Supporting Information. Sustainable Manganese-Catalyzed Solvent-Free Synthesis of Pyrroles from 1,4-Diols and Primary Amines

Transcription

1 S1 Sustainable Manganese-Catalyzed Solvent-Free Synthesis of Pyrroles from 1,4-Diols and Primary Amines Jannik C. Borghs, Yury Lebedev, Magnus Rueping* and Osama El-Sepelgy*

2 S2 Table of Contents I - General Information II - Synthesis of the Manganese complexes III - General Procedures and characterization of the products IV - NMR Spectra of the products V - References

3 S3 I - General Information Reactions were carried out under ambient atmosphere unless otherwise noted. All air-sensitive compounds and reactions were performed under an inert atmosphere of argon using standard Schlenk and glovebox techniques. All glassware was stored in an oven or flame-dried prior to use. Anhydrous solvents were obtained either by filtration through drying columns on an mbraun system (Acetonitrile, Et 2 O, DCM, Pentane, Toluene). Purified compounds were further dried under high vacuum ( Torr). Yields refer to purified and spectroscopically pure compounds. Analytical thin-layer chromatography (TLC) was performed using silica gel 60 pre-coated aluminium plates (Macherey- Nagel 0.20 mm thickness) with a fluorescent indicator UV254. Visualization was performed with standard phosphomolybdic acid stain (10 g in 100 ml EtOH) or UV light. Column chromatography was performed using Macherey-Nagel Aluminium oxide 90 neutral ( μm). Solvent mixtures are understood as volume/volume. 1 H-NMR, 13 C-NMR and 31 P-NMR spectra were recorded on VNMRS- 400, VNMRS-600 or Mercury 300 spectrometer in CDCl 3. Chemical shifts (δ) are reported in ppm and multiplicities are indicated: s (singlet), d (doublet), dd (doublet of doublet, t (triplet), dt (doublet) of triplet), td (triplet of doublet), q, (quartet), quint (quintet) m (multiplet); coupling constants (J) are in Hertz (Hz). Mass spectra (MS)-EI, 70 ev) were conducted on Finnigan MAT SSQ 700, unless otherwise specified, respectively. IR spectra were recorded on a Perkin Elmer Spectrum 100 spectrometer and are reported in terms of frequency of absorption (cm -1 ).

4 S4 II Synthesis of the Manganese Complexes Synthesis of the Manganese Complex (Mn-1) V. Zubar; Y. Lebedev; L. M. Azofra, L. Cavallo, O. El-Sepelgy; M. Rueping, Angew. Chem. Int. Ed. 2018, 57, A 50 ml Schlenk tube was charged with the PNN pincer ligand (300 mg, 1.07 mmol, 1 eq.) and Mn(CO) 5 Br (293 mg, 1.07 mmol, 1.0 eq.). The Schlenk tube was evacuated and backfilled with argon for several time. Afterwards, 15 ml of degassed THF was added and the reaction mixture was stirred at 80 C for 20 h. The suspension was allowed to cool to room temperature and the yellow precipitate was filtered off and washed with diethyl ether and n-hexane. The remaining solid was dried under vacuum to afford the complex Mn-1 as a yellow powder (0.49 g, 84% yield). 1 H NMR: (600 MHz, DMSO-d 6 ): δ (m, 1H), (m, 2H), (m, 1H), (m, 4H), (m, 1H), (m, 2H), (m, 2H), (m, 1H), (m, 1H), 4.38 (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H). 13 C NMR: (151 MHz, DMSO-d 6 ): δ 221.2, 219.9, 215.3, 162.1, 153.0, 139.2, 132.4, 132.0, 131.1, 131.0, 130.9, 130.8, 129.9, 129.8, 129.6, 125.0, 122.4, 59.8, 53.8 (d, J = 8.8 Hz), 22.7 (d, J = 22.7 Hz). 31 P NMR: (242 MHz, DMSO-d 6 ): δ IR (ATR): ν 3045, 2891, 2024, 1914, 1843, 1477, 1434, 1099, 892, 752, 693 cm -1 HRMS (ESI): calc. for C 23 H 21 MnN 2 O 3 P [M-Br] + : , found

5 S5 Synthesis of the Manganese Complex (Mn-2) A flame dried Schlenk tube was charged with manganese pentacarbonyl bromide (420 mg, 1.53 mmol, 1.0 eq.) and the PNP ligand (800 mg, 1.68 mmol, 1.1 eq.). The tube was evacuated and backfilled with argon for three times. THF (25 ml) was added and the resulting orange suspension was heated to 60 C and stirred for 20 h. The solution was allowed to cool to room temperature and THF was removed in vacuo. The work-up was done under ambient atmosphere. The yellow solid was washed three times with n-hexane (3 x 5 ml). The crude yellow powder was taken into dichloromethane and transferred into a 50 ml round bottom flask to remove insoluble inorganic side products. The solution was concentrated under reduced pressure and the complex Mn-2 was isolated as a yellow powder (1.02 g, 95% yield). Crystals suitable for X-ray diffraction analysis were obtained by diffusion crystallization method using acetone/hexane. m.p. : 302 C 1 H NMR (300 MHz, CD 2 Cl 2 ) = 8.09 (s, 2H), (m, 21H), 4.65 (s, 4H). 31 P NMR (243 MHz, CD 2 Cl 2 ) δ = (s, 2P). IR (ATR): ν 1918 (ν3co), 1840 (ν3co), 1571, 1435, 1284, 1172, 1097, 964, 833, 696 cm 1. MS (ESI+): m/z = [M-(CO) 3 Br] + HRMS (ESI+): calc. for C 34 H 27 MnNO 3 P 2 [M Br] + : , found Elemental analysis: calc. for C 34 H 27 BrMnNO 3 P 2 : C, 58.81; H, 3.92; N, Found: C, 57.48; H, 4.11; N, 1.89.

6 S6 Synthesis of the Manganese Complex (Mn-3) a) Ligand Synthesis Synthesis of bis(2-(diphenylphosphanyl)ethyl)amine hydrochloride (L1) Bis[2-(diphenylphosphino)ethyl]amine hydrochloride (L1) was prepared according to literature [1] by using bis(2-chloroethyl)amine hydrochloride, diphenylphosphine and potassium tert-butoxide as a base. 1 H NMR (600 MHz, CDCl 3 ) δ = 9.98 (s, 2H), (m, 20H), (m, 4H), (m, 4H) ppm. 31 P NMR (243 MHz, CDCl 3 ) δ = ppm. b) Complex Synthesis A flame dried Schlenk tube was charged with ligand L1 (478 mg, 1.0 mmol, 1.0 equiv.), toluene (8 ml), water (2 ml) and NaOH (120 mg, 3.0 mmol, 3.0 equiv.). The reaction mixture was stirred at 45 C for 30 min. The two phases were separated, and the organic layer was washed with water (5 5 ml). The ph-value was checked until the solution turned neutral. The organic layer was concentrated under reduced pressure. Subsequently, toluene (12 ml) and Mn(CO) 5 Br precursor were added to the Schlenk tube. The reaction mixture was heated up to 110 C and the atmosphere was exchanged three times by evacuating and backfilled with argon. After the mixture was stirred for 20 h at reflux temperature, it was cooled to room temperature and concentrated in vacuo. The crude precipitate was washed with pentane and extracted with dichloromethane/diethylether to remove insoluble inorganic side products. The solution was concentrated under reduced pressure and dried to afford the complex Mn-3 as a yellow powder (570 mg, 90%). Single crystals suitable for X-ray diffraction analysis were obtained by slow diffusion of pentane into a solution of Mn-3 in CH 2 Cl 2. 1 H NMR (600 MHz, CD 2 Cl 2 ) δ = (m, 4H, CH Ar ), (m, 4H, CH Ar ), (m, 12H, CH Ar ), (m, 2H, NCH 2 CH 2 ), 3.52 (br, 1H, NH), (m, 2H, NCH 2 CH 2 ), (m, 2H, NCH 2 CH 2 ), (m, 2H, NCH 2 CH 2 ) ppm. 31 P{ 1 H}NMR (243 MHz, CD 2 Cl 2 ) δ = 69.7 (s) ppm. 13 C{ 1 H}NMR (151 MHz, CD 2 Cl 2 ) δ =231.6 (br, CO), (br, CO), (vt, J = 19.1 Hz, PC Ar,ipso ), (vt, J = 19.1 Hz, PC Ar, ipso ), (vt, J = 5.0 Hz, CH Ar ), (vt, J = 5.0 Hz, CH Ar ), (s, CH Ar ), (s, CH Ar ), (vt, J = 4.3 Hz, CH Ar ), (vt, J = 4.6 Hz, CH Ar ), 53.0 (vt, J = 4.7 Hz, NCH 2 CH 2 ), 28.4 (vt, J = 8.9 Hz, NCH 2 CH 2 ) ppm. IR (ATR): ν ( CO ), 1826 ( CO ) cm -1. MS (ESI+): m/z =496 [M-(CO) 2 Br] + HRMS (ESI+): calc. for C 30 H 29 MnNO 2 P 2 [M Br] + : , found Note: The abbreviation vt corresponds to a virtual triplet due to scalar coupling with two magnetically inequivalent phosphorus nuclei. The observed splitting does not represent the true coupling constants.

7 S7 NMR Spectra of Mn-1 1 H-NMR of Mn-1 13 C-NMR of Mn-1

8 S8 31 P-NMR of Mn-1 NMR Spectra of Mn-2 1 H-NMR of Mn-2

9 S9 13 C-NMR of Mn-2 31 P-NMR of Mn-2

10 S10 NMR Spectra of L1 1 H-NMR of L1 31 P-NMR of L1

11 S11 NMR Spectra of Mn-3 1 H-NMR of Mn-3 13 C-NMR of Mn-3

12 S12 31 P-NMR of Mn-3

13 S13 Crystallographic Data of Mn-3 Table S1. Crystal Data and Structure Refinement Details for Compound Mn-3. chemical formula C 30 H 29 BrMnNO 2 P 2 formula weight T / K 293(2) wavelength / Å Crystal system Orthorhombic space group Pbca a / Å (6) b / Å (7) c / Å (10) α / deg 90 β / deg 90 γ / deg 90 V / Å (4) Z 8 D calcd / g cm absorp. coeff. / mm R a) wr2 b) a) R = Σ F 0 F c /Σ F 0. 1 b) wr 2 = [Σw(F 0 2 F c 2 ) 2 /Σw(F 0 2 ) 2 ] 1/2. Selected bond lengths and bond angles: Bond Length / Å Bond Angle / deg Mn1 N (19) N1-Mn1-P (6) Mn1 P (7) N1-Mn1-P (6) Mn1 P (8) P1-Mn1-P (3) C29 Mn (3) C29-Mn1-Br (8) C30 Mn (3) C30-Mn1-Br (8) C29 O (3) C30-Mn1-C (11) C30 O (3) P1-Mn1-Br (2) Br1-Mn (4) P2-Mn1-Br (2)

14 S14 Figure 1: Molecular structure of complex Mn-3 in the crystal. Displacement ellipsoids are drawn at the 50% probability level.

15 S15 III - General Procedures and Characterization of the Products Table S1: Base Optimization for the Coupling Reaction of 2,5-Hexanediol and n-hexylamine. entry Catalyst (mol%) Base (mol%) GC-yield [%] b 1 3 K 2 CO 3 (5) KOtBu (5) KOH (5) Cs 2 CO 3 (5) Cs 2 CO 3 (2) Cs 2 CO 3 (2) 57 Representative Procedure for the Catalytic Pyrrole Synthesis A glass pressure tube (10 ml) equipped with a magnetic stir bar was charged with Mn catalyst Mn-3 (3.2 mg, mmol), K 2 CO 3 (0.7 mg, 0.01 mmol) and 1,4-butanediol (44 L, 45.1 mg, 0.5 mmol). A rubber septum was attached to the tube and the reaction vessel was evacuated and backfilled with argon for three times. Under an inert atmosphere 1-hexylamine (131 L, 101 mg, 1.0 mmol) was added and the tube was closed with a screw cap. The resulting mixture was stirred at 150 C for 24 h under argon atmosphere. Upon cooling down to room temperature the residue was directly purified by flash column chromatography on silica gel eluting with pentane:diethyl ether (100:1) to give 1-hexyl- 1H-pyrrole (3a) as a colorless oil (55 mg, 73%). Representative Procedure for the Catalytic Gram-Scale Pyrrole Synthesis A glass pressure tube (50 ml) equipped with a magnetic stir bar was charged with catalyst Mn-3 (47.6 mg, mmol), Cs 2 CO 3 (49 mg, 0.15 mmol), tryptamine (2.40 g, 15.0 mmol) and 2,6-hexandiol (886 mg, 7.5 mmol). A septum was attached, and the pressure tube was evacuated and backfilled with argon for three times. The tube was sealed with a Teflon screw cap and the resulting mixture was stirred at 150 C for 24 h under argon atmosphere. Upon cooling down to room temperature the residue was filtered over a short plug of Na 2 SO 4 and Celite. After concentrating in vacuo the crude mixture was recrystallized from hexane:etoac (1:1) to give the clean desired product (1.61 g, 90%).

16 S16 1-hexyl-1H-pyrrole (3a) [2] MS (EI): m/z = 151 [M] + Yield: 55 mg (73%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), 6.14 (m, 2H), 3.87 (t, J = 7.2 Hz, 2H), 1.76 (p, J = 7.0 Hz, 2H), (m, 6H), 0.86 (t, J = 6.8 Hz, 3H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 120.6, 107.9, 49.8, 31.7, 31.5, 26.6, 22.7, 14.2 ppm. 1-dodecyl-1H-pyrrole (3b) [3] Yield: 88 mg (75%), light yellow oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 2H), 3.88 (t, J = 7.2 Hz, 2H), (m, 2H), (m, 18H), 0.90 (t, J = 7.0 Hz, 3H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 120.6, 107.9, 49.8, 32.1, 31.7, 29.8, 29.7, , 29.4, 26.9, 22.8, 14.3 ppm. MS (EI): m/z = 235 [M] + 1-cyclohexyl-1H-pyrrole (3c) [3] Yield: 51 mg (68%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 2H), 3.81 (tt, J = 11.9, 3.8 Hz, 1H), (m, 2H), (m, 2H), 1.74 (m, 1H), (qd, J = 12.6, 3.6 Hz, 2H), (m, 2H), (m, 1H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 118.6, 107.5, 58.8, 34.8, 25.9, 25.6 ppm. MS (EI): m/z = 149 [M] + 1-phenethyl-1H-pyrrole (3d) [3] Yield: 71 mg (83%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 1H), (m, 2H), (m, 2H), (m, 2H), 4.14 (t, J = 7.4 Hz, 2H), 3.09 (t, J = 7.5 Hz, 2H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 138.6, 128.8, 128.7, 126.7, 120.6, 108.1, 51.3, 38.5 ppm. MS (EI): m/z = 171 [M] +

17 S17 3-(2-(1H-pyrrol-1-yl)ethyl)-1H-indole (3e) [4] Yield: 82 mg (78%), white solid 2H).ppm. 1 H NMR (600 MHz, CDCl 3 ) δ = 7.90 (br, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 6.69 (t, J = 2.1 Hz, 2H), 6.19 (t, J = 2.1 Hz, 2H), (m, 2H), (m, 13 C NMR (151 MHz, CDCl 3 ) δ = 136.2, 127.2, 122.3, 122.2, 120.7, 119.6, 118.6, 112.6, 111.4, 108.0, 50.2, 27.9 ppm. MS (EI): m/z = 210 [M] + 1-benzyl-1H-pyrrole (3f) [3] Yield: 61 mg (78%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 1H), (m, 2H), (m, 2H), (m, 2H), 5.10 (s, 2H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 138.3, 128.8, 127.8, 127.1, 121.3, 108.6, 53.4 ppm. MS (EI): m/z = 157 [M] + 1-(4-bromobenzyl)-1H-pyrrole (3g) [5] Yield: 107 mg (91%), light yellow oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 2H), (m, 2H), (m, 2H), 5.03 (s, 2H) ppm. ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 137.4, 132.0, 128.7, 121.7, 121.2, 108.9, 52.8 MS (EI): m/z = 235 [M] + 1-(4-methoxybenzyl)-1H-pyrrole (3h) [5] Yield: 74 mg (79%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 2H), (m, 2H), (m, 2H), 5.02 (s, 2H), 3.81 (s, 3H) ppm ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 159.2, 130.3, 128.6, 121.1, 114.2, 108.5, 55.4, MS (EI): m/z = 187 [M] +

18 S18 1-(3-methoxybenzyl)-1H-pyrrole (3i) [6] Yield: 86 mg (92%), light yellow oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 1H), ,82 (m, 1H), (m, 1H), (m, 2H), (m, 1H), 5.06 (s, 2H), 3.78 (s, 3H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 160.0, 139.9, 129.9, 121.3, 119.4, 113.0, 112.8, 108.6, 55.31, 53.4 ppm. MS (EI): m/z = 187 [M] + 3-((1H-pyrrol-1-yl)methyl)pyridine (3j) [3] Yield: 64 mg (81%), white-solid 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 1H), (m, 1H), (m, 1H), (m, 1H), 6.69 (t, J = 2.1 Hz, 2H), 6.21 (t, J = 2.2 Hz, 2H), 5.08 (s, 2H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 149.3, 148.5, 134.7, 133.7, 123.8, 121.1, 109.1, 50.8 ppm. MS (EI): m/z = 158 [M] + 1-(furan-2-ylmethyl)-1H-pyrrole (3k) [3] MS (EI): m/z = 147 [M] + Yield: 45 mg (61%), light yellow oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 2H), 5.04 (s, 2H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 150.9, 142.8, 120.8, 110.5, 108.6, 108.3, 46.2 ppm. 1-(1-phenylethyl)-1H-pyrrole (3l) [7] Yield: 65 mg (76%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 1H), (m, 2H), 6.79 (t, J = 2.2 Hz, 2H), 6.23 (t, J = 2.2 Hz, 2H), 5.31 (q, J = 7.1 Hz, 1H), 1.86 (d, J = 7.1 Hz, 3H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 143.7, 128.8, 127.5, 126.0, 119.6, 108.1, 58.2, 22.2 ppm. MS (EI): m/z = 171 [M] +

19 S19 1-benzhydryl-1H-pyrrole (3m) [8] Yield: 62 mg (53%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 6H), (m, 4H), 6.64 (t, J = 2.2 Hz, 2H), 6.49 (s, 1H), 6.21 (t, J = 2.2 Hz, 2H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 140.8, 128.7, 128.4, 128.0, 121.2, 108.3, 67.0 ppm. MS (EI): m/z = 233 [M] + 1-(4-methoxyphenyl)-1H-pyrrole (3n) [3] Yield: 36 mg (42%), white solid 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), 7.01 (t, J = 2.2 Hz, 2H), (m, 2H), 6.34 (t, J = 2.2 Hz, 2H), 3.84 (s, 3H). 13 C NMR (151 MHz, CDCl 3 ) δ = 157.8, 134.6, 122.3, 119.8, 114.7, 110.0, 55.7 ppm. MS (EI): m/z = 173 [M] + 1,3-bis((1H-pyrrol-1-yl)methyl)benzene (3o) [9] Yield: 73 mg (62%), white solid ppm. 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 1H), (m, 2H), 6.94 (s, 1H), 6.70 (t, J = 2.2 Hz, 4H), 6.23 (t, J = 2.1 Hz, 4H), 5.06 (s, 4H) 13 C NMR (151 MHz, CDCl 3 ) δ = 138.9, 129.3, 126.4, 125.7, 121.2, 108.7, 53.2 ppm. MS (EI): m/z = 236 [M] + 1-hexyl-2,5-dimethyl-1H-pyrrole (5a) [10] Yield: 89 mg (94%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = 5.81 (s, 2H), 3.75 (t, J = 8.0 Hz, 2H), 2.26 (s, 6H), (m, 2H), (m, 6H), 0.95 (t, J = 7.0 Hz, 3H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 127.4, 105.0, 43.8, 31.6, 31.1, 26.8, 22.7, 14.13, 12.6 ppm. MS (EI): m/z = 179 [M] +

20 S20 1-cyclohexyl-2,5-dimethyl-1H-pyrrole (5b) [10] Yield: 59 mg (67%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = 5.76 (s, 2H), (m, 1H), 2.32 (s, 6H), (m, 6H), (m, 1H), (m, 2H), (m, 1H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 128.0, 106.1, 56.5, 32.5, 26.8, 25.8, 14.6 ppm. MS (EI): m/z = 177 [M] + 3-(2,5-dimethyl-1H-pyrrol-1-yl)propan-1-ol (5c) [11] Yield: 36 mg (47%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = 5.78 (s, 2H), (t, J = 7.24 Hz, 2H), 3.69 (t, J = 6.0 Hz, 2H), 2.24 (s, 6H), (m, 2H), 1.71 (brs, 1H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 127.6, 105.3, 60.2, 40.5, 33.7, 12.6 ppm. MS (EI): m/z =153 [M] + 2,5-dimethyl-1-phenethyl-1H-pyrrole (5d) [10] Yield: 73 mg (73%), colorless oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 1H), (m, 2H), 5.81 (s, 2H), 3.98 (t, J = 7.7 Hz, 2H), 2.92 (t, J = 7.7 Hz, 2H), 2.18 (s, 6H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 138.7, 129.0, 128.7, 127.5, 126.8, 105.3, 45.4, 37.7, 12.5 ppm. MS (EI): m/z = 199 [M] + 1-benzyl-2,5-dimethyl-1H-pyrrole (5e) [10] Yield: 89 mg (96%), off-white solid 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 1H), (m, 2H), 5.92 (s, 2H), 5.06 (s, 2H), 2.19 (s, 6H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 138.6, 128.8, 128.1, 127.1, 125.7, 105.5, 46.8, 12.6 ppm. MS (EI): m/z = 185 [M] +

21 S21 1-(4-chlorobenzyl)-2,5-dimethyl-1H-pyrrole (5f) [7] Yield: 87 mg (79%), off-white solid 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 2H), (m, 2H), 5.90 (s, 2H), 5.00 (s, 2H), 2.16 (s, 6H) ppm ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 137.2, 132.9, 129.0, 127.9, 127.1, 105.8, 46.2, MS (EI): m/z =219 [M] + 1-(4-bromobenzyl)-2,5-dimethyl-1H-pyrrole (5g) Yield: 105mg (80%), off-white solid 1 H NMR (600 MHz, CDCl 3 ) δ = 7.43 (m, 2H), 6.76 (m, 2H), 5.88 (s, 2H), 4.97 (s, 2H), 2.14 (s, 6H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 137.7, 131.9, 128.0, 127.5, 121.0, 105.8, 46.3, 12.5 ppm. MS (EI): m/z =263 [M] + IR (ATR): ν = 2919, 1522, 1485, 1402, 1347, 1299, 1069, 1009, 915, 801, 756 cm -1. HRMS (ESI+): calc. for C 13 H 15 BrN [M + H] + : , found (4-methoxybenzyl)-2,5-dimethyl-1H-pyrrole (5h) [10] Yield: 89 mg (83%), off-white solid 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 4H), 5.90 (s, 2H), 4.99 (s, 2H), 3.81 (s, 3H), 2.19 (s, 6H) ppm. 46.3, 12.6 ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 158.7, 130.6, 128.0, 126.9, 114.2, 105.4, 55.3, MS (EI): m/z =215 [M] + 1-(3,4-dichlorobenzyl)-2,5-dimethyl-1H-pyrrole (5i) MS (EI): m/z =253 [M] + Yield: 74 mg (58%), white solid 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 1H), (m, 1H), (m, 1H), 5.88 (s, 2H), 4.96 (s, 2H), 2.14 (s, 6H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 139.1, 133.1, 131.2, 130.9, 127.8, 127.8, 125.2, 106.1, 45.8, 12.5 ppm. IR (ATR): ν = 2920, 2855, 1725, 1466, 1442, 1398, 1333, 1301, 1129, 1027, 924, 870, 816, 763, 693 cm -1. HRMS (ESI+): calc. for C 13 H 14 Cl 2 N [M + H] + : , found

22 S22 1-(4-methoxyphenyl)-2,5-dimethyl-1H-pyrrole (5j) [10] Yield: 33 mg (33%), white solid 1 H NMR (600 MHz, CDCl 3 ) δ = δ (m, 2H), (m, 2H), 5.89 (s, 2H), 3.86 (s, 3H), 2.02 (s, 6H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 159.0, 131.9, 129.4, 129.2, 114.3, 105.4, 55.6, 13.1 ppm. MS (EI): m/z =201 [M] + 1-hexyl-2,5-diphenyl-1H-pyrrole (5k) [12] Yield: 68 mg (45%), yellow oil 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 4H), (m, 4H), (m, 2H), 6.28 (s, 2H), (t, J = 7.5 Hz, 2H), (m, 2H), (m, 2H), (m, 4H), 0.72 (t, J = 7.4 Hz, 3H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 136.6, 134.3, 129.1, 128.5, 127.0, 109.5, 45.2, 31.0, 30.6, 25.9, 22.4, 14.0 ppm. MS (EI): m/z = 303 [M] + 1-benzyl-2-phenyl-1H-pyrrole (5l) [13] Yield: 55 mg (47%), yellow oil 1 H NMR (600 MHz, CDCl 3 ) δ = 7.34 (m, 4H), (m, 4H), (m, 2H), (m, 1H), (m, 2H), 5.17 (s, 2H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 139.0, 135.1, 133.4, 129.0, 128.8, 128.5, 127.4, 127.1, 126.6, 123.0, 109.0, 108.6, 50.8 ppm. MS (EI): m/z = 233 [M] + 1,2-bis(2,5-dimethyl-1H-pyrrol-1-yl)ethane (5m) [14] Yield: 73 mg (68%), white solid 1 H NMR (600 MHz, CDCl 3 ) δ = 5.79 (s, 4H), 3.97 (s, 4H), 2.05 (s, 12H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 127.7, 105.8, 44.0, 12.0 ppm. MS (EI): m/z = 216 [M] +

23 S23 1,3-bis((2,5-dimethyl-1H-pyrrol-1-yl)methyl)benzene (5n) [9] Yield: 113 mg (77%), white solid 1 H NMR (600 MHz, CDCl 3 ) δ = (m, 1H), (m, 2H), 6.58 (s, 1H), 5.89 (s, 4H), 4.99 (s, 4H), 2.15 (s, 12H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 139.2, 129.4, 128.0, 124.5, 123.2, 105.6, 46.8, 12.6 ppm. MS (EI): m/z = 292 [M] + 3-(2-(2,5-dimethyl-1H-pyrrol-1-yl)ethyl)-1H-indole (7) [15] MS (EI): m/z =238 [M] + Yield: 113 mg (95%), off-white powder 1 H NMR (600 MHz, CDCl 3 ) δ = 7.94 (brs, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 6.92 (s, 1H), 5.90 (s, 2H), 4.09 (t, J = 7.7 Hz, 2H), 3.12 (t, J = 7.7 Hz, 2H), 2.29 (s, 6H) ppm. 13 C NMR (151 MHz, CDCl 3 ) δ = 136.3, 127.6, 127.3, 122.2, 122.1, 119.6, 118.5, 112.7, 111.3, 105.2, 44.4, 27.0, 12.6 ppm.

24 S24 IV - NMR Spectra of the Products 1 H NMR of 3a 13 C NMR of 3a

25 S25 1 H NMR of 3b 13 C NMR of 3b

26 S26 1 H NMR of 3c 13 C NMR of 3c

27 S27 1 H NMR of 3d 13 C NMR of 3d

28 S28 1 H NMR of 3e 13 C NMR of 3e

29 S29 1 H NMR of 3f 13 C NMR of 3f

30 S30 1 H NMR of 3g 13 C NMR of 3g

31 S31 1 H NMR of 3h 13 C NMR of 3h

32 S32 1 H NMR of 3i 13 C NMR of 3i

33 S33 1 H NMR of 3j 13 C NMR of 3j

34 S34 1 H NMR of 3k 13 C NMR of 3k

35 S35 1 H NMR of 3l 13 C NMR of 3l

36 S36 1 H NMR of 3m 13 C NMR of 3m

37 S37 1 H NMR of 3n 13 C NMR of 3n

38 S38 1 H NMR of 3o 13 C NMR of 3o

39 S39 1 H NMR of 5a 13 C NMR of 5a

40 S40 1 H NMR of 5b 13 C NMR of 5b

41 S41 1 H NMR of 5c 13 C NMR of 5c

42 S42 1 H NMR of 5d 13 C NMR of 5d

43 S43 1 H NMR of 5e 13 C NMR of 5e

44 S44 1 H NMR of 5f 13 C NMR of 5f

45 S45 1 H NMR of 5g 13 C NMR of 5g

46 S46 1 H NMR of 5h 13 C NMR of 5h

47 S47 1 H NMR of 5i 13 C NMR of 5i

48 S48 1 H NMR of 5j 13 C NMR of 5j

49 S49 1 H NMR of 5k 13 C NMR of 5k

50 S50 1 H NMR of 5l 13 C NMR of 5l

51 S51 1 H NMR of 5m 13 C NMR of 5m

52 S52 1 H NMR of 5n 13 C NMR of 5n

53 S53 1 H NMR of 7 13 C NMR of 7

54 S54 V - References [1] R. G. Nuzzo, S. L. Haynie, M. E. Wilson, G. M. Whitesides, J. Org. Chem. 1981, 46, [2] V. D. Yadav, S. U. Dighea and S. Batra, RSC Adv., 2014, 4, [3] T.Yan, K. Barta, ChemSusChem 2016, 9, [4] B. Emayavaramban, M. Sen, B. Sundararaju, Org. Lett. 2017, 19, 6 9. [5] B. S. Cho, H. J. Bae and Y. K. Chung, J. Org. Chem. 2015, 80, [6] C. K. Lee, J. H. Jun, J. S. Yu, Journal of Heterocyclic Chemistry 2000, 37, [7] N. Scalacci, G. W. Black, G. Mattedi, N. L. Brown, N. J. Turner, D. Castagnolo, ACS Catal. 2017, 7, [8] I. Deb, D. J. Coiroa, D. Seidel, Chem. Commun. 2011, 47, [9] H. Mahmoudi, A. Ali Jafari, ChemCatChem 2013, 5, [10] P. Daw, S. Chakraborty, J. A. Garg, Y. B.-David, D. Milstein, Angew. Chem. Int. Ed. 2016, 55, [11] J. A. Schiffner, T. H. Wöste, M. Oestreich, Eur. J. Org. Chem. 2010, [12] S. Handy, K. Lavender, Tetrahedron Lett. 2013, 54, [13] A. Aponick, C.-Y. Li, J. Malinge, E. F. Marques, Org. Lett. 2009, 11, [14] X. Chen, M. Yang, M. Zhou, Tetrahedron Lett. 2016, 57, [15] H. Veisi, Tetrahedron Lett. 2010, 51,