Supplemental material for: Concise Total Syntheses of (±)-Mesembrane and (±)-Crinane. Table of Contents

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2015 Das, De, Shubhashish and Bisai Supporting Information 1 Supplemental material for: Concise Total Syntheses of (±)-Mesembrane and (±)-Crinane Mrinal Kanti Das, Subhadip De, Shubhashish, Alakesh Bisai* Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal, MP - 462 066, INDIA. E-Mail: alakesh@iiserb.ac.in Both authors contributed equally to this work. Table of Contents Materials and Methods S2 General Procedure for Stork-Danheiser s Sequence (±)-7a-b S3-S4 Characterization of (±)-7a-b S4 General Procedure for Synthesis of 3-Aryl-cyclohexenol (±)-5a-b S5 Characterization of (±)-5a-b S5-S6 General Procedure for Eschenmoser-Claisen Rearrangement S6-S7 Characterization of (±)-4a-b S7 General Procedure for Synthesis of Iodolactone Intermediates (±)-3a-b S8 Characterization of (±)-3a-b S8-S9 General Procedure and Characterization of diols (±)-8a-b S9-S10 General Procedure and Characterization of (±)-9a-b S11-S12 General Procedure and Characterization of ketoaldehyde (±)-10a-b S12-S13 Procedure and Characterization of Sec-amine (±)-11a S14-S15 Synthesis and Characterization of Amine Derivatives (±)-12a-b S15-S16 Total Synthesis and Characterization of mesembrane (±)-1a S16-S17 Total Synthesis and Characterization of crinane (±)-2a S18-S19 Synthesis and Characterization of Amine Derivatives (±)-14a-b S19-S20 1 H-NMR, 13 C-NMR and Mass Spectra S22-S87 S1

Das, De, Shubhashish and Bisai Supporting Information 2 EXPERIMENTAL SECTION Materials and Methods Unless otherwise stated, reactions were performed in oven-dried glassware fitted with rubber septa under a nitrogen atmosphere and were stirred with Teflon-coated magnetic stirring bars. Liquid reagents and solvents were transferred via syringe using standard Schlenk techniques. Tetrahydrofuran (THF), diethyl ether (Et 2 O) was distilled over sodium/benzophenone ketyl. Dichloromethane (CH 2 Cl 2 ), toluene, and benzene were distilled over calcium hydride. All other solvents such as chloroform, methanol, ethanol, p-xylene, DMSO and reagents such as 1,3-cyclohexanedione, p-tsa.h 2 O, 2-butanol, veratrole, 4-bromoveratrole, 4-bromo-1,2-(methylenedioxy)benzene, cerium(iii) chloride heptahydrate, sodium borohydride, N,N-dimethylacetamide dimethyl acetal, methyl chloroformate, LiAlH 4, iodine, DBU, oxalyl chloride, triethylamine, sodium cyanoborohydride, acetic acid, trifluoroacetic acid, benzyl chloroformate, ammonium acetate, methylamine, Eschenmoser's salt etc. were used as received, unless otherwise noted. Thin layer chromatography was performed using Merck Silicagel 60 F-254 precoated plates (0.25 mm) and visualized by UV irradiation, 2,4-DNP, anisaldehyde stain and other stains. Silicagel from Merck (particle size 100-200 mesh), basic alumina was used for flash chromatography. Melting points were recorded on a digital melting point apparatus from Jyoti Scientific (AN ISO 9001:2000) and are uncorrected. 1 H and 13 C NMR spectra were recorded on Bruker 400, 500 MHz spectrometers with 13 C operating frequencies of 100, 125 MHz, respectively. Chemical shifts (δ) are reported in ppm relative to the residual solvent signal (δ = 7.26 for 1 H NMR and δ = 77.0 for 13 C NMR). Data for 1 H NMR spectra are reported as follows: chemical shift (multiplicity, coupling constants, number of hydrogen). Abbreviations are as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad). IR spectra were recorded on a FT-IR system (Spectrum BX) from PerkinElmer spectrometer and are reported in frequency of absorption (cm -1 ). Only selected IR absorbencies are reported. Highresolution mass spectrometry (HRMS) data were recorded on MicrOTOF-Q-II mass spectrometer using methanol as solvent. High resolution mass spectra and NMR data were obtained from the Central Instrumentation Facility (CIF) at the Indian Institute of Science Education and Research (IISER) Bhopal. S2

Das, De, Shubhashish and Bisai Supporting Information 3 Synthesis of vinylogous ester (6): A mixture of 1,3-cyclohexanedione (20.0 g, 178.36 mmol, 1.0 equiv.), p-toluenesulfonic acid monohydrate (1.69 g, 8.92 mmol) and 2-butanol (50 ml) in benzene (150 ml) was held at reflux in dean-stark apparatus for 12 h and then cooled to RT. Most of the solvent was removed under vacuum and the resulting residue was poured into brine and extracted with ether. The organic phase was dried (anhydrous Na 2 SO 4 ), filtered and concentrated to give a crude residue which on purification by flash chromatography afforded 27.6 g (92% yields) of compound 6 as yellow oil. R f = 0.49 (30% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ: 5.30 (s, 1H), 4.18-4.11 (m, 1H), 2.33-2.27 (m, 4H), 1.91 (p, J = 6.49 Hz, 2H), 1.66-1.57 (m, 1H), 1.56-1.46 (m, 1H), 1.19 (d, J = 6.10 Hz, 3H), 0.85 (t, J = 7.46 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 200.1, 177.5, 102.9, 75.9, 36.6, 29.5, 28.6, 21.2, 18.6, 9.5; IR (film) υ max 2945, 2882, 1634, 1377, 1330, 1222, 1186, 1137, 1099, 1029, 995, 930, 875, 826, 759 cm -1 ; HRMS (ESI) m/z 191.1063 [M + Na] + ; calculated for [C 10 H 16 O 2 + Na] + : 191.1043. General Procedure for Stork-Danheiser s Sequence of Vinylogous Esters ±-(7a-b): A flame-dried round-bottom flask was charged with vinylogous ester 6 (20.0 mmol), dry THF (30 ml) and cooled to 0 ºC. To this solution, aryl magnesium bromide (24.0 mmol) in dry THF (20 ml) was added dropwise via syringe over 10 min. After stirring S3

Das, De, Shubhashish and Bisai Supporting Information 4 for 6-8 h at RT, the reaction mixture was quenched by the addition of 1(N) HCl (20 ml) at 0 ºC. The reaction mixture was stirred for 3 h while it was allowed to warm to room temperature and then neutralized by the addition of saturated NaHCO 3 solution. The resulting mixture was extracted with EtOAc (4 x 30 ml). The combined organic layers were dried over Na 2 SO 4 and concentrated under vacuum. The crude product was purified by flash chromatography (hexanes and EtOAc as eluents) to give 3-arylcyclohexenone 7. 3',4'-Dimethoxy-5,6-dihydro-[1,1'-biphenyl]-3(4H)-one (7a): 3.4 g, 73% yield as yellow solid, R f = 0.30 (30% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 7.15 (dd, J = 8.4, 2.0 Hz, 1H), 7.08 (d, J = 1.9 Hz, 1H), 6.89 (d, J = 8.4 Hz, 1H), 6.41 (s, 1H), 3.92 (s, 3H), 3.91 (s, 3H), 2.77 (t, J = 5.7 Hz, 2H), 2.48 (t, J = 6.4 Hz, 2H), 2.15 (t, J = 6.4 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 200.0, 159.4, 150.9, 149.0, 131.1, 123.9, 119.5, 110.9, 108.9, 55.97, 55.94, 37.2, 27.9, 22.8; IR (film) υ max 3322, 2943, 2844, 1650, 1597, 1519, 1455, 1255, 1185, 1024, 964, 885, 440 cm -1 ; HRMS (ESI) m/z 255.0994 [(M + Na) + ; calculated for [C 14 H 16 O 3 + Na] + : 255.0992]; mp 118 120 C. O O O (7b) 3-(Benzo[d][1,3]dioxol-5-yl)cyclohex-2-enone (7b): 3.7 g, 85% yield as colorless crystalline solid, R f = 0.45 (50% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 7.04 (dd, J = 8.2, 1.8 Hz, 1H), 6.98 (d, J = 1.7 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 6.29 (s, 1H), 5.97 (s, 2H), 2.69-2.66 (m, 2H), 2.44-2.40 (m, 2H), 2.09 (p, J = 6.4 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 199.8, 159.1, 149.3, 148.2, 132.8, 124.2, 120.7, 108.4, 106.2, 101.6, 37.2, 28.1, 22.8; IR (film) υ max 2916, 1660, 1649, 1591, 1445, 1254, 1110, 1035, 879 cm -1 ; mp 102-104 C, [lit. (G. E. Keck and R. R. Webb, J. Am. Chem. Soc., 1981, 103, 3173) 100-103 C]. S4

Das, De, Shubhashish and Bisai Supporting Information 5 General Procedure for Synthesis of 3-Aryl-cyclohexenol (±)-5a-b: In a round-bottom flask, 3-aryl-cyclohexenone 7 (15.0 mmol, 1.0 equiv) was dissolved in MeOH (40 ml). To this solution was added CeCl 3.7H 2 O (6.7 g, 18.0 mmol, 1.2 equiv). The reaction mixture was stirred at RT for 15 minutes and then was cooled to 0 ºC. NaBH 4 (681 mg, 18.0 mmol, 1.2 equiv) was added to the reaction mixture over 15 minutes. The reaction mixture was continued stirring. At the completion of the reaction (TLC, 30 min), it was quenched with saturated aq. NH 4 Cl (10 ml) and aq. NaHCO 3 (10 ml). After stirring vigorously for 30 mins, the solvent was removed under reduced pressure. Water (20 ml) was added to the crude reaction mixture and it was extracted with CH 2 Cl 2 (3 X 30 ml). The combined organic extracts were washed with saturated aq. NaCl (20 ml), dried over Na 2 SO 4, and concentrated under reduced pressure. The crude product was purified by flash chromatography to provide of allylic alcohol 5. 3',4'-Dimethoxy-3,4,5,6-tetrahydro-[1,1'-biphenyl]-3-ol ±(5a): 3.2 g, 92% yield as colorless crystalline solid, R f = 0.25 (30% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.94-6.93 (m, 2H), 6.82-6.79 (m, 1H), 6.054-6.051 (m, 1H), 4.37 (s, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 2.44-2.31 (m, 2H), 1.94-1.84 (m, 2H), 1.77-1.61 (m, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 148.7, 148.6, 139.7, 134.3, 125.3, 117.8, 110.9, 108.7, 66.4, 55.9, 55.8, 31.8, 27.6, 19.4; IR (film) υ max 3445, 2921, 2840, 1615, 1458, 1406,1259, S5

Das, De, Shubhashish and Bisai Supporting Information 6 1175, 1029, 743 cm -1 ; mp 96 98 C, [lit.( G. E. Keck and R. R. Webb, J. Org. Chem.,1982, 47, 1302) 97-98 C]. 3-(Benzo[d][1,3]dioxol-5-yl)cyclohex-2-enol (5b): 3.1 g, 96% yield as white solid, R f = 0.40 (50% EtOAc in hexane). 1 H NMR (500 MHz, CDCl 3 ) δ 6.92 (d, J = 1.8 Hz, 1H), 6.88 (dd, J = 8.1, 1.8 Hz, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.04-6.02 (m, 1H), 5.95 (s, 2H), 4.37-4.36 (m, 1H), 2.43-2.36 (m, 1H), 2.33-2.26 (m, 1H), 2.18 (brs, 1H), 1.96-1.86 (m, 2H), 1.76-1.62 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 147.7, 146.9, 139.4, 135.8, 125.7, 118.9, 108.0, 106.0, 101.0, 66.3, 31.6, 27.7, 19.5; IR (film) υ max δ 3402, 2932, 1720, 1650, 1606, 1505, 1486, 1372, 1247, 1160, 1104, 1040, 970, 936, 865, 807, 738, 703, 634 cm -1 ; mp 105-108 C. General Procedure For Eschenmoser-Claisen Rearrangement: An oven-dried Schlenk flask was charged with a solution of alcohol (±)-5 (generally in 3.0 mmol scale, 1.0 equiv) in p-xylene followed by addition of N, N-dimethylacetamide dimethyl acetal (3.07 ml, 21.0 mmol, 7.0 equiv). The solution was sparged with N 2 and then sealed and heated at 160 ºC for 18 h. The reaction mixture was allowed to cool to room temperature and concentrated. The crude product was purified by flash chromatography to give of amide 4. S6

Das, De, Shubhashish and Bisai Supporting Information 7 2-(3',4'-Dimethoxy-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-yl)-N,N-imethylacetamide ±(4a): 746 mg, 82% yield as yellow gel, R f = 0.20 (40% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.87-6.85 (m, 2H), 6.78-6.76 (m, 1H), 6.14 (d, J = 10.2 Hz, 1H), 5.89-5.85 (m, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 2.81 (s, 3H), 2.71 (s, 3H), 2.69-2.67 (m, 2H), 2.10-1.90 (m, 4H), 1.59-1.54 (m, 1H), 1.41-1.33 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 170.8, 148.4, 147.0, 140.3, 133.1, 128.0, 118.8, 110.7, 110.5, 55.9, 55.8, 45.1, 41.8, 37.8, 36.5, 35.4, 25.3, 18.8; IR (film) υ max 2934, 1640, 1519, 1258, 1238, 1179, 1145, 1028, 757 cm -1 ; HRMS (ESI) m/z 304.1905 [(M + H) + ; calculated for [C 18 H 25 NO 3 + H] + : 304.1907]. 2-(1-(Benzo[d][1,3]dioxol-5-yl)cyclohex-2-en-1-yl)-N,N-dimethylacetamide ±(4b): 750 mg, 87% yield as yellow gel, R f = 0.25 (40% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.82 (m, 1H), 6.76 (dd, J = 8.2, 1.6 Hz, 1H), 6.68 (d, J = 8.2 Hz, 1H), 6.10 (d, J = 10.7 Hz, 1H), 5.87 (s, 2H), 5.85-5.82 (m, 1H), 2.8 (s, 3H), 2.79 (s, 3H), 2.66 (ABq, J =14.7 Hz, 2H), 2.0-1.95 (m, 3H), 1.89-1.82 (m, 1H), 1.55-1.48 (m, 1H), 1.39-1.33 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 170.5, 147.4, 145.3, 141.8, 143.0, 128.1, 119.8, 107.6, 107.4, 100.8, 44.8, 42.0, 37.8, 37.2, 35.3, 25.2, 18.7; IR (film) υ max 2931, 1643, 1487, 1433, 1238, 1143, 1101, 1039, 935, 812, 745 cm -1 ; HRMS (ESI) m/z 288.1607 [(M + H) + ; calculated for [C 17 H 21 NO 3 + H] + : 288.1594]. General Procedure for Synthesis of Iodolactone Intermediates (±)-3a-b: S7

Das, De, Shubhashish and Bisai Supporting Information 8 A solution of amide 4 (5 mmol, 1 equiv), in 1:1 mixture of THF:Water (20 ml) was added iodine (1.5 g, 6 mmol, 1.2 equiv) and the reaction mixture was heated at 60 ºC for 4h and cooled to room temperature. This was followed by reductive work up with saturated aqueous sodium bisulphate solution. The reaction mixture was extracted with EtOAc (3 X 20 ml). The combined organic extracts were washed with saturated aq. NaCl (30 ml), dried over Na 2 SO 4, and concentrated under reduced pressure. The crude product was purified by flash chromatography to provide of 3 as a solid. (3,4-Dimethoxyphenyl)-7-iodohexahydrobenzofuran-2(3H)-one ±(3a): 1.73 g, 86% yield as white solid, R f = 0.35 (40% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.91-6.89 (m, 1H), 6.84-6.80 (m, 2H), 5.0 (d, J = 6.8 Hz, 1H), 4.23-4.18 (m, 1H), 3.86 (s, 3H), 3.83 (s, 3H), 2.71 (ABq, J = 17.2 Hz, 2H), 2.76-2.24 (m, 1H), 2.08-1.93 (m, 3H), 1.79-1.75 (m, 1H), 1.62-1.53 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 174.1, 149.2, 148.4, 135.5, 118.2, 111.2, 109.6,88.5, 56.2, 55.9, 46.7, 41.7, 34.1, 32.6, 25.6, 21.9; IR (film) υ max 2920, 2838, 1770, 1590, 1519, 1455, 1251, 1098, 1028, 946, 914, 806, 739 cm -1 ; HRMS (ESI) m/z 403.0418 [(M + H) + ; calculated for [C 16 H 19 IO 4 + H] + : 403.0401]; mp 125-127 C. S8

Das, De, Shubhashish and Bisai Supporting Information 9 (Benzo[d][1,3]dioxol-5-yl)-7-iodohexahydrobenzofuran-2(3H)-one ±(3b): 1.64 g, 85% yield as white solid, R f = 0.35 (30% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.86-6.82 (m, 2H), 6.77 (d, J = 8.1 Hz, 1H), 5.95 (s, 2H), 4.97 (d, J = 6.8 Hz, 1H), 4.25-4.2 (m, 1H), 2.71 (ABq, J = 21.8 Hz, 2H), 2.31-2.24 (m, 1H), 2.1-1.92 (m, 3H), 1.84-1.75 (m, 1H), 1.63-1.53 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 173.9, 148.3, 146.8, 136.9, 119.1,108.3, 106.6, 101.4, 88.5, 46.8, 42.0, 34.0, 32.7, 25.3, 21.8; IR (film) υ max 2930, 2859, 1783, 1489, 1447, 1238, 1204, 1169, 1040, 1017, 935, 812, 735 cm -1 ; HRMS (ESI) m/z 387.0069 [(M + H) + ; calculated for [C 15 H 15 IO 4 + H] + : 387.0088]; mp 171-173 C. General Procedure for Synthesis of diols (±)-8a-b: To a suspension of lithium aluminium hydride, (605 mg, 16.0 mmol, 4.0 equiv) in THF (30 ml) at 0 C was added a solution of compound 3 (4.0 mmol, 1.0 equiv) in THF (30 ml). The reaction mixture was allowed to warm to room temperature, fitted with a water condenser, heated to 80 ºC and held at reflux for 20h. The reaction mixture was cooled to RT and then to 0 ºC and quenched with EtOAc, basified with 4(N) NaOH solution and extracted with EtOAc (3 X 25 ml). The combined organic extracts were washed with saturated aq. NaCl (30 ml), dried over Na 2 SO 4, and concentrated under reduced pressure. The crude product was purified by flash chromatography to provide 8. S9

Das, De, Shubhashish and Bisai Supporting Information 10 2-(3,4-Dimethoxyphenyl)-2-(2-hydroxyethyl)cyclohexanol ±(8a): 1.004 g, 90% yield as yellow gel, R f = 0.15 (50% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.94-6.93 (m, 2H), 6.83-6.81 (m, 1H), 4.23 (brs, 1H), 3.86 (s, 3H), 3.85 (s, 3H), 3.58-3.53 (m, 1H), 3.49-3.43 (m, 1H), 2.78 (brs, 2H), 2.25-2.18 (m, 1H), 1.82-1.73 (m, 6H), 1.5-1.49 (m, 1H), 1.38-1.36 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 148.8, 147.1, 137.9, 119.2, 111.0, 110.6, 72.7, 59.3, 56.0, 55.8, 45.4, 29.8, 29.7, 22.7, 21.6, 20.6; IR (film) υ max 3352, 2935, 2110, 1781, 1649, 1506, 1454, 1355, 1238, 1204, 1169, 1109, 1039, 1017, 935, 808, 736 cm -1 ; HRMS (ESI) m/z 303.1601 [(M + Na) + ; calculated for [C 16 H 24 O 4 + Na] + : 303.1567]. 2-(Benzo[d][1,3]dioxol-5-yl)-2-(2-hydroxyethyl)cyclohexanol ±(8b): 973 mg, 92% yield as white solid, R f = 0.2 (50% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.90 (d, J = 1.7 Hz, 1H), 6.84 (dd, J = 6.5, 1.7 Hz, 1H), 6.75 (d, J = 8.2 Hz, 1H), 5.91 (s, 2H), 4.16-4.14 (m, 1H), 3.54-3.49 (m, 1H), 3.45-3.39 (m, 1H), 3.05 (brs, 2H), 2.22-2.14 (m, 1H), 1.83-1.64 (m, 6H), 1.52-1.44 (m, 1H), 1.39-1.32 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 147.8, 145.4, 139.5, 119.9, 108.0, 107.6, 100.9, 72.5, 59.1, 45.7, 38.8, 35.8, 29.8, 22.7, 21.5; IR (film) υ max 3351, 2935, 2866, 1612, 1489, 1437, 1240, 1040, 937, 913, 738, 431 cm -1 ; HRMS (ESI) m/z 287.1254 [(M + Na) + ; calculated for [C 15 H 20 O 4 + Na] + : 287.1254]; mp 90-92 C. General Procedure for Synthesis of (±)-9a-b: S10

Das, De, Shubhashish and Bisai Supporting Information 11 A solution of iodolactone 3 (0.5 mmol, 1 equiv), in toluene (7 ml) was added DBU (112 µl, 0.75 mmol, 1.5 equiv) and the reaction mixture was refluxed at 110 ºC for 5h. Upon completion of the reaction (monitoring by TLC), it was diluted by 10 ml EtOAc. The whole reaction mixture was taken in a separatory funnel and extracted with 10 ml of water. The organic filtrate was dried over anhydrous Na 2 SO 4 and concentrated in a rotary evaporator under vacuum. The crude product was purified by flash chromatography to provide 9. 3a-(3,4-Dimethoxyphenyl)-3,3a,4,5-tetrahydrobenzofuran-2(7aH)-one ±(9a): 129 mg, 94% yield as colorless gel, R f = 0.30 (20% EtOAc in hexane). 1 H NMR (500 MHz, CDCl 3 ) δ 6.82 (d, J = 8.3 Hz, 1H), 6.70-6.67 (m, 2H), 6.28-6.25 (m, 1H), 6.16-6.13 (m, 1H), 4.94 (d, J = 4.2 Hz, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 2.89 (ABq, J = 16.9 Hz, 2H), 2.10-2.04 (m, 1H), 1.85-1.73 (m, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 175.0, 149.0, 148.1, 135.9, 135.0, 122.8, 118.0, 111.1, 109.4, 78.2, 56.0, 55.9, 44.6, 44.2, 31.6, 22.0; IR (film) υ max 2921, 1780, 1592, 1520, 1468, 1255, 1201, 1150, 1027, 978, 809 cm -1 ; HRMS (ESI) m/z 313.0839 [(M + K) + ; calculated for [C 16 H 18 O 4 + K] + : 313.0837]. S11

Das, De, Shubhashish and Bisai Supporting Information 12 3a-(Benzo[d][1,3]dioxol-5-yl)-3,3a,4,5-tetrahydrobenzofuran-2(7aH)-one ±(9b): 119 mg, 92% yield as white solid, R f = 0.40 (20% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.74 (d, J = 8.1 Hz, 1H), 6.62 (d, J = 1.8 Hz, 1H), 6.56 (dd, J = 8.1, 1.9 Hz, 1H), 6.25-6.21 (m, 1H), 6.12-6.09 (m, 1H), 5.93 (s, 2H), 4.86 (d, J = 4.2 Hz, 1H), 2.83 (ABq, J = 13.2 Hz, 2H), 2.08-2.0 (m, 1H), 1.85-1.61 (m, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 174.8, 148.0, 146.5, 136.3, 136.0, 122.7, 118.9, 108.3, 106.6, 101.2, 78.1, 44.8, 44.4, 31.7, 21.9; IR (film) υ max 2920, 2856, 2343, 1775, 1460, 1237, 1196, 1106, 1037, 810 cm -1 ; HRMS (ESI) m/z 259.0983 [(M + H) + ; calculated for [C 15 H 14 O 4 + H] + : 259.0965]; mp 96-98 C. General Procedure for Synthesis of ketoaldehyde (±)-10a-b: A flame-dried round-bottom flask was charged with DMSO (528 µl, 10.0 mmol, 10 equiv), CH 2 Cl 2 (8 ml) and cooled to -78 ºC. In a separate flask, oxalyl chloride (257 µl 3.0 mmol, 3 equiv) was dissolved in CH 2 Cl 2 (6 ml). The oxalyl chloride solution was added dropwise to the DMSO/ CH 2 Cl 2 solution at -78 ºC via syringe over 15 mins. After stirring for 30 mins at -78 ºC, diol (±)-8 (1.0 mmol, 1.0 equiv) in CH 2 Cl 2 (10 ml) was added dropwise over 30 mins and the reaction mixture was stirred at -78 ºC for an additional 2.5 h. Triethylamine (1.4 ml, 10.0 mmol, 10 equiv) was added dropwise and then the reaction mixture was stirred at that temperature for an hour and then allowed to slowly warm to RT. After stirring at RT for 1 h, the reaction mixture was poured into a separatory funnel and washed with water (20 ml). The aqueous layer was extracted with CH 2 Cl 2 (2 X 20 ml). The combined organic extracts were dried over Na 2 SO 4 and concentrated under vacuum. The crude product was purified by flash chromatography to afford of (±)-10. S12

Das, De, Shubhashish and Bisai Supporting Information 13 2-(1-(3,4-Dimethoxyphenyl)-2-oxocyclohexyl)acetaldehyde ±(10a): 246 mg, 89% yield as colorless gel, R f = 0.56 (40% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 9.55 (s, 1H), 6.85 (d, J = 8.4 Hz, 1H), 6.76 (dd, J = 8.4, 1.8 Hz, 1H), 6.64 (s,1h), 3.85 (s, 3H), 3.83 (s, 3H), 2.70-2.65 (m, 3H), 2.46-2.33 (m, 2H), 2.02-1.89 (m, 2H), 1.79-1.65 (m, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 212.0, 201.7, 149.6, 148.3, 131.7, 118.9, 111.6, 109.7, 56.0, 55.9, 55.7, 53.4, 39.5, 35.9, 27.7, 21.3; IR (film) υ max 2939, 2865, 1707, 1589, 1519, 1465, 1259, 1153, 1026, 811 cm -1 ; HRMS (ESI) m/z 299.1249 [(M + Na) + ; calculated for [C 16 H 20 O 4 + Na] + : 299.1254]. 2-(1-(Benzo[d][1,3]dioxol-5-yl)-2-oxocyclohexyl)acetaldehyde ±(10b): 239 mg, 92% yield as white solid, R f = 0.35 (20% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 9.55 (s, 1H), 6.78 (d, J = 8.1 Hz, 1H), 6.72-6.69 (m, 1H), 6.63-6.61 (m, 1H), 5.95 (s, 2H), 2.66-2.57 (m, 3H), 2.47-2.33 (m, 2H), 1.98-1.89 (m, 2H), 1.77-1.68 (m, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 211.8, 201.6, 148.7, 146.9, 133.3, 120.0, 108.9, 106.9, 101.3, 55.8, 53.4, 39.5, 36.1, 27.8, 21.3; IR (film) υ max 2939, 2866, 1713, 1706, 1610, 1489, 1345, 1241, 1039, 934, 814 cm -1 ; HRMS (ESI) m/z 261.1122 [(M + H) + ; calculated for [C 15 H 16 O 4 + H] + : 261.1121], mp 38-40 ºC. Optimization of reductive amination of (±)-10: S13

Das, De, Shubhashish and Bisai Supporting Information 14 a 2.0 equiv. of NH 4 OAc and 3.0 equiv. NaBH 3 CN were used in each case and all the reactions were performed on a 0.20 mmol of (±)- 10a in 2 ml of solvent under inert atmosphere. b isolated yields after column chromatography. An oven-dried round-bottom flask was charged with ketoaldehyde (±)-10a (50 mg, 0.181 mmol, 1.0 equiv) in EtOH (3 ml), followed by addition of NH 4 OAc (28 mg, 0.362 mmol, 2.0 equiv), NaBH 3 CN (45 mg, 0.724 mmol, 4.0 equiv) and protic acid (0.087 mmol, 0.1 equiv) respectively. The reaction mixture was stirred at room temperature for indicated time. The reaction mixture was then basified with 2(N) NaOH and extracted with CH 2 Cl 2. The combined organic layers were dried over anhydrous K 2 CO 3 and concentrated under vacuum. The crude product was purified by flash chromatography to give amine 11a as a light yellow gel. 3a-(3,4-dimethoxyphenyl)octahydro-1H-indole ±(11a): 42 mg, 89% yield as colorless gel, R f = 0.3 (1 ml MeOH + 30 ml CH 2 Cl 2 + 1 ml Et 3 N). 1 H NMR (400 MHz, CDCl 3 ) δ 6.95-6.91 (m, 2H), 6.84 (d, J = 8.2 Hz, 1H), 3.91 (s, 3H), 3.89 (s, 3H), 3.48 (t, J = 4.3 Hz, 1H), 3.2-3.13 (m, 1H), 3.07-3.00 (m, 1H), 2.08-2.02 (m, 2H), 1.99-1.87 (m, 3H), 1.82-1.67 (m, 3H), 1.55-1.48 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ S14

Das, De, Shubhashish and Bisai Supporting Information 15 149.1, 147.8, 134.7, 118.3, 111.2, 109.7, 61.0, 56.1, 55.9, 46.9, 41.3, 40.3, 23.7, 22.7, 21.1, 19.7; IR (film) υ max 3400, 2982, 2853, 1501, 1473, 1231, 1099, 1011, 911 cm -1 ; HRMS (ESI) m/z 262.1818 [(M + H) + ; calculated for [C 16 H 23 NO 2 + H] + : 262.1802]. Synthesis of Amine Derivatives ±(12a-b): A round-bottom flask was charged with amine (±)-11a (0.25 mmol; 1.0 equiv.) in toluene : NaHCO 3 (1:1) (7 ml) at room temperature. To this reaction mixture chloroformate (0.3 mmol, 1.2 equiv) was added dropwise and it was stirred for 30 min at room temperature. Upon completion of the reaction (monitoring by TLC), it was diluted by 10 ml EtOAc. The whole reaction mixture was taken in a separatory funnel and extracted with 5 ml of water. The organic filtrate was dried over anhydrous Na 2 SO 4 and concentrated in a rotary evaporator under vacuum. The crude product was purified by flash chromatography to give product 12 as a light yellow gel. Methyl 3a-(3,4-dimethoxyphenyl)octahydro-1H-indole-1-carboxylate ±(12a): 68 mg, 85% yield as colorless gel, R f = 0.30 (30% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.83-6.77 (m, 3H), 4.25-4.11 (m, 1H), 3.85 (s, 3H), 3.84 (s, 3H), 3.69-3.62 (m, 3H), 3.39-3.34 (m, 1H), 3.09-3.07 (m, 1H), 2.39-2.31 (m, 1H), 2.15-2.02 (m, 3H), 1.92-1.90 (m, 1H), 1.66-1.55 (m, 4H), 1.49-1.43 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 155.3, 148.7, 147.2, 140.1, 117.7, 111.0, 109.3, 59.6, 55.9, 55.8, 52.1, 57.1, 43.3, 35.6, 33.3, 29.7, 23.2, 22.3; IR (film) υ max 2928, 2856, 1696, 1520, 1454, 1392, 1256, 1155, S15

Das, De, Shubhashish and Bisai Supporting Information 16 1029, 769 cm -1 ; HRMS (ESI) m/z 320.1859 [(M + H) + ; calculated for [C 18 H 25 NO 4 + H] + : 320.1856]. Benzyl 3a-(3,4-dimethoxyphenyl)octahydro-1H-indole-1-carboxylate ±(12b): 81 mg, 82% yield as yellow gel, R f = 0.55 (30% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 7.35-7.25 (m, 5H), 6.86-6.71 (m, 3H), 5.19-5.03 (m, 2H), 4.29-4.16 (m, 1H), 3.84 (s, 3H), 3.78-3.75 (m, 3H), 3.41 (t, J = 9.4 Hz, 1H), 3.18-3.12 (m, 1H), 2.40-2.32 (m, 1H), 2.17-2.04 (m, 2H), 1.97-1.89 (m, 1H), 1.66-1.43 (m, 6H); 13 C NMR (100 MHz, CDCl 3 ) (rotameric mixture) δ 154.64, 154.61, 148.73, 148.71, 147.28, 147.22, 140.14, 140.11, 137.19, 137.17, 128.47, 128.39, 127.86, 127.75, 127.65, 127.52, 117.68, 117.48, 111.05, 111.01, 109.25, 109.23, 66.59, 66.33, 59.67, 59.60, 55.84, 55.80, 47.86, 47.12, 43.57, 43.42, 35.93, 35.54, 33.38, 31.92, 31.58, 29.70, 29.32, 28.37, 23.54, 23.24, 22.35, 22.28; IR (film) υ max 3055, 2929, 2855, 1696, 1519, 1454, 1416, 1348, 1265, 1154, 1029, 805 cm -1 ; HRMS (ESI) m/z 396.2179 [(M + H) + ; calculated for [C 24 H 29 NO 4 + H] + : 396.2169]. Total Synthesis of (±)-mesembrane: S16

Das, De, Shubhashish and Bisai Supporting Information 17 An oven-dried round-bottom flask was charged with ketoaldehyde (±)-10a (20 mg, 0.072 mmol, 1.0 equiv) in EtOH (3 ml), followed by addition of methylamine in THF (364 µl, 0.72 mmol, 10.0 equiv), NaBH 3 CN (19 mg, 0.291 mmol, 4.0 equiv) and protic acid (0.0072 mmol, 0.1 equiv) respectively. The reaction mixture was stirred at room temperature for indicated time. The reaction mixture was then basified with 2(N) NaOH and extracted with CH 2 Cl 2. The combined organic layers were dried over anhydrous K 2 CO 3 and concentrated under vacuum. The crude product was purified by flash chromatography to give amine 1a and 13 as a light yellow gel. 3a-(3,4-dimethoxyphenyl)-1-methyloctahydro-1H-indole ±(1a): 17 mg, 88% yield as colorless gel, R f = 0.45 (1 ml MeOH + 30 ml CH 2 Cl 2 + 1 ml Et 3 N). 1 H NMR (400 MHz, CDCl 3 ) δ 6.94-6.90 (m, 2H), 6.84-6.81 (m, 1H), 3.89 (s, 3H), 3.88 (s, 3H), 3.28-3.23 (m, 1H), 2.59 (brs, 1H), 2.33 (s, 3H), 2.32-2.29 (m, 1H), 1.96-1.80 (m, 4H), 1.67-1.65 (m, 3H), 1.50-1.45 (m, 2H), 1.39-1.36 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 148.6, 146.8, 140.3, 118.9, 110.7, 110.6, 68.7, 55.9, 55.8, 54.4, 47.5, 41.0, 40.7, 36.1, 23.7, 22.9, 20.4; IR (film) υ max 2932, 2856, 1589, 1519, 1464, 1410, 1326, 1257, 1148, 1030, 805 cm -1 ; HRMS (ESI) m/z 276.1965 [(M + H) + ; calculated for [C 17 H 25 NO 2 + H] + : 276.1958]. 3a-(Benzo[d][1,3]dioxol-5-yl)-1-methyloctahydro-1H-indole ±(13): 23 mg, 91% yield as colorless gel, R f = 0.50 (1 ml MeOH + 30 ml CH 2 Cl 2 + 1 ml Et 3 N). 1 H NMR (400 MHz, CDCl 3 ) δ 6.84 (d, J = 1.7 Hz, 1H), 6.80 (dd, J = 8.2, 1.7 Hz, 1H), 6.72 (d, J = 8.2 Hz, 1H), 5.90 (s, 2H), 3.31-3.25 (m, 1H), 2.59 (brs, 1H), 2.33 (s, 3H), 2.32-2.28 (m, 1H), 1.91-1.73 (m, 5H), 1.60-1.57 (m, 2H), 1.47-1.44 (m, 1H), 1.36-1.34 (m, 1H), 1.16-1.10 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 147.6, 145.2, 141.3, 119.6, 107.7, S17

Das, De, Shubhashish and Bisai Supporting Information 18 107.6, 100.8, 68.9, 54.2, 47.7, 40.9, 40.7, 35.9, 23.5, 22.7, 20.3; IR (film) υ max 2920, 2857, 2787, 1726, 1612, 1505, 1485, 1455, 1360, 1340, 1265, 1237, 1191, 1110, 1082, 976 cm -1 ; HRMS (ESI) m/z 260.1650 [(M + H) + ; calculated for [C 16 H 21 NO 2 + H] + : 260.1645]. Total Synthesis of Crinane ±(2a): Same procedure as reductive amination of 11a. 3a-(Benzo[d][1,3]dioxol-5-yl)octahydro-1H-indole ±(11b): 21 mg, 88% yield as yellow gel, R f = 0.40 (1 ml MeOH + 30 ml CH 2 Cl 2 + 1 ml Et 3 N). 1 H NMR (400 MHz, CDCl 3 ) δ 6.85 (d, J = 1.8 Hz, 1H), 6.80 (dd, J = 8.2 Hz, 1H), 6.73 (d, J = 8.2 Hz, 1H), 5.91 (s, 2H), 3.40 (s, 1H), 3.16-3.09 (m, 1H), 3.02-2.96 (m, 1H), 2.5 (brs, 1H), 2.02-1.96 (m, 1H), 1.91-1.85 (m, 1H), 1.77-1.73 (m, 3H), 1.69-1.62 (m, 1H), 1.55-1.39 (m, 4H); 13 C NMR (100 MHz, CDCl 3 ) δ 147.7, 145.3, 140.6, 119.4, 107.8, 107.5, 100.8, 60.9, 47.9, 42.9, 41.2, 33.8, 29.7, 26.1, 22.0; IR (film) υ max 3382, 2924, 2857, 1472, 1234, 1119, 1040, 936, 808 cm -1 ; HRMS (ESI) m/z 246.1469 [(M + H) + ; calculated for [C 15 H 19 NO 2 + H] + : 246.1489. S18

Das, De, Shubhashish and Bisai Supporting Information 19 2,3,4,4a-Tetrahydro-1H,6H-5,11b-ethano[1,3]dioxolo[4,5-j]phenanthridine ±(2a): An oven-dried round-bottom flask was charged with (±)-11b (21 mg, 0.082 mmol, 1.0 equiv) in dry THF (7 ml). To the reaction mixture, Eschenmoser's salt (23 mg, 0.124 mmol, 1.5 equiv) was added and heated the reaction mixture at 40 C for 30h. Upon completion of the reaction (monitoring by TLC), THF was removed under vacuum and then 10 ml EtOAc and 1(N) NaOH was added until the solution became basic. The organic phases were combined and dried over anhydrous K 2 CO 3 and concentrated under vacuum. The crude product was purified by flash chromatography with basic alumina to give amine 2a as a light yellow gel. 16 mg, 72% yield as light yellow gel, R f = 0.40 (10% MeOH in CH 2 Cl 2 ). 1 H NMR (400 MHz, CDCl 3 ) δ 6.69 (s, 1H), 6.43 (s, 1H), 5.86 (s, 2H), 4.31 (d, J = 16.8 Hz, 1H), 3.72 (d, J = 16.8 Hz, 1H), 3.27-3.34 (m, 1H), 2.74-2.83 (m, 2H), 2.31-2.34 (m, 1H), 2.15-2.22 (m, 1H), 1.70-1.84 (m, 1H), 1.56-1.61 (m, 1H), 1.47-1.51 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 146.1, 145.5, 142.3, 126.2, 106.2, 103.3, 100.6, 57.3, 62.1, 51.9, 42.8, 37.9, 29.0, 27.6, 24.4, 21.8; IR (film) υ max 2929, 2916, 2881, 1649, 1484, 1454, 1238, 1040, 935, 867 cm -1 ; HRMS (ESI) m/z 258.1501 [(M + H) + ; calculated for [C 167 H 19 NO 2 + H] + : 258.1489]. Synthesis of Amine Derivatives 14a-b: A round-bottom flask was charged with amine (±)-11b (0.03 mmol; 1.0 equiv.) in toluene : NaHCO 3 (1:1) (5 ml) at room temperature. To this reaction mixture chloroformate (0.036 mmol, 1.2 equiv) was added dropwise and it was stirred for 30 S19

Das, De, Shubhashish and Bisai Supporting Information 20 min at room temperature. Upon completion of the reaction (monitoring by TLC), it was diluted by 10 ml EtOAc. The whole reaction mixture was taken in a separatory funnel and extracted with 7 ml of water. The organic filtrate was dried over anhydrous Na 2 SO 4 and concentrated in a rotary evaporator under vacuum. The crude product was purified by flash chromatography to give product 14 as a light yellow gel. Methyl 3a-(benzo[d][1,3]dioxol-5-yl)octahydro-1H-indole-1-carboxylate ±(14a): 7 mg, 74% yield as light yellow gel, R f = 0.40 (30% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 6.84-6.72 (m, 3H), 5.93 (s, 2H), 4.19-4.08 (m, 1H), 3.70-3.64 (m, 3H), 3.41-3.37 (m, 1H), 3.13 (m, 1H), 2.38-2.30 (m, 1H), 2.17-2.12 (m, 1H), 2.04-1.92 (m, 2H), 1.68-1.29 (m, 6H); 13 C NMR (100 MHz, CDCl 3 ) (rotameric mixture) δ 155.32, 155.26, 147.79, 145.68, 141.61, 141.45, 118.38, 107.98, 106.63, 106.47, 100.93, 59.82, 52.26, 52.08, 48.21, 47.45, 43.53, 43.31, 36.26, 35.91, 33.09, 31.51, 29.14, 28.24, 23.45, 23.17, 22.31; IR (film) υ max 2928, 2862, 2357, 2321, 1695, 1649, 1454, 1394, 1266, 1236, 1193, 1155, 1116, 1041, 939, 807, 770, 738, 705 cm -1 ; HRMS (ESI) m/z 304.1562 [(M + H) + ; calculated for [C 17 H 21 NO 4 + H] + : 304.1543]. Benzyl 3a-(benzo[d][1,3]dioxol-5-yl)octahydro-1H-indole-1-carboxylate ±(14b): 9 mg, 83% yield as colorless gel, R f = 0.50 (20% EtOAc in hexane). 1 H NMR (400 MHz, CDCl 3 ) δ 7.38-7.31 (m, 5H), 6.86-6.67 (m, 3H), 5.94 (s, 2H), 5.20-5.07 (m, 2H), 4.25-4.12 (m, 1H), 3.46-3.41 (m, 1H), 3.23-3.16 (m, 1H), 2.40-2.32 (m, 1H), 2.19-1.92 (m, 3H), 1.69-1.37 (m, 6H); 13 C NMR (100 MHz, CDCl 3 ) (rotameric mixture) δ 154.63, 154.44, 147.82, 145.69, 141.41, 141.38, 140.94, 137.22, 128.56, 128.48, 128.39, 127.83, 127.74, 127.64, 127.48, 126.98, 118.38, 118.30, 107.95, 106.69, 106.56, 106.46, 100.94, 100.93, 66.59, 66.34, 59.88, 59.82, 48.21, 47.47, 43.59, 43.40, 37.17, 35.81, 33.16, S20

Das, De, Shubhashish and Bisai Supporting Information 21 31.49, 29.70, 29.27, 23.50, 23.16, 22.33, 22.28; IR (film) υ max 2929, 2857, 1696, 1649, 1415, 1348, 1265, 1236, 1154, 1098, 1040, 938, 808, 739, 700 cm -1 ; HRMS (ESI) m/z 380.1856 [(M + H) + ; calculated for [C 23 H 25 NO 4 + H] + : 380.1856]. S21

Das, De, Shubhashish and Bisai Supporting Information 22 1 H, 13 C and Mass spectral traces 1.03 5.3027 1.08 4.1845 4.1693 4.1540 4.1388 4.1236 4.1084 4.12 2.10 1.00 1.07 3.07 3.10 2.3300 2.3153 2.3009 2.2856 2.2687 1.6631 1.8757 1.4567 1.1802 0.8704 0.8518 0.8331 1 H NMR (400 MHz, CDCl 3 ) of compound (6) S22

Das, De, Shubhashish and Bisai Supporting Information 23 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 13 C NMR (100 MHz, CDCl 3 ) of compound (6) S23

Das, De, Shubhashish and Bisai Supporting Information 24 Scanned copy of mass spectrum of (6) S24

Das, De, Shubhashish and Bisai Supporting Information 25 1 H NMR (400 MHz, CDCl 3 ) of compound (7a) S25

Das, De, Shubhashish and Bisai Supporting Information 26 200 200.0401 190 180 170 160 150 159.4108 150.9261 149.0241 140 130 120 131.1130 123.8967 119.4914 110 100 f1 (ppm) 110.9223 108.9285 90 80 77.3956 77.0774 76.7595 70 60 55.9780 55.9413 50 40 37.1861 30 20 27.9085 22.7633 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound (7a) S26

Das, De, Shubhashish and Bisai Supporting Information 27 Scanned copy of mass spectrum of (7a) S27

Das, De, Shubhashish and Bisai Supporting Information 28 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 1.01 1.00 1.00 1.00 2.05 7.0544 7.0499 7.0340 7.0295 6.9890 6.9847 6.8055 6.7850 6.2946 5.9702 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 2.02 2.02 2.01 2.6888 2.6745 2.6614 2.6588 2.4037 2.1212 2.1054 2.0890 2.0731 2.0577 1.0 0.5 0.0 1 H NMR (400 MHz, CDCl 3 ) of compound (7b) S28

Das, De, Shubhashish and Bisai Supporting Information 29 13 C NMR (100 MHz, CDCl 3 ) of compound (7b) S29

Das, De, Shubhashish and Bisai Supporting Information 30 16 15 14 13 12 11 10 9 8 7 6 f1 (ppm) 2.02 1.01 1.00 6.9443 6.9402 6.9326 6.8153 6.8045 6.7932 6.0546 6.0510 5 4 3 2 1 0-1 -2-3 -4 1.00 6.15 2.09 2.03 3.03 4.3717 3.8734 3.8579 2.3991 2.3498 2.3053 1.9560 1.9315 1.9201 1.9065 1.8953 1.8801 1.8599 1.8434 1.7730 1.7552 1.7197 1.7069 1.6898 1.6760 1.6610 1.6513 1.6353 1.6129 1 H NMR (400 MHz, CDCl 3 ) of compound (5a) S30

Das, De, Shubhashish and Bisai Supporting Information 31 210 200 190 180 170 160 150 140 130 120 110 100 f1 (ppm) 148.7110 148.6715 139.7143 134.2784 125.2864 117.7866 110.8883 108.7384 90 80 70 60 50 77.3640 77.0462 76.7286 66.3731 55.9149 55.8656 40 30 20 31.7565 27.6083 19.4409 10 0-10 13 C NMR (100 MHz, CDCl 3 ) of compound (5a) S31

Das, De, Shubhashish and Bisai Supporting Information 32 Scanned copy of mass spectrum of ±(5a) S32

Das, De, Shubhashish and Bisai Supporting Information 33 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 1 H NMR (500 MHz, CDCl 3 ) of compound (5b) S33

Das, De, Shubhashish and Bisai Supporting Information 34 13 C NMR (125 MHz, CDCl 3 ) of compound (5b) S34

Das, De, Shubhashish and Bisai Supporting Information 35 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 f1 (ppm) 2.01 1.07 1.00 0.96 6.8668 6.8501 6.7791 6.7568 6.1587 6.1332 5.8876 5.8795 5.8709 5.8629 5.8541 5.8460 4.5 4.0 3.5 6.00 3.8349 3.8261 3.0 2.5 2.0 1.5 1.0 0.5 3.00 2.96 1.92 4.10 1.00 1.04 2.8093 2.7104 2.6866 2.6716 2.0214 1.9906 1.9023 1.5587 1.5440 1.4134 1.4071 1.3906 1.3834 1.3690 1.3629 1.3293 1 H NMR (400 MHz, CDCl 3 ) of compound ±(4a) S35

Das, De, Shubhashish and Bisai Supporting Information 36 200 190 180 170 170.7681 160 150 140 130 148.3879 147.0201 140.2669 133.1131 128.0260 120 110 118.7777 110.6721 110.4788 100 f1 (ppm) 90 80 70 77.3611 77.0433 76.7255 60 50 40 30 20 55.8759 55.7977 45.0818 41.8475 37.7863 36.5185 35.3645 25.2573 18.8510 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(4a) S36

Das, De, Shubhashish and Bisai Supporting Information 37 Scanned copy of mass spectrum of ±(4a) S37

Das, De, Shubhashish and Bisai Supporting Information 38 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 f1 (ppm) 1.00 1.01 0.98 1.03 3.05 6.8236 6.8198 6.7715 6.7675 6.7510 6.7470 6.6954 6.6750 6.1098 6.0831 5.8685 5.8539 5.8450 5.8374 5.8280 5.8195 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 5.98 2.15 3.01 1.03 1.16 1.03 2.7992 2.7931 2.7292 2.6921 2.6427 2.6057 1.9615 1.8871 1.8259 1.5077 1.4851 1.3912 1.3842 1.3685 1.3611 1.3554 1.3418 1 3352 1 H NMR (400 MHz, CDCl 3 ) of compound ±(4b) S38

Das, De, Shubhashish and Bisai Supporting Information 39 200 190 180 170 170.5514 160 150 140 130 120 110 100 f1 (ppm) 147.3771 145.3044 141.8416 133.0481 128.0652 119.8004 107.6500 107.4159 100.7837 90 80 77.4340 77.1156 76.7976 70 60 50 40 30 20 44.8430 41.9935 37.7628 37.1085 35.3382 25.1989 18.7040 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(4b) S39

Das, De, Shubhashish and Bisai Supporting Information 40 Scanned copy of mass spectrum of ±(4b) S40

Das, De, Shubhashish and Bisai Supporting Information 41 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 1.03 2.02 6.9091 6.8879 6.8376 6.8329 6.8221 6.8008 6.0 5.5 5.0 f1 (ppm) 1.00 5.0138 4.9967 4.5 4.0 3.5 1.01 6.05 4.2079 4.1959 4.1846 3.8577 3.8305 3.0 2.5 2.0 1.5 1.0 0.5 2.03 1.04 3.06 1.01 1.05 2.7895 2.7465 1.9963 2.6967 2.6537 1.9337 1.7929 1.7842 1.7756 1.7666 1.7584 1.7506 1.6167 1.5927 1.5829 1.5693 1.5598 1 5359 1 H NMR (400 MHz, CDCl 3 ) of compound ±(3a) S41

Das, De, Shubhashish and Bisai Supporting Information 42 200 190 180 174.1270 170 160 150 149.1644 148.3909 140 135.5542 130 120 110 118.1762 111.1895 109.5656 100 f1 (ppm) 90 88.5470 80 77.4575 77.1392 76.8211 70 60 50 40 30 20 56.1905 55.9282 46.7543 41.7220 34.1561 32.5882 25.6469 21.8755 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(3a) S42

Das, De, Shubhashish and Bisai Supporting Information 43 Scanned copy of mass spectrum of ±(3a) S43

Das, De, Shubhashish and Bisai Supporting Information 44 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 2.05 0.99 2.02 6.8565 6.8520 6.8449 6.8402 6.8245 6.8195 6.7839 6.7636 5.9516 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) 1.00 1.00 1.99 1.07 3.08 1.08 1.06 4.9945 4.9775 4.2269 4.2229 4.2168 4.2102 4.1997 2.7827 2.7396 2.6850 2.6420 2.2540 2.0340 1.9986 1.9719 1.9450 1.9179 1.8215 1.7949 1.7685 1.6332 1.6008 1.5659 1.5564 1 H NMR (400 MHz, CDCl 3 ) of compound ±(3b) S44

Das, De, Shubhashish and Bisai Supporting Information 45 190 180 170 173.8918 160 150 140 148.3010 146.8072 136.9056 130 120 110 100 90 f1 (ppm) 119.0601 108.2949 106.5880 101.3638 88.5270 80 70 60 50 40 30 20 46.8386 41.9926 33.9942 32.6875 25.3072 21.7675 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(3b) S45

Das, De, Shubhashish and Bisai Supporting Information 46 Scanned copy of mass spectrum of ±(3b) S46

Das, De, Shubhashish and Bisai Supporting Information 47 OMe OMe OH (8a) OH 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 1.98 0.98 6.9381 6.9261 6.8329 6.8105 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 1.00 6.03 1.03 1.04 2.03 4.2341 3.8616 3.8505 3.5669 3.4714 3.4344 2.7797 2.5 2.0 1.5 1.0 0.5 1.11 6.12 1.03 1.98 2.2197 2.1846 1.8163 1.7971 1.7848 1.7719 1.7429 1.7330 1.6662 1.5008 1.4929 1.3816 1 3578 1 H NMR (400 MHz, CDCl 3 ) of compound ±(8a) S47

Das, De, Shubhashish and Bisai Supporting Information 48 210 200 190 180 170 160 150 140 148.8155 147.1460 137.9848 130 120 110 100 f1 (ppm) 119.1726 111.0481 110.6192 90 80 70 72.6871 60 50 59.2823 56.0320 55.8154 45.4597 40 30 20 29.8029 29.6955 22.7559 21.5644 20.5820 10 0-10 13 C NMR (100 MHz, CDCl 3 ) of compound ±(8a) S48

Das, De, Shubhashish and Bisai Supporting Information 49 Scanned copy of mass spectrum of ±(8a) S49

Das, De, Shubhashish and Bisai Supporting Information 50 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 1.01 1.04 1.02 6.9092 6.9049 6.8552 6.8508 6.8346 6.8301 6.7588 6.7382 6.0 2.00 5.9079 5.5 5.0 4.5 f1 (ppm) 4.0 3.5 1.00 1.03 1.04 4.1645 4.1496 4.1398 3.4900 3.4274 3.3954 3.0 2.02 3.0479 2.5 2.0 1.5 1.0 0.5 0.0 1.08 6.15 1.05 2.07 2.1945 2.1654 2.1443 1.7922 1.7725 1.7493 1.7241 1.6501 1.5190 1.4746 1.4538 1.3924 1.3698 1.3461 1 3283 1 H NMR (400 MHz, CDCl 3 ) of compound ±(8b) S50

Das, De, Shubhashish and Bisai Supporting Information 51 200 190 180 170 160 150 140 147.8499 145.3600 139.5051 130 120 119.8895 110 100 f1 (ppm) 108.0245 107.5941 100.8717 90 80 70 77.3661 77.0483 76.7306 72.4904 60 59.0613 50 45.6845 40 30 20 35.7764 29.8084 22.7077 21.5502 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(8b) S51

Das, De, Shubhashish and Bisai Supporting Information 52 Scanned copy of mass spectrum of ±(8b) S52

Das, De, Shubhashish and Bisai Supporting Information 53 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 1 H NMR (400 MHz, CDCl 3 ) of compound ±(9a) S53

Das, De, Shubhashish and Bisai Supporting Information 54 200 190 180 170 160 150 140 130 120 110 100 f1 (ppm) 90 80 70 60 50 40 30 20 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(9a) S54

Das, De, Shubhashish and Bisai Supporting Information 55 Scanned copy of mass spectrum of ±(9a) S55

Das, De, Shubhashish and Bisai Supporting Information 56 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 1.05 0.99 1.02 1.01 1.01 2.00 6.7496 6.7294 6.6271 6.6226 6.5761 6.5714 6.5559 6.5512 6.2102 6.1128 6.0946 6.0879 5.9358 5.0 4.5 f1 (ppm) 1.05 4.8690 4.8585 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0-0.5 2.05 1.00 3.09 2.8880 2.8456 2.8126 2.7702 2.0800 2.0664 2.0536 2.0352 2.0325 2.0231 2.0053 1.8148 1.8072 1.7827 1.7593 1.7274 1.7138 1.6931 1.6879 1.6830 1 H NMR (400 MHz, CDCl 3 ) of compound ±(9b) S56

Das, De, Shubhashish and Bisai Supporting Information 57 200 190 180 174.8245 170 160 150 140 147.9786 146.5198 136.3092 136.0122 130 120 122.6608 118.8581 110 100 f1 (ppm) 108.2688 106.5945 101.1839 90 80 70 78.1112 77.3524 77.0349 76.7171 60 50 40 44.7966 44.3709 30 31.7142 20 21.9163 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(9b) S57

Das, De, Shubhashish and Bisai Supporting Information 58 Scanned copy of mass spectrum of ±(9b) S58

Das, De, Shubhashish and Bisai Supporting Information 59 10.0 9.5 1.00 9.5474 9.0 8.5 8.0 7.5 7.0 6.5 6.0 0.98 1.01 0.95 6.8570 6.8361 6.7714 6.7668 6.7505 6.7459 6.6447 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 6.09 3.8545 3.8305 3.0 2.5 2.0 1.5 1.0 0.5 3.00 2.01 2.10 3.02 2.7015 2.6960 2.6534 2.3350 2.0177 1.9740 1.9445 1.9198 1.9088 1.8974 1.7982 1.7647 1.7366 1.6886 1.6569 1 H NMR (400 MHz, CDCl 3 ) of compound ±(10a) S59

Das, De, Shubhashish and Bisai Supporting Information 60 210 211.9943 200 201.7024 190 180 170 160 150 149.6572 148.3598 140 130 131.7590 120 110 f1 (ppm) 118.9079 111.6371 109.6711 100 90 80 70 77.3485 77.0309 76.7132 60 50 56.0359 55.8897 55.6664 53.3957 40 30 20 39.5166 35.8717 27.7282 21.3518 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(10a) S60

Das, De, Shubhashish and Bisai Supporting Information 61 Scanned copy of mass spectrum of ±(10a) S61

Das, De, Shubhashish and Bisai Supporting Information 62 10.0 9.5 1.01 9.5518 9.0 8.5 8.0 7.5 7.0 6.5 6.0 1.00 1.05 1.05 2.04 6.7916 6.7714 6.6960 6.6926 6.6290 6.6085 5.9512 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 3.00 2.11 2.6181 2.5785 2.5726 2.4743 2.4590 2.4405 2.4254 2.4075 2.3931 2.3645 2.3302 2.0 1.5 1.0 0.5 0.0 2.14 3.12 1.9521 1.9430 1.9353 1.9234 1.9129 1.8991 1.8878 1.7728 1.7399 1.7145 1.6898 1 6792 1 H NMR (400 MHz, CDCl 3 ) of compound ±(10b) S62

Das, De, Shubhashish and Bisai Supporting Information 63 210 211.7728 200 201.5867 190 180 170 160 150 148.6821 146.8502 140 130 133.2950 120 120.0484 110 f1 (ppm) 100 108.8816 106.8818 101.3500 90 80 70 77.3494 77.0317 76.7141 60 50 55.8329 53.4013 40 30 20 39.4990 36.0692 27.7896 21.2852 10 13 C NMR (100 MHz, CDCl 3 ) of compound ±(10b) S63

Das, De, Shubhashish and Bisai Supporting Information 64 Scanned copy of mass spectrum of ±(10b) S64

Das, De, Shubhashish and Bisai Supporting Information 65 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 f1 (ppm) 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 1 H NMR (400 MHz, CDCl 3 ) of compound ±(11a) S65

Das, De, Shubhashish and Bisai Supporting Information 66 Scanned copy of mass spectrum of ±(11a) S66

Das, De, Shubhashish and Bisai Supporting Information 67 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 3.14 6.8324 6.7953 6.7758 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 1.03 6.00 2.99 0.90 1.09 1.04 3.11 1.06 4.01 1.00 4.2477 4.1101 3.8391 3.6223 3.3403 3.0897 3.0683 2.3329 2.3093 2.1051 2.0225 1.9039 1.6595 1.5851 1.5556 1.4922 1.4831 1.4615 1.4393 1.4312 0.0 1 H NMR (400 MHz, CDCl 3 ) of compound ±(12a) S67

Das, De, Shubhashish and Bisai Supporting Information 68 Scanned copy of mass spectrum of ±(12a) S68

Das, De, Shubhashish and Bisai Supporting Information 69 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 1 H NMR (400 MHz, CDCl 3 ) of compound ±(12b) S69

Das, De, Shubhashish and Bisai Supporting Information 70 190 180 170 160 150 140 130 120 110 100 f1 (ppm) 90 80 70 60 50 40 30 20 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(12b) S70

Das, De, Shubhashish and Bisai Supporting Information 71 Scanned copy of mass spectrum of ±(12b) S71

Das, De, Shubhashish and Bisai Supporting Information 72 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 1 H NMR (400 MHz, CDCl 3 ) of compound ± (1a) S72

Das, De, Shubhashish and Bisai Supporting Information 73 Scanned copy of mass spectrum of ±(1a) S73

Das, De, Shubhashish and Bisai Supporting Information 74 1.01 1.01 1.02 2.00 6.8480 6.8438 6.8106 6.8063 6.7901 6.7858 6.7379 6.7175 5.9034 1.01 1.00 4.04 2.05 5.07 1.00 1.00 1.01 3.3090 3.2968 3.2858 3.2738 3.2630 3.2508 2.5866 2.2759 1.8900 1.8692 1.8526 1.8368 1.7966 1.7693 1.7574 1.7258 1.5936 1.5656 1.4447 1.3562 1.1605 1.1361 1 1195 1 H NMR (400 MHz, CDCl 3 ) of compound ±(13) S74

Das, De, Shubhashish and Bisai Supporting Information 75 147.5929 145.1580 141.3299 119.5579 107.6777 107.6482 100.8182 68.9477 54.2431 47.7417 40.6943 35.8970 23.4518 22.7208 20.3184 13 C NMR (100 MHz, CDCl 3 ) of compound ±(13) S75

Das, De, Shubhashish and Bisai Supporting Information 76 Scanned copy of mass spectrum of ±(13) S76

Das, De, Shubhashish and Bisai Supporting Information 77 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 0.96 0.99 0.96 6.8550 6.8506 6.8132 6.8086 6.7927 6.7882 6.7456 6.7252 6.0 2.00 5.9090 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 1.01 1.00 1.03 1.06 1.28 1.12 3.04 1.00 3.96 3.4069 3.0903 2.9945 2.9567 2.4977 1.9896 1.8609 1.8363 1.7740 1.7512 1.7321 1.6856 1.6296 1.5547 1.5129 1.4812 1.4622 1.4415 1 3956 1 H NMR (400 MHz, CDCl 3 ) of compound ±(11b) S77

Das, De, Shubhashish and Bisai Supporting Information 78 Scanned copy of mass spectrum of ±(11b) S78

Das, De, Shubhashish and Bisai Supporting Information 79 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 1.05 0.98 6.6892 6.4356 6.0 2.00 5.8638 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 1.04 1.03 1.11 2.07 1.07 1.01 6.08 1.21 1.08 4.3384 4.2965 3.7421 3.7002 3.3075 3.2738 2.7780 2.3387 2.7398 2.1939 2.1521 1.7025 1.6389 1.6284 1.6062 1.5964 1.5732 1.5640 1.5070 1.4984 1.4742 1 4664 13 C NMR (100 MHz, CDCl 3 ) of compound ±(2a) S79

Das, De, Shubhashish and Bisai Supporting Information 80 00 190 180 170 160 150 140 146.1335 145.4933 142.3139 130 126.1731 120 110 100 f1 (ppm) 106.1984 103.2595 100.6198 90 80 70 60 77.3402 77.0226 76.7050 67.3113 62.1442 50 51.9346 40 42.7712 37.9320 30 20 28.9707 27.6117 24.3963 21.7588 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(2a) S80

Das, De, Shubhashish and Bisai Supporting Information 81 Scanned copy of mass spectrum of ±(2a) S81

Das, De, Shubhashish and Bisai Supporting Information 82 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0. 1 H NMR (400 MHz, CDCl 3 ) of compound ±(14a) S82

Das, De, Shubhashish and Bisai Supporting Information 83 200 190 180 170 160 150 140 130 120 110 100 f1 (ppm) 90 80 70 60 50 40 30 20 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(14a) S83

Das, De, Shubhashish and Bisai Supporting Information 84 Scanned copy of mass spectrum of ±(14a) S84

Das, De, Shubhashish and Bisai Supporting Information 85 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 f1 (ppm) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 1 H NMR (400 MHz, CDCl 3 ) of compound ±(14b) S85

Das, De, Shubhashish and Bisai Supporting Information 86 200 190 180 170 160 150 140 130 120 110 100 f1 (ppm) 90 80 70 60 50 40 30 20 10 0 13 C NMR (100 MHz, CDCl 3 ) of compound ±(14b) S86

Das, De, Shubhashish and Bisai Supporting Information 87 Scanned copy of mass spectrum of ±(14b) S87