One-pot Synthesis of 1-Alkyl-1H-indazoles. Supporting Information

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One-pot Synthesis of 1-Alkyl-1H-indazoles from 1,1-Dialkylhydrazones via Aryne Annulation ataliya A. Markina, Anton V. Dubrovskiy, and Richard C. Larock* Department of Chemistry, Iowa State University, Ames, IA, 50011, USA larock@iastate.edu Supporting Information Table of contents General procedure for the synthesis of,-dialkylhydrazones S2 Fluorohydrazone 7a S5 Characterization data for indazoles prepared via CS chlorination S6 General procedure for the preparation of 2-acetyl-1-methylindazolines S12 Characterization data for indazoles prepared via anion trap/deprotection S14 Procedure for the preparation of 1-benzyl-3-phenyl-1H-indazole S16 Copies of 1 H and 13 C MR spectra ( 19 F MR data for 7a ) S17-S80 OE data for compound 15l S81-S82 Copies of GC/MS spectra for crude 7a and 15a S83-84 S1

General procedure for the preparation of hydrazones 6 The starting hydrazones were prepared according to the procedure described in our recent communication. 1 The characterization of hydrazones 6a-6c, 6g, 6h, 6j-6m, 6p and 6r can be found therein. (E)-Methyl 4-[(2,2-dimethylhydrazono)methyl]benzoate 2 (6d) MeO 2 C Compound 6d was obtained as a colorless solid in a 96% yield: M. P. 65-66 C; 1 H MR (400 MHz, CDCl 3 ) δ 2.97 (s, 6H), 3.85 (s, 3H), 7.09 (s, 1H), 7.55 (d, J = 8.5 Hz, 2H), 7.94 (d, J = 8.5 Hz, 2H); 13 C MR (100 MHz, CDCl 3 ) δ 42.55, 51.93, 124.99, 128.02, 129.63, 129.83, 141.55, 167.00; MS (EI) m/z (%) 206 (M +, 97%), 163 (59%), 130 (100%), 102 (46%), 76 (23%), 44 (21%). IR (CH 2 Cl 2, cm -1 ) 2953 (w), 1716 (s), 1581 (m), 1550 (m). (E)-4-[(2,2-dimethylhydrazono)methyl]benzonitrile 2 (6e) C Compound 6e was obtained as a colorless solid in a 92% yield: M. P. 141-143 C; 1 H MR (300 MHz, CDCl 3 ) δ 3.04 (s, 6H), 7.05 (s, 1H), 7.50-7.61 (m, 4H); 13 C MR (75 MHz, CDCl 3 ) δ 42.63, 109.38, 119.58, 125.51, 128.06, 132.37, 141.75. MS (EI) m/z (%) 173 (M +, 100%), 158 (24%), 128 (67%), 42 (21%); IR (CH 2 Cl 2, cm -1 ) 2866 (w), 2223 (s), 1576 (s), 1545 (s), 1054 (s). 1 A. V. Dubrovskiy, R. C. Larock, Org. Lett. 2011, 13, 4136. 2 M. Giurg, J. Mlochowski, A. Ambrozak, Polish J. Chem. 2002, 76, 1713. S2

4-Ethynylbenzaldehyde dimethylhydrazone (6f) Compound 6f was obtained as a light yellow solid in a 94% yield: M. P. 79-80 C; 1 H MR (300 MHz, CDCl 3 ) δ 3.00 (s, 6H), 3.10 (s, 1H), 7.16 (s, 1H), 7.40-7.47 (m, 2H), 7.47-7.53 (m, 2H); 13 C MR (75 MHz, CDCl 3 ) δ 42.90, 77.63, 84.26, 120.52, 125.42, 131.07, 132.50, 137.68; MS (EI) m/z (%) 172 (M +, 100%); HRMS (ESI) calcd for [M+H] + C 11 H 13 2 173.1073, found 172.1000; IR (CH 2 Cl 2, cm -1 ) 3295 (s), 2863 (w), 2105 (w), 1578 (s), 1546 (m), 1040 (s). Thiophene-2-carbaldehyde dimethylhydrazone 3 (6i) S Compound 6i was obtained as a green liquid in a 99% yield: 1 H MR (400 MHz, CDCl 3 ) δ 2.94 (s, 6H), 6.94-7.02 (m, 2H), 7.13 (d, J = 4.9 Hz, 1H), 7.42 (s, 1H); 13 C MR (75 MHz, CDCl 3 ) δ 43.04, 124.25, 124.72, 127.19, 128.00, 142.83; MS (EI) m/z (%) 154 (M +, 100%), 109 (27%); IR (neat, cm -1 ) 3084 (doublet, w), 2854 (m), 1570 (m), 1034 (m), 699 (m). (E)--Benzylidenepiperidin-1-amine 4 (6n) Compound 6n was obtained as a colorless solid in a 72% yield: M. P. 69-70 C; 1 H MR (400 MHz, CDCl 3 ) δ 1.57 (ddt, J = 11.7, 8.4, 4.8 Hz, 2H), 1.78 (p, J = 5.9 Hz, 4H), 3.10-3.30 (m, 4H), 7.28 (t, J = 7.3 Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H), 7.57 (s, 1H), 7.59-7.71 (m, 2H); 13 C MR (75 MHz, CDCl 3 ) δ 24.12, 25.16, 51.99, 125.89, 127.65, 128.38, 134.26, 3 D. Perdicchia, E. Licandro, S. Maiorana, C. Baldoli, C. Giannini, Tetrahedron 2003, 59, 7733. 4 H. Bohme, S. Ebel, Chem. Ber. 1965, 98, 1819. S3

136.74; MS (EI) m/z (%) 188 (M +, 100%), 131 (22%), 103 (26%), 77 (18%); IR (CH 2 Cl 2, cm -1 ) 2939 (m), 2856 (m), 1592 (m), 1565 (m), 1363 (m), 1087 (m), 992 (m). Dihydrocinnamaldehyde dimethylhydrazone 5 (6o) Compound 6o was obtained as a light yellow liquid in a 74% yield: 1 H MR (400 MHz, CDCl 3 ) δ 2.56 (q, J = 7.2, 6.6 Hz, 2H), 2.73 (s, 6H), 2.82 (t, J = 7.8 Hz, 2H), 6.67 (d, J = 5.5 Hz, 1H), 7.20 (dd, J = 12.4, 6.5 Hz, 3H), 7.29 (t, J = 7.5 Hz, 2H); 13 C MR (100 MHz, CDCl 3 ) δ 34.31, 34.96, 43.51, 126.07, 128.53, 128.61, 138.31, 141.61; MS (EI) m/z (%) 176 (M +, 15%), 91 (30%), 85 (100%), 44 (19%); IR (neat, cm -1 ) 3061 (w), 2952 (s), 2852 (s), 1603 (m), 1496 (s), 1029 (s), 699 (s). 2,4,6-Trimethoxybenzaldehyde dimethylhydrazone (6q) MeO OMe OMe Compound 6q was obtained as a light brown liquid in a 94% yield: 1 H MR (400 MHz, CDCl 3 ) δ 2.87 (s, 6H), 3.76 (s, 3H), 3.83 (d, J = 5.1 Hz, 6H), 6.42 (s, 1H), 7.37 (s, 1H), 7.53 (s, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 43.11, 55.94, 56.15, 56.55, 97.34, 107.51, 117.37, 129.41, 143.51, 149.36, 151.23; MS (EI) m/z (%) 238 (M +, 81%), 193 (93%), 179 (100%), 164 (25%), 151 (34%), 121 (23%), 44 (49%); HRMS (ESI) calcd for [M+H] + C 12 H 19 2 O 3 239.139, found 238.1317; IR (neat, cm -1 ) 3005 (w), 2941 (m), 2839 (m), 1676 (w), 1592 (s), 1468 (m), 1126 (s). 5 S. Denmark, J. P. Edwards, T. weber, D. W. Piotrowski, Tetrahedron Asymmetry 2010, 21, 1278 S4

(E)-Ethyl 2-(2,2-dimethylhydrazono)acetate 6 (6s) O EtO Compound 6s was obtained as a yellow liquid in a 69% yield: 1 H MR (400 MHz, CDCl 3 ) δ 1.28 (t, J = 7.1 Hz, 3H), 3.09 (s, 6H), 4.22 (q, J = 7.1 Hz, 2H), 6.35 (s, 1H); 13 C MR (75 MHz, CDCl 3 ) δ 14.42, 42.50, 60.15, 117.37, 165.08; MS (EI) m/z (%) 144 (M +, 77%), 99 (34%), 71 (45%), 44 (100%); IR (neat, cm -1 ) 2981 (m), 1720 (s), 1545 (s), 1273 (s), 1184 (s), 1083 (s), 837 (m). Benzaldehyde dibenzylhydrazone 7 (6t) Compound 6t was obtained as a colorless solid in an 85% yield: M. P. 84-86 C; 1 H MR (400 MHz, CDCl 3 ) δ 4.57 (s, 4H), 6.61-7.49 (m, 14H), 7.55 (d, J = 7.3 Hz, 2H); 13 C MR (100 MHz, CDCl 3 ) δ 58.09, 125.73, 127.36, 127.82, 128.58, 128.72, 128.73, 131.98, 137.10, 137.76; MS (EI) m/z (%) 300 (M +, 47%), 181 (14%), 166 (13%), 103 (15%), 91 (100%); IR (CH 2 Cl 2, cm -1 ) 3086 (w), 3029 (m), 2845 (w), 1589 (s), 1562 (s), 1494 (s), 1452 (s), 1129 (m). Data for the crude ','-dimethylbenzohydrazonoyl fluoride (7a ) F 6 T. Hoffman, Helv. Chim. Acta 1997, 80, 1843. 7 P.. Anderson, J. T. Sharp, J. Chem. Soc. Perkin Trans. 1 1984, 2855. S5

1 H MR (400 MHz, CD 3 C) δ 2.83 (s, 6H), 7.44 (m, 3H), 7.73 (d, J = 7.9 Hz, 2H) (succinimide peak: δ 2.60); 19 F MR (400 MHz, CD 3 C) δ -66.6; MS (EI) m/z (%) 166 (M +, 100%), 103 (20%), 77 (19%), 42 (21%); HRMS (ESI) calcd for [M+H] + C 9 H 12 F 2 167.0907, found 167.0975. Characterization data for indazoles 15 prepared via CS-chlorination. 1-Methyl-3-(naphthalen-2-yl)-1H-indazole (15b) H 3 C Product 15b was isolated as a yellow oil in a 76% yield: 1 H MR (400 MHz, CDCl 3 ) δ 4.19 (s, 3H), 7.27 (ddd, J = 7.7, 5.2, 2.0 Hz, 1H), 7.46 (d, J = 5.2 Hz, 2H), 7.53 (td, J = 5.2, 4.6, 2.1 Hz, 2H), 7.90 (d, J = 8.6 Hz, 1H), 7.98 (t, J = 7.9 Hz, 2H), 8.17 (d, J = 8.4 Hz, 2H), 8.44 (s, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 35.81, 109.47, 121.25, 121.61, 121.95, 125.67, 126.19, 126.45, 126.52, 127.94, 128.42, 128.65, 131.37, 133.14, 133.82, 141.69, 143.73; MS (EI) m/z (%) 258 (M +, 100%); HRMS (EI) calcd for [M+H] + C 15 H 15 2 O 259.123, found 259.1234; IR (CH 2 Cl 2, cm -1 ) 2937 (m), 1615 (s), 1494 (m). 3-(4-Methoxyphenyl)-1-methyl-1H-indazole (15c) H 3 C OCH 3 Product 15c was isolated as a yellow oil in a 72% yield: 1 H MR (400 MHz, CDCl 3 ) δ 3.88 (s, 3H), 4.11 (s, 3H), 7.05 (dd, J = 9.0, 2.2 Hz, 2H), 7.20 (ddd, J = 7.9, 5.5, 2.3 Hz, 1H), 7.41 (d, J = 5.4 Hz, 2H), 7.90 (dd, J = 9.0, 2.2 Hz, 2H), 7.99 (d, J = 8.2 Hz, 1H); 13 C S6

MR (100 MHz, CDCl 3 ) δ 35.66, 55.53, 109.29, 114.42, 120.83, 121.52, 121.64, 126.38, 126.50, 128.74, 141.53, 143.73, 159.55; MS (EI) m/z (%) 238 (M +, 100%), 223 (61%), 195 (22%); HRMS (EI) calcd for [M+H] + C 15 H 15 2 O 239.1179, found 239.1179; IR (CH 2 Cl 2, cm -1 ) 3007 (w), 2938 (m), 2838 (m), 1614 (s), 1530 (s), 1035 (s). Methyl 4-(1-methyl-1H-indazol-3-yl)benzoate (15d) H 3 C CO 2 Me Product 15d was isolated as a yellow solid in a 59% yield: M. P. 117-121 C; 1 H MR (400 MHz, CDCl 3 ) δ 3.95 (s, 3H), 4.14 (s, 3H), 7.25 (dt, J = 8.1, 4.2 Hz, 1H), 7.44 (d, J = 3.5 Hz, 2H), 8.04 (dd, J = 11.3, 8.5 Hz, 3H), 8.16 (d, J = 8.5 Hz, 2H); 13 C MR (100 MHz, CDCl 3 ) δ 35.91, 52.34, 109.61, 121.29, 121.65, 121.82, 126.63, 127.12, 129.24, 130.30, 138.38, 141.68, 142.57, 167.17; MS (EI) m/z (%) 266 (M +, 100%), 235 (61%), 208 (12%), 192 (13%); HRMS (EI) calcd for [M+H] + C 16 H 15 2 O 2 267.1128, found 267.1133; IR (CH 2 Cl 2, cm -1 ) 2951 (m), 1720 (s), 1611 (s), 1114 (s). 4-(1-Methyl-1H-indazol-3-yl)benzonitrile (15e) H 3 C C Product 15e was isolated as a light yellow solid in a 45% yield: M. P. 144-147 C; 1 H MR (400 MHz, CDCl 3 ) δ 4.15 (s, 3H), 7.25-7.30 (m, 1H), 7.46 (d, J = 3.6 Hz, 2H), 7.74-7.79 (m, 2H), 7.99 (d, J = 8.3 Hz, 1H), 8.09 (d, J = 8.5 Hz, 2H); 13 C MR (100 MHz, CDCl 3 ) δ 36.02, 109.82, 111.08, 119.26, 120.96, 121.68, 122.02, 126.81, 127.63, 132.79, S7

132.96, 138.50, 141.61, 141.76 (the latter peak possibly appears due to the conformational restriction at the C-3 carbon of the indazole); MS (EI) m/z (%) 233 (M +, 100%); HRMS (EI) calcd for [M+H] + C 15 H 12 3 234.1026, found 234.1025; IR (CH 2 Cl 2, cm -1 ) 2941 (w), 2228 (s), 1610 (s). 3-(4-Ethynylphenyl)-1-methyl-1H-indazole (15f) H 3 C Product 15f was isolated as a yellow solid in a 67% yield: M. P. 106-108 C; 1 H MR (400 MHz, CDCl 3 ) δ 3.16 (s, 1H), 4.13 (s, 3H), 7.18-7.28 (m, 1H), 7.43 (s, 2H), 7.63 (d, J = 8.2 Hz, 2H), 7.95 (d, J = 8.2 Hz, 2H), 8.00 (d, J = 8.2 Hz, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 35.84, 78.04, 83.91, 109.53, 115.50, 121.33, 121.42, 121.70, 126.57, 127.20, 132.76, 134.36, 141.63, 142.87; MS (EI) m/z (%) 232 (M +, 100%); HRMS (EI) calcd for [M+H] + C 16 H 13 2 233.1073, found 233.1078; IR (CH 2 Cl 2, cm -1 ) 3296 (s), 2940 (w), 2107 (w), 1615 (m), 1493 (m). 3-(2-Bromophenyl)-1-methyl-1H-indazole (15g) H 3 C Br Product 15g was isolated as a yellow oil in a 65% yield: 1 H MR (400 MHz, CDCl 3 ) δ 4.15 (s, 3H), 7.18 (ddd, J = 7.8, 5.6, 2.1 Hz, 1H), 7.30 (td, J = 7.7, 1.7 Hz, 1H), 7.38-7.48 (m, 3H), 7.55 (dd, J = 7.6, 1.7 Hz, 1H), 7.68 (d, J = 8.2 Hz, 1H), 7.72-7.77 (m, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 35.86, 109.31, 120.76, 122.13, 122.66, 123.54, 126.49, 127.47, 129.91, 132.61, 133.46, 134.54, 140.78, 143.93; MS (EI) m/z (%) 288 ([M+2] +, 90%), 286 S8

(M +, 100%), 206 (15%); HRMS (EI) calcd for [M+H] + C 14 H 12 Br 2 287.0178, found 287.0183; IR (CH 2 Cl 2, cm -1 ) 2939 (m), 1617 (m), 1495 (m), 1027 (m). (E)-1-Methyl-3-styryl-1H-indazole (15h) H 3 C Ph Product 15h was isolated as a light brown solid in a 32% yield: M. P. 72-75 C; 1 H MR (400 MHz, CDCl 3 ) δ 4.09 (s, 3H), 7.24 (s, 2H), 7.40 (dd, J = 9.5, 6.6 Hz, 3H), 7.43-7.54 (m, 2H), 7.60 (d, J = 7.4 Hz, 2H), 8.02 (d, J = 8.2 Hz, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 35.76, 109.43, 120.19, 121.13, 121.20, 122.21, 126.64, 126.68, 127.91, 128.93, 130.45, 137.61, 141.46, 142.29; MS (EI) m/z (%) 234 (M +, 90%), 233 ([M-H] +, 100%), 218 (48%); HRMS (EI) calcd for [M+H] + C 16 H 15 2 235.1230, found 235.123; IR (CH 2 Cl 2, cm -1 ) 3082 (w), 2937 (m), 1614 (m), 1493 (m), 962 (s). 1-Methyl-3-(thiophen-2-yl)-1H-indazole (15i) H 3 C S Product 15i was isolated as a yellow-green oil in a 60% yield: 1 H MR (300 MHz, CDCl 3 ) δ 4.10 (s, 3H), 7.17 (dd, J = 4.9, 3.7 Hz, 2H), 7.20-7.26 (m, 2H), 7.33-7.37 (m, 2H), 7.38-7.46 (m, 3H), 7.63 (d, J = 3.6 Hz, 1H), 8.03 (d, J = 8.2 Hz, 1H); 13 C MR (75 MHz, CDCl 3 ) δ 35.75, 109.44, 121.29, 121.32, 124.46, 124.94, 126.77, 127.82, 136.23, 138.98, 141.48; MS (EI) m/z (%) 214 (M +, 100%), 199 (25%); HRMS (EI) calcd for [M+H] + C 12 H 11 2 S 215.0637, found 215.0640; IR (CH 2 Cl 2, cm -1 ) 3397 (m), 2948 (m), 2842 (m), 2798 (m), 1595 (m), 1494 (m). S9

1-Methyl-3-phenyl-1H-benzo[f]indazole (15j) H 3 C Product 15j was isolated as a yellow solid in a 63% yield: M. P. 137-139 C; 1 H MR (400 MHz, CDCl 3 ) δ 4.20 (s, 3H), 7.33-7.39 (m, 1H), 7.46 (q, J = 6.6 Hz, 2H), 7.58 (t, J = 7.6 Hz, 2H), 7.78 (s, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.99 (d, J = 8.5 Hz, 1H), 8.10 (d, J = 7.3 Hz, 2H), 8.57 (s, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 35.87, 104.18, 120.32, 123.15, 123.52, 126.22, 127.60, 127.77, 128.19, 129.09, 129.45, 132.57, 133.71, 140.52, 143.73; MS (EI) m/z (%) 258 (M +, 100%); HRMS (EI) calcd for [M+H] + C 18 H 14 2 259.1230, found 259.1224. 5,6-Dimethoxy-1-methyl-3-phenyl-1H-indazole (15k) H 3 C MeO MeO Product 15k was isolated as a yellow solid in a 62% yield: M. P. 128-130 C; 1 H MR (400 MHz, CDCl 3 ) δ 3.95 (s, 3H), 3.99 (s, 3H), 4.06 (s, 3H), 6.74 (s, 1H), 7.28 (s, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.89 (d, J = 7.3 Hz, 2H); 13 C MR (100 MHz, CDCl 3 ) δ 35.84, 56.25, 56.46, 90.65, 100.77, 114.67, 127.29, 127.73, 128.97, 134.08, 137.28, 143.19, 146.53, 150.82; MS (EI) m/z (%) 268 (M +, 100%), 253 (62%), 210 (17%);HRMS (EI) calcd for [M+H] + C 16 H 17 2 O 2 269. 1285, found 269.1290; IR (CH 2 Cl 2, cm -1 ) 3008 (w), 2937 (m), 2832 (m), 1713 (s), 1630 (s), 1206 (s). S10

4-Methoxy-1-methyl-3-phenyl-1H-indazole (15l) H 3 C OCH 3 Product 15l was isolated as a yellow solid in a 64% yield: M. P. 96-97 C; 1 H MR (400 MHz, CDCl 3 ) δ 3.90 (s, 3H), 4.09 (s, 3H), 6.52 (d, J = 7.7 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 7.31-7.42 (m, 2H), 7.45 (t, J = 7.4 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H); 13 C MR (100 MHz, CDCl 3 ) δ 35.86, 55.39, 99.92, 101.98, 112.91, 127.71, 127.78, 127.96, 129.70, 134.15, 143.57, 144.55, 154.72; MS (EI) m/z (%) 238 (M +, 100%), 223 (18%), 208 (20%);HRMS (EI) calcd for [M+H] + C 15 H 15 2 O 239.1179, found 239.1179; IR (CH 2 Cl 2, cm -1 ) 2937 (m), 2840 (w), 1614 (s), 1584 (s), 1507 (s), 1358 (s), 1182 (m). 1-[2-(2-(3-Phenyl-1H-indazol-1-yl)ethoxy)ethyl]pyrrolidine-2,5-dione (15m) O O O Ph Product 15m was isolated as a colorless oil in a 60% yield: 1 H MR (300 MHz, CDCl 3 ) δ 2.39 (s, 4H), 3.53-3.60 (m, 2H), 3.60-3.66 (m, 2H), 3.95 (t, J = 5.2 Hz, 2H), 4.56 (t, J = 5.3 Hz, 2H), 7.16-7.25 (m, 1H), 7.38-7.46 (m, 2H), 7.46-7.56 (m, 3H), 7.95 (d, J = 8.0 Hz, 2H), 7.99 (d, J = 8.8 Hz, 1H); 13 C MR (75 MHz, CDCl 3 ) δ 28.09, 38.19, 49.22, 67.23, 69.82, 110.21, 121.20, 121.26, 121.71, 126.51, 127.70, 128.10, 129.02, 133.83, 142.00, 144.36, 177.20; MS (EI) m/z (%) 363 (M +, 30%), 220 (28%), 207 (100%), 194 (32%), 77 (16%); HRMS (EI) calcd for [M+H] + C 21 H 22 3 O 3 364.1656, found 364.1664; IR (CH 2 Cl 2, cm -1 ) 2944 (m), 2873 (m), 2798 (m), 1776 (m), 1704 (s), 1399 (m), 1123 (s). S11

1-[5-(3-Phenyl-1H-indazol-1-yl)pentyl]pyrrolidine-2,5-dione (15n) O O Ph Product 15n was isolated as an orange oil in a 60% yield: 1 H MR (400 MHz, CDCl 3 ) δ 1.35 (m, 2H), 1.62 (m, 2H), 1.99 (m, 2H), 2.62 (s, 4H), 3.48 (t, J = 7.3 Hz, 2H), 4.42 (t, J = 7.1 Hz, 2H), 7.20 (t, J = 7.0 Hz, 1H), 7.39 (dd, J = 14.4, 6.7 Hz, 3H), 7.50 (t, J = 7.6 Hz, 2H), 7.96 (d, J = 7.6 Hz, 2H), 8.01 (d, J = 8.2 Hz, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 24.27, 27.41, 28.28, 29.55, 38.66, 48.75, 109.40, 121.05, 121.54, 121.77, 126.34, 127.61, 127.93, 128.94, 133.90, 141.06, 143.86, 177.35; MS (EI) m/z (%) 361 (M +, 100%), 249 (53%), 194 (48%), 77 (29%); HRMS (EI) calcd for [M+H] + C 22 H 24 3 O 2 362.1863, found 362.1870; IR (CH 2 Cl 2, cm -1 ) 2937 (m), 2862 (m), 1773 (m), 1693 (s), 1491 (s), 1351 (s). General procedure for the preparation of 2-acetyl-1-methylindazoles 17 [1-(1-Methyl-3-phenyl-1H-indazol-2(3H)-yl)ethanone (17a) as an example]. O To a mixture of benzaldehyde dimethylhydrazone 6a (37 mg, 0.25 mmol), CsF (114 mg, 0.75 mmol, 3 equiv), acetic anhydride (51 mg, 0.50 mmol, 2 equiv) and 5 ml of acetonitrile in a 10 ml vial, o-(trimethylsilyl)phenyl triflate (84 mg, 0.28 mmol, 1.1 equiv) was added. The vial was capped and the reaction mixture was allowed to stir for 10 h at 65 C. Then the reaction mixture was poured into 25 ml of water in a separatory funnel. After shaking the layers, the organic fraction was separated and the aqueous layer was extracted with dichloromethane (2 10 ml). All organic fractions were combined and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel S12

using hexanes/etoac as the eluent to afford the -acetylated product 17a. Product 17a was isolated as a light brown amorphous solid in an 83% yield as an inseparable mixture of diastereomers (ratio ~5:1): major diastereomer 1 H MR (400 MHz, CDCl3) δ 2.30 (s, 3H), 3.05 (s, 3H), 6.45 (s, 1H), 7.00 (d, J = 7.9 Hz, 1H), 7.10 (t, J = 7.4 Hz, 1H), 7.19-7.28 (m, 2H), 7.31 (t, J = 6.5 Hz, 3H), 7.37 (d, J = 6.9 Hz, 3H); minor diastereomer (selected peaks) 1 H MR (400 MHz, CDCl3) δ 1.96 (s, 0.67H), 3.36 (s, 0.61H) 6.06 (s, 0.19H) 6.94 (s, 0.5H); 13 C MR (100 MHz, CDCl 3 ) (all of the peaks listed for the mixture of diastereomers) δ 21.45, 22.85, 45.71, 48.55, 64.20, 64.23, 67.97, 112.73, 113.82, 115.41, 123.27, 124.08, 124.19, 126.37, 127.75, 127.84, 128.65, 129.01, 129.32, 130.76, 142.02, 150.43, 173.66; MS (EI) m/z (%) 252 (M +, 14%), 209 (100%), 194 (15%); HRMS (EI) calcd for [M+H] + C 16 H 17 2 O 253.1335, found 253.1332; IR (CH 2 Cl 2, cm -1 ) 2921 (m), 1666 (s), 1610 (m), 1483 (m), 1381 (s). 1-[1-Methyl-3-phenethyl-1H-indazol-2(3H)-yl]ethanone (17o) O Product 17o was isolated as a light yellow amorphous solid in a 95% yield: 1 H MR (400 MHz, CDCl 3 ) δ 2.03 (dd, J = 12.0, 6.5 Hz, 1H), 2.09-2.23 (m, 1H), 2.29 (s, 3H), 2.75 (d, J = 14.6 Hz, 1H), 2.88 (td, J = 12.7, 6.1 Hz, 1H), 3.09 (s, 3H), 5.45 (t, J = 5.6 Hz, 1H), 6.94 (d, J = 7.9 Hz, 1H), 7.07 (t, J = 7.4 Hz, 1H), 7.15-7.24 (m, 4H), 7.28 (t, J = 7.2 Hz, 3H); 13 C MR (100 MHz, CDCl 3 ) δ 21.44, 32.48, 41.10, 48.61, 61.70, 113.78, 117.52, 122.95, 123.80, 125.97, 128.33, 128.47, 132.41, 141.87, 150.05, 174.45; MS (EI) m/z (%) 280 (M +, 14%), 237 (85%), 175 (24%), 145 (71%), 133 (100%), 104 (33%), 77 (22%); HRMS (EI) calcd for [M+H] + C 18 H 21 2 O 281.1648, found 281.1656; IR (CH 2 Cl 2, cm -1 ) 2920 (w), 2863 (w), 1660 (s), 1610 (w), 1385 (s). S13

Characterization data for indazoles 15 obtained via methods A and B. 3-Mesityl-1-methyl-1H-indazole 1 (15p) Product 15p was isolated as a red amorphous solid in a 91% yield (method A): 1 H MR (400 MHz, CDCl 3 ) δ 2.08 (s, 6H), 2.38 (s, 3H), 4.15 (s, 3H), 7.00 (s, 2H), 7.12 (t, J = 7.2 Hz, 1H), 7.38-7.49 (m, 3H); 13 C MR (100 MHz, CDCl 3 ) δ 20.56, 21.37, 35.65, 109.12, 120.33, 121.30, 123.53, 126.25, 128.32, 129.14, 137.90, 138.31, 140.76, 143.93; MS (EI) m/z (%) 250 (M +, 73%), 249 ([M-H] +, 100%), 235 (13%), 219 (11%); HRMS (EI) calcd for [M+H] + C 17 H 19 2 251.1543, found 251.1549; IR (CH 2 Cl 2, cm -1 ) 3004 (m), 2921 (s), 2858 (m), 1614 (s), 1492 (s), 1337 (s). 1-Methyl-3-(2,4,6-trimethoxyphenyl)-1H-indazole (15q) OMe MeO OMe Product 15q was isolated as a yellow solid in a 76% yield (method A): M. P. 164-166 C; 1 H MR (400 MHz, CDCl 3 ) δ 3.71 (s, 6H), 3.89 (s, 3H), 4.13 (s, 3H), 6.27 (s, 2H), 7.08 (t, J = 7.2 Hz, 1H), 7.33-7.42 (m, 2H), 7.46 (d, J = 8.1 Hz, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 35.70, 55.55, 56.08, 90.95, 109.02, 119.91, 121.85, 124.45, 125.88, 138.24, 140.71, 157.27, 160.12, 161.79; MS (EI) m/z (%) 298 (M +, 100%), 297 ([M-H] +, 39%), 267 (16%); HRMS (EI) calcd for [M+H] + C 17 H 19 2 O 3 299.1390, found 299.1399; IR (CH 2 Cl 2, cm -1 ) 3009 (w), 2940 (m), 2839 (m), 1615 (s), 1587 (s), 1337 (s), 1127 (s). S14

1-Methyl-3-(pyridin-3-yl)-1H-indazole (15r) Product 15r was isolated as an orange amorphous solid in a 29% yield (method A): 1 H MR (400 MHz, CDCl 3 ) δ 4.07 (s, 3H), 7.18 (dt, J = 8.1, 4.0 Hz, 1H), 7.34 (dd, J = 7.9, 4.9 Hz, 1H), 7.37 (d, J = 3.6 Hz, 2H), 7.91 (d, J = 8.2 Hz, 1H), 8.17 (dt, J = 7.9, 1.8 Hz, 1H), 8.55 (dd, J = 4.7, 1.3 Hz, 1H), 9.15 (s, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 35.89, 109.63, 121.02, 121.67, 121.72, 123.90, 126.75, 129.98, 134.54, 140.76, 141.62, 148.55, 148.99; MS (EI) m/z (%) 209 (M +, 100%), 208 ([M-H] +, 33%), 181 (10%); HRMS (ESI) calcd for [M+H] + C 13 H 12 3 210.1026, found 210.1029; IR (CH 2 Cl 2, cm -1 ) 3392 (w, broad), 2939 (m), 1618 (s), 1496 (s), 1153 (s). (E)-Ethyl 2-(acetylimino)-2-[2-(dimethylamino)phenyl]acetate (20) O O O Product 20 was isolated as an orange amorphous solid in a 54% yield (method A): 1 H MR (400 MHz, CDCl 3 ) δ 1.23 (t, J = 7.1 Hz, 3H), 2.36 (s, 3H), 2.66 (s, 6H), 4.22 (q, J = 7.1 Hz, 2H), 7.09-7.21 (m, 2H), 7.47 (t, J = 7.7 Hz, 1H), 7.56 (d, J = 7.7 Hz, 1H); 13 C MR (75 MHz, CDCl 3 ) δ 14.26, 25.12, 45.00, 62.08, 119.80, 124.15, 130.18, 130.37, 132.72, 154.07, 157.34, 163.42, 185.62.; MS (EI) m/z (%) 262 (M +, 11%), 203 (82%), 189 (29%), 175 (19%), 158 (84%), 147 (100%), 131 (31%), 43 (26%); HRMS (ESI) calcd for [M+H] + C 14 H 19 2 O 3 263.1390, found 263.1397; IR (CH 2 Cl 2, cm -1 ) 2942 (m), 2867 (m), 2835 (m). 2792 (m), 1736 (s), 1708 (s), 1652 (s), 1595 (s), 1490 (s). S15

Procedure for the preparation of 1-benzyl-3-phenyl-1H-indazole 8 (15t). To a mixture of benzaldehyde dibenzylhydrazone 6t (75 mg, 0.25 mmol), CsF (151 mg, 1.00 mmol, 4 equiv), and 5 ml of acetonitrile in a 10 ml vial, o-(trimethylsilyl)phenyl triflate (149 mg, 0.50 mmol, 2.0 equiv) was added. The vial was capped and the reaction mixture was allowed to stir for 10 h at 65 C. Then the reaction mixture was poured into 25 ml of water in a separatory funnel. After shaking the layers, the organic fraction was separated and the aqueous layer was extracted with dichloromethane (2 10 ml). All organic fractions were combined and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using hexanes/etoac as the eluent to afford 15t as a yellow amorphous solid in a 51% yield: 1 H MR (400 MHz, CDCl 3 ) δ 5.68 (s, 2H), 7.16-7.34 (m, 6H), 7.37 (d, J = 4.1 Hz, 2H), 7.42 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 8.02 (d, J = 7.1 Hz, 2H), 8.05 (d, J = 8.2 Hz, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 53.29, 109.83, 121.29, 121.61, 122.30, 126.56, 127.33, 127.72, 127.88, 128.07, 128.88, 128.98, 133.86, 137.07, 141.26, 144.36; MS (EI) m/z (%) 284 (M +, 100%), 91 (79%); HRMS (ESI) calcd for [M+H] + C 20 H 16 2 285.1386, found 285.1394; IR (CH 2 Cl 2, cm -1 ) 2927 (m), 2854 (w), 1614 (s), 1493 (s), 1350 (s). 8 V. Collot, P. Dallemagne, P. R. Bovy, S. Rault, Tetrahedron 1999, 55, 6917. S16

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