-117.5853-117.0-116.0-115.0-114.0-113.0-112.0-150 -145-140 -135-130 -125-120 -115-110 -105-100 -95-90 -85-80 -75-70 -65-60 -55-50 Et SiMe 3 11b 19 NMR 282 MHz S78