Supporting Information. Palladium-Catalyzed Formylation of Aryl Iodides with HCOOH as

Supporting Information Palladium-Catalyzed Formylation of Aryl Iodides with HCOOH as CO Source Guanglong Sun,,, Xue Lv,,, Yinan Zhang, Min Lei,*,, and Lihong Hu*, Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Stake Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, PR China Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China University of Chinese Academy of Sciences, Beijing 100049, PR China G. Sun and X. Lv contributed equally. E-mail: mlei@simm.ac.cn (Lei M.); lhhu@simm.ac.cn (Hu L.) 1

Table of Contents General information... 1 Table S1. Solvent Screen a... 2 Table S2. Solvent Equivalencies Screen a... 2 Table S3. Palladium Screen a... 3 Table S4. Palladium Equivalencies Screen a... 3 Table S5. HCOOH Equivalencies Screen a... 4 Table S6. Base Screen a... 5 Table S7. I 2 Equivalencies Screen a... 5 Table S8. PPh 3 Equivalencies Screen a... 6 Table S9. Temperature Screen a... 7 Table S10. Time Screen a... 7 Table S11. Leaving groups studies a... 8 Experimental Procedures... 9 References... 21 1 H and 13 C NMR of 3a... 22 1 H and 13 C NMR of 3b... 23 1 H and 13 C NMR of 3c... 24 1 H and 13 C NMR of 3d... 25 1 H and 13 C NMR of 3e... 26 1 H and 13 C NMR of 3f... 27 1 H and 13 C NMR of 3g... 28 1 H and 13 C NMR of 3h... 29 1 H and 13 C NMR of 3i... 30 1 H and 13 C NMR of 3j... 31 1 H and 13 C NMR of 3k... 32 1 H and 13 C NMR of 3l... 33 1 H and 13 C NMR of 3m... 34 1 H and 13 C NMR of 3n... 35 1

1 H and 13 C NMR of 3o... 36 1 H and 13 C NMR of 3p... 37 1 H and 13 C NMR of 3q... 38 1 H and 13 C NMR of 3r... 39 1 H and 13 C NMR of 3s... 40 1 H and 13 C NMR of 3t... 41 1 H and 13 C NMR of 3u... 42 1 H and 13 C NMR of 3v... 43 1 H and 13 C NMR of 3w... 44 1 H and 13 C NMR of 3x... 45 1 H and 13 C NMR of 3y... 46 1 H and 13 C NMR of 4a... 47 1 H and 13 C NMR of 5a... 48 1 H and 13 C NMR of 6a... 49 1 H and 13 C NMR of 7a... 50 1 H and 13 C NMR of 8a... 51 1 H and 13 C NMR of 9a... 52 1 H and 13 C NMR of 10... 53 1 H and 13 C NMR of Ph 3 PO... 54 2

General information All reactions were performed in flame-dried glassware using sealed tube. Liquids and solutions were transferred with syringes. All solvents and chemical reagents were obtained from commercial sources and used without further purifications. 1 H and 13 C NMR spectra were recorded with tetramethylsilane as an internal reference at 400 MHz and 101 MHz, respectively. Spectra were referenced to the residual solvent peak of CDCl 3 or DMSO-d 6 unless otherwise noted. Low and high-resolution mass spectra were obtained in the ESI mode. Flash column chromatography on silica gel (200-300 mesh) was used for the routine purification of reaction products. The column output was monitored by analytical thin-layer chromatography (TLC) on silica gel (100-200 mesh) precoated on glass plates (15 x 50 mm), and spots were visualized by ultraviolet light at 254 or 365 nm. Melting points were recorded on a WRS-1B melting point apparatus and are uncorrected. Commercially available chemicals were obtained from Acros Organics, Strem Chemicals, Alfa Aesar, Adamas-beta, J&K and TCI. Initial screening quickly identified Scheme S1 as a workable condition with a moderate yield. Table S1-S10 summarizes in-depth condition tuning for the reaction of 4-methoxyiodobenzene with HCOOH. Scheme S1. Reaction of Aryl Iodides with HCOOH. Reaction conditions: I 2 (1.3 mmol, 1.3 equiv), PPh 3 (1.5 mmol, 1.5 equiv), Pd(OAc) 2 (5 mol %), Et 3 N (10 mmol, 10 equiv), 1a (1 mmol, 1 equiv) and 2 (8 mmol, 8 equiv) were stirred in CH 3 CN (4 ml) at 80 C for 2 h. a Yield was determined by LC-MS. 1

Table S1. Solvent Screen a Entry Solvent Yield b (%) 1 CH 3CN 57 2 Toluene 77 3 DMF 48 4 DCM 71 5 Py 67 6 THF 53 a Reaction conditions: I 2 (1.3 mmol, 1.3 equiv), PPh 3 (1.5 mmol, 1.5 equiv), Pd(OAc) 2 (5 mol%), Et 3 N (10 mmol, 10 equiv), 1a (1 mmol, 1 equiv) and 2 (8 mmol, 8 equiv) were stirred in solvent (4 ml) at 80 C for 2 h. b Yields were determined by LC-MS. Table S2. Solvent Equivalencies Screen a Entry Toluene (ml) Yield b (%) 1 2 64 2 3 68 3 4 77 4 6 74 5 8 70 2

a Reaction conditions: I2 (1.3 mmol, 1.3 equiv), PPh 3 (1.5 mmol, 1.5 equiv), Pd(OAc) 2 (5 mol %), Et 3 N (10 mmol, 10 equiv), 1a (1 mmol, 1 equiv) and 2 (8 mmol, 8 equiv) were stirred in toluene at 80 C for 2 h. b Yields were determined by LC-MS. Table S3. Palladium Screen a Entry [Pd] Yield b (%) 1 Pd(OAc) 2 77 2 Pd(TFA) 2 75 3 PdSO 4 66 4 PdCl 2 73 5 Pd 2(dba) 3 60 a Reaction conditions: I2 (1.3 mmol, 1.3 equiv), PPh 3 (1.5 mmol, 1.5 equiv), Palladium (5 mol %), Et 3 N (10 mmol, 10 equiv), 1a (1 mmol, 1 equiv) and 2 (4 mmol, 8 equiv) were stirred in toluene (4 ml) at 80 C for 2 h. b Yields were determined by LC-MS. Table S4. Palladium Equivalencies Screen a Entry Pd(OAc) 2 (mol%) Yield b (%) 1 1 27 2 2 62 3 3 80 3

4 4 80 5 5 77 6 6 70 7 7 69 a Reaction conditions: I2 (1.3 mmol, 1.3 equiv), PPh 3 (1.5 mmol, 1.5 equiv), Pd(OAc) 2, Et 3 N (10 mmol, 10 equiv), 1a (1 mmol, 1 equiv) and 2 (8 mmol, 8 equiv) were stirred in toluene (4 ml) at 80 C for 2 h. b Yield was determined by LC-MS. Table S5. HCOOH Equivalencies Screen a Entry HCOOH (equiv) Yield b (%) 1 2 42 2 3 68 3 4 76 4 5 76 5 6 77 6 8 80 a Reaction conditions: I2 (1.3 mmol, 1.3 equiv), PPh 3 (1.5 mmol, 1.5 equiv), Pd(OAc) 2 (3 mol %), Et 3 N (10 mmol, 10 equiv), 1a (1 mmol, 1 equiv) and 2 were stirred in toluene (4 ml) at 80 C for 2 h. b Yields were determined by LC-MS. 4

Table S6. Base Screen a Entry Base equiv Yield b (%) 1 Et 3N 10 78 2 DIPEA 10 71 3 K 2CO 3 10 2 4 DMAP 10 0 5 DBU 10 54 6 DABCO 10 0 7 TMEDA 10 64 8 Et 3N 4 11 9 Et 3N 5 38 10 Et 3N 6 78 11 Et 3N 7 78 12 Et 3N 8 75 a Reaction conditions: I2 (1.3 mmol, 1.3 equiv), PPh 3 (1.5 mmol, 1.5 equiv), Pd(OAc) 2 (3 mol %), Base, 1a (1 mmol, 1 equiv) and 2 (4 mmol, 4 equiv) were stirred in toluene (4 ml) at 80 C for 2 h. b Yields were determined by LC-MS. Table S7. I 2 Equivalencies Screen a Entry I 2 [equiv] Yield b (%) 1 1.0 34 5

2 1.1 59 3 1.2 78 4 1.3 78 5 1.4 73 a Reaction conditions: I2, PPh 3 (1.5 mmol, 1.5 equiv), Pd(OAc) 2 (3 mol %), Et 3 N (6 mmol, 6 equiv), 1a (1 mmol, 1 equiv) and 2 (4 mmol, 4 equiv) were stirred in toluene (4 ml) at 80 C for 2 h. b Yields were determined by LC-MS. Table S8. PPh 3 Equivalencies Screen a Entry PPh 3 [equiv] Yield b (%) 1 1.1 75 2 1.2 86 3 1.3 82 4 1.4 80 1.5 78 5 2.0 24 a Reaction conditions: I2 (1.2 mmol, 1.2 equiv), PPh 3, Pd(OAc) 2 (3 mol %), Et 3 N (6 mmol, 6 equiv), 1a (1 mmol, 1 equiv) and 2 (4 mmol, 4 equiv) were stirred in toluene (4 ml) at 80 C for 2 h. b Yields were determined by LC-MS. 6

Table S9. Temperature Screen a Entry Temperature [ C] Yield b (%) 1 40 0 2 60 29 3 70 60 4 80 86 5 90 86 6 100 85 a Reaction conditions: I2 (1.2 mmol, 1.2 equiv), PPh 3 (1.2 mmol, 1.2 equiv), Pd(OAc) 2 (3 mol %), Et 3 N (6 mmol, 6 equiv), 1a (1 mmol, 1 equiv) and 2 (2 mmol, 4 equiv) were stirred in toluene (4 ml) for 2 h. b Yields were determined by LC-MS. Table S10. Time Screen a Entry Time [h] Yield b (%) 1 0.5 52 2 1 76 3 2 86 4 3 86 5 4 86 7

a Reaction conditions: I2 (1.2 mmol, 1.2 equiv), PPh 3 (1.2 mmol, 1.2 equiv), Pd(OAc) 2 (3 mol %), Et 3 N (6 mmol, 6 equiv), 1a (1 mmol, 1 equiv) and 2 (2 mmol, 4 equiv) were stirred in toluene (4 ml) at 80 C. b Yields were determined by LC-MS. Table S11. Leaving groups studies a Entry -X equiv Yield b (%) 1 TsO- 10 7 2 TfO- 10 10 3 Br- 12 5 4 Cl- 12 0 a Reaction conditions: I2 (1.2 mmol, 1.2 equiv), PPh 3 (1.2 mmol, 1.2 equiv), Pd(OAc) 2 (3 mol %), Et 3 N (6 mmol, 6 equiv), 1 (1 mmol, 1 equiv) and 2 (4 mmol, 4 equiv) were stirred in toluene (4 ml) at 80 C for 10-12 h. b Yields were determined by LC-MS. 8

Scheme S2. Ph 3 PO as a by-product was formed. Experimental Procedures Synthesis of 3a-y and 7-9a: PPh 3 (1.2 mmol, 1.2 equiv), I 2 (1.2 mmol, 1.2 equiv) and toluene (4 ml) were added to a 10 ml test tube equipped with a stir bar, which was stirred for 10 min at room temperature. Then aryl iodides 1a-y or 7-9 (1 mmol, 1 equiv), Pd(OAc) 2 (6.8 mg, 3 mol %), and Et 3 N (6 mmol, 6 equiv) were added into the solution. After HCOOH (4 mmol, 4 equiv) was added, the tube was immediately sealed and the mixture was stirred at 80 o C for 2-4 h. Then the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate 10:1) to provide the corresponding products 3a-y and 7-9a. Compounds of 7-9 were synthesized according to the reported methods. 1 9

Synthesis of 4-6a: PPh 3 (2.4 mmol, 2.4 equiv), I 2 (2.4 mmol, 2.4 equiv) and toluene (8 ml) were added to a 25 ml test tube equipped with a stir bar, which was stirred for 10 min at room temperature. Then aryl di-iodides 4, 5 or 6 (1 mmol, 1 equiv), Pd(OAc) 2 (13.6 mg, 6 mol %), and Et 3 N (12 mmol, 12 equiv) were added into the solution. After HCOOH (8 mmol, 8 equiv) was added, the tube was immediately sealed and the mixture was stirred at 80 o C for 4 h. Then the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate 10:1) to provide the corresponding products 4-6a. Synthesis of 10: PPh 3 (1.2 mmol, 1.2 equiv), I 2 (1.2 mmol, 1.2 equiv) and toluene (4 ml) were added to a 10 ml test tube equipped with a stir bar, which was stirred for 10 min at room temperature. Then 1a (1 mmol, 1 equiv), Pd(OAc) 2 (6.8 mg, 3 mol %), and Et 3 N (6 mmol, 6 equiv) were added into the solution. After DCOOD (4 mmol, 4 equiv) was added, the tube was immediately sealed and the mixture was stirred at 80 o C for 4 h. Then the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate 10:1) to provide the corresponding products 10. 4-methoxybenzaldehyde (3a): O H O Colorless oil; 118 mg (86%). 1 H NMR (400 MHz, CDCl 3 ) δ 9.85 (s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 3.86 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 190.9, 164.7, 132.0 (2C), 130.0, 114.4 (2C), 55.6. ESI-MS m/z 137.5, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 8 O 2, 137.0597; found 137.0599. 2-methylbenzaldehyde (3b): 10

Colorless oil; 86 mg (71%). 1 H NMR (400 MHz, CDCl 3 ) δ 10.24 (s, 1H), 7.77 (dd, J = 8.0, 1.2 Hz, 1H), 7.45 (td, J = 8.0, 1.2 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 2.65 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 192.9, 140.6, 134.2, 133.7, 132.1, 131.8, 126.3, 19.6. ESI-MS m/z 121.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 8 O, 121.0648; found 121.0652. 3-methylbenzaldehyde (3c): Colorless oil; 93 mg (77%). 1 H NMR (400 MHz, CDCl 3 ) δ 9.96 (s, 1H), 7.65-7.66 (m, 2H), 7.37-7.43 (m, 2H), 2.40 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 192.6, 138.9, 136.5, 135.3, 130.0, 128.9, 127.2, 21.2. ESI-MS m/z 121.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 8 O, 121.0648; found 121.0649. 4-methylbenzaldehyde (3d): Colorless oil; 100 mg (83%). 1 H NMR (400 MHz, CDCl 3 ) δ 9.81 (s, 1H), 7.63 (d, J = 7.6 Hz, 2H), 7.17 (d, J = 7.6 Hz, 2H), 2.27 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 191.5, 145.2, 134.0, 129.5 (2C), 129.4 (2C), 21.4. ESI-MS m/z 121.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 8 O, 121.0648; found 121.0658. 2-methoxybenzaldehyde (3e): White crystal; 93 mg (68%); mp = 39-40 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.45 (s, 1H), 11

7.79-7.81 (m, 1H), 7.50-7.55 (m, 1H), 6.95-7.00 (m, 2H), 3.90 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 189.7, 161.8, 136.0, 128.4, 124.8, 120.6, 111.7, 55.6. ESI-MS m/z 137.5, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 8 O 2, 137.0597; found 137.0609. 3-methoxybenzaldehyde (3f): Yellow oil; 110 mg (80%). 1 H NMR (400 MHz, CDCl 3 ) δ 9.81 (s, 1H), 7.23-7.31 (m, 3H), 7.02 (d, J = 7.2 Hz, 1H), 3.69 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 191.8, 159.9, 137.6, 129.8, 123.0, 121.0, 112.0, 55.0 ESI-MS m/z 137.5, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 8 O 2, 137.0597; found 137.0579. benzaldehyde (3g): Colorless oil; 96 mg (90%). 1 H NMR (400 MHz, CDCl 3 ) δ 9.97 (s, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.59 (t, J = 8.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 192.4, 136.4, 134.4, 129.7 (2C), 129.0 (2C). ESI-MS m/z 107.6, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 6 O, 107.0491; found 107.0482. 3,4-dimethoxybenzaldehyde (3h): White crystal; 137 mg (82%); mp = 41-42 C. 1 H NMR (400 MHz, CDCl 3 ) δ 9.83 (s, 1H), 7.43 (dd, J = 8.0, 1.6 Hz, 1H), 7.38 (d, J = 1.6 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 3.94 (s, 3H), 3.92 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 191.0, 154.5, 149.6, 130.2, 127.0, 110.4, 108.9, 56.2, 56.1. 12

ESI-MS m/z 167.5, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 9 H 10 O 3, 167.0703; found 167.0710. 3,4,5-trimethoxybenzaldehyde (3i): White crystal; 154 mg (78%); mp = 68-70 C. 1 H NMR (400 MHz, CDCl 3 ) δ 9.83 (s, 1H), 7.09 (s, 2H), 3.90 (s, 3H), 3.89 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 191.1, 153.6, 143.5, 131.7 (2C), 106.7 (2C), 61.0, 56.3 (2C). ESI-MS m/z 197.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 10 H 12 O 4, 197.0708; found 197.0702. 2-chlorobenzaldehyde (3j): Colorless oil; 122 mg (86%). 1 H NMR (400 MHz, CDCl 3 ) δ 10.44 (s, 1H), 7.87 (dd, J = 8.0, 1.6 Hz, 1H), 7.47-7.52 (m, 1H), 7.40 (dd, J = 8.0, 1.6 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ 189.7, 137.9, 135.1, 132.5, 130.6, 129.4, 127.3. ESI-MS m/z 141.6, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 5 ClO, 141.0102; found 141.0115. 3-chlorobenzaldehyde (3k): Colorless oil; 133 mg (94%). 1 H NMR (400 MHz, CDCl 3 ) δ 9.94 (s, 1H), 7.81 (s, 1H), 7.73 (t, J = 8.0 Hz, 1H), 7.53-7.57 (m, 1H), 7.45 (d, J = 8.0 Hz, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ 190.9, 137.8, 135.5, 134.4, 130.4, 129.3, 128.0. ESI-MS m/z 141.6, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 5 ClO, 141.0102; found 141.0105. 13

4-chlorobenzaldehyde (3l): White solid; 130 mg (92%); mp = 47-48 C. 1 H NMR (400 MHz, CDCl 3 ) δ 9.97 (s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 190.9, 141.0, 134.8, 131.0 (2C), 129.5 (2C). ESI-MS m/z 141.6, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 5 ClO, 141.0102; found 141.0102. 4-bromobenzaldehyde (3m): Yellow crystal; 148 mg (80%); mp = 56-57 C. 1 H NMR (400 MHz, CDCl 3 ) δ 9.96 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 191.1, 135.2, 132.5 (2C), 131.1 (2C), 129.9. ESI-MS m/z 185.0, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 5 BrO, 184.9597; found 184.9583. 4-fluorobenzaldehyde (3n): Colorless oil; 95 mg (76%). 1 H NMR (400 MHz, CDCl 3 ) δ 9.91 (s, 1H), 7.84-7.88 (m, 2H), 7.13-7.18 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 190.6, 167.8 and 165.2 (d, 1 J CF = 257.5 Hz, 1C), 133.0 and 132.9 (d, 4 J CF = 2.5 Hz, 1C), 132.3 and 132.2 (d, 3 J CF = 9.7 Hz, 2C), 116.5 and 116.2 (d, 2 J CF = 22.4 Hz, 2C). ESI-MS m/z 125.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 5 FO, 125.0397; found 125.0397. 4-formylbenzonitrile (3o): 14

Yellow solid; 74 mg (56%); mp = 99-100 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.08 (s, 1H), 7.98 (d, J = 8.0 Hz, 2H), 7.83 (d, J = 8.0 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 190.7, 138.8, 133.0 (2C), 129.9 (2C), 117.8, 117.6. ESI-MS m/z 132.7, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 5 NO, 132.0444; found 132.0443. 4-nitrobenzaldehyde (3p): White crystal; 59 mg (39%); mp = 104-106 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.14 (s, 1H), 8.36 (d, J = 8.8 Hz, 2H), 8.06 (d, J = 8.8 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 190.4, 151.2, 140.1, 130.5 (2C), 124.3 (2C). ESI-MS m/z 152.5, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 5 NO 3, 152.0342; found 152.0355. 2-hydroxybenzaldehyde (3q): Colorless oil; 98 mg (80%). 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.71 (s, 1H), 10.25 (s, 1H), 7.66 (dd, J = 8.0, 1.6 Hz, 1H), 7.48-7.52 (m, 1H), 7.01 (d, J = 8.0, 1H), 6.94 (t, J = 8.0 Hz, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 192.0, 161.8, 136.4, 129.4, 122.3, 119.5, 117.2. ESI-MS m/z 123.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 6 O 2, 123.0441; found 123.0442. 3-hydroxybenzaldehyde (3r): 15

White crystal; 108 mg (88%); mp = 103-105 C. 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.94 (s, 1H), 9.91 (s, 1H), 7.40 (t, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.25-7.26 (m, 1H), 7.09-7.12 (m, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 193.1, 158.0, 137.7, 130.3, 121.8, 121.1, 114.7. ESI-MS m/z 123.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 6 O 2, 123.0441; found 123.0446. 4-hydroxybenzaldehyde (3s): White crystal; 103 mg (84%); mp = 116-118 C. 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.59 (s, 1H), 9.79 (d, J = 1.6 Hz, 1H), 7.76 (dd, J = 8.0, 2.0 Hz, 2H), 6.94 (dd, J = 8.0, 1.6 Hz, 2H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 190.9, 163.3, 132.1 (2C), 128.4, 115.8 (2C). ESI-MS m/z 123.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 7 H 6 O 2, 123.0441; found 123.0433. 3-formylbenzoic acid (3t): White solid; 124 mg (82%); mp = 171-173 C. 1 H NMR (400 MHz, DMSO-d 6 ) δ 13.35 (s, 1H), 10.10 (s, 1H), 8.44 (s, 1H), 8.22-8.25 (m, 1H), 8.12-8.15 (m, 1H), 7.71-7.76 (m, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 192.8, 166.4, 136.4, 134.8, 133.1, 131.7, 130.3, 129.6. ESI-MS m/z 151.6, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 6 O 3, 151.0390; found 151.0381. 4-formylbenzoic acid (3u): White solid; 116 mg (77%); mp = 245-246 C. 1 H NMR (400 MHz, DMSO-d 6 ) δ 13.40 (s, 1H), 10.10 (s, 1H), 8.13 (d, J = 8.0 Hz, 2H), 8.01 (d, J = 8.0 Hz, 2H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 193.0, 166.6, 138.9, 135.6, 129.9 (2C), 129.5 (2C). ESI-MS m/z 151.6, [M+H] + ; HRMS (ESI): 16

[M+H] + calculated for C 8 H 6 O 3, 151.0390; found 151.0412. nicotinaldehyde (3v): Colorless oil; 75 mg (70%). 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.10 (s, 1H), 9.07 (d, J = 1.6 Hz, 1H), 8.84 (dd, J = 4.8, 1.6 Hz, 1H), 8.23 (td, J = 8.0, 1.6 Hz, 1H), 7.61 (dd, J = 4.8, 8.0 Hz, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 192.5, 154.6, 151.5, 136.0, 131.3, 124.4. ESI-MS m/z 108.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 6 H 5 NO, 108.0444; found 108.0440. isonicotinaldehyde (3w): Yellow oil; 68 mg (63%). 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.08 (s, 1H), 8.86 (dd, J = 8.4, 1.6 Hz, 2H), 7.78 (dd, J = 8.4, 1.6 Hz, 2H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 193.3, 151.1 (2C), 141.3, 122.1 (2C). ESI-MS m/z 108.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 6 H 5 NO, 108.0444; found 108.0442. furan-2-carbaldehyde (3x): Reddish brown oil; 58 mg (60%). 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.61 (s, 1H), 8.08 (d, J = 1.6 Hz, 1H), 7.53 (d, J = 3.6 Hz, 1H), 7.53 (dd, J = 3.6, 1.6 Hz, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 178.4, 152.5, 149.1, 123.0, 112.9. ESI-MS m/z 97.6, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 5 H 4 O 2, 97.0284; found 97.0283. thiophene-2-carbaldehyde (3y): 17

Yellow oil; 72 mg (64%). 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.90 (s, 1H), 7.75 (dd, J = 4.0, 1.2 Hz, 1H), 7.73 (td, J = 4.8, 1.2 Hz, 1H), 7.17 (dd, J = 4.8, 4.0 Hz, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 183.1, 143.9, 136.5, 135.2, 128.4. ESI-MS m/z 113.4, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 5 H 4 OS, 113.0056; found 113.0059. o-phthalaldehyde (4a): White crystal; 15 mg (11%); mp = 52-54 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.49 (s, 2H), 7.92-7.96 (m, 2H), 7.73-7.77 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 192.5 (2C), 136.4 (2C), 133.8 (2C), 131.2 (2C). ESI-MS m/z 135.5, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 6 O 2, 135.0441; found 135.0440. m-phthalaldehyde (5a): White crystal; 102 mg (76%); mp = 88-90 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.09 (s, 2H), 8.35 (s, 1H), 8.13 (d, J = 7.6 Hz, 2H), 7.71 (t, J = 7.6 Hz, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ 191.1 (2C), 137.1 (2C), 134.7 (2C), 131.0, 130.0. ESI-MS m/z 135.5, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 6 O 2, 135.0441; found 135.0452. 1,4-phthalaldehyde (6a): 18

White crystal; 69 mg (51%); mp = 113-114 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.11 (t, J = 2.0 Hz, 2H), 8.02 (d, J = 2.0 Hz, 4H). 13 C NMR (101 MHz, CDCl 3 ) δ 191.6 (2C), 140.1 (2C), 130.2 (4C). ESI-MS m/z 135.5, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 6 O 2, 135.0441; found 135.0446. 15-formyl-vindoline (7a): Yellow solid; 364 mg (75%); mp = 259-260 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.15 (s, 1H), 9.71 (s, 1H), 7.54 (s, 1H), 5.93 (s, 1H), 5.86-5.90 (m, 1H), 5.34 (s, 1H), 5.25 (d, J = 10.0 Hz, 1H), 3.94 (s, 1H), 3.92 (s, 3H), 3.80 (s, 3H), 3.40-3.51 (m, 2H), 2.78-2.86 (m, 5H), 2.55-2.62 (m, 1H), 2.26-2.33 (m, 2H), 2.07 (s, 3H), 1.56-1.65 (m, 1H), 1.03-1.12 (m, 1H), 0.52 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 187.2, 171.8, 170.7, 165.5, 158.5, 130.2, 125.6, 124.4, 122.3, 116.9, 90.4, 83.2, 79.4, 76.0, 66.8, 55.8, 52.5, 52.2, 51.5, 51.0, 43.8, 42.9, 36.4, 31.1, 21.1, 7.6. ESI-MS m/z 485.7, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 26 H 32 N 2 O 7, 485.2282; found 485.2296. 10-formyl-tabersonine (8a): O N H N H O O Yellow solid; 311 mg (85%); mp > 300 C. 1 H NMR (400 MHz, CDCl 3 ) δ 9.83 (s, 1H), 9.29 (s, 1H), 7.77 (s, 1H), 7.67 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 5.80 (dd, J = 10.0, 3.6 Hz, 1H), 5.69 (d, J = 10.0 Hz, 1H), 3.77 (s, 3H), 3.46 (dd, J = 16.0, 4.0 Hz, 1H), 3.22 (d, J = 16.0 Hz, 1H), 3.06 (t, J = 6.8 Hz, 1H), 2.74-2.79 (m, 2H), 2.56 (d, J = 16.0 Hz, 1H), 2.45 (d, J = 16.0 Hz, 1H), 2.02-2.10 (m, 1H), 1.80 (dd, J = 11.6, 4.4 Hz, 1H), 0.92-0.99 (m, 1H), 0.84-0.89 (m, 1H), 0.63 (t, J = 7.6 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 190.9, 168.8, 164.9, 149.0, 139.1, 133.9, 19

132.7, 130.2, 125.2, 121.4, 109.0, 95.4, 69.9, 54.5, 51.4, 51.0, 50.5, 44.8, 41.4, 28.7, 27.0, 7.6. ESI-MS (m/z) 365.6, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 22 H 24 N 2 O 3, 365.1860; found 365.1869. 10-formyl-apovincamine (9a): Yellow solid; 248 mg (68%); mp > 300 C. 1 H NMR (400 MHz, CDCl 3 ) δ 10.03 (s, 1H), 8.01 (s, 1H), 7.70 (dd, J = 9.2, 1.2 Hz, 1H), 7.32 (d, J = 8.8 Hz, 1H), 6.30 (s, 1H), 4.13 (s, 1H), 3.97 (s, 3H), 3.38 (dd, J = 14.0, 6.0 Hz, 1H), 3.22-3.30 (m, 1H), 3.02-3.11 (m, 1H), 2.53-2.66 (m, 3H), 1.85-2.00 (m, 2H), 1.67-1.71 (m, 1H), 1.53-1.56 (m, 1H), 1.40-1.45 (m, 1H), 1.02 (t, J = 7.6 Hz, 3H), 0.95 (dd, J = 14.0, 3.6 Hz, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ 192.3, 163.3, 137.4, 133.3, 130.8, 129.6, 129.3, 127.7, 123.2, 121.7, 113.0, 110.3, 55.5, 52.7, 51.2, 44.9, 37.8, 28.6, 27.2, 20.2, 16.2, 8.7. ESI-MS (m/z) 365.6, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 22 H 24 N 2 O 3, 365.1860; found 365.1851. compound (10): Colorless oil; 113 mg (82%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (dd, J = 8.4, 1.6 Hz, 2H), 6.89 (dd, J = 8.4, 1.6 Hz, 2H), 3.76 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 190.5 and 190.3 and 190.0 (t, 1 J CD = 26.4 Hz, 1C), 164.5, 131.7 (2C), 129.7, 114.1 (2C), 55.4. ESI-MS (m/z) 138, [M+H] + ; HRMS (ESI): [M+H] + calculated for C 8 H 8 DO 2, 138.0660; found 138.0658. triphenyl phosphine oxide: 20

O P White solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.63-7.68 (m, 6H), 7.51-7.55 (m, 3H), 7.42-7.47 (m, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 133.2 (3C), 132.2 and 132.1 (d, 2 J CP = 9.9 Hz, 6C), 132.0 (3C), 128.7 and 128.5 (d, 3 J CP = 12.2 Hz,6C). ESI-MS (m/z) 279, [M+H] +. References 1 (a) Johnson, P. D.; Sohn, J. H.; Rawal, V. H. J. Org. Chem. 2006, 71, 7899. (b) Lewin, G.; Rolland, Y.; Poisson, J. Heterocycles. 1980, 14, 1915. (c) Gabor, M.; Tibor, K. Synth. Commun. 1989, 19, 3415. 21

1 H and 13 C NMR of 3a 22

1 H and 13 C NMR of 3b 23

1 H and 13 C NMR of 3c 24

1 H and 13 C NMR of 3d 25

1 H and 13 C NMR of 3e 26

1 H and 13 C NMR of 3f 27

1 H and 13 C NMR of 3g 28

1 H and 13 C NMR of 3h 29

1 H and 13 C NMR of 3i 30

1 H and 13 C NMR of 3j 31

1 H and 13 C NMR of 3k 32

1 H and 13 C NMR of 3l 33

1 H and 13 C NMR of 3m 34

1 H and 13 C NMR of 3n 35

1 H and 13 C NMR of 3o 36

1 H and 13 C NMR of 3p 37

1 H and 13 C NMR of 3q 38

1 H and 13 C NMR of 3r 39

1 H and 13 C NMR of 3s 40

1 H and 13 C NMR of 3t 41

1 H and 13 C NMR of 3u 42

1 H and 13 C NMR of 3v 43

1 H and 13 C NMR of 3w 44

1 H and 13 C NMR of 3x 45

1 H and 13 C NMR of 3y 46

1 H and 13 C NMR of 4a 47

1 H and 13 C NMR of 5a 48

1 H and 13 C NMR of 6a 49

1 H and 13 C NMR of 7a 50

1 H and 13 C NMR of 8a 51

1 H and 13 C NMR of 9a 52

1 H and 13 C NMR of 10 53

1 H and 13 C NMR of Ph 3 PO 54