Supplement: Intramolecular N to N acyl migration in conformationally mobile 1 -acyl-1- systems promoted by debenzylation conditions (HCOONH 4

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1 Cent. Eur. J. Chem. 9(5) 2011 S164-S175 DI: /s y Central European Journal of Chemistry Supplement: Intramolecular to acyl migration in conformationally mobile 1 -acyl-1- benzyl-3,4 -dihydro-1 -spiro[piperidine-4,2 quinoline] systems promoted by debenzylation conditions (C 4 /Pd/C) Supplementary Information Leonor Y. Vargas Méndez 1, Vladimir V. Kouznetsov 2* 1 Environmental Research Group, Environmental Chemistry Faculty, Santo Tomas University, A.A. 1076, Bucaramamga, Colombia 2 Laboratory of rganic & Biomolecular Chemistry, School of Chemistry, Industrial University of Santander, A.A. 678, Bucaramamga, Colombia Materials and methods IR spectra were obtained on Infralum FT-02 spectrometer with potassium bromide pellets. 1 MR spectra were recorded at 400 Mz in CDCl 3 using TMS internal standard. 13 C MR spectral measurements were performed at 100 Mz using CDCl 3 as an internal standard. Chemical shifts (δ) and J values are reported in ppm and z, respectively. A ewlett-packard (P) 5890 A series II Gas Chromatograph interfaced to a P 5972 Mass Selective Detector with a P MS ChemStation Data system was used for MS identification. Elemental analyses were performed on a Perkin Elmer 2400 Series II analyzer. The reaction progress was monitored using thin layer chromatography on a Silufol UV 254 TLC aluminum sheets. Column chromatography was carried out using Merck Kieselgel 60 ( mesh). All reagents were purchased from Merck, Sigma and Aldrich Chemical Co and used without further purification. Final purification of all products for elemental analyses was done by recrystallization. General procedure for synthesis of 1 -acyl-1-benzyl- 3,4 -dihydro-1 -spiro[piperidine-4,2 -quinolines] 3a-l. Formylation (Compounds 3a, 3d, 3i, 3k). A solution of Ac 2 (2.00 mmol), C (3.00 mmol) and two drops of pyridine was added to the respective 1-benzyl-4 - methyl-3,4 -dihydro-1 -spiro[piperidine-4,2 -quinolines] 2 (1.00 mmol) at 0ºC. The reaction mixture was stirred fo h at the same temperature. Then, the reaction mixture was treated with 4 to get a p 7-8, and then it was extracted with C 2 (3 10 ml). rganic extracts were washed with water and dried over a 2 S 4, then concentrated. Crude products 3 of the reaction were purified by column chromatography (alumina). Acetylation (Compounds 3b and 3e). A mixture of the respective 1-benzyl-4 -methyl-3,4 -dihydro-1 spiro[piperidine-4,2 -quinolines] 2 (1.00 mmol) and Ac 2 (3.00 mmol) was refluxed for 1-2 h in the presence of Et 3 (two drops). Then, reaction mixture was treated with 4 to get a p 7-8, and then it was extracted with C 2 (3 10 ml). rganic extracts were washed with water, dried over a 2 S 4, and then concentrated. Crude products 3 of the reaction were purified by column chromatography (alumina). Benzoylation (Compounds 3c and 3f). A solution of PhCCl (2.00 mmol) in dry toluene (10 ml) was dropped slowly to the solution of the respective 1-benzyl-4 - methyl-3,4 -dihydro-1 -spiro[piperidine-4,2 -quinolines] 2 (1.00 mmol) and Et 3 (1.00 mmol) in dry toluene (20 ml) at 0ºC. The reaction mixture was stirred for 2-3 h at the room temperature. Then, the reaction mixture was treated with 4 to get a p 7-8, and then it was extracted with C 2 (3 10 ml). rganic extracts were washed with water, dried over a 2 S 4, and then concentrated. Crude products 3 of the reaction were purified by column chromatography (alumina). S164 * kouznet@uis.edu.co

2 L. Y. Vargas Méndez, V. V. Kouznetsov Chloroacetylation (Compounds 3g and 3l). A solution of ClC 2 CCl (2.00 mmol) in dry C 2 (10 ml) was dropped slowly to the solution of the respective 1-benzyl-4 -methyl-3,4 -dihydro-1 spiro[piperidine-4,2 -quinolines] 2 (1.00 mmol) and Et 3 (1.00 mmol) in dry C 2 (20 ml) at 0ºC. The reaction mixture was stirred for 1-2 h at the same temperature. Then, the reaction mixture was treated with 4 to get a p 7-8, and then it was extracted with C 2 (3 10 ml). rganic extracts were washed with water and dried over a 2 S 4, and then concentrated. Crude products 3 of the reaction were purified by column chromatography (alumina). itrobenzoylation (Compound 3h). A p- 2 PhCCl (1.73 g, 9.30 mmol) was added in small portions to the solution of 1-benzyl-4 -methyl-3,4 -dihydro-1 spiro[piperidine-4,2 -quinoline] 2a (1.49 g, 4.65 mmol) y Et 3 (0.46 g, 1 mmol) in dry toluene (20 ml) at 0ºC. After 5 min, reaction mixture was treated with 4 to get a p 7-8, and then it was extracted with C 2 (3 10 ml). rganic extracts were washed with water, dried over a 2 S 4, and then concentrated. Crude product 3h of the reaction was purified by column chromatography (alumina). 1-Benzyl-1 -formyl-4 -methyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3a 1 -Acetyl-1-benzyl-4 -methyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3b 3 C Colorless, viscous oil, 89%. IR (neat): 1657 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.16 (1, bs, 3 - a), 1.25 (1, bs, 3-a), 1.33 (3, d, J = 6.9 z, 4 - ), 1.51 (1, bd, J = 11.6 z, 5-a), 2.00 (3, s, - C), 2.21 (1, bs, 2-a), 2.32 (1, dd, J = 13.0, 4.8 z, 3 -e), 2.39 (1, td, J = 10.4, 3.0 z, 2-e), 2.59 (1, dd, J = 11.6, 5.8 z, 6-a), 2.69 (1, bs, 2-e), 2.75 (1, sp, J = 6.1 z, 4 -), 2.88 (1, bs, 3-e), 3.03 (1, bs, 5-e), 3.52 (2, s, C 2 -Ph), 7.00 (1, dd, J = 6.0, 2.4 z, 5 -), (8, m, Ar and Bn ). 13 C-MR (100 Mz) δ (ppm):18.4, 26.6, 29.2, 31.5, 36.7, 44.7, 50.3, 50.8, 61.2, 62.7, 125.8, 125.9, 126.5, 126.8, (3C), (3C), 138.6, 140.4, GC-MS: m/z (%): t R min, 348 (M +, 5), 305 (28), 257 (32), 216 (8), 186 (25), 172 (19), 162 (36), 146 (60), 120 (17), 91 (100). Elemental analysis calcd (%) for C (348.48): C, 79.27;, 8.10;, 8.04; found C, 79.41;, 8.33;, Benzyl-1 -benzoyl-4 -methyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3c Colorless, viscous oil, 95%. IR (neat):1676 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.22 (1, bs, 3-a), 1.35 (3, d, J = 6.7 z, 4 - ), 1.47 (1, bs, 3 -a), 1.75 (1, bs, 5-a), 1.86 (1, bs, 2-a), 2.29 (2, bs, 6-a and 3 -e), 2.37 (1, td, J = 11.8, 2.8 z, 2-e), 2.49 (1, bs, 6-e), 2.70 (1, bs, 3-e), 2.90 (1, bs, 4 -), 3.10 (2, bs, 5-e), 3.53 (2, s, C 2 - Ph), (9, m, Ar and Bn ), 8.62 (1, s, -C). 13 C-MR (100 Mz) δ (ppm): 18.7/21.0, 28.2/29.4, 33.5, 35.5/36.2, 43.1/43.5, 49.5, 50.2/50.4, 56.9/60.3, 62.8, 121.3, 124.7/125.1, 125.6/126.0, 126.6/126.8, 127.0, (2C), (3C), 134.4/135.2, 138.2/138.5, 160.1/ GC-MS: m/z (%): t R min; 334 (M +, 1), 306 (44), 243 (13), 215 (7), 186 (16), 172 (31), 160 (11), 146 (44), 130 (10), 120 (19), 91 (100). Elemental analysis calcd (%) for C (334.20): calcd. C, 79.00;, 7.84;, 8.38; found C, 79.15;, 7.60;, Yellow crystals, mp o C, 82 %. IR (KBr): 1648 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.07 (1, td, J = 12.8, 1.2 z, 3 -a), 1.36 (1, dd, J = 12.5, 2.3 z, 3-a), 1.44 (3, d, J = 6.8 z, 4 - ), 1.57 (1, dd, J = 12.8, 2.3 z, 5-a), 2.06 (1, td, J = 12.0, 2.3 z, 2-a), 2.38 (1, td, J = 12.0, 2.9 z, 6-a), 2.54 (1, dd, J = 12.9, 3.0 z, 3 -e), 2.81 (1, bdt, J = 11.7, 2.0 z, 2-e), 2.89 (1, J = 6.7 z, sp, 4 -), 2.94 (1, dt, J = 11.8, 2.3 z, 6-e), 3.29 (1, td, J = 12.7, 4.5 z, 3-e), 3.41 (1, td, J = 12.2, 4.1, 1.2 z, 5-e), 3.59 (2, s, C 2 -Ph), 6.50 (1, d, J = 7.9 z, 5 -), 6.76 (1, t, J = 7.5 z, 7 -), 6.97 (1, t, J = 7.5 z, 6 -), (11, m, 8 -, Bn, and Bz ). 13 C-MR (100 Mz) δ (ppm): 17.2, 28.4, 28.8, 35.9, 44.9, 50.3, 50.8, 61.0, 62.2, 122.5, 124.3, 125.6, 126.8, 127.6, S165

3 Supplement: Intramolecular to acyl migration in conformationally mobile 1 -acyl-1-benzyl-3,4 -dihydro-1 -spiro[piperidine-4,2 -quinoline] systems promoted by debenzylation conditions (C 4 /Pd/C) Supplementary Table 1. Main ions and possible fragmentation in the MS of compound 3. R A F 1 B F 3 C F 4 F 5 R Bn F 2 m/z, (I, %) Φ 1 Φ 2 Φ 3 Φ 4 Φ 5 Compound M +. [M +. - [M +. - [M +. - [M +. - [M +. -( (CR ). ] (C 7 7 ). ] (ArC 2 6 CR ). ] (ArC 5 10 CR ). ] ArC CR ). ] 3a 334 (1) 305 (4) 243 (13) 186 (16) 146 (44) 91 (100) 3b 348 (5) 305 (28) 257 (32) 186 (25) 146 (60) 91 (100) 3c (61) 319 (5) 186 (12) 146 (77) 91 (100) 3d 348 (1) 319 (4) 257 (9) 186 (50) 146 (47) 91 (100) 3e 362 (8) 319 (32) 271 (30) 186 (42) 146 (65) 91 (100) 3f (67) 333 (4) 186 (24) 146 (79) 91 (100) 3g 396 (1) 319 (4) 305 (10) 186 (15) 146 (26) 91 (100) 3h (20) 91 (100) 3i 352 (0.5) 323 (4) 261 (17) 186 (18) 146 (39) 91 (100) 3k 362 (1) 333 (4) 271 (7) 186 (19) 146 (51) 91 (100) 3l (4) 319 (9) 186 (14) 146 (42) 91 (100) (2C), (2C), 128.9, 129.0, 129.9, 138.8, 138.9, 139.4, 140.6, GC-MS: m/z (%): t R min, 319 (M + -C 7 7, 5), 305 (M + -C 7 5, 61), 224 (9), 186 (12), 172 (17), 159 (5), 146 (77), 105 (57), 91 (100). Elemental analysis calcd (%) for C (410.55): C, 81.91;, 7.37;, 6.82; found C, 81.85;, 7.45; Benzyl-1 -formyl-4,6 -dimethyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3d (1, s, -C). 13 C-MR (100 Mz) δ (ppm): 18.8/21.1, 18.9/21.2, 28.2/29.6, 33.5, 35.4/36.2, 43.2/ 43.7, 49.6, 50.3/50.4, 56.8/59.6, 62.9, 121.2, 125.5/125.9, 126.7/127.1, (2C), (3C), 132.0, 134.9, 138.2, 138.6, 160.1/ GC-MS: m/z (%): t R min, 348 (M +, 1), 320 (53), 257 (9), 229 (6), 201 (6), 186 (50), 73 (20), 172 (10), 162 (20), 146 (47), 134 (19), 91 (100). Elemental analysis calcd (%) for C (348.48): C, 79.27;, 8.10;, 8.04; found C, 79.39;, 8.24;, Acetyl-1-benzyl-4,6 -dimethyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3e 3 C 3 C White crystals, mp o C, 85 %. IR (KBr): 1677 (ν - C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.23 (1, bs, 3-a), 1.33 (3, d, J = 6.5 z, 4 - ), 1.46 (1, t, J = 13.3 z, 3 -a), 1.73 (1, bs, 5-a), 1.85 (1, bs, 2-a), 2.23 (1, bs, 2-e), (2, bs, 3 -e y 6-a), 2.32 (3, s, 6 - ), 2.48 (1, s, 6-e), 2.68 (1, bs, 3-e), 2.87 (1, bs, 4 -), 3.08 (1, bs, 5-e), 3.52 (2, s, C 2 -Ph), 7.00 (1, d, J = 8.2 z, 7 -), 7.04 (1, s, 5 -), (6, m, Bn and 8 -), C White crystals, mp o C, 86 %. IR (KBr): 1663 (ν - C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.16 (2, bs, 3 -a), 1.31 (4, d, J = 6.9 z, 4 - y 3-a), 1.49 (2, bd, J = 12.3 z, 5-a), 1.99 (3, s, -C), 2.21 (1, bs, 2-a), 2.29 (1, bd, J = 13.0 z, 3 -e), 2.34 (3, s, 6 - ), 2.38 (1, td, J = 11.9, 2.9 z, 2-e), 2.58 (1, dd, J = 11.2, 5.8 z, 6-a), 2.68 (1, bs, 6-e), S166

4 L. Y. Vargas Méndez, V. V. Kouznetsov 7 6 Ph c Ph 5-e 3-e 6-e 4-3 -e 6-a 2-e 2-a 5-a 4-3-a 3 -a 8 -, Ph Bn ppm (f1) C ppm (f1) Supplementary Figure 1. 1 MR spectrum of benzoyl derivative 3c (1, st, J = 6.5 z, 4 -), 2.86 (1, d, J = 11.7 z, 3-e), 3.02 (1, bs, 5-e), 3.51 (2, s, C 2 -Ph), 6.89 (1, d, J = 7.9 z, 7 -), 6.97 (1, d, J = 8.0 z, 8 -), 7.00 (1, s, 5 -), (5, m, Bn ). 13 C-MR (100 Mz) δ (ppm): 18.7, 21.2, 26.6, 29.2, 31.7, 36.7, 44.7, 50.3, 50.9, 61.2, 62.8, 126.4, 126.5, 126.8, (2C), (2C), 130.0, 135.6, 137.8, 138.7, 140.1, GC-MS: m/z (%): t R min, 362 (M +, 8), 319 (32), 271 (30), 230 (10), 186 (42), 176 (45), 172 (15), 158 (16), 146 (65), 134 (17), 91 (100). Elemental analysis calcd (%) for C (362.51): C, 79.52;, 8.34;, 7.73; found C, 79.74;, 8.56;, Benzyl-1 -benzoyl-4,6 -dimethyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3f 126.8, 127.4, (2C), (2C), (2C), (2C), 129.8, 134.0, 138.0, 139.0, 139.0, 139.1, GC-MS: m/z (%): t R min, 333 (M + -C 7 7, 4), 319 (M + -C 7 5, 67), 238 (11), 186 (24), 172 (10), 158 (9), 146 (79), 105 (58), 91 (100). Elemental analysis calcd (%) for C (424.58): C, 82.04;, 7.60;, 6.60; found C, 82.15;, 7.73;, Benzyl-1 -(2-chloroacetyl)-4,6 -dimethyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3g 3 C Cl 3 C Yelllow, viscous oil, 81 %. IR (neat): 1641 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 0.98 (1, t, J = 11.9 z, 3 -a), 1.27 (1, dd, J = 12.6, 2.4 z, 3-a), 1.34 (3, d, J = 6.8 z, 4 - ), 1.48 (1, dd, J = 12.8, 2.4 z, 5-a), 1.99 (1, td, J = 11.9, 2.4 z, 2-a), 2.15 (3, s, 6 - ), 2.30 (1, td, J = 12.0, 2.9 z, 2-e), 2.43 (1, dd, J = 12.9, 2.9 z, 3 -e), 2.73 (1, btd, J = 11.9, 1.6 z, 6-a), 2.79 (1, sp, J = 6.8 z, 4 -), 2.86 (1, td, J = 11.8, 2.2 z, 6-e), 3.18 (1, td, J = 12.7, 4.5 z, 3-e), 3.34 (1, td, J = 12.7, 4.2 z, 5-e), 3.51 (2, s, C 2 -Ph), 6.50 (1, d, J = 8.0 z, 7 -), 6.76 (1, bd, J = 7.6 z, 8 -), 6.88 (1, s, 5 -), (10, m, Bn and Bz ). 13 C-MR (100 Mz) δ (ppm): 17.2, 21.1, 28.5, 28.8, 35.8, 45.0, 50.3, 50.8, 60.9, 62.2, 123.4, 126.2, White crystals, mp o C, 89 %. IR (KBr): 1669 (ν - C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.10 (1, bs, 3 -a), 1.25 (4, d, J = 6.8 z, 4 - y 3-a), 1.45 (1, d, J = 12.3 z, 5-a), 2.12 (1, bs, 2-a), 2.23 (1, bs, 3 -e), 2.26 (3, s, 6 - ), 2.32 (1, ddd, J = 11.2, 9.2, 2.6 z, 2-e), 2.51 (1, dd, J = 11.7, 5.6 z, 6-a), 2.60 (1, bs, 6-e), 2.66 (1, st, J = 6.8 z, 4 -), 2.96 (1, bs, 3-e), 3.08 (1, bs, 5-e), 3.44 (2, s, C 2 -Ph), 3.92 (2, s, C 2 -Cl), 6.86 (1, d, J = 7.8 z, 7 -), 6.93 (1, d, J = 8.0 z, 8 -), 6.96 (1, s, 5 -), (5, m, Bn ). 13 C-MR (100 Mz) δ (ppm): 21.2 (2C), 29.1, 36.5, 44.4, 44.8, 50.1, 50.7, 62.1, 62.6, 125.2, 126.8, 126.9, (3C), (2C), 136.1, 136.6, 138.6, 140.4, GC-MS: m/z (%): t R min, 396 (M + for 35 Cl, 1), 359 (13), 319 (4), 305 (10), 269 (19), 228 (7), 214 (13), 186 (15), 172 (26), 158 (10), 146 (26), 134 (6), 117 (4), 91 (100). Elemental analysis calcd (%) for C (396.95): C, 72.62;, 7.36;, 7.06; found C; 72.55;, 7.49;, S167

5 Supplement: Intramolecular to acyl migration in conformationally mobile 1 -acyl-1-benzyl-3,4 -dihydro-1 -spiro[piperidine-4,2 -quinoline] systems promoted by debenzylation conditions (C 4 /Pd/C) 1-Benzyl-4,6 -dimethyl-1 -(4-nitrobenzoyl)-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3h 2 3 C range crystals, mp o C, 70 %. IR (KBr): 648 (ν - C= ), 1519, 1342 (ν 2 ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.00 (1, t, J = 12.4 z, 3 -a), 1.30 (1, dd, J = 12.5, 2.2 z, 3-a), 1.36 (3, d, J = 6.7 z, 4 - ), 1.51 (1, dd, J = 12.8, 2.3 z, 5-a), 1.99 (1, td, J = 11.9, 2.1 z, 2-a), 2.17 (3, s, 6 - ), 2.30 (1, ddd, J = 12.0, 9.2, 2.9 z, 2-e), 2.45 (1, dd, J = 12.9, 2.9 z, 3 -e), 2.73 (1, bd, J = 11.9 z, 2-e), 2.79 (1, sp, J = 6.6 z, 4 -), 2.87 (1, bdt, J = 11.7, 1.9 z, 6-e), 3.10 (1, td, J = 12.6, 4.4 z, 3-e), 3.30 (1, td, J = 12.0, 3.2 z, 5-e), 3.50 (2, s, C 2 -Ph), 6.24 (1, d, J = 8.0 z, 7 -), 6.50 (1, bd, J = 7.8 z, 8 -), 6.91 (1, s, 5 -), (10, m, Bn and Bz ). 13 C- MR (100 Mz) δ (ppm): 17.2, 21.1, 28.5, 28.8, 35.7, 44.6, 50.2, 50.8, 61.6, 62.3, (2C), 124.0, 126.5, 126.9, 127.4, (2C), (2C), (2C), 135.2, 136.9, 138.8, 139.5, 145.1, 148.0, GC-MS: m/z (%): t R min, 279 {M + -[(. )-(C )]}, 172 (24), 150 (12), 146 (20), 91 (100), 82 (58). Elemental analysis calcd (%) for C (469.58): C, 74.18;, 6.65;, 8.95; found C, 74.26;, 6.76;, Benzyl-1 -formyl-4 -methyl-6 -fluor-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3i F Colorless viscous oil, 90%. IR (neat): 1666 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.20 (1, bs, 3-a), 1.33 (3, d, J = 6.8 z, 4 - ), 1.47 (1, t, J = 11.8 z, 3 -a), 1.74 (1, bs, 5-a), 1.86 (1, bs, 2-a), 2.20 (1, bs, 2-e), 2.27 (1, bd, J = 12.7 z, 3 -e), 2.36 (1, td, J = 11.8, 2.8 z, 6-a), 2.48 (1, s, 6-e), 2.63 (1, bs, 3-e), 2.88 (1, bs, 4 ), 3.06 (1, bs, 5-e), 3.52 (2, s, C 2 -Ph), (8, m, Ar and Bn ), 8.60 (1, s, -C). 13 C-MR (100 Mz) δ (ppm): 18.6/20.9, 28.5/29.5, 33.5, 35.5/36.2, 42.5/43.2, 49.5/50.2, 57.0/59.8, 62.9, 113.1/112.1 (J = 12.0 z), 122.5, 127.2, 127.8, (2C), (3C), 130.5, 137.6/138.1, (d, J = z), 160.1/ GC-MS: m/z (%): t R min, 352 (M +, 0.5), 351 (1), 324 (50), 261 (17), 233 (9), 205 (6), 190 (23), 186 (18), 177 (16), 172 (5), 162 (14), 146 (39), 134 (12), 118 (7), 91 (100). Elemental analysis calcd (%) for C F 2 (352.45): C, 74.97;, 7.15;, 7.95; found C, 74.83;, 7.22;, Benzyl-1 -formyl-4,5,7 -trimethyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3k 3 C Yellow viscous oil, 90%. IR (neat): 1660 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.18 (3, d, J = 6.8 z, 4 - ), 1.27 (1, bs, z, 3-a), 1.44 (1, bs, 3 -a), 1.57 (1, bs, 5-a), 1.68 (1, dd, J = 13.6, 5.0 z, 2-a), 1.99 (1, bt, J = 10.8 z, 2-e), 2.15 (1, bt, J = 10.4 z, 6-a), 2.26 (3, s, 5 - ), 2.28 (3, s, 7 - ), (2, bs, 2-a, 3 -e), 2.54 (1, bs, 3-e), 2.63 (1, bs, 5-e), 3.08 (1, sp, J = 6.5 z, 4 -), 3.49 (2, s, C 2 -Ph), 6.83 (1, s, 8 -), 7.10 (1, s, 6 -), (5, m, Bn ), 8.58 (1, s, -C). 13 C-MR (100 Mz) δ (ppm): 18.8/19.1, 20.9/21.4, 23.1, 26.6/27.3, 33.6, 35.3/35.4, 43.2/44.7, 49.4/49.5, 56.9, 59.4/59.6, 63.0, 125.1, 126.9, 127.1, (2C), (2C), 129.4, 133.1, 134.8, 135.3, 138.1, 160.0/ GC-MS: m/z (%): t R min, 362 (M +, 1), 334 (50), 271 (7), 243 (6), 215 (10), 200 (44), 186 (19), 172 (22), 158 (16), 146 (51), 91 (100). Elemental analysis calcd (%) for C (362.51): C, 79.52;, 8.34;, 7.73; found C, 79.45;, 8.55;, Benzyl-1 -(2-chloroacetyl)-4,5,7 -trimethyl-3,4 dihydrospiro[piperidine-4,2 -quinoline] 3l 3 C Cl White crystals, mp o C, 79 %. IR (KBr): 1668 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.13 (1, ddd, J = 13.6, 11.6, 3.0 z, 3-a), 1.19 (3, d, J = 7.2 z, 4 - ), 1.57 (1, bs, 3 -a), 1.78 (1, ddd, J = 13.6, 11.2, 3.2 z, 5-a), 1.91 (1, dd, J = 13.9, 8.6 z, 2-e), 2.11 (1, dd, J = 13.9, 3.8 z, 2-a), 2.18 (1, t, J = 9.4 z, 6-a), 2.27 (3, s, 5 - ), 2.29 (3, s, 7 - ), 2.32 (1, bs, 3 -e), 2.58 (1, td, J = 10.4, 2.4 z, 6-e), 2.67 (1, bs, 3-e), 3.10 (1, st, J = 7.4 z, 4 -), 3.35 (1, dt, J = 13.5, 2.8 z, 5-e), 3.48 (2, s, C 2 - Ph), 3.86 (1, d, J = 13.4 z, C A -Cl), 4.20 (1, d, J = S168

6 L. Y. Vargas Méndez, V. V. Kouznetsov Supplementary Figure 2. 1 MR spectrum of 1-benzyl-1 -formyl-4,5,7 -trimethyl-3,4 -dihydrospiro[piperidine-4,2 -quinoline] 3k. Supplementary Figure 3. CSY experiment of 1-benzyl-1 -benzoyl-4 -methyl-3,4 -dihydrospiro[piperidine-4,2 -quinoline] 3c (aliphatic zone) z, C B -Cl), 6.74 (1, s, 8 -), 6.91 (1, s, 6 -), (5, m, Bn ). 13 C-MR (100 Mz) δ (ppm): 18.7, 20.8, 22.4, 27.4, 35.3, 36.7, 42.8, 45.1, 49.6, 51.1, 62.5, 63.0, 125.1, 126.8, (2C), (2C), 130.2, 135.1, 135.8, 136.0, 138.6, 138.6, GC-MS: m/z (%): t R min, 410 (0), 409 (0.3), 373 (27), 333 (4), 319 (9), 283 (21), 242 (5), 224 (22), 200 (11), 186 (14), 172 (35), 158 (6), 146 (42), 91 (100). Elemental analysis calcd (%) for C (410.98): C, 73.06;, 7.60;, 6.82; found C, 73.23;, 7.78;, Typical Experimental Procedure for synthesis of 1-acyl -3,4 -dihydro-1 -spiro[piperidine- 4,2 -quinolines] 4a-k. A mixture of compound 3 (1.00 mmol), C 4 (315.3 mg, 5.00 mmol) and 2.5 % molar amounts of 10% Pd/C was refluxed in methanol (20 ml) for 7-15 min. The reaction mixture was filtered and the solvent was taken off. Crude products 4 were purified by alumina column chromatography 1-Formyl-4 -methyl-3,4 -dihydrospiro[piperidine-4,2 - (1 -)quinoline] 4a White crystals, mp o C, 93 %. IR (KBr): 3388 (ν ), 1676 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.35 (3, d, J = 6.7 z, 4 - ), 1.44 (1, td, J = 12.8, 2.2 z, 3 -a), (4, m, 3(5)-), 1.94 (1, ddd, J = 13.2, 9.2, 5.5 z, 3 -e), 2.92 (1, st, J = 6.3 z, 4 -), (3, m, 2-a and 6-), 3.74 [1: 3.66 (½, dt, J = 13.9, 5.3 z, for rotamer A), 3.80 (½, dt, J = 14.0, 5.8 z, for rotamer B), 2-e], 3.99 (1, bs, -), 6.53 (1, ddd, J = 8.0, 2.2, 1.1 z, 8 -), 6.69 (1, t, J = 7.5 z, 6 -), 7.00 (1, t, J = 7.3 z, 7 -), 7.16 (1, S169

7 Supplement: Intramolecular to acyl migration in conformationally mobile 1 -acyl-1-benzyl-3,4 -dihydro-1 -spiro[piperidine-4,2 -quinoline] systems promoted by debenzylation conditions (C 4 /Pd/C) Supplementary Figure 4. 1 MR spectrum of -formyl piperidine derivative 4a. d, J = 7.7 z, 5 -), 8.04/8.05 (1, s, -C=). 13 C-MR (100 Mz) δ (ppm): 20.2/20.2, 26.5/26.6, 34.5/35.6, 35.7, 38.0/39.4, 41.7/41.5, 41.8/41.9, 50.0/50.0, 114.5, 117.5/117.6, 125.4/125.5, 126.9/126.9 (2C), 142.5, 160.6/ GC-MS: m/z (%): t R min, 244 (M +, 98), 229 (29), 215 (13), 207 (6), 201 (12), 172 (63), 159 (75), 156 (81), 144 (100), 130 (21), 115 (14), 103 (6), 91 (13), 77 (16), 58 (20). ). Elemental analysis calcd (%) for C (244.33): C, 73.74;, 8.25;, 11.47; found C, 73.95;, 8.43;, (2C), 142.6, 168.8/ GC-MS: m/z (%): t R min, 258 (M +, 61), 243 (25), 215 (14), 172 (83), 159 (17), 156 (100), 144 (54), 130 (12), 117 (8), 91 (7), 56 (15). Elemental analysis calcd (%) for C (258.36): C, 74.38;, 8.58;, 10.84; found C, 74.45;, 8.69;, Benzoyl-4 -methyl-3,4 -dihydrospiro[piperidine-4,2 - (1 -)quinoline] 4c 1-Acetyl-4 -methyl-3,4 -dihydrospiro[piperidine-4,2 - (1 -)quinoline] 4b White crystals, mp o C, 91 %. IR (KBr): 3348 (ν ), 1623 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.35 (3, d, J = 6.7 z, 4 - ), 1.43 (1, t, J = 12.7 z, 3 -a), (4, m, 3(5)-), 1.90 (1, td, J = 12.6, 5.5 z, 3 -e), 2.10/2.12 (3, s, - C), 2.92 (1, st, J = 6.4 z, 4 -), (3, m, 2-a and 6-), 3.86 [1: 3.79 (½, dt, J = 13.9, 5.3 z, for rotamer A), 3.94 (½, dt, J = 14.3, 5.5 z, for rotamer B), 2-e], 3.98 (1, bs, -), 6.52 (1, d, J = 8.0 z, 8 -), 6.68 (1, t, J = 7.5 z, 6 -), 6.99 (1, t, J = 7.6 z, 7 -), 7.16 (1, d, J = 7.6 z, 5 -). 13 C- MR (100 Mz) δ (ppm): 20.2/20.2, 21.4, 26.5/26.6, 34.9/35.7, 37.3/37.5, 38.4/39.4, 41.7/41.9, 42.4/42.4, 49.2/49.3, 114.4/114.4, 117.3/117.4, 124.6/125.5, Yellowish crystals, mp o C, 90 %. IR (KBr): 3437 (ν ), 1645 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.20 (1, t, J = 12.4 z, 3 -a), 1.45 (3, d, J = 6.8 z, 4 - ), 1.57 (1, d, J = 13.4 z, 3-a), 1.79 (1, d, J = 13.3 z, 5-a), 2.55 (1, dd, J = 13.0, 3.3 z, 3 -e), 2.82 (1, td, J = 12.8, 2.7 z, 3-e), 2.91 (1, st, J = 6.6 z, 4 -), 3.14 (1, td, J = 12.2, 2.7 z, 5-e), (2, m, 2(6)-a), 3.35 (1, bt, J = 13.2 z, 2-e), 3.43 (1, bt, J = 12.8 z, 6-e), 4.50 (1, s, -), 6.50 (1, d, J = 7.3 z, 8 -), 6.77 (1, t, J = 7.7 z, 6 -), 7.00 (1, t, J = 7.5 z, 7 -), (6, m, 5 - and Bz ). 13 C-MR (100 Mz) δ (ppm): 17.1/17.3, 28.0/28.3, 28.7/28.9, 35.4, 42.5, 42.7, 44.9, 59.9/61.3, 122.5/123.0, 124.3/124.8, 125.6/125.8, 127.6, 127.7/127.8 (2C), 128.9/129.0 (2C), 129.0/130.1, 138.3, 138.9, 139.9, 171.8/ GC-MS: m/z (%): t R min, 320 (M +, 47), 305 (12), 215 (8), 201 (16), 172 (100), 159 (20), 156 (46), 144 (44), 130 (10), 105 (90), S170

8 L. Y. Vargas Méndez, V. V. Kouznetsov 77 (74). Elemental analysis calcd (%) for C (320.43): C, 78.71;, 7.55;, 8.74; found C, 78.57;, 7.74;, Formyl-4 6 -dimethyl-3,4 -dihydrospiro[piperidine- 4,2 -(1 -)quinoline] 4d 3 C White crystals, mp o C, 91 %. IR (KBr): 3394 (ν ), 1679 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.34 (3, d, J = 6.7 z, 4 - ), 1.43 (1, td, J = 11.2, 1.7 z, 3 -a), (4, m, 3(5)-), 1.92 (1, ddd, J = 13.2, 9.2, 5.7 z, 3 -e), 2.24 (3, s, 6 - ), 2.90 (1, st, J = 6.2 z, 4 -), (3, m, 2-a and 6-), (2, m, 2-e and -), 6.46 (1, dd, J = 8.0, 2.2 z, 7 -), 6.82 (1, d, J = 8.0 z, 8 -), 6.98 (1, s, 5 -), 8.05/8.03 (1, s, -C). 13 C- MR (100 Mz) δ (ppm): 20.4/20.4, 20.6, 26.6/26.7, 34.1/35.4, 35.6/35.8, 38.0/39.5, 41.8/41.9, 42.0/42.0, 50.0/50.1, 114.8, 125.5/125.6, 126.8/126.9, 127.5/127.6, 127.6/127.6, 140.1, 160.7/ GC-MS: m/z (%): t R min, 258 (M +, 100), 243 (27), 229 (8), 215 (7), 186 (47), 173 (70), 170 (82), 158 (74), 143 (17), 132 (6), 115 (10). Elemental analysis calcd (%) for C (258.36): C, 74.38;, 8.58;, 10.84; found C, 74.55;, 8.41;, Acetyl-4 6 -dimethyl-3,4 -dihydrospiro[piperidine- 4,2 -(1 -)quinoline] 4e 3 C White crystals, mp o C, 88 %. IR (KBr): 3354 (ν ), 1635 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.34 (3, d, J = 6.7 z, 4 - ), 1.42 (1, t, J = 12.6 z, 3 -a), (4, m, 3(5)-), (1, m, 3 -e), 2.10/2.11 (3, s, -C), 2.24 (3, s, 6 - ), 2.89 (1, st, J = 6.5 z, 4 -), (3, m, 2-a and 6-), (2, m, 2-e and -), 6.45 (1, dd, J = 8.1, 1.8 z, 7 -), 6.82 (1, d, J = 8.0 z, 8 -), 6.98 (1, s, 5 -). 13 C-MR (100 Mz) δ (ppm): 20.4/20.5 (4 - ), 20.6 (6 - ), 21.5 ( -C), 26.6/26.7 (4 -C), 34.6/35.4 (3-C), 37.4/37.6 (2-C), 38.5/39.4 (5-C), 42.0/42.3 (3 -C), 42.4/42.5 (6-C), 49.2/49.3 (C-spiro), 114.7/114.8 (7 -C), 125.6/125.7 (4 a-c), 126.6/126.8 (8 a-c), 127.5/127.6 (2C, 5 (8 )-C), (6 -C), 168.9/168.9 (C=). GC-MS: m/z (%): t R min, 272 (M +, 67), 257 (22), 229 (12), 186 (76), 185 (95), 173 (17), 170 (100), 158 (44), 143 (15), 134 (6), 56 (13). Elemental analysis calcd (%) for C (272.39): C, 74.96;, 8.88;, 10.28; found C, 74.78;, 8.95;, Benzoyl-4,6 -dimethyl-3,4 -dihydrospiro[piperidine- 4,2 -(1 -)quinoline] 4f 3 C Yellowish crystals, mp o C, 75 %. IR (KBr): 3420 (ν ), 1641 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.27 (1, t, J = 12.6 z, 3 -a), 1.43 (3, d, J = 6.8 z, 4 - ), 1.66 (1, d, J = 13.9 z, 3-a), 1.88 (1, dd, J = 11.6, 4.1 z, 5-a), 2.23 (3, s, 6 - ), 2.47 (1, dd, J = 13.1, 3.7 z, 3 -e), 2.88 (1, bst, J = 6.2 z, 4 -), 3.01 (1, t, J = 14.0 z, 3-e), (3, m, 5-e and 2(6)-a), (2, m, 2(6)-e), 5.60 (1, s, -), 6.36 (1, d, J = 8.0 z, 8 -), 6.57 (1, d, J = 8.0 z, 7 -), 6.97 (1, s, 5 -), (5, m, Bz ). 13 C-MR (100 Mz) δ (ppm): 17.1/17.6, 21.0, 27.3/27.6, 28.7/28.8, 33.5/34.8, 41.8/41.9, 44.8/44.9, 48.2/48.6, 59.1/60.7, 123.4/124.1, 126.2/126.5, 127.3/127.4, 127/ (2C), 128.8/128.9 (2C), 129.8/130.0, 134.0/134.8, 137.0/137.7, 138.1/138.2, 138.8/138.9, 171.6/ GC-MS: m/z (%): t R min, 334 (M +, 48), 319 (8), 229 (6), 215 (13), 186 (90), 173 (30), 170 (52), 158 (44), 143 (17), 105 (100), 91 (6), 77 (74), 56 (15), 51 (15). Elemental analysis calcd (%) for C (334.46): C, 79.00;, 7.84;, 8.38; found C, 79.18;, 7.74; (4-Aminobenzoyl)-4,6 -dimethyl-3,4 dihydrospiro[piperidine-4,2 -(1 -)quinoline] 4g 3 C 2 Yellowish crystals, mp o C, 92 %. IR (KBr): 3471, 3338, 3212 (ν y ν 2 ), 1622 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.09 (1, t, J = 12.4 z, 3 - a), 1.42 (4, d, J = 6.7 z, 4 - and 3-a), 1.62 (1, d, J = 13.2 z, 5-a), 2.24 (3, s, 6 - ), 2.48 (1, dd, J = 12.9, 2.8 z, 3 -e), 2.61 (1, td, J = 12.6, 2.6 z, 3-e), (1, bs, 4 -), 2.97 (1, td, J = 12.1, 2.8 z, 5-e), (4, m, 2(6)-), 3.54 (3, bs, S171

9 Supplement: Intramolecular to acyl migration in conformationally mobile 1 -acyl-1-benzyl-3,4 -dihydro-1 -spiro[piperidine-4,2 -quinoline] systems promoted by debenzylation conditions (C 4 /Pd/C) Supplementary Figure 5. MBC experiment for compound 4d. Supplementary Figure 6. VT- 1 MR (CDCl 3 ) for 4e. S172

10 L. Y. Vargas Méndez, V. V. Kouznetsov Supplementary Figure 7. VT- 1 MR (acetone-d6) for 4e. Supplementary Figure 8. Gated decoupling 13 C MR experiment (T = 25ºC, sequence delay time: 20 s, number of sequences: 1024) of compound 4e. S173

11 Supplement: Intramolecular to acyl migration in conformationally mobile 1 -acyl-1-benzyl-3,4 -dihydro-1 -spiro[piperidine-4,2 -quinoline] systems promoted by debenzylation conditions (C 4 /Pd/C) - and 2 ), 6.38 (2, d, J = 8.6 z, 3(5)- Bz ), 6.43 (1, d, J = 8.0 z, 8 -), 6.62 (1, bd, J = 7.8 z, 7 -), 6.95 (1, s, 5 -), 7.08 (2, d, J = 8.4 z, 2(6)- Bz ). 13 C- MR (100 Mz) δ (ppm): 17.1, 21.1, 28.8, 29.1, 36.7, 42.9, 43.2, 45.2, 59.8, (2C), 123.3, 126.4, 127.1, 128.0, (2C), 133.6, 138.4, 138.5, 148.4, GC-MS: m/z (%): t R min, 349 (M +, 8), 229 (41), 201 (3), 186 (13), 185 (16), 174 (14), 173 (5), 170 (5), 158 (9), 120 (100), 92 (17). Elemental analysis calcd (%) for C (349.47): C, 75.61;, 7.79;, 12.02; found C, 75.85;, 7.60;, Fluoro-1-formyl-4 -methyl-3,4 dihydrospiro[piperidine-4,2 -(1 -)quinoline] 4h 26.9/26.9, 34.2/35.5, 35.6/35.8, 38.0/39.5, 41.2/41.4, 41.9/41.9, 50.1/50.2, (d, J = 22.2 z), (d, J = 22.3 z), (d, J = 7.6 z), 127.0/127.1 (d, J = 6.3 z), 138.7/138.7, 156.0/156.0 (d, J = z), 160.7/ GC-MS: m/z (%): t R min, 262 (100), 247 (33), 233 (11), 219 (10), 190 (69), 177 (82), 174 (98), 162 (97), 148 (21), 135 (11), 58 (18). Elemental analysis calcd (%) for C F 2 (262.32): C, 68.68;, 7.30;, 10.68; found C, 68.85; 7.48;, Formyl-4,5,7 -trimethyl-3,4 dihydrospiro[piperidine-4,2 -(1 -)quinoline] 4i 3 C F White crystals, mp o C, 97 %. IR (KBr): 3343 (ν ), 1665 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.33 (3, d, J = 6.7 z, 4 - ), 1.41 (1, td, J = 13.4, 1.5 z, 3 -a), (4, m, 3(5)-), 1.94 (1, ddd, J = 13.5, 9.0, 5.7 z, 3 -e), 2.90 (1, st, J = 6.3 z, 4 -), (3, m, 2-a and 6-), (2, m, J = 2-e and -), 6.45 (1, ddd, J = 8.8, 4.8, 2.6 z, 8 -), 6.72 (1, td, J = 8.4, 2.7 z, 7 -), 6.88 (1, dd, J = 10.0, 2.7 z, 5 -), 8.04/8.05 (1, s, -C). 13 C-MR (100 Mz) δ (ppm): 20.2/20.3, Colorless crystals, mp o C, 98 %. IR (KBr): 3343 (ν ), 1669 (ν -C= ) cm MR (CDCl 3, 400 Mz) δ (ppm): 1.29 (3, d, J = 7.0 z, 4 - ), (5, m, 3 -a and 3(5)-), 1.96 [1, dd, J = 7.1, 3.7 z, 3 -e], 2.19 (3, s, 7 - ), 2.25 (3, s, 5 - ), 3.08 (1, st, J = 6.8 z, 4 -), (3, m, 2-a and 6-), (1, m, 2-e), 3.78 (1, bs, -), 6.25 (1, s, 8 -), 6.40 (1, s, 6 -), 8.03/8.04 (1, s, -C). 13 C-MR (100 Mz) δ (ppm): 19.6/19.7, 20.8, 21.7/21.7, 26.7/26.8, 35.8/36.1, 36.4/37.3, 37.6/38.9, 41.7/41.9, 42.0/42.3, 50.1/50.2, 113.6/113.7, 121.6/121.7, 122.3/122.5, Supplementary Figure 9. MBC experiment for compound 4e. S174

12 L. Y. Vargas Méndez, V. V. Kouznetsov Supplementary Figure 10. Results of crossover experiment for a mixture of an acetamide 3b and a formamide 3i /136.1, 136.6, 142.4/142.5, 160.7/ GC-MS: m/z (%): t R min, 272 (M +, 82), 257 (31), 243 (10), 229 (13), 200 (52), 187 (77), 184 (100), 172 (90), 157 (28), 115 (10), 56 (8). Elemental analysis calcd (%) for C (272.38): C, 74.96;, 8.88;, 10.28; found C, 74.79;, 8.75;, Acetyl-4,5,7 -trimethyl-3,4 -dihydrospiro[piperidine- 4,2 -(1 -)quinoline] 4k 3 C White crystals, mp ºC, 100%. IR (KBr): 3405 (ν), 1657 (ν-c=) cm C-MR (100 Mz) δ (ppm): 19.6, 21.1, 21.6, 21.8, 22.9, 32.7 (2C), 39.9 (2C), 55.4, 110.1, 122.5, 122.7, 134.3, 136.3, 145.5, GC-MS: m/z (%): t R min, 286 (M +, 40), 271 (16), 243 (10), 200 (54), 187 (8), 184 (100), 172 (29), 157 (14), 115 (5), 56 (8). Elemental analysis calcd (%) for C (286.41): C, 75.48;, 9.15;, 9.78; found C, 75.33;, 9.22;, S175