1,5-Electrocyclization of conjugated azomethine ylides derived from 3-formyl chromene and N-alkyl amino acids/esters

Transcription

1 Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 7 Supporting Information for,5-electrocyclization of conjugated azomethine ylides derived from 3-formyl chromene and -alkyl amino acids/esters E. Pravardhan Reddy, a A. Sumankumar, b B. Sridhar, c Y. Hemasri, d Y. Jayaprakash Rao,* a,e and B. V. Subba Reddy* b a Department of Chemistry, smania University, Hyderabad- 7, India. e Department of Chemistry, Telangana University, izamabad-3 322, India. d Department of Chemistry, izam College, smania University,, India. b Centre for Semiochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad, 7, India. c Laboratory of X-ray Crystallography, yjpr_9@yahoo.com CH R H C 2 Me Ph Xylene, reflux, 6h R Ph Table of Contents. General Methods & Experimental Procedures...S2 2. Characterization data of products...s MR Spectra of products...s X-ray crystallography...s32 S

2 . General Methods All solvents were dried according to standard literature procedures. Unless otherwise noted, reactions were performed in flame-dried glassware under an atmosphere of dry argon. Dichloromethane was dried over Calcium hydride prior to use. H MR spectra were recorded at MHz, MHz and MHz and 3 C MR at 25 MHz, MHz and 75MHz. For H MR, tetramethylsilane (TMS) was used as internal standard (δ = ) and the values are reported as follows: chemical shift, multiplicity, integration (s = singlet, d = doublet, t= triplet, q = quartet, m = multiplet, dd = doublet of doublet), and the coupling constants in Hz. For 3 C MR, CDCl3 (δ = ) was used as internal standard and spectra were obtained with complete proton decoupling. Low-resolution MS and HRMS data were obtained using ESI ionization. IR spectra were recorded on FT-IR spectrometer (KBr) and reported in reciprocal centimeters (cm - ). Melting points were measured on micro melting point apparatus. Crude products were purified by column chromatography on silica gel of or - mesh. Thin layer chromatography plates were visualized by exposure to ultraviolet light and/or by exposure to iodine vapours and/or by exposure to methanolic acidic solution of 2-napthol followed by heating (< min) on a hot plate (~2 C). Experimental procedure Preparation of -Benzyl-7-chloro-3-phenethylchromeno [3, 4-b] pyrrol-4(3h)-one (3) H R CH R 3 C R 2 Me 2 R 2 R = -H, Cl, Br, Me R 2 = -H, Ph, -methoxy phenyl Xylene, o C, 6h R 2 3 R 3 = -Me, Bn, CH 2 -CH 2 -Ph R 3 A mixture of 2H-chromene-3-carbaldehyde (. equiv) and -alkylated amino ester 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (EtAc/hexane) to give the pure product. S2

3 2. Characterization data of products -Benzyl-3-methylchromeno [3, 4-b] pyrrol-4(3h)-one (3a): A mixture of 2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and ethyl -methylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (:9 of EtAc/hexane) to give the pure product 3a. White solid, m.p C; H MR ( MHz, CDCl 3 ) δ 7.75 (dd, J = 7.9,.4 Hz, H), 7.39 (dd, J = 8.3,. Hz, H), (m, 3H), (m, 3H), 7. (m, H), 6.73 (s, H), 4.24 (s, 2H), 4.6 (s, 3H); 3 C MR ( MHz, CDCl3) δ 55.4, 5.3, 39.3, 32.8, 28.7, 28.5, 27., 26.9, 2, 24., 2, 8.9, 7.7, 7.3, 7.2, 3, 32.7; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 29; HRMS (EI): m/z calcd for C 9 H 5 2 : 2928; found: Chloro--(2-methoxybenzyl)-3-phenethylchromeno [3, 4-b] pyrrol-4(3h)-one (3b):- A mixture of 6-chloro-2-(2-methoxyphenyl)-2H-chromene-3-carbaldehyde (. equiv) and methyl phenethylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (3:7 of EtAc/hexane) to give the pure product 3b. Cl Me S3

4 White solid, m.p C; H MR ( MHz, CDCl 3 ) δ 7.73 (d, J = 2.3 Hz, H), (m, 6H), 8 (d, J = 6.4 Hz, 2H), 6.92 (d, J = 8.2 Hz, H), 6.83 (d, J = 4.4 Hz, 2H), 4 (s, H), 4.62 (t, J = Hz, 2H), 4.8 (s, 2H), 3.9 (s, 3H), 3.3 (t, J = Hz, 2H) ppm. 3 C MR (25 MHz, CDCl 3 ) δ 56.9, 54.6, 49.6, 37.8, 32.6, 29.7, 29.2, 28.9, 28.5, 27.7, 27.2, 26.9, 26.7, 26.2, 23.4,.6,.2, 8.2,, 6.2,.2, 55.4,.7, 38., 25.6 ppm; IR (KBr): ν max 3456, 2987, 655, 484, 9 cm - ; MS (EI): m/z ([M+]): 444; HRMS (EI): m/z calcd for C 27 H 22 Cl 3 : ; found: Benzyl-7-methoxy-3-methylchromeno [3,4-b]pyrrol-4(3H)-one(3c):- A mixture of 6-methoxy-2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and ethyl methylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (2:8 of EtAc/hexane) to give the pure product 3c. Me White solid, m.p.29- C; H MR ( MHz, CDCl 3 ) δ (m, 4H), 7.24 (d, J = 7.3 Hz, 2H), (d, J = 2.9 Hz, H), 6.86 (dd, J = 9., 2.9 Hz, H), 6.8 (s, H), 4.24 (s, 2H), 4.8 (s, 3H), 3.63 (s, 3H). 3 C MR (25 MHz, CDCl 3 ) δ 55.8, 45.6, 39.3, 32.8, 28.7, 28.3, 26.9, 2, 7.9, 7.6, 7., 4.3, 6.9, 55.6, 3, 32.6.; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 3; HRMS (EI): m/z calcd for C H 7 3 : 3.84; found: Benzyl-7-bromo-3-methylchromeno [3, 4-b] pyrrol-4(3h)-one (3d):- A mixture of 6-bromo-2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and ethyl methylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (:9 of EtAc/hexane) to give the pure product 3d. S4

5 Br White solid, m.p C; H MR ( MHz, CDCl 3 ) δ 7.86 (d, J = 2.3 Hz, H), 7.39 (dd, J = 8.8, 2.3 Hz, H), 7.34 (dd, J =., 4.8 Hz, 2H), (m, 4H), 6.74 (s, H), 4. (s, 2H), 4.5 (s, 3H). 3 C MR (25 MHz, CDCl 3 ) δ 52.8, 4.5, 3, 3., 28.6, 28.3, 25.8, 24., 23., 2,.8, 6.3, 6.,.8, 36.3, 3.7; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 368; HRMS (EI): m/z calcd for C 9 H 4 Br 2 : 3679; found: Benzyl-7-chloro-3-methylchromeno [3,4-b]pyrrol-4(3H)-one (3e):- A mixture of 6-chloro-2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and ethyl methylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (:9 of EtAc/hexane) to give the pure product 3e. Cl White solid, m.p C; H MR ( MHz, CDCl 3 ) δ 7. (s, H), 7.34 (dd, J = 3.8, 6.6 Hz, 2H), 7.27 (dd, J = 3.3, Hz, 5H), 6.73 (s, H), 4. (s, 2H), 4.5 (s, 3H).; 3 C MR (25 S5

6 MHz, CDCl 3 ) δ 54.9, 49.6, 38.9, 32.9, 29.3, 28.8, 28.6, 2, 26.6, 25.7, 23.2,., 8.4, 8.3, 7.4, 36., 32.7.; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 324; HRMS (EI): m/z calcd for C 9 H 4 Cl 2 : ; found: Benzyl-7-chloro-3-phenethylchromeno [3, 4-b] pyrrol-4(3h)-one (3f):- A mixture of 6-chloro-2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and methyl phenethylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (2:8 of EtAc/hexane) to give the pure product 3f. Cl White solid, m.p C; H MR ( MHz, CDCl 3 ) δ 7.67 (t, J =.6 Hz, H), (m, 8H), 3 (m, 4H), 6.44 (s, H), 4.6 (t, J = Hz, 2H), 4. (s, 2H), 3.2 (t, J = Hz, 2H) ppm; 3 C MR ( MHz, CDCl 3 ) δ 55., 5.3, 39.2, 37.9, 32.6, 28.9, 28.6, 28.5, 28.5, 27.4, 27.2, 26.6, 26.4, 24., 23.6, 8.9, 7.2, 7., 6.2,.7, 38., 32.6; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 44; HRMS (EI): m/z calcd for C 26 H Cl 2 : 44.92; found: Benzyl--(6-methylhept-5-en-2-yl) chromeno [3, 4-b] pyrrol-4(3h)-one (3g):- A mixture of 2-methyl-2-(4-methylpent-3-en--yl)-2H-chromene-3-carbaldehyde (. equiv) and ethyl benzylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (3:7 of EtAc/hexane) to give the pure product 3g. S6

7 White solid, m.p C; H MR ( MHz, CDCl 3 ) δ (m, H), (m, 8H), 5 (m, H), 5. (q, J = 5. Hz, 2H), (m, H), (m, H), (m, 2H), (m, H),.69 (s, 3H),. (dd, J = 4.8, Hz, H),.53 (s, 3H),.33 (d, J = 6.8 Hz, 3H); 3 C MR (25 MHz, CDCl 3 ) δ 55.3, 5.2, 37.6, 32., 29., 28.8, 28.4, 27.8, 27.4, 27., 26.6, 26.4, 24., 23.7, 9., 7.3, 6.4, 5.8, 37.4,.4, 25.8,.9, 7.6 ; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 386; HRMS (EI): m/z calcd for C 26 H 27 2 : ; found: Benzyl-7-methoxy-3-phenethylchromeno [3, 4-b] pyrrol-4(3h)-one (3h):- A mixture of 6-methoxy-2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and methyl phenethylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (3:7 of EtAc/hexane) to give the pure product 3h. Me White solid, m.p C; H MR ( MHz, CDCl 3 ) δ (m, 7H), (dd, J =.6, Hz, 5H), 6.87 (dd, J = 9., 2.9 Hz, H), (s, H), 4.63 (t, J = Hz, 2H), 4.4 (s, 2H), 3.62 (s, 3H), 3.4 (t, J = Hz, 2H).; 3 C MR (25 MHz, CDCl 3 ) δ 55.8, 55.2, 45.6, S7

8 39.3, 3, 32.6, 29., 28.6, 28.5, 28.3, 27.4, 26.6, 26.4, 9., 7.9,, 4.5, 6.8, 55.6,.7, 38., 3.; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): ; HRMS (EI): m/z calcd for C 27 H 23 3 :.6779; found: Chloro--methyl-3-phenethylchromeno [3, 4-b] pyrrol-4(3h)-one (3i):- A mixture of 6-chloro-2H-chromene-3-carbaldehyde (. equiv) and methyl phenethylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (3:7 of EtAc/hexane) to give the pure product 3i. Cl White solid, m.p.-5 C; H MR ( MHz, CDCl 3 ) δ 2 (d, J = 2.3 Hz, H), 7.46 (dd, J = 8.8, 2.3 Hz, H), (m, 5H), (m, 2H), 6.73 (s, H), (m, 2H), 3.4 (t, J = 7.3 Hz, 2H), 2.4 (d, J = Hz, 3H).; 3 C MR (25 MHz, CDCl 3 ) δ 54.5,., 37.8, 3.9, 29.8, 28.9, 28.5, 26.7, 26.3, 25.8, 2.2, 8.8, 6.8,, 4., 5, 38.3, 2..; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 338; HRMS (EI): m/z calcd for C H 6 Cl 2 : ; found: ,3-Dimethylchromeno [3, 4-b] pyrrol-4(3h)-one (3j):- A mixture of 2H-chromene-3-carbaldehyde (. equiv) and ethyl methylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (:9 of EtAc/hexane) to give the pure product 3j. S8

9 H MR ( MHz, CDCl 3 ) δ 7.92 (dd, J = 7.8,.5 Hz, H), 7.36 (dd, J = 9.8, 8.3 Hz, 2H), (m, H), 6.9 (s, H), 4.7 (s, 3H), 2.46 (s, 3H) ppm; 3 C MR (25 MHz, CDCl 3 ) δ 53.6, 4.7, 3.3, 25.7, 2, 2.9,.7, 2, 7., 4.6, 36.3, 32. ppm; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 24; HRMS (EI): m/z calcd for C 3 H 2 : ; found: Methyl-3-phenethylchromeno [3, 4-b] pyrrol-4(3h)-one (3k):- A mixture of 2H-chromene-3-carbaldehyde (. equiv) and methyl phenethylglycinate 2 ( equiv) in xylene (5 ml) was stirred at ºC for 6 h. The progress of the reaction was monitored by TLC. Up on completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (3:7 of EtAc/hexane) to give the pure product 3k. White solid, m.p C; H MR ( MHz, CDCl 3 ) δ 7.92 (dd, J = 7.8,.5 Hz, H), 7.42 (dd, J = 8.2,.3 Hz, H), (m, H), (m, 2H), (m, 2H), (m, 2H), 6. (s, H), (m, 2H), 3.2 (t, J = 7.3 Hz, 2H), 2. (s, 3H). 3 C MR ( MHz, CDCl3) δ 5.2, 4, 3, 3.7, 28.9, 28.5, 27.6, 2, 26.6, 23.9, 23.2, 9.4, 7., 5, 38.3, 2.2; IR (KBr): ν max 3449, 2925, 652, 489, 8, 766 cm - ; MS (EI): m/z ([M+]): 4; HRMS (EI): m/z calcd for C H 7 2 : ; found: Preparation of 2-(4-benzyl--methyl-H-pyrrol-3-yl)phenol (5) S9

10 CH R CH H R 2 R 2 R = -H, Cl, Br, Me R 2 = -H, Ph xylene, o C,6h H 5 R 2 Typical experimental procedure: A mixture of 2H-chromene-3-carbaldehyde (. equiv) and sarcocine (4) ( equiv) in xylene (5 ml) at ºC for 6 h and then the mixture was cooled and filtered. The progress of the reaction was monitored by TLC; upon completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (EtAc/hexane) to give the pure product. 2-(4-Benzyl--methyl-H-pyrrol-3-yl) phenol (5a):- A mixture of 2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and sarcocine (4) ( equiv) in xylene (5 ml) at ºC for 6 h and then the mixture was cooled and filtered. The progress of the reaction was monitored by TLC; upon completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (2:8 of EtAc/hexane) to give the pure product. H Colorless liquid ; H MR ( MHz, CDCl 3 ) δ (m, 7H), 6.95 (dd, J = 8., 2.2 Hz, H), 6.87 (tdd, J = 7.4, 2.4,. Hz, H), 9 (d, J = 2. Hz, H), 6.36 (s, H), 4 (m, H), 3.68 (s, 2H), 9 (s, 3H). 3 C MR (25 MHz, CDCl 3 ) δ 53.6, 4.9, 3., 28.6, 28.4, 28.3, 25.7, 23.2, 2.9,.7, 2, 7.3, 4.6, 36.3, 3.7; IR (KBr): ν max 3487, 59, 29, 49, 6, 36, 76 cm - ; MS (EI): m/z ([M+]): 264; HRMS (EI): m/z calcd for C 8 H 7 : 264.; found: S

11 2-(4-Benzyl--methyl-H-pyrrol-3-yl)-4-chlorophenol (5b):- A mixture of 6-chloro-2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and sarcocine (4) ( equiv) in xylene (5 ml) at ºC for 6 h and then the mixture was cooled and filtered. The progress of the reaction was monitored by TLC; upon completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (3:7 of EtAc/hexane) to give the pure product. Cl H Colorless liquid; H MR ( MHz, CDCl 3 ) δ (m, 2H), (m, 2H), 7 (dd, J =.9, 4.9 Hz, 3H), 6.86 (d, J = 8.6 Hz, H), 9 (d, J = 2.2 Hz, H), 6.38 (d, J =.7 Hz, H), 5.45 (s, H), 3.66 (s, 2H), 3.6 (s, 3H). 3 C MR ( MHz, CDCl 3 ) δ 52.8, 4.5, 3, 3., 28.6, 28.3, 25.8, 24., 23., 2,.8, 6.3, 6.,.8, 36.3, 3.7; IR (KBr): ν max 3487, 59, 29, 49, 6, 36, 76 cm ; MS (EI): m/z ([M+]): 298; HRMS (EI): m/z calcd for C 8 H 6 Cl: 29924; found: (4-Benzyl--methyl-H-pyrrol-3-yl)-4-bromophenol (5c):- A mixture of 6-bromo-2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and sarcocine (4) ( equiv) in xylene (5 ml) at ºC for 6 h and then the mixture was cooled and filtered. The progress of the reaction was monitored by TLC; upon completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (3:7 of EtAc/hexane) to give the pure product. Br H Colorless liquid ; H MR ( MHz, CDCl 3 ) δ (m, H), (m, 2H), 7. (d, J = Hz, H), (m, H), 7. 7 (m, 2H), 6.82 (d, J = 8.6 Hz, H), 6. (d, J = 2.4 Hz, H), 6.39 (d, J = 2.3 Hz, H), 5.48 (s, H), 3.66 (s, 2H), 3.62 (s, 3H) ppm. 3 C MR S

12 ( MHz, CDCl 3 ) δ 52.8, 4.5, 3, 3., 28.6, 28.3, 25.8, 24., 23., 2,.8, 6.3, 6.,.8, 36.3, 3.7 ppm. IR (KBr): ν max 3487, 59, 29, 49, 6, 36, 76 cm - ; MS (EI): m/z ([M+]): 342; HRMS (EI): m/z calcd for C 8 H 6 Br: ; found: (4-Benzyl--methyl-H-pyrrol-3-yl)-4-methoxyphenol (5d):- A mixture of 6-methoxy-2-phenyl-2H-chromene-3-carbaldehyde (. equiv) and sarcocine (4) ( equiv) in xylene (5 ml) at ºC for 6 h and then the mixture was cooled and filtered. The progress of the reaction was monitored by TLC; upon completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (3:7 of EtAc/hexane) to give the pure product. Me H Colorless liquid ; H MR ( MHz, CDCl 3 ) δ 7.23 (dd, J = 7.9, 7. Hz, 2H), 7.6 (m, 3H), 6.87 (dd, J = 8.8,. Hz, H), 6.75 (ddd, J = 8.8,,. Hz, H), (m, 2H), (m, H), 5.8 (d, J = Hz, H), 3.7 (s, 2H), 3.66 (s, 3H), 3.6 (s, 3H). 3 C MR ( MHz, CDCl 3 ) δ 52.9, 47.6, 4.9, 28.6, 28.2, 27.4, 25.7, 22.9, 22.3, 2,.7, 7.6, 5.9, 5., 4., 55.7, 36.3, 3.7; IR (KBr): ν max 3487, 59, 29, 49, 6, 36, 76 cm - ; MS (EI): m/z ([M+]): 294; HRMS (EI): m/z calcd for C 9 H 2 : ; found: Bromo-2-(-methyl-4-(6-methylhept-5-en-2-yl)-H-pyrrol-3-yl) phenol (5e):- A mixture of 6-bromo-2-methyl-2-(4-methylpent-3-en--yl)-2H-chromene-3-carbaldehyde (. equiv) and sarcocine (4) ( equiv) in xylene (5 ml) at ºC for 6 h and then the mixture was cooled and filtered. The progress of the reaction was monitored by TLC; upon completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (:9 of EtAc/hexane) to give the pure product. S2

13 Br H Colorless liquid ; H MR ( MHz, CDCl 3 ) δ (m, 2H), 6.83 (d, J = 8.5 Hz, H), 2 (dd, J = 2.2, 2.3 Hz, 2H), 5.48 (s, H), 4.95 (dd, J = 7.7, Hz, H), 3.66 (d, J = 2.3 Hz, 3H), (m, H),.85 (dd, J = 4.9, 7.4 Hz, 2H),.63 (s, 3H), (m, 3H),.26 (s, 3H),.8 (d, J = 6.9 Hz, 3H) ppm. 3 C MR (25 MHz, CDCl 3 ) δ 5.9, 33.4, 3.4,, 3, 24.6, 24.4, 2, 9.5, 6., 5.4,.7, 38.8, 36.3, 29.7, 2, 25.6, 22.2, 7.6 ppm; IR (KBr): ν max 3487, 59, 29, 49, 6, 36, 76 cm - ; MS (EI): m/z ([M+]): 362; HRMS (EI): m/z calcd for C 9 H 24 Br: 3643; found: (, 4-Dimethyl-H-pyrrol-3-yl) phenol (5f):- A mixture of 2H-chromene-3-carbaldehyde (. equiv) and sarcocine (4) ( equiv) in xylene (5 ml) at ºC for 6 h and then the mixture was cooled and filtered. The progress of the reaction was monitored by TLC; upon completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (:9 of EtAc/hexane) to give the pure product. H Colorless liquid; H MR ( MHz, CDCl 3 ) δ (m, 2H), 6.86 (m, 2H), 6.63 (m, 2H), 5 (s, H), 3.65 (s, 3H),.99 (s, 3H) ppm; 3 C MR ( MHz, CDCl 3 ) δ 53.6, 4.7, 3.3, 25.7, 2, 2.9,.7, 2, 7., 4.6, 36.3, 32. ppm; IR (KBr): ν max 3487, 59, 29, 49, 6, 36, 76 cm - ; MS (EI): m/z ([M+]): 88; HRMS (EI): m/z calcd for C 2 H 3 : ; found: (4-(2-methoxybenzyl)--methyl-H-pyrrol-3-yl)phenol (5g):- A mixture of 2-(2-methoxyphenyl)-2H-chromene-3-carbaldehyde (. equiv) and sarcocine (4) ( equiv) in xylene (5 ml) at ºC for 6 h and then the mixture was cooled and filtered. The S3

14 progress of the reaction was monitored by TLC; upon completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (:9 of EtAc/hexane) to give the pure product. H Me Colorless liquid; H MR ( MHz, CDCl 3 ) δ (m, 3H), 4 (dd, J = 7.4,.6 Hz, H), 6.97 (dd, J = 8.,. Hz, H), (m, 3H), 7 (d, J = 2.4 Hz, H), 6.29 (d, J = 2.3 Hz, H), 5.8 (s, H), 3.76 (s, 3H), 3.66 (s, 2H), 9 (s, 3H); 3 C MR ( MHz, CDCl 3 ) δ 57., 53.7, 3.2,.3,., 28.3, 27., 2, 22., 2.7, 2,.4, 9.9, 5, 4.6,.3, 55.3, 36.3, 2; IR (KBr): ν max 3489, 58, 293, 493, 9, 38, 767 cm - ; MS (EI): m/z ([M+]): 294; HRMS (EI): m/z calcd for C 9 H 2 : ; found: S4

15 3. MR spectra of products 3a f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 3a a 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 3a S5

16 Cl Me 3b f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 3b Cl Me 3b 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 3b S6

17 Me 3c f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 3c Me 3c 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 3c S7

18 Br 3d f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 3d Br 3d 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 3d S8

19 Cl 3e f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 3e Cl 3e 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 3e S9

20 Cl 3f f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 3f Cl 3f 9 8 f (ppm) 3 C MR ( MHz, CDCl 3 ) spectrum of compound 3f S

21 3g f (ppm).5. - H MR ( MHz, CDCl 3 ) spectrum of compound 3g g 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 3g S2

22 Me 3h f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 3h Me 3h 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 3h S22

23 Cl 3i f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 3i Cl 3i 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 3i S23

24 3j f (ppm).5. - H MR ( MHz, CDCl 3 ) spectrum of compound 3j j f (ppm) C MR (25 MHz, CDCl 3 ) spectrum of compound 3j S24

25 3k f (ppm).5. - H MR ( MHz, CDCl 3 ) spectrum of compound 3k k 9 8 f (ppm) 3 C MR ( MHz, CDCl 3 ) spectrum of compound 3k S25

26 H 5a f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 5a H 5a 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 5a S26

27 Cl H 5b f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 5b Cl H 5b 9 8 f (ppm) 3 C MR ( MHz, CDCl 3 ) spectrum of compound 5b S27

28 Br H 5c f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 5c Br H 5c 9 8 f (ppm) 3 C MR ( MHz, CDCl 3 ) spectrum of compound 5c S28

29 Me H 5d f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 5d Me H 5d 9 8 f (ppm) 3 C MR ( MHz, CDCl 3 ) spectrum of compound 5d S29

30 Br H 5e f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 5e Br H 5e 9 8 f (ppm) 3 C MR (25 MHz, CDCl 3 ) spectrum of compound 5e S

31 H 5f f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 5f H 5f f (ppm) C MR ( MHz, CDCl 3 ) spectrum of compound 5f S3

32 H Me 5g f (ppm).5. H MR ( MHz, CDCl 3 ) spectrum of compound 5g H Me 5g 9 8 f (ppm) 3 C MR ( MHz, CDCl 3 ) spectrum of compound 5g S32

33 4. X-ray Crystallography. X-ray data for the compounds were collected at room temperature using a Bruker Smart Apex CCD diffractometer with graphite monochromated MoK radiation ( =.73Å) with ω-scan method []. Preliminary lattice parameters and orientation matrices were obtained from four sets of frames. Integration and scaling of intensity data was accomplished using SAIT program []. The structure was solved by direct methods using SHELXS [2] and refinement was carried out by fullmatrix least-squares technique using SHELXL [2]. Anisotropic displacement parameters were included for all non-hydrogen atoms. All H atoms were positioned geometrically and treated as riding on their parent C atoms with U iso (H).2U eq (C). Crystal Data for 3b: C 27 H 22 3 Cl (M = g/mol): monoclinic, space group P2 /n (no. 4), a = 549() Å, b = 8.69(8) Å, c = 2.744(9) Å, β = 3.92(), V = 253.3(3) Å 3, Z = 4, T = K, μ(mo Kα) =.8 mm -, Dcalc =.3693 g/cm 3, 244 reflections measured (3.96 2Θ ), 5229 unique (R int = 29, R sigma = 67) which were used in all calculations. The final R was 449 (I>2σ(I)) and wr 2 was.4 (all data). CCDC contains supplementary Crystallographic data for the structure. These data can be obtained free of charge at [or from the Cambridge Crystallographic Data Centre (CCDC), 2 Union Road, Cambridge CB2 EZ, UK; fax: +44() ; deposit@ccdc.cam.ac.uk].. Bruker (). SAIT (Version 6.28a) & SMART (Version 5.625). Bruker AXS Inc., Madison, Wisconsin, USA. 2. Sheldrick G. M. (5) Acta Crystallogr C7: 3-8. Figure Caption Fig.. A view of 3b, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the % probability level and H atoms are represented by circles of arbitrary radii. S33