6-endo heck cyclization of 3-(2-iodophenoxy)methylbenzofurans: A useful approach to pterocarpenes

Article abstract of DOI:10.1080/00397911.2012.661910

Mitsunobu coupling of 3-hydroxymethylbenzofurans with o-iodophenols affords 3-(2-iodophenoxy)methylbenzofurans which under go a useful 6-endo Heck cyclization under Jeffery conditions to afford pterocarpene-type heterocycles. The unsubstituted parent pterocarpene thus prepared was readily converted to coumestan via subsequent PCC oxidation. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2012.661910

6-Endo Heck Cyclization of 3-(2-iodophenoxy)methylbenzofurans:
A Useful Approach to Pterocarpenes
Kathryn J. Fowler, Jillian L. Ellis and Gary W. Morrow
Department of Chemistry, University of Dayton, Dayton, Ohio, USA
Supplementary Information
General Procedures: All NMR spectra were recorded at 300 MHz (1H) and 125 MHz (13C) on a
Bruker Avance spectrometer and were measured in deuteriochloroform with tetramethylsilane
(TMS) as internal standard unless otherwise specified. Signals are reported in δ values (ppm)
downfield from TMS. Melting points were determined in open capillary tubes on a Thomas-
Hoover apparatus and are uncorrected. Elemental analyses were provided by Galbraith
Laboratories, Knoxville, TN. HRMS data were provided by the Chemical Instrumentation
Center, The Ohio State University. Standard workup refers to extraction of the material into the
indicated solvent, washing the organic layer with brine solution, drying over Drierite (CaSO4),
concentration in vacuo, and drying to constant weight under vacuum (1-2 Torr). The following
abbreviations are using throughout the experimental section: thin layer chromatography (TLC),
ethyl acetate (EtOAc), dimethyl formamide (DMF), tetrahydrofuran (THF) hexane (Hxa),
diisobutylaluminum hydride (DIBAL-H), diisopropylazodicarboxylate (DIAD). All
commercially available compounds and reagents were obtained from the Aldrich Chemical Co.
Preparation of 6-hydroxybenzo[d][1,3]dioxole-5-carbaldehyde (5c)
Sesamol (5.7 g, 41.0 mmol), paraformaldehyde (8.6 g, 287 mmol), and anhydrous magnesium
chloride (5.9 g, 61.5 mmol) were dissolved in dry CH3CN (200 mL). Triethylamine (15.5 g, 154
mmol, 22 mL) was added and the mixture was heated at reflux under N2 with stirring for 6 h.
The reaction mixture was then concentrated to ~ ¼ volume, diluted with 100 mL H2O, 50 mL of
20% HCl (aq), and 100 mL Et2O. The layers were shaken and separated and the aqueous phase
extracted with additional Et2O (2 x 100 mL). The combined organic layers were washed with
brine (100 mL), filtered through a CaSO4 cone, then concentrated in vacuo to give a dark brown
solid that was recrystallized from CH2Cl2 to yield 1.76 g (26%) of 5c as a light brown solid, m.p.
o
o
1
125-126 C (lit.[1] mp 125–126 C). H NMR (CDCl3): 6.01 (s, 2H), 6.46 (s, 1H), 6.85 (s, 1H),
9.62 (s, 1H), 11.53 (s, 1H).
[1.] K. Fukui and M. Nakayama, Bull. Soc. Chem. Jpn., 1962, 35, 1321.
Correspondence to: Prof. Gary W. Morrow, gmorrow1@udayton.edu, telephone (937) 229-2048; fax (937) 229-2635

Preparation of 2-iodo-5-methoxyphenol (2b)
To a solution of silver trifluoroacetate (5.52 g, 25 mmol) and 3-methoxyphenol (3.1 g, 25 mmol,
2.74 mL) in CHCl3 (25 mL) was added dropwise a solution of I2 (6.35 g, 25 mmol) in CHCl3
(200 mL) under N2 over 1.5 h. After an additional hour, AgI precipitate was removed by vacuum
filtration and the resulting filtrate was shaken with 1.0M NaHSO3 solution (50 mL) to discharge
excess I2. The organic phase was then washed with saturated NaHCO3 solution (100 mL) then
brine (50 mL) and was dried through a CaSO4 cone. After concentration in vacuo, the resulting
dark brown solid was chromatographed on silica gel with CHCl3 as the eluent to afford 2b (1.9 g,
o
o
48%) as a crystalline solid, m.p. 71-72.5 C (lit.[2] mp 71.5-72.5 C). 1H NMR (CDCl3): 3.77 (s,
3H), 5.27 (s, 1H), 6.33 (dd, J = 8.8, 2.8 Hz, 1H), 6.59 (d, J = 2.8 Hz, 1H), 7.49 (d, J = 8.8 Hz,
1H).
[2.] Winkle, M. R. and Ronald, R. C., J. Org. Chem. 1982, 47, 2101-08
Preparation of ethyl benzofuran-3-carboxylate (6a)
To a solution of 5a (16.4 mmol) in CH2Cl2 (5 mL) was added HBF4-Et2O complex (0.223 mL).
To the resulting dark red mixture was added a solution of ethyl diazoacetate (85%, 3.18 mL) in
CH2Cl2 (25 mL) dropwise at 25-30°C via addition funnel with evolution of N2. After 1h, the
mixture was concentrated to approx. 2/3 original volume and 1.0 mL of conc. H2SO4 was added.
After stirring for 15 min, solid NaHCO3 was added until CO2 evolution ceased. The mixture was
then filtered through a Celite pad, concentrated in vacuo and the residue chromatographed on
1
silica gel (3% EtOAc/Hxa as eluent) to afford 6a as a clear, colorless oil (2.09 g, 67%); H
NMR: 1.42 (t, J = 7.1 Hz, 3H), 4.40 (q, J = 7.1 Hz, 2H), 7.35 (m, 2H) 7.51 (m, 1H), 8.07 (m,
1H). 8.25 (s, 1H); 13C NMR: 14.39, 60.56, 111.67, 114.73, 122.05, 124.13, 124.63, 125.25,
150.95, 155.59, 163.46. All data consistent with literature values.[3]
[3.] Dudley, M. E., Morshed, M. M., Hossain, M. M., Synthesis, 2006, 1711–1714.
Preparation of ethyl 6-methoxybenzofuran-3-carboxylate (6b)
To a solution of 5b (16.4 mmol) in CH2Cl2 (5 mL) was added HBF4-Et2O complex (0.223 mL).
To the resulting mixture was added a solution of ethyl diazoacetate (85%, 3.18 mL) in CH2Cl2
(25 mL) dropwise at 25-30°C with evolution of N2. After 1h, the mixture was concentrated to
approx. 2/3 original volume and 1.0 mL of conc. H2SO4 was added. After stirring for 15 min,
solid NaHCO3 was added until CO2 evolution ceased. The mixture was then filtered through a
Celite pad, concentrated in vacuo and the residue chromatographed on silica gel (20%
EtOAc/Hxa as eluent) to afford 6b as white needles (1.16 g, 40%); m.p. 55-57°C (lit[4] mp 55-
1
56°C); H NMR: 1.42 (t, J = 7.1 Hz, 3H), 3.86 (s, 3H), 4.39 (q, J = 7.1 Hz, 2H), 7.00 (m, 1H)
7.90 (d, J = 8.6 Hz, 1H), 8.16 (s, 1H); 13C NMR: 14.37, 55.67, 60.49, 95.93, 113.24, 114.66,
117.86, 122.11, 149.93, 156.60, 158.56, 163.53. All data consistent with literature values.[4]

[4]. Noyce, D. S, Nichols, R. W., J. Org. Chem., 1972, 37, 4311-4315
Ethyl 5,6-methylenedioxybenzofuran-3-carboxylate (6c)
To a solution of 5c (16.4 mmol) in CH2Cl2 (5 mL) was added HBF4-Et2O complex (0.223 mL).
To the resulting mixture was added a solution of ethyl diazoacetate (85%, 3.18 mL) in CH2Cl2
(25 mL) dropwise at 25-30°C with evolution of N2. After 1h, the mixture was concentrated to
approx. 2/3 original volume and 1.0 mL of conc. H2SO4 was added. After stirring for 15 min,
solid NaHCO3 was added until CO2 evolution ceased. The mixture was then filtered through a
Celite pad, concentrated in vacuo and the residue chromatographed on silica gel (10%
EtOAc/Hxa as eluent) to afford 6c as white needles, m.p. 83-84°C (2.07 g, 73%); 1H NMR: 1.41
(t, J = 7.13 Hz, 3H); 4.38 (q, J = 7.13 Hz, 2H); 6.02 (s, 2H); 6.99 (s, 1H); 7.42 (s, 1H), 8.15 (s,
1H). 13C NMR: 14.37, 60.51, 93.58, 100.36, 101.62, 115.02, 118.23, 145.65, 146.84, 150.07,
150.83, 163.48.
Anal. Calcd for C12H10O5: C, 61.54; H, 4.30. Found: C, 61.18; H, 4.21.
Preparation of 3-hydroxymethylbenzofuran (1a)
To a -78°C solution of 6a (1.72 g, 9.05 mmol) in CH2Cl2 (20 mL) was added DIBAL-H (1.0 M
in hexanes, 22.62 mL in 50 mL CH2Cl2) dropwise. After 1 h, the mixture was warmed to room
temperature and slowly poured into 5% HCl(aq) solution (75 mL). EtOAc (100 mL) was added,
the layers shaken and separated and the organic phase washed with 5% HCl (aq) (2 x 50 mL),
then brine (2 x 50 mL), dried through a CaSO4 cone, then concentrated in vacuo to give 1.26 g
1
(94%) of a white solid, m.p. 44-45°C. (lit.[5] m.p. 45-46°C); H NMR: 2.70 (br s, 1H), 4.67 (s,
2H), 7.1-7.56 (m, 5H); 13C NMR: 55.93, 111.61, 119.94, 120.41, 122.79, 124.66, 126.68, 142.35,
155.62. All data consistent with literature values.[5]
[5.] Katritzky, A., Kirichenko, K., Ji, Y., Steel, P., Karelson, M., ARKIVOC, 2003 6, 49-56.
Preparation of 6-methoxy-3-hydroxymethylbenzofuran (1b)
To a -78°C solution of 6b (2.0 g, 9.08 mmol) in CH2Cl2 (20 mL) was added DIBAL-H (1.0 M in
hexanes, 22.62 mL in 50 mL CH2Cl2) dropwise. After 1 h, the mixture was warmed to room
temperature and slowly poured into 5% HCl(aq) solution (75 mL). EtOAc (100 mL) was added,
the layers shaken and separated and the organic phase washed with 5% HCl (aq) (2 x 50 mL),
then brine (2 x 50 mL), dried through a CaSO4 cone, then concentrated in vacuo to give 1.57 g
1
(97%) as an off-white solid, m.p. 67-68.5°C. (lit.[5] m.p. 69-70°C); H NMR: 1.65 (br s, 1H),
3.85 (s, 3H), 4.80 (s, 2H), 6.90 (d, J = 8.6 Hz, 1H), 7.01 (s, 1H), 7.51 (s, 1H), 7.52 (d, J = 8.6 Hz,
1H). Data consistent with literature values.[5]

Preparation of 5,6-methylenedioxy-3-hydroxymethylbenzofuran (1c)
To a -78°C solution of 6c (2.0 g, 8.54 mmol) in CH2Cl2 (20 mL) was added DIBAL-H (1.0 M in
hexanes, 21.35 mL in 50 mL CH2Cl2) dropwise. After 1 h, the mixture was warmed to room
temperature and slowly poured into 5% HCl(aq) solution (75 mL). EtOAc (100 mL) was added,
the layers shaken and separated and the organic phase washed with 5% HCl (aq) (2 x 50 mL),
then brine (2 x 50 mL), dried through a CaSO4 cone, then concentrated in vacuo to give 1.51 g of
1
1c (97%) as a white solid, m.p. 106-107°C; H NMR: 1.96 (s, 1H); 4.72 (s, 2H); 5.97 (s, 2H);
13
6.95 (s, 1H); 6.70 (s, 1H); 7.90 (s, 1H). C NMR: 55.84, 93.69, 98.40, 101.36, 119.95, 120.72,
141.78, 144.58, 146.40, 150.78; HRMS, m/z 194.0427, calc’d for C10H8O4 194.0422.
Preparation of 3-((2-iodophenoxy)methyl)benzofuran (3a)
To a solution of o-iodophenol (2a, 1.034 g, 4.70 mmol), 1a (0.663 g, 4.48 mmol), and
triphenylphosphine (1.23 g, 4.70 mmol) in THF (12 mL) was added DIAD (0.95 g, 4.70 mmol,
0.925 mL) dropwise at room temperature. The resulting mixture was stirred for 20 min, then
heated at reflux for 2h. Concentration in vacuo gave an amber oil which was chromatographed
1
on silica gel (5% EtOAc/Hxa) to give 3a (0.943 g, 60%) as a clear, thick oil. H NMR: 5.24 (s,
2H); 6.71 (m, 1H); 6.97 (d, J = 8.13 Hz, 1H); 7.30-7.27 (m, 3H), 7.51-7.48 (m, 1H); 7.80-7.73
(m, 3H). 13C NMR: 62.69, 86.96, 111.65, 112.63, 116.49, 120.47, 122.93, 123.13, 124.80,
126.58, 129.51, 139.72, 143.20, 155.60, 157.08; HRMS m/z 349.9790, calc’d for C15H11IO2
349.9804.
Preparation of 3-((2-iodo-5-methoxyphenoxy)methyl)-6-methoxybenzofuran (3b)
To a solution of o-iodophenol (2b, 1.0 g, 4.0 mmol), 1b (0.678 g, 2.8 mmol), and
triphenylphosphine (1.04 g, 4.0 mmol) in THF (12 mL) was added DIAD (0.81 g, 4.0 mmol,
0.787 mL) dropwise at room temperature. The resulting mixture was stirred for 20 min, then
heated at reflux for 2h. Concentration in vacuo gave an oil which was chromatographed on silica
gel (5% EtOAc/Hxa) to give 3b (0.831 g (53%) as a white solid: m.p. 103-105°C. 1H NMR: 3.78
(s, 3H); 3.86 (s, 3H); 5.19 (s, 2H); 6.34 (dd, J = 8.63, 2.65 Hz, 1H); 6.55 (d, J = 2.65 Hz, 1H),
6.92 (dd, J = 8.57, 2.39 Hz, 1H); 7.02 (d, J = 2.16 Hz, 1H); 7.65-7.60 (m, 3H). 13C NMR: 55.55,
55.73, 62.70, 75.59, 96.08, 100.69, 107.61, 111.97, 116.25, 119.87, 120.57, 139.32, 142.15,
156.62, 157.79, 158.36, 161.22. HRMS, m/z 410.0001, calc’d for C17H15IO4, 410.0015.
Preparation of 3-((2-iodo-5-methoxyphenoxy)methyl)-5,6-methylene-dioxybenzofuran (3c)
To a solution of o-iodophenol (2b, 1.0 g, 4.0 mmol), 1c (0.538 g, 2.8 mmol), and
triphenylphosphine (1.04 g, 4.0 mmol) in THF (12 mL) was added DIAD (0.81 g, 4.0 mmol,
0.787 mL) dropwise at room temperature. The resulting mixture was stirred for 20 min, then
heated at reflux for 2h. Concentration in vacuo gave an oil which was chromatographed on silica

1
gel (5% EtOAc/Hxa) to give 3c (0.544 g (46%) as a white solid: m.p. 129.5-132°C. H NMR:
3.80 (s, 3H); 5.15 (s, 2H); 5.99 (s, 2H); 6.34 (dd, J = 8.6 Hz, 2.6 Hz, 1H); 6.54 (d, J = 2.6 Hz,
1H); 6.97 (s, 1H); 7.13 (s, 1H); 7.61-7.64 (m, 2H); 13C NMR: 55.56, 62.60, 75.60, 93.68, 98.97,
100.71, 101.41, 107.62, 116.66, 119.86, 139.34, 142.56, 144.69, 146.59, 150.83, 157.72, 161.20;
HRMS, m/z 423.9821, calc’d for C17H13IO5 423.9808.
Preparation of 6H-benzofuro[3,2-c]chromene (4a)
To a solution of 3a (0.150 g, 0.428 mmol) in DMF (2.0 mL) was added Bu4NBr (0.276 g, 0.856
mmol, 2.0 equiv), and KOAc (0.210 g, 2.14 mmol, 5.0 equiv) followed by Pd(OAc)2 (0.276 g,
0.856 mmol, 0.1 equiv) and the resulting mixture was heated to 100°C with stirring. After 3 h,
TLC (4:1 Hxa/EtOAc), indicated no 3 remaining. After standard workup (EtOAC), the residue
was chromatographed on silica gel (5% EtOAc/Hxa) to give 4 (85 mg, 89%) as a white solid,
m.p. 89.5-91°C (lit.[5,6] m.p. 76-76.9°C, 87-89°C); all NMR data (1H, 13C) were in good
agreement with literature values.[5]
[5.] Takeda, N., Miyata, O., Naito, T., Eur. J. Org. Chem. 2007, 1491–1509.
[6.] Suginome, H., Iwadare, T., Bull. Chem. Soc. Japan, 1966, 39, 1535-1541.
Preparation of 3,9-dimethoxypterocarpene (4b) (anhydrovariabilin)
To a solution of 7 (0.150 g, 0.366 mmol), Bu4NBr (0.236 g, 2.0 equiv.) and KOAc (0.180 g, 5.0
equiv., 1.83 mmol) in DMF (2.0 mL) was added Pd(OAc)2 (8.2 mg, 0.1 equiv., 0.0366 mmol)
and the resulting mixture was heated to 100°C for 3 h. After cooling and standard workup
(EtOAC), the residue was chromatographed on silica gel (5% EtOAc/Hxa) to give 8 (71.4 mg,
1
69%) as a white solid: m.p. 110-112°C (lit.[7] m.p. 109-111°C); H NMR: 3.81 (s, 3H); 3.87 (s,
3H); 5.57 (s, 2H); 6.50 (d, J = 2.2 Hz, 1H); 6.54 (dd, J = 2.2 Hz, 8.4 Hz, 1H); 6.87 (dd, J = 2.2
13
Hz, 8.4 Hz, 1H); 7.22 (d, J = 8.4, 1H); 7.39 (d, J = 8.2 Hz, 1H). C NMR (d6 acetone): 55.78,
55.42, 65.63, 96.67, 102.43, 105.74, 107.12, 109.85, 111.67, 118.49, 119.30, 121.01, 147.23,
155.04, 156.30, 157.68, 160.85.
[7.] Miki, Y., Kobyashi, S., Ogawa, N., Hachikin, H., SynLett, 1994, 1001-1002.
Preparation of flemichapparin B (4c) (anhydropisatin)
To a solution of 13 (0.150 g, 0.354 mmol), Bu4NBr (0.228 g, 0.708 mmol, 2.0 equiv), and KOAc
(0.174 g, 1.77 mmol, 5.0 equiv) in 2.5 mL DMF was added Pd(OAc)2 (0.0079 g, 0.0354 mmol,
0.1 equiv) and the mixture was heated to 100°C for 3.5 hours. After cooling and standard workup
(EtOAC), the residue was chromatographed on silica gel (5% EtOAc/Hxa) to give the title
compound (0.067 g, 64%) as a white solid, m.p. 178-179°C (lit.[8] m.p. 179-180°C). 1H NMR (d6
acetone): 3.80 (s, 3H); 5.51 (s, 2H); 5.99 (s, 2H); 6.49 (d, J = 2.4 Hz, 1H); 6.53 (dd, J = 8.3 Hz,

13
2.4 Hz, 1H); 6.72 (s, 1H); 7.01 (s, 1H); 7.36 (d, J = 8.3 Hz, 1H). C NMR (d6 acetone): 55.77,
65.95, 99.58, 98.54, 102.48, 103.28, 107.77, 108.03, 110.49, 120.02, 121.54, 145.67, 146.85,
148.23, 151.28, 155.99, 162.01.
[8.] Fukui, K., Nakayama, M., Bull. Chem. Soc. Japan, 1969, 42, 1408-1411.
Preparation of coumestan (7)
To a solution of 4a (50 mg, 0.225 mmol) in CH2Cl2 (4.5 mL) was added pyridinium
chlorochromate (97.0 mg, 2.0 equiv) all at once. After 20 h, TLC showed reaction was complete.
Concentration in vacuo and purification of the residue by chromatography on silica gel (10%
EtOAc/Hxa) gave 7 as a white powder (39.3 mg, 74%) mp 180-181°C (lit.[9] mp 179-180°C); all
analytical data (IR, 1H NMR, 13C NMR) were in good agreement with literature values.[9]
[9.] Kraus, G. A., Zhang, N., J. Org. Chem., 2000, 65, 5644-5646.
Preparation of 6,6’-dimethoxy-3,3'(2H,2'H)-spirobibenzofuran (8)
To a solution of 3b (0.150 g, 0.366 mmol) in DMF (1 mL) was added NaOAc (0.079 g, 0.96
mmol), HCO2Na (0.031 g, 0.46 mmol), Et4NCl-H2O (0.085 g, 0.46 mmol) and Pd(OAc)2 (1.0
mg) and the resulting mixture was heated with stirring at 85-95°C for 1 h. Standard workup and
chromatography on silica gel (15% EtOAc/Hxa) gave 8 (0.062 g, 60%) as a white waxy solid;
mp 88.5-90°C; 1H NMR: 6.92 (d, J = 7.1 Hz, 2H), 6.51 (dd, J = 7.1 Hz, J = 2.4 Hz, 2H), 6.46 (d,
J = 2.4 Hz, 2H), 4.73 (d, J = 9.2 Hz, 2H), 4.49 (d, J = 9.2 Hz, 2H), 3.78 (s, 6H); 13C NMR: 162.3
(2C), 162.2 (2C), 124.8 (2C), 124.5 (2C), 108.2 (2C), 96.7 (2C), 84.7 (2C), 55.9 (1C), 55.8 (2C);
HRMS, m/z 284.1041, calc’d for C17H16O4 284.1048.

O
O
O
H
OH
Figure S1: 1H NMR spectrum of 6-hydroxybenzo[d][1,3]dioxole-5-carbaldehyde (5c), CDCl3.

O
O
OCH2CH3
O
O
Figure S2: 1H NMR spectrum of Ethyl 5,6-methylenedioxybenzofuran-3-carboxylate (6c), CDCl3.

O
O
OCH2CH3
O
O
Figure S3: 13C NMR spectrum of ethyl 5,6-methylenedioxybenzofuran-3-carboxylate (6c), CDCl3.

OH
O
O
O
Figure S4: 1H NMR spectrum of 5,6-methylenedioxy-3-hydroxymethylbenzofuran (1c), CDCl3.

OH
O
O
O
Figure S5: 13C NMR spectrum of 5,6-methylenedioxy-3-hydroxymethylbenzofuran (1c), CDCl3

I
O
O
Figure S6: 1H NMR spectrum of 3-((2-iodophenoxy)methyl)benzofuran (3a), CDCl3

I
O
O
Figure S7: 13C NMR spectrum of 3-((2-iodophenoxy)methyl)benzofuran (3a), CDCl3

O
O
Figure S8: 1H NMR spectrum of 6H-benzofuro[3,2-c]chromene (4a), CDCl3

O
O
Figure S9: 13C NMR spectrum of 6H-benzofuro[3,2-c]chromene (4a), d6 acetone

O
OCH3
I
O
H3CO
Figure S10: 1H NMR spectrum of 3-((2-iodo-5-methoxyphenoxy)methyl)-6-methoxybenzofuran (3b), CDCl3

O
OCH3
I
O
H3CO
Figure S11: 13C NMR spectrum of 3-((2-iodo-5-methoxyphenoxy)methyl)-6-methoxybenzofuran (3b), CDCl3

O
OCH3
O
H3CO
Figure S12: 1H NMR spectrum of 3,9-dimethoxypterocarpene (4b) (anhydrovariabilin), d6 acetone

O
OCH3
O
H3CO
Figure S13: 13C NMR spectrum of 3,9-dimethoxypterocarpene (4b) (anhydrovariabilin), d6 acetone

O
OCH3
O
O
I
O
Figure S14: 1H NMR spectrum of 3-((2-iodo-5-methoxyphenoxy)methyl)-5,6-methylene-dioxybenzofuran (3c), CDCl3

O
OCH3
O
O
I
O
Figure S15: 13C NMR spectrum of 3-((2-iodo-5-methoxyphenoxy)methyl)-5,6-methylene-dioxybenzofuran (3c), CDCl3

O
OCH3
O
O
O
Figure S16: 1H NMR spectrum of flemichapparin B (4c) (anhydropisatin), d6 acetone

O
OCH3
O
O
O
Figure S17: 13C NMR spectrum of flemichapparin B (4c) (anhydropisatin), d6 acetone

OCH3
O
O
H3CO
Figure S18: 1H NMR spectrum of 6,6’-dimethoxy-3,3'(2H,2'H)-spirobibenzofuran (8)), d6 acetone

OCH3
O
O
H3CO
Figure S19: 13C NMR spectrum of 6,6’-dimethoxy-3,3'(2H,2'H)-spirobibenzofuran (8), d6 acetone

HO
I
OCH3
Figure S20: 1H NMR spectrum of 2-iodo-5-methoxyphenol (2a), CDCl3