Supplementary Information Full experimental and characterization details pages 1-10 NMR spectra of new compounds pages 11-31

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1 1 New Gas-phase Cascade Reactions of Stabilized Phosphorus Ylides Leading to Ring-fused Indoles and to Quinolines R. Alan Aitken* and Lorna Murray School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, U.K. Supplementary Information Full experimental and characterization details pages 1-10 NMR spectra of new compounds pages General Experimental Details 1 H NMR (300 MHz), 13 C NMR (75 MHz) and 31 P NMR (121 MHz) spectra were recorded in CDCl 3 with internal TMS (H and C) or external H 3 PO 4 (P) as reference. The 13 C NMR spectra of ylides were recorded at 55 C and all other NMR spectra at 25 C. Organic solutions were dried using anhydrous MgSO 4. Flash vacuum pyrolysis (FVP) was carried out in a conventional flow system by subliming the starting material through a horizontal quartz tube ( cm) externally heated by a tube furnace to 700 C and maintained at a pressure of torr by a rotary vacuum pump. Products were collected in a liquid N 2 cooled U-shaped trap and purified as noted. 2-(N-Methylamino)benzoic acid To a solution of sodium carbonate (8.0 g, 75.5 mmol) in water (100 ml), anthranilic acid (20.0 g, mmol) was added with stirring. Methyl iodide (10.89 ml, mmol) was added to the stirred solution, which was then heated under reflux for 4 h. The solution was cooled and the product filtered off and oven dried to give the title product (21.05 g, 96%) as a yellow powder, mp C (Lit C). 1 H NMR δ 7.99 (d, J = 8 Hz, 1H), 7.43 (t, J = 8 Hz, 1H), 6.70 (d, J = 8 Hz, 1H), 6.63 (t, J = 8 Hz, 1H), 2.94 (s, 3H). 2-(N-Methyl-N-p-toluenesulfonylamino)benzoic acid (7) To a solution of aqueous sodium hydroxide (2 M, 50 ml), 2-(N-methylamino)benzoic acid (10 g, 72.9 mmol) was added while stirring at C. Once dissolved, p- toluenesulfonyl chloride (22.0 g, mmol) was added in 4 portions while the mixture was stirred for 4 h. The mixture was filtered and the filtrate acidified using hydrochloric acid and the resulting precipitate was filtered off and dried to give the title product (13.29 g, 60%) as a yellow solid, mp C (Lit C). 1 H NMR δ 8.01 (d, J = 9 Hz, 1H), 7.57 (d, J = 9 Hz, 2H), (m, 2H), 7.29 (d, J = 9 Hz, 2H), 6.93 (d, J = 9 Hz, 1H), 4.06 (br s, 1H), 3.28 (s, 3H), 2.42 (s, 3H). 2-(N-Methyl-N-p-toluenesulfonylamino)benzoyl chloride The acid 7 (5.00 g, 16.4 mmol) was added to thionyl chloride (10.0 ml) which was heated under reflux for 5 h. The excess thionyl chloride was evaporated to give the title product (5.23 g, 99%) as a pale yellow solid, mp ºC (Lit ºC ). 1 H NMR δ

2 (d, J = 8 Hz, 1H), (m, 4H), 7.28 (d, J = 8 Hz, 2H), 6.94 (d, J = 8 Hz, 1H), 3.23 (s, 3H), 2.44 (s, 3H). [1-(2-N-Methyl-N-p-toluenesulfonylamino)benzoyl)1- propylidene]triphenylphosphorane (8) A suspension of propyltriphenylphosphonium bromide (6.19 g, 16.1 mmol) in THF (50 ml) was stirred under nitrogen while a solution of BuLi (6.44 ml, 2.5 M, 16.1 mmol) in hexanes was added. The resulting brightly colored solution was stirred for 2 h and a solution of 2-(N-methyl-N-tosylamino)benzoyl chloride (2.60 g, 8.1 mmol) in THF (5 ml) was added and the mixture was stirred for a further 18 h. Water (50 ml) was added to the solution and the mixture was extracted using ethyl acetate (2 50 ml). The combined extracts were washed with water, dried and evaporated. The resulting solid was recrystallized (Et 2 O/EtOAc) to give the title product (1.58 g, 31%) as yellow crystals, mp ºC; IR (Nujol) 1493 (CO), 1377 (SO 2 ), 1162 cm 1 (SO 2 ); 1 H NMR δ (m, 7H), (m, 10H) 7.32 (d, J = 8 Hz, 2H), (m, 2H), 7.11 (t, J = 8 Hz, 1H), 6.65 (d, J = 8 Hz, 1H), 3.26 (s, 3H), 2.46 (s, 3H), 1.68 (br s, 2H), 0.63 (t, J = 7 Hz, 3H); 13 C NMR δ (d, J = 7 Hz, C), (d, J = 14 Hz, C), (C), (d, J = 10 Hz, 6CH), (C), (C), (d, J = 3 Hz, 3CH), (2CH), (2CH), (d, J = 12 Hz, 6CH), (CH), (CH), (CH), (CH), (d, J = 89 Hz, 3C), 69.3 (d, J = 97 Hz, C), 41.0 (CH 3 ), 21.5 (CH 3 ), 20.9 (d, J = 13 Hz, CH 2 ), 18.3 (CH 3 ); 31 P NMR δ 17.8; HRMS (ESI, M+Na ion) calcd for C 36 H 34 NaNO 3 PS , found [1-(2-N-Methyl-N-ptoluenesulfonylamino)benzoyl)benzylidene]triphenylphosphorane (9) A suspension of benzyltriphenylphosphonium bromide (6.26 g, 16.1 mmol) in THF (50 ml) was stirred under nitrogen while a solution of BuLi (6.44 ml, 2.5 M, 16.1 mmol) in hexanes was added. The resulting brightly colored solution was stirred for 2 h and a solution of 2-(N-methyl-N-tosylamino)benzoyl chloride (2.60 g, 8.1 mmol) in THF (5 ml) was added and the mixture was stirred for a further 18 h. Water (50 ml) was added to the solution and the mixture was extracted using ethyl acetate (2 50 ml). The combined extracts were washed with water, dried and evaporated. The resulting solid was recrystallized (Et 2 O/EtOAc) to give the title product (2.23 g, 43%) as pale yellow crystals, mp ºC; IR (Nujol) 1496 (CO), 1342 (SO 2 ), 1154 (SO 2 ) cm 1 ; 1 H NMR δ (m, 8H), (m, 9H), 7.30 (d, J = 8 Hz, 2H), 7.20 (d, J = 8 Hz, 1H), 7.14 (d, J = 8 Hz, 2H), (m, 2H), (m, 3H), 6.43 (d, J = 8 Hz, 1H), 3.13 (s, 3H), 2.46 (s, 3H); 13 C NMR δ (d, J = 6 Hz, C), (d, J = 12 Hz, C), (C), (C), (d, J = 12 Hz, C), (C), (d, J = 5 Hz, 2CH), (d, J = 10 Hz, 6CH), (d, J = 3 Hz, 3CH), (CH), (2CH), (d, J = 12 Hz, 6CH), (2CH), (CH), (3CH), (d, J = 91 Hz, 3C), (CH), (d, J = 2 Hz, CH), 74.0 (d, J = 107 Hz, C), 41.1 (CH 3 ), 21.6 (CH 3 ); 31 P NMR δ 16.2; HRMS (ESI, M+Na ion) calcd for C 40 H 34 NaNO 3 PS , found FVP of ylide 8 giving 3-ethylquinoline (22) Ylide 8 (0.250g, 0.42 mmol) was subjected to FVP at 700 C and torr. NMR analysis of crude product showed the presence of Ph 3 PO, toluene and 3-ethylquinoline.

3 3 Purification by acid/base extraction gave 3-ethylquinoline (0.047g, 71%) as a brown oil; 1 H NMR δ 8.63 (d, J = 2 Hz, 1H), 7.97 (d, J = 8 Hz, 1H), 7.81 (d, J = 2 Hz, 1H), 7.62 (d, J = 8 Hz, 1H), 7.51 (t, J = 8 Hz, 1H), 7.37 (t, J = 8 Hz, 1H), 2.67 (q, J = 8 Hz, 2H), 1.18 (t, J = 8 Hz, 3H) [good agreement with Lit. 4 ]. FVP of ylide 9 giving 3-phenylquinoline (23) Ylide 9 (0.690 g, 1.08 mmol) was subjected to FVP at 700 C and torr. NMR analysis of crude product showed a mixture of Ph 3 PO, toluene and 3-phenylquinoline. Purification by acid/base extraction gave 3-phenylquinoline ( g, 32%) as a brown solid, mp C (Lit C); 1 H NMR δ 9.19 (d, J = 2 Hz, 1H), 8.32 (d, J = 2 Hz, 1H), 8.15 (d, J = 8 Hz, 1H), 7.90 (d, J = 8 Hz, 1H), 7.73 (d, J = 8 Hz, 2H), (m, 4H), 7.45 (t, J = 8 Hz, 1H) [good agreement with Lit. 6 ]. Methyl 2-(N-methyl-N-p-toluenesulfonylamino)benzoate (10) The acid 7 (10.0 g, mmol) and potassium acetate (9.32 g, 94.9 mmol) were stirred in DMF (50 ml) for 20 min and dimethyl sulfate (3.41 ml, 36.0 mmol) was added. The mixture was stirred for 30 min and then heated to 60 ºC and stirred for a further 30 min. The mixture was then poured into water (60 ml) and extracted with diethyl ether (2 60 ml) and combined extracts washed with water (100 ml), dried, evaporated. Recrystallization of the residue (MeOH) gave the title product (5.04 g, 48%) as a colorless solid, mp ºC (Lit ºC); 1 H NMR δ 7.85 (d, J = 8 Hz, 1H), 7.53 (d, J = 8 Hz, 2H), (m, 2H), 7.26 (d, J = 8 Hz, 2H), 6.91 (d, J = 8 Hz, 1H), 3.85 (s, 3H), 3.26 (s, 3H), 2.43 (s, 3H). 2-(N-Methyl-N-p-toluenesulfonylamino)benzyl alcohol Under a nitrogen atmosphere, a solution of methyl 2-(N-methyl-N-tosylamino)benzoate (11.0 g, 34.4 mmol) in dry THF (100 ml) was added dropwise to a stirred suspension of LAH (1.44 g, 37.8 mmol) in dry THF (15 ml) and the resulting mixture was heated under reflux for 4 h. To destroy the excess of LAH, water (1.5 ml) in THF (10.5 ml) was added to the mixture followed by 15% solution sodium hydroxide (1.5 ml) and finally water (4.5 ml). The suspension was stirred for 0.5 h and extracted using Et 2 O (2 80 ml) which was washed with water, dried and evaporated to give the title product (9.10 g, 90%) as colorless prisms, mp ºC; IR (Nujol) (OH), 1340 (SO 2 ), 1172 (SO 2 ) cm -1 ; 1 H NMR δ 7.59 (d, J = 7.5 Hz, 1H), 7.54 (d, J = 8 Hz, 2H), (m, 3H), 7.14 (t, J = 7.5 Hz, 1H), 6.46 (d, J = 8 Hz, 1H), 4.98 (br s, 1H), 4.61 (br s, 1H), 3.21 (s, 1H), 3.15 (s, 3H), 2.47 (s, 3H); 13 C NMR δ (C), (C), (C), (C), (CH), (2CH), (CH), (CH), (2CH), (CH), 61.1 (CH 2 ), 39.5 (CH 3 ), 21.6 (CH 3 ); MS (ESI) 314 (M+Na +, 100%). 2-(N-Methyl-N-p-toluenesulfonylamino)benzyltriphenylphosphonium bromide (13) A solution of 2-(N-methyl-N-p-toluenesulfonylamino)benzyl alcohol (9.10 g, 31.1 mmol) in toluene (100 ml) was stirred with phosphorus bromide (1.43 ml, 15 mmol) at room temperature for 18 h. The mixture was added to water (100 ml) and the organic layer separated, washed with water and dried. The dried organic solution was heated under reflux with triphenylphosphine (8.26 g, 31.5 mmol) for 8 h. The precipitate was filtered

4 4 off, washed with diethyl ether and oven dried to give the title product (13.22 g, 68%) as a colorless solid, mp ºC; 1 H NMR δ 7.84 (t, J = 7 Hz, 3H), (m, 12H), 7.43 (d, J = 7 Hz, 1H), (m, 4H), (m, 2H), 6.31 (d, J = 7 Hz, 1H, 3- H), 5.67 (t, J = 14 Hz, 1H, CH 2 P), 5.10 (t, J = 14 Hz, 1H, CH 2 P), 2.44 (s, 3H), 2.26 (s, 3H); 13 C NMR δ (C), (d, J = 6 Hz, C), (d, J = 3 Hz, 3CH), (d, J = 10 Hz, 6CH), (d, J = 5 Hz, CH), (C), (d, J = 13 Hz, 6CH), (d, J = 4 Hz, CH), (2CH), (d, J = 3 Hz, CH), (2CH), (C), (d, J = 3 Hz, CH), (d, J = 86 Hz, 3C), 38.5 (CH 3 ), 27.3 (d, J = 49 Hz, CH 2 ), 21.6 (CH 3 ); 31 P NMR δ 24.0; MS 536 (M + Br, 100%). [(α-benzoyl)(2-(n-methyl-n-ptoluenesulfonylamino)benzylidene]triphenylphosphorane (16) A suspension of salt 13 (2.5 g, 4.05 mmol) in dry THF (50 ml) was stirred under nitrogen while a solution of BuLi (1.78 ml, 2.5 M, 4.46 mmol) in hexanes was added. The resulting brightly colored solution was stirred for 2 h and a solution of benzoyl chloride (0.26 ml, 2.28 mmol) was added in THF (5 ml) and the mixture was stirred for a further 18 h. Water (50 ml) was added to the solution and the mixture was extracted using ethyl acetate (2 50 ml). The combined extracts were washed with water, dried and evaporated. The resulting solid was recrystallized (Et 2 O/EtOAc) to give the title product (0.15 g, 5%) as bright yellow crystals, mp ºC; IR (Nujol) 1502 (CO), 1344 (SO 2 ), 1171 (SO 2 ) cm 1 ; 1 H NMR δ (m, 4H), (m, 14H), 7.18 (d, J = 8 Hz, 3H), 7.07 (t, J = 8 Hz, 3H), (m, 1H), (m, 2H), 6.34 (d, J = 8 Hz, 1H), 2.39 (s, 3H), 1.80 (s, 3H); 13 C NMR δ (CO), (d, J = 9 Hz, C), (d, J = 11 Hz, C), (d, J = 3 Hz, CH), (C), (d, J = 10 Hz, CH), (CH), (br s), (2CH), (2CH), (2CH), (CH), (br s), (2CH), (CH), (d, J = 2 Hz, CH), (d, J = 1 Hz, CH), 37.3 (CH 3 ), 21.5 (CH 3 ) [signals due to PPh and C=P could not be accurately observed due to peak broadening]; 31 P NMR δ +17.4; MS (ESI) 662 (M + +Na, 100%), 640 (M + +H, 70%); Anal. Calcd for C 40 H 34 NPO 3 S: C, 75.10; H, 5.36; N, Found: C, 74.62; H, 5.22; N, FVP of ylide 16 giving 3-phenylquinoline (23) Ylide 16 ( g, mmol) was subjected to FVP at 700 C and torr. NMR analysis of crude product showed a mixture of Ph 3 PO, toluene and 3- phenylquinoline. Purification by acid/base extraction gave 3-phenylquinoline (0.003 g, 28%) as a brown solid, mp C (Lit C). Methyl 2-(N-methanesulfonylamino)benzoate Triethylamine (27.67 ml, mmol) was added to a stirred solution of methyl 2- aminobenzoate (18.07 ml, mmol) in diethyl ether (80 ml) cooled to 0 ºC. Methanesulfonyl chloride (15.36 ml, mmol) in ethyl acetate (110 ml) was slowly added dropwise to the solution. After stirring at 0 ºC for 0.5 h, the mixture was allowed to warm to rt and stirred for 8 h. Water (150 ml) was added and the mixure was extracted with ethyl acetate (2 x 75 ml) and the combined extracts were washed with water, dried, evaporated. Recrystallization of the residue (MeOH) gave the title product (30.77 g,

5 5 68%) as colorless crystals, mp ºC (Lit ºC); 1 H NMR δ (s, 1H), 8.07 (d, J = 8 Hz, 1H), 7.75 (d, J = 8 Hz, 1H), 7.56 (t, J = 8 Hz, 1H), 7.13 (t, J = 8 Hz, 1H), 3.94 (s, 3H), 3.07 (s, 3H). Methyl 2-(N-methyl-N-methanesulfonylamino)benzoate (11) Sodium hydride (60% dispersion in oil) (2.6 g, 65.4 mmol) was washed with hexane (30 ml) and DMF (30 ml) was added. The resulting suspension was stirred while a solution of methyl 2-(N-methanesulfonylamino)benzoate (10.0 g, 43.6 mmol) in DMF (100 ml) was added. The solution was stirred for 45 min and then a solution of methyl iodide (8.31 ml, mmol) in diethyl ether (120 ml) was added and the mixture stirred for 72 h. The mixture was cooled and acidified with HCl. The solution was added to water (150 ml) and extracted with diethyl ether (4 100 ml). The combined extracts were washed with water, dried and evaporated and the resulting yellow oil was triturated with diethyl ether (150 ml) to give the title product (5.83 g, 55%) as a colorless crystalline solid, mp ºC (Lit ºC); 1 H NMR δ 7.91 (d, J = 8 Hz, 1H), 7.56 (t, J = 8 Hz, 1H), (m, 2H), 3.93 (s, 3H), 3.31 (s, 3H), 2.97 (s, 3H). 2-(N-Methyl-N-methanesulfonylamino)benzyl alcohol Under a nitrogen atmosphere, a solution of 11 (64.13 g, 0.3 mol) in dry THF (250 ml) was added dropwise to a stirred suspension of LAH (5.49 g, 0.1 mol) in dry THF (50 ml) and the resulting mixture was heated under reflux for 4 h. To destroy the excess of LAH, water (5.5 ml) in THF (38.5 ml) was carefully added to the mixture followed by 15% solution sodium hydroxide (5.5 ml) and finally water (15 ml). The suspension was stirred for 0.5 h and extracted using diethyl ether (2 200 ml) and the combined extracts washed with water, dried and evaporated to give the title product (51.74 g, 92%) as a pale yellow oil; 1 H NMR δ 7.58 (d, J = 8 Hz, 1H), (m, 2H), 7.27 (d, J = 8 Hz, 1H), 4.72 (br s, 2H), 3.35 (br s, 1H), 3.24 (s, 3H), 2.95 (s, 3H); 13 C NMR δ (C), (C), (CH), (CH), (CH), (CH), 60.4 (CH 2 ), 38.8 (CH 3 ), 35.3 (CH 3 ); HRMS (ESI, M+Na ion) calcd for C 9 H 13 NaNO 3 S , found (N-Methyl-N-methanesulfonylamino)benzyltriphenylphosphonium bromide (14) A solution of 2-(N-methyl-N-methanesulfonylamino)benzyl alcohol (14.30 g, 66.4 mmol) in toluene (100 ml) was stirred with phosphorus bromide (14.51 ml, mmol) at rt for 18 h. The mixture was added to water (70 ml) and the organic layer separated, washed with water (2 x 50 ml) and dried. The dried organic solution was heated under reflux with triphenylphosphine (17.45 g, 66.5 mmol) for 8 h. The precipitate was filtered off, washed with diethyl ether and oven dried to give the title product (33.45 g, 93%) as a colorless solid, mp ºC; IR (Nujol) 1335 (SO 2 ), 1165 (SO 2 ) cm 1 ; 1 H NMR δ 7.84 (t, 3H, J = 8 Hz), (m, 14H), (m, 2H), 5.56 (t, J = 15 Hz, 1H), 4.92 (t, J = 15 Hz, 1H), 2.94 (s, 3H), 2.53 (s, 3H); 13 C NMR δ (d, J = 6 Hz), (d, J = 3 Hz, 3CH), (d, J = 10 Hz, 6CH), (d, J = 5 Hz, CH), (d, J = 3 Hz, CH), (d, J = 13 Hz, 6CH), (d, J = 3 Hz, CH), (d, J = 8 Hz, C), (d, J = 3 Hz, CH), (d, J = 86 Hz, 3C), 38.7 (CH 3 ), 34.7 (CH 3 ), 27.4 (d, J = 50 Hz, CH 2 ); 31 P NMR δ 23.8; MS (ESI) 460 (M + -Br, 100%); Anal. Calcd for C 27 H 27 BrNO 2 PS: C, 60.00; H, 5.04; N, Found: C, 59.88; H, 5.10; N, 2.49.

6 6 [(α-cinnamoyl)(2-n-methyl-nmethanesulfonylamino)benzylidene]triphenylphosphorane (17) A suspension of salt 14 (2.00 g, 3.7 mmol) in THF (50 ml) was stirred under nitrogen while a solution of BuLi (1.65 ml, 2.5 M, 4.1 mmol) in hexanes was added. The resulting brightly colored solution was stirred for 2 h and a solution of cinnamoyl chloride (0.35 g, 2.1 mmol) in THF (5 ml) was added and the mixture was stirred for a further 18 h. Water (50 ml) was added to the solution and the mixture was extracted using ethyl acetate (2 50 ml). The combined extracts were washed with water, dried and evaporated. Recrystallization of the residue (Et 2 O/EtOAc)gave the title product (0.43 g, 20%) as a bright yellow powder, mp ºC; 1 H NMR δ 8.08 (br s, 2H), 7.48 (br s, 5H), 7.39 (d, J = 15 Hz), (m, 7H), (m, 6H), 6.93 (br s, 2H), 6.75 (d, J = 15 Hz, 1H), 2.84 (br s, 3H) 2.64 (br s, 3H); 13 C NMR δ (d, J = 6 Hz, C), (d, J = 6 Hz, C), (br s, CH), (d, J = 11 Hz, C), (C), (CH), (d, J = 3 Hz, 3CH), (br s), (CH), (CH), (2CH), (br s), (d, J = 12 Hz, CH), 71.2 (d, J = 110 Hz, C), 38.7 (CH 3 ), 37.8 (CH 3 ) [signals due to PPh could not be accurately observed due to peak broadening]; 31 P NMR δ 16.8; HRMS (ESI, M+1 ion) calcd for C 36 H 33 NO 3 PS , found FVP of ylide 17 giving N-methylbenzo[c]carbazole (24) Ylide 17 ( g, mmol) was subjected to FVP at 700 C at torr. NMR analysis of crude product showed a mixture of products. The mixture was purified by preparative TLC (15:85 hexane:diethyl ether) to give the title product ( g, 75%) mp 110 C (Lit ºC); 1 H NMR δ 8.80 (d, J = 8 Hz, 1H), 8.60 (d, J = 8 Hz, 1H), 8.02 (d, J = 8, 1H), 7.93 (d, J = 8 Hz, 1H), 7.71 (t, J = 8 Hz, 1H), 7.68 (d, J = 8 Hz, 1H), (m, 3H), 7.39 (t, J = 8 Hz, 1H), 4.02 (s, 3H) [good agreement with Lit. 10 ]. Ethyl 2-(N-benzyl-N-methylamino)benzoate (12) To chilled ethanol (1 L), 2-fluorobenzoyl chloride (100 g, 0.64 mol) was added slowly with stirring. The resulting solution was heated under reflux for 3 h and the ethanol evaporated to give ethyl 2-fluorobenzoate (105.6 g, 98%) as a pale yellow oil. A mixture of ethyl 2-fluorobenzoate (30.0 g, mmol) and K 2 CO 3 (28.25 g, mmol) was stirred in toluene (500 ml) while benzylmethylamine (26.50 ml, mmol) was added. The mixture was heated under reflux for 5 days and on cooling was poured into water (300 ml) and was extracted using ethyl acetate (2 x 300 ml). To the combined organic fractions 2 M HCl (200 ml) was added and seperated. The organic fraction was washed with water, dried and evaporated to give starting material ethyl 2- fluorobenzoate (8.10 g, 28%). The acid was then brought to ph 8 using 2 M NaOH and extracted using ethyl acetate (2 x 200 ml). The combined organic fractions were washed with water, dried and evaporated. The resulting oil was then distilled at 2.5 mmhg at 110 C to remove unreacted benzylmethylamine leaving the pure title product (27.05 g, 68%) as a pale yellow oil; 1 H NMR δ 7.65 (d, J = 8 Hz, 1H), (m, 6H), 6.97 (d, J = 8 Hz, 1H), 6.88 (t, J = 8 Hz, 1H), (m, 4H), 2.73 (s, 3H) and 1.34 (t, J = 7 Hz, 3H) [good agreement with Lit. 11 ]. 2-(N-Benzyl-N-methylamino)benzyl alcohol

7 7 Under a nitrogen atmosphere, a solution of 12 (19.92 g, mmol) in dry THF (400 ml) was added dropwise to a stirred suspension of LAH (3.09 g, mmol) in dry THF (80 ml) and the resulting mixture was stirred at room temperature for 18 h. To destroy the excess of LAH, water (3 ml) in THF (21 ml) was added to the mixture followed by 15% solution sodium hydroxide (3 ml) and finally water (9 ml). The suspension was stirred for 0.5 h and MgSO 4 was added and stirred overnight. The mixture was filtered, the solid washed with ethyl acetate and the combined filtrate and washings evaporated to give the title product (14.08 g, 84%) as a yellow oil; 1 H NMR δ (m, 8H), 7.09 (t, J = 8 Hz, 1H), 5.25 (br s, 1H), 4.80 (s, 2H), 4.00 (s, 2H), 2.58 (s, 3H); 13 C NMR δ (C), (C), (C), (2CH), (2CH), (CH), (CH), (CH), (CH), (CH), 63.8 (CH 2 ), 61.6 (CH 2 ), 41.3 (CH 3 ); HRMS (ESI, M+Na ion) calcd for C 15 H 17 NaNO , found (N-Benzyl-N-methylamino)benzyltriphenylphosphonium bromide (15) A solution of 2-(N-benzyl-N-methylamino)benzyl alcohol (12.61 g, 55.3 mmol) in toluene (500 ml) was stirred with phosphorus tribromide (12.11 ml, mmol) at room temperature for 18 h. The mixture was added to water (200 ml), stirred for 0.5 h and the organic layer separated, washed with water (2 50 ml) and dried. The dried toluene solution was heated under reflux with triphenylphosphine (14.48 g, 55.3 mmol) for 8 h. The precipitate was filtered off, washed with diethyl ether and oven dried to give the title product (12.89 g, 39%) as a colorless solid, mp ºC; 1 H NMR δ (m, 5H), (m, 14H), (m, 5H), 5.35 (br d, J = 15 Hz, 2H), 3.73 (br s, 2H), 2.04 (br s, 3H); 13 C NMR δ (d, J = 6 Hz, C), (C), (d, J = 2 Hz, 3CH), (d, J = 10 Hz, 6CH), (d, J = 5 Hz, CH), (d, J = 13 Hz, 6CH), (d, J = 3 Hz, CH), (2CH), (2CH), (CH), (d, J = 3 Hz, CH), (d, J = 8 Hz, C), (d, J = 4 Hz, CH), (d, J = 85 Hz, 3C), 62.1 (CH 2 ), 40.6 (CH 3 ), 25.5 (d, J = 47 Hz, CH 2 ); 31 P NMR δ 23.0; Anal. Calcd for C 33 H 31 NPBr: C, 71.74; H, 5.66; N, Found: C, 71.59; H, 5.63; N, (3-Phenylpropenoyl)benzotriazole To a stirred solution of 1H-1,2,3-benzotriazole (11.90 g, 100 mmol) in CH 2 Cl 2 (125 ml), thionyl chloride (1.9 ml, 25 mmol) was added dropwise. The mixture was stirred at rt for 0.5 h and cinnamic acid (3.70 g, 25 mmol) was added. The mixture was stirred for a further 3h at rt and the solid was filtered off and washed with CH 2 Cl 2. The combined filtrate was washed with 2M aqueous NaOH, water and brine. Drying and evaporation followed by recrystallization of the residue (hexane/etoac) gave the title product (5.2 g, 84%) as colorless needles, mp ºC (Lit ºC); 1 H NMR δ 8.43 (d, J = 8 Hz, 1H), (m, 3H), 7.79 (m, 2H), 7.69 (t, J = 8 Hz, 1H), 7.54 (t, J = 8 Hz, 1H), (m, 3H). 1-(3-(2-Furyl)propenoyl)benzotriazole To a stirred solution of 1H-1,2,3-benzotriazole (6.91 g, 58 mmol) in CH 2 Cl 2 (125 ml), thionyl chloride (1.05 ml, 14.5 mmol) was added dropwise. The mixture was stirred at rt for 0.5 h and (E)-3-(2-furyl)prop-2-enoic acid (2.00 g, 14.5 mmol) was added. The mixture was stirred for a further 3h at rt and the solid was filtered off and washed with CH 2 Cl 2. The combined filtrate was washed with 2M aqueous NaOH, water and brine. Drying and evaporation followed by recrystallization of the residue (hexane/ch 2 Cl 2 )

8 8 gave the title product (9.96 g, 54%) as pale brown prisms, mp ºC (Lit ºC); 1 H NMR δ 8.40 (d, J = 8 Hz, 1H), 8.14 (d, J = 8 Hz, 1H), 7.97 (d, J = 15 Hz, 1H), 7.87 (d, J = 15 Hz, 1H), 7.67 (t, J = 8 Hz, 1H), 7.61 (d, J = 2 Hz, 1H), 7.52 (t, J = 8 Hz, 1H), 6.87 (d, J = 4 Hz, 1H), 6.54 (dd, J = 4, 2 Hz, 1H). 1-(3-(2-Thienyl)propenoyl)benzotriazole To a stirred solution of 1H-1,2,3-benzotriazole (15.45 g, mmol) in CH 2 Cl 2 (125 ml), thionyl chloride (2.35 ml, 32.4 mmol) was added dropwise. The mixture was stirred at rt for 0.5 h and (E)-3-(2-thienyl)prop-2-enoic acid (5.00 g, 32.4 mmol) was added. The mixture was stirred for a further 3h at rt and the solid was filtered off and washed with CH 2 Cl 2. The combined filtrate was washed with 2M aqueous NaOH, water and brine. Drying and evaporation followed by recrystallization of the residue (hexane/ch 2 Cl 2 ) gave the title product (5.45 g, 66%) as yellow needles, mp ºC (Lit ºC) 1 H NMR δ 8.41 (d, J = 8 Hz, 1H), 8.26 (d, J = 15 Hz, 1H), 8.16 (d, J = 8 Hz, 1H), 7.90 (d, J = 15 Hz, 1H), 7.89 (t, J = 8 Hz, 1H), (m, 3H), 7.15 (t, J = 4 Hz, 1H). [(2-(N-Methyl-N-benzylamino)phenyl)(3- phenylpropenoyl)methylene]triphenylphosphorane (18) A suspension of salt 15 (0.3 g, 0.54 mmol) in THF (10 ml) was stirred under nitrogen while a solution of BuLi (0.23 ml, 2.25 M, 0.54 mmol) in hexanes was added. The resulting brightly colored solution was stirred for 2 h and a solution of 1-(3- phenylpropenoyl)benzotriazole ( g, 0.54 mmol) in THF (5 ml) was added and the mixture was stirred for a further 18 h. Water (20 ml) was added to the solution and the mixture was extracted using ethyl acetate (2 20 ml). The combined extracts were washed with water, dried and evaporated. Recrystallization of the residue (Et 2 O/EtOAc) gave the title product ( g, 74%) as yellow crystals, mp C; IR (Nujol) 1627 (C=C) cm 1 ; 1 H NMR δ 7.57 (d, J = 16 Hz, 1H), 7.56 (d, J = 8 Hz, 1H), (m, 25H), 6.99 (t, J = 8 Hz, 1H), 6.87 (d, J = 8 Hz, 1H), 6.42 (d, J = 8 Hz, 1H), 4.46 (d, J = 14 Hz, 1H), 3.76 (d, J = 14 Hz, 1H), 2.11 (s, 3H); 13 C NMR (55 C) δ (d, J = 6 Hz, C), (d, J = 4 Hz, C), (d, J = 5 Hz, CH), (C), (C), (d, J = 2 Hz, CH), (br d, J = 9 Hz, 6CH), (d, J = 8 Hz, C), (br, 3CH), (2CH), (2CH), (br s, 6CH), (CH), (2CH), (2CH), (d, J = 3, CH), (CH), (d, J = 12 Hz, CH), (d, J = 1 Hz, CH), (d, J = 2 Hz, CH), 73.3 (d, J = 109 Hz, C), 59.7 (CH 2 ), 39.3 (CH 3 ); 31 P NMR δ 15.3; HRMS (ESI, M+1 ion) calcd for C 42 H 37 NOP , found [(2-(N-Methyl-N-benzylamino)phenyl)(3-(2- furyl)propenoyl)methylene]triphenylphosphorane (19) A suspension of salt 15 (1.00 g, 1.81 mmol) in THF (10 ml) was stirred under nitrogen while a solution of BuLi (0.80 ml, 2.25 M, 1.81 mmol) in hexanes was added. The resulting brightly colored solution was stirred for 2 h and a solution of 1-(3-(2- furyl)propenoyl)benzotriazole (0.43 g, 1.81 mmol) in THF (5 ml) was added and the mixture was stirred for a further 18 h. Water (20 ml) was added to the solution and the mixture was extracted using ethyl acetate (2 20 ml). The combined extracts were washed with water, dried and evaporated. The resulting solid was recrystallized

9 9 (Et 2 O/EtOAc) to give the title product (0.45 g, 53%) as yellow crystals, mp C; IR (Nujol) 1617 (C=C) cm 1 ; 1 H NMR δ 7.46 (d, J = 8 Hz, 1 H), (m, 20H), (m, 4H), 6.91 (d, J = 8 Hz, 1H), 6.41 (d, J = 8 Hz, 1H), 6.27 (dd, J = 6, 3 Hz, 1H), 6.21 (s, 1H), 4.40 (d, J = 14 Hz, 1H), 3.79 (d, J = 14 Hz, 1H), 2.10 (s, 3H); 13 C NMR (55 C) δ (d, J = 6 Hz, C), (d, J = 4 Hz, C), (d, J = 2 Hz, C), (CH), (d, J = 5 Hz, CH), (C), (d, J = 10 Hz, 6CH), (d, J = 10 Hz, C), (d, J = 3 Hz, 3CH), (2CH), (d, J = 12 Hz, 6CH), (2CH), (d, J = 3 Hz, CH), (d, J = 90 Hz, 3C), (CH), (d, J = 13 Hz, CH), (d, J = 2 Hz, CH), (d, J = 2 Hz, CH), (CH), (CH), 74.9 (d, J = 108 Hz, C), 60.0 (CH 2 ), 39.5 (CH 3 ); 31 P NMR δ 16.8; HRMS (ESI, M+1 ion) calcd for C 40 H 35 NO 2 P , found [(2-(N-Methyl-N-benzylamino)phenyl)(3-(2- thienyl)propenoyl)methylene]triphenylphosphorane (20) A suspension of salt 15 (1.00 g, 1.81 mmol) in THF (10 ml) was stirred under nitrogen while a solution of BuLi (0.80 ml, 2.25 M, 1.81 mmol) in hexanes was added. The resulting brightly colored solution was stirred for 2 h and a solution of 1-(3-(2- thienyl)propenoyl)benzotriazole ( g, 1.81 mmol) in THF (5 ml) was added and the mixture was stirred for a further 18 h. Water (20 ml) was added to the solution and the mixture was extracted using ethyl acetate (2 20 ml). The combined extracts were washed with water, dried and evaporated. The resulting solid was recrystallized (Et 2 O/EtOAc) to give the title product (0.48 g, 44%) as orange crystals, mp C; IR (Nujol) 1635 (C=C) cm 1 ; 1 H NMR δ 7.58 (d, J = 14 Hz, 2H), (m, 13H), (m, 4H), 7.09 (d, J = 8 Hz, 1H), 7.04 (m, 4H), 6.09 (m, 4H), 6.36 (d, J = 8 Hz, 1H), 4.47 (d, J = 14 Hz, 1H), 3.75 (d, J = 14 Hz, 1H), 2.07 (s, 3H); 13 C NMR (55 C) δ (d, J = 5 Hz, C), (d, J = 4 Hz, C), (d, J = 2 Hz, C), (d, J = 5 Hz, CH), (C), (d, J = 10 Hz, 6CH), (d, J = 10 Hz, C), (d, J = 3 Hz, 3CH), (2CH), (d, J = 12 Hz, 6CH), (CH), (d, J = 2 Hz, CH), (2CH), (d, J = 3 Hz, CH), (CH), (CH), (d, J = 89 Hz, 3C), (d, J = 13 Hz, CH), (CH), (d, J = 2 Hz, CH), (d, J = 2 Hz, CH), 60.1 (CH 2 ), 39.4 (CH 3 ) [signal due to P=C could not be observed due to low intensity and peak broadening]; 31 P NMR δ 16.6; HRMS (ESI, M+1 ion) calcd for C 40 H 35 NOPS , found FVP of ylide 18 giving N-methylbenzo[c]carbazole (24) Ylide 18 (0.512 g, 0.85 mmol) was subjected to FVP at 700 C at torr. NMR analysis of crude product showed a mixture of Ph 3 PO, bibenzyl and other products. The mixure was purified by preparative TLC 1:1 DCM:hex to give the title product (0.130 g, 66%) as colorless crystals, mp 110 C (Lit ºC); 1 H NMR as above. FVP of ylide 19 giving N-Methylfuro[2,3-c]carbazole (25) Ylide 19 (0.56 g, 0.95 mmol) was subjected to FVP at 700 C at torr. NMR analysis of crude product showed a mixture of Ph 3 PO, bibenzyl and other products. The mixture was purified by preparative TLC (80:20 diethyl ether:hexane) to give the title product (0.136 g, 65%), mp C; 1 H NMR δ 8.20 (dt, J = 8, 1 Hz, 1H), 7.82 (dd, J = 2.4, 0.3 Hz, 1H), 7.65 (dd, J = 9, 1 Hz, 1H), 7.48 (dd, J = 6, 1 Hz, 1H), 7.47 (dd, J = 2.7,

10 10 1 Hz, 1H), 7.35 (dd, J = 9, 1 Hz, 1H), (dd, J = 2.4, 1 Hz, 1H), 7.29 (ddd, J = 8, 6, 2.7 Hz, 1H), 3.92 (s, 3H); 13 C NMR δ (C), (CH), 140.7(C), 137.2(C), (CH), (C), (CH), (C), (CH), (C), (CH), (CH), (CH), (CH), 29.5(CH 3 ) ; HRMS (ESI, M+1 ion) calcd for C 15 H 12 NO , found FVP of ylide 20 giving N-Methylthieno[2,3-c]carbazole (26) Ylide 20 (0.524 g, 0.86 mmol) was subjected to FVP at 700 C at torr. NMR analysis of crude product showed a mixture of Ph 3 PO, bibenzyl and other products. The mixture was purified by preparative TLC (1:1 diethyl ether:hexane) to give the title product (0.123 g, 60%), mp C; 1 H NMR δ 8.34 (dt, J = 8, 1 Hz, 1H), 8.07 (dd, J = 5.4, 0.5 Hz, 1H), 7.96 (ddd, J = 8.8, 1, 0.5 Hz, 1H), 7.69 (d, J = 5.4 Hz, 1H), (m, 3H), 7.33 (ddd, J = 8, 4.8, 3.6 Hz, 1H), 3.96 (s, 3H); HRMS (ESI, M+1 ion) calcd for C 15 H 12 NS , found References (1) Houben, J.; Brassert, W. Ber. Dtsch. Chem. Ges. 1906, 39, (2) Schroetev, G. Liebigs Ann. Chem. 1919, 418, (3) Flowers, W. T.; Holt, G.; Poulos, C. P.; Poulos, K. J. Chem. Soc., Perkin Trans , (4) O'Murchu, C. Synthesis 1989, (5) Cadogan, J. I. G. J. Chem. Soc. 1962, (6) Cacchi, S.; Fabrizi, G.; Marinelli, F.; Moro, L.; Pace, P. Tetrahedron 1996, 52, (7) Chernova, N. I.; Ryabokobylko, Yu. S.; Brudz', V. G.; Bolotin, B. M. Russ. J. Org. Chem. (Engl. Transl.) 1971, 7, (8) Lombardino, J. G. J. Heterocycl. Chem. 1972, 9, (9) Campaigne, E.; Ergener, L.; Hallum, J. V.; Lake, R. D. J. Org. Chem. 1959, 24, (10) Grellmann, K. H.; Schmitt, U. J. Am. Chem. Soc. 1982, 104, (11) Léost, F.; Chantegrel, B.; Deshayes, C. Tetrahedron 1997, 53, (12) Katritzky, A. R.; Zhang, Y.; Singh, S. K. Synthesis 2003, (13) Katritzky, A. R.; Wang, M.; Zhang, S. Arkivoc 2001, ix,

11 11 1 H NMR spectrum of ylide 8 31 P NMR spectrum of ylide 8

12 12 13 C NMR spectrum of ylide 8 1 H NMR spectrum of ylide 9

13 13 31 P NMR spectrum of ylide 9 13 C NMR spectrum of ylide 9

14 14 1 H NMR spectrum of 3-phenylquinoline from FVP of 9 1 H NMR spectrum of 2-(N-methyl-N-tosylamino)benzyl alcohol

15 15 13 C NMR spectrum of 2-(N-methyl-N-tosylamino)benzyl alcohol 1 H NMR spectrum of salt 13

16 16 31 P NMR spectrum of salt C NMR spectrum of salt 13

17 17 1 H NMR spectrum of ylide P NMR spectrum of ylide 16

18 18 13 C NMR spectrum of ylide 16 1 H NMR spectrum of 2-(N-Methyl-N-methanesulfonylamino)benzyl alcohol

19 19 13 C NMR spectrum of 2-(N-Methyl-N-methanesulfonylamino)benzyl alcohol 1 H NMR spectrum of salt 14

20 20 31 P NMR spectrum of salt C NMR spectrum of salt 14

21 21 1 H NMR spectrum of ylide P NMR spectrum of ylide 17

22 13 C NMR spectrum of ylide 17 22

23 23 1 H NMR spectrum of 2-(N-benzyl-N-methylamino)benzyl alcohol 13 C NMR spectrum of 2-(N-benzyl-N-methylamino)benzyl alcohol

24 24 1 H NMR spectrum of salt P NMR spectrum of salt 15

25 25 13 C NMR spectrum of salt 15 1 H NMR spectrum of ylide 18

26 26 31 P NMR spectrum of ylide C NMR spectrum of ylide 18

27 27 1 H NMR spectrum of ylide P NMR spectrum of ylide 19

28 28 13 C NMR spectrum of ylide 19 1 H NMR spectrum of ylide 20

29 29 31 P NMR spectrum of ylide C NMR spectrum of ylide 20

30 30 1 H NMR spectrum of N-methylfuro[2,3-c]carbazole C NMR spectrum of N-methylfuro[2,3-c]carbazole 25

31 1 H NMR spectrum of N-methylthieno[2,3-c]carbazole 26 31