7klvs4 4a 3e 76.1, 77.9, 108.8, 112.9, 122.1, 122.5, 123.4, 123.5, 126.3, 129.1, 129.3, 130.2,...

S1

Supporting Information

for

Copper-catalyzed synthesis of spiro-indolofurobenzopyrans:

tandem reactions of diazoamides and O-propargyl salicylaldehydes

Sengodagounder Muthusamya,* Ammasi Prabua and Eringathodi Sureshb

aSchool of Chemistry, Bharathidasan University, Tiruchirappalli-620 024, India

bCSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar-364002, India

* Tel: +91-431-2407053; Fax: +91-431-2407045; E-mail: [email protected]

CONTENTS

General information S2

General procedure for spiro-indolooxiranes 3 S2

Characterization of the product 3 S3-S4

General procedure for spiro-indolofurobenzopyrans 4 S4

Characterization of the product 4 S4-S14

Procedure for the synthesis of compound 5 S14

Characterization of the product 5-9 S14-S16

1H and 13C NMR spectra of the product 3 S17-S22

1H and 13C NMR spectra of the product 4 S23-S58

1H and 13C NMR spectra of the products 5-9 S59-S68

Solid-state arrangement of compound 4i S69-S70

Energy minimization MM2 calculations S71

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2019

mailto:[email protected]

S2

General information

Melting points were determined on a capillary melting point apparatus and uncorrected. IR

spectra were recorded using ATR technique on a Bruker Alpha FT-IR spectrophotometer. All

compounds were fully characterized. Proton nuclear magnetic resonance (1H NMR) spectra were

recorded at 400 MHz using CDCl3 in ppm (δ) related to tetramethylsilane (δ=0.00) as an internal

standard and are reported as follows; chemical shift (ppm), multiplicity (br = broad, s = singlet, d

= doublet, t = triplet, dd = doublet of doublet, m = multiplet), ABq = AB quartet, ABqd = AB

quartet of doublet and coupling constant (Hz). Carbon-13 nuclear magnetic resonance (13C

NMR) spectra were recorded at 100 MHz in CDCl3. Chemical shifts are reported in delta (δ)

units, parts per million (ppm) relative to the center of the triplet at 77.7 ppm for CDCl3. Carbon

types were determined from 13C NMR and DEPT experiments. The residual solvent signals were

used as references and the chemical shifts converted to the TMS scale (CDCl3: δH = 7.26 ppm, δC

= 77.7 ppm). High resolution mass analyses were performed using electrospray ionization (ESI)

technique on a Thermo Exactive Orbitrap mass spectrometer. All solvents were purified by

distillation following standard procedure. Thin layer chromatography was performed on silica or

alumina plates and components visualized by observation under iodine/UV light at 254 nm.

Column chromatography was performed on silica gel (100-200 mesh). All the reactions were

conducted in oven-dried glassware under a positive pressure of nitrogen with magnetic stirring.

Reagents were added via syringes through septa. The propargyl bromide (80% solution in

toluene), DMAD, NPM, Rh2(OAc)4, Cu(I)TC and other commercial chemicals were purchased

from M/s Sigma Aldrich and used as provided. The o-hydroxyaldehydes were purchased from

Aldrich and Alfa Aesar Chemicals. K2CO3 was dried by heating at 110 °C for 12 h and left to

cool under nitrogen atmosphere.

Experimental Section

General experimental procedure I for the synthesis of spiro-indolooxiranes (3)

To an oven-dried flask, a solution containing the appropriate aldehyde 2 (1.1 mmol) and 5 mol%

of copper(I) thiophenecarboxylate dissolved in 5 mL of dry DCE under a nitrogen atmosphere

was added a solution of 3-diazoindol-2-one 1 (1 mmol) in dry DCE (4 mL) at ambient

temperature to afford until the reaction completed (monitored using TLC). After the completion

S3

3a

3b

of reaction, the solvent was removed under reduced pressure. The residue was subjected to

column chromatography (silica gel, 100-200 mesh, EtOAc/hexane 30:70) to furnish spiro-

indolooxiranes 3.

Synthesis of 1-benzyl-3'-(2-(prop-2-yn-1-yloxy)phenyl)spiro[indoline-3,2'-oxiran]-2-one (3a)

A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry dichloroethane (4

mL) was added quickly to a solution containing 2-[(prop-2-yn-1-yl)oxy]benzaldehyde 2a (71

mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5

mol%) at ambient temperature to afford 3a (130 mg, 85%) as a white solid according to general

procedure I. Rf = 0.28 (EtOAc/hexane = 1:4, v/v); mp 104-105 °C; IR (neat): νmax 3287, 2924,

2118(w), 1724, 1610, 1462, 1354, 1022, 748 cm−1; 1H NMR (CDCl3, 400

MHz) δ = 2.41 (t, J = 2.4 Hz, 1H, ≡CH), 4.62 (ABqd, ΔδAB = 0.03, J1 = 16

Hz, J2 = 2 Hz, 2H, OCH2), 4.81-4.89 (m, 3H, NCH2/OCH), 6.77 (d, J = 8

Hz, 1H, ArH), 7.00 (d, J = 8.4 Hz, 1H, ArH), 7.07-7.15 (m, 2H, ArH), 7.24-

7.31 (m, 7H, ArH), 7.33-7.37 (m, 1H, ArH), 7.78 (d, J = 7.6 Hz, 1H, ArH)

ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.0, 56.0, 61.5, 64.0, 75.7, 78.4,

109.6, 111.5, 121.1, 121.6, 121.9, 122.6, 123.7, 127.4, 127.7, 128.8, 129.0, 129.6, 130.0, 135.6,

143.8, 155.5, 170.3 ppm; HRMS (ESI) Calculated for C25H19NO3 (M+Na)+: 404.1263 found:

404.1251.

Synthesis of 3'-(5-chloro-2-(prop-2-yn-1-yloxy)phenyl)-1-ethylspiro[indoline-3,2'-oxiran]-2-

one (3b)

A solution of 3-diazo-1-ethylindolin-2-one 1b (100 mg, 0.53 mmol) in dry dichloroethane (4

mL) was added quickly to a solution containing 5-chloro-2-(prop-2-yn-1-yloxy)benzaldehyde 2b

(114 mg, 0.58 mmol) ) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (5 mg,

5 mol%) at ambient temperature to afford 3b (148 mg, 79%) as a white

solid according to general procedure I. Rf = 0.33 (EtOAc/hexane = 1:4,

v/v); mp 157-158 °C; IR (neat): νmax 3292, 2924, 2123(w), 1727, 1617,

1484, 1364, 1019, 761 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.22 (t, J =

7.2 Hz, 3H, CH3), 2.42 (t, J = 2.4 Hz, 1H, ≡CH), 3.66-3.76 (m, 2H, NCH2),

4.55-4.64 (m, 2H, OCH2), 4.74 (s, 1H, CH), 6.90-6.93 (m, 2H, ArH), 7.09-

7.13 (m, 1H, ArH), 7.23-7.29 (m, 2H, ArH), 7.40 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H, ArH), 7.75

(d, J = 2.4 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 12.6, 35.0, 56.3, 61.4, 62.9,

S4

4a

3e

76.1, 77.9, 108.8, 112.9, 122.1, 122.5, 123.4, 123.5, 126.3, 129.1, 129.3, 130.2, 143.9, 154.1,

169.5 ppm; HRMS (ESI) Calculated for C20H1635ClNO3 (M+Na)

+: 376.0716 found: 376.0715.

Synthesis of 1-benzyl-3'-(5-nitro-2-(prop-2-yn-1-yloxy)phenyl)spiro[indoline-3,2'-oxiran]-2-

one (3e)


mL) was added quickly to a solution containing 5-nitro-2-(prop-2-yn-1-yloxy)benzaldehyde 2d

(90 mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5

mol%) at ambient temperature conditions to afford 3e (138 mg, 81%) as a white solid according

to general procedure I. Rf = 0.21 (EtOAc/hexane = 1.5:3.5, v/v); mp 187-189 °C; IR (neat): νmax

3287, 2923, 2124(w), 1725, 1613, 1418, 1341, 1268, 1006, 742 cm−1; 1H

NMR (CDCl3, 400 MHz) δ = 2.52 (t, J = 2.4 Hz, 1H, ≡CH), 4.73-4.74 (m,

2H, OCH2), 4.79-4.89 (m, 3H, OCH/NCH2), 6.81 (d, J = 8 Hz, 1H, ArH),

7.08-7.13 (m, 2H, ArH), 7.23-7.32 (m, 8H, ArH), 8.26 (dd, J1 = 6.8 Hz, J2

= 2.4 Hz, 1H, ArH), 8.68 (d, J = 2.8 Hz, 1H, ArH) ppm; 13C NMR (CDCl3,

100 MHz) δ = 44.1, 56.6, 61.4, 62.5, 76.8, 77.4, 109.8, 111.4, 122.1.

122.8, 122.9, 125.5, 125.7, 127.3, 127.8, 128.9, 130.5, 135.3, 141.8, 143.9, 159.8, 169.7 ppm;

HRMS (ESI) Calculated for C25H18N2O5 (M+H)+: 427.1294 found: 427.1285.

General experimental procedure II for the synthesis of spiro-indolofurobenzopyrans (4)

To an oven-dried flask, a solution containing the appropriate aldehyde 2 (1.1 mmol) and 5 mol%

of copper(I) thiophenecarboxylate dissolved in 5 mL of dry dichloroethane under a nitrogen

atmosphere was added a solution of 3-diazoindol-2-one 1 (1 mmol) in dry DCE (4 mL) using

syringe pump with the rate of addition of 0.5 mL/h at reflux conditions and continued until the

reaction completed (monitored using TLC). After the completion of reaction, the solvent was

removed under reduced pressure. The residue was subjected to column chromatography (silica

gel, 100-200 mesh, EtOAc/hexane 15:85) to furnish spiro-indolobenzofuropyrans 4.

Synthesis of 1'-benzyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-

indol]-2'(1'H)-one (4a)

A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in dry

dichloroethane (4 mL) was added dropwise to a solution containing 2-

[(prop-2-yn-1-yl)oxy]benzaldehyde 2a (71 mg, 0.44 mmol) dissolved in dry

DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%) at reflux

S5

4b

4c

conditions to afford 4a (129 mg, 84%) as a white solid according to general procedure II. Rf =

0.35 (EtOAc/hexane = 1:4, v/v); mp 114-115 °C; IR (neat): νmax 2924, 1723, 1613, 1490, 1360,

1215, 745 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.90 (ABq, ΔδAB = 0.04, J = 15.6 Hz, 2H,

CH2), 5.62 (s, 1H, CH), 6.30 (s, 1H, CH), 6.70 (d, J = 8 Hz, 1H, ArH), 6.89-6.99 (m, 4H, ArH),

7.15-7.27 (m, 4H, ArH), 7.28-7.38 (m, 4H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.1,

63.7, 81.4, 92.7, 109.5, 116.8, 121.5, 121.8, 123.4, 125.5, 126.0, 126.8, 127.4, 127.8, 128.3,

128.9, 129.2, 130.4, 135.4, 139.9, 142.7, 152.8, 175.2 ppm; HRMS (ESI) Calculated for

C25H19NO3 (M+H)+: 382.1443 found: 382.1439.

Synthesis of 7-chloro-1'-ethyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-

one (4b)

A solution of 3-diazo-1-ethylindolin-2-one 1b (100 mg, 0.53 mmol) in dry dichloroethane (4

mL) was added dropwise to a solution containing 5-chloro-2-(prop-2-yn-1-yloxy)benzaldehyde

2b (114 mg, 0.58 mmol) dissolved in dry DCE (5 mL) and copper(I)

thiophenecarboxylate (5 mg, 5 mol%) at reflux conditions to afford 4b

(135 mg, 72%) as a white solid according to general procedure II. Rf =

0.23 (EtOAc/hexane = 1:4, v/v); mp 186-187 °C; IR (neat): νmax 2929,

1722, 1612, 1474, 1361, 1216, 754 cm−1; 1H NMR (CDCl3, 400 MHz) δ

= 1.30 (t, J = 7.2 Hz, 3H, CH3), 3.68-3.84 (m, 2H, NCH2), 4.96 (s, 2H,

CH2), 5.59 (s, 1H, CH), 6.19 (s, 1H, CH), 6.82-6.86 (m, 2H, ArH), 6.92-6.94 (m, 1H, ArH) 6.97-

7.10 (m, 1H, ArH), 7.17 (dd, J1 = 8.8 Hz, J2 = 2.8 Hz, 1H, ArH), 7.29-7.34 (m, 2H, ArH) ppm;

13C NMR (CDCl3, 100 MHz) δ = 12.6, 35.0, 63.8, 80.8, 92.7, 108.6, 118.2, 122.4, 123.2, 125.6,

126.3, 126.4, 127.4, 128.2, 129.2, 130.6, 138.8, 142.7, 151.4, 174.4 ppm; HRMS (ESI)

Calculated for C20H1635ClNO3 (M+H)

+: 354.0897 found: 354.0896.

Synthesis of 7-chloro-1'-benzyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-

one (4c)

A solution of 1-benzyl-3-diazoindolin-2-one 1a (100 mg, 0.40 mmol) in

dry dichloroethane (4 mL) was added dropwise to a solution containing

5-chloro-2-(prop-2-yn-1-yloxy)benzaldehyde 2b (85 mg, 0.44 mmol)

dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg,

5 mol%) at reflux conditions to afford 4c (114 mg, 69%) as a white solid

according to general procedure II. Rf = 0.29 (EtOAc/hexane = 1:4, v/v);

S6

4d

mp 201-202 °C; IR (neat): νmax 2966, 1724, 1650, 1470, 1361, 1211, 751 cm−1; 1H NMR (CDCl3,

400 MHz) δ = 4.91-5.06 (m, 4H, CH2), 5.69 (s, 1H, CH), 6.28 (s, 1H, CH), 6.76 (d, J = 7.6 Hz,

1H, ArH), 6.89 (d, J = 8.8 Hz, 1H, ArH), 6.97-7.03 (m, 2H, ArH), 7.20-7.26 (m, 2H, ArH), 7.30-

7.39 (m, 6H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.1, 63.8, 80.9, 92.8, 109.6, 118.3,

122.4, 123.5, 125.5, 126.3, 126.5, 127.3, 127.4, 127.8, 127.9, 128.9, 129.2, 130.6, 135.3, 139.1,

142.7, 151.4, 174.9 ppm; HRMS (ESI) Calculated for C25H1835ClNO3 (M+H)

+: 416.1054 found:

416.1054.

Synthesis of 7-bromo-1'-propyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-

one (4d)

A solution of 3-diazo-1-propylindolin-2-one 1c (100 mg, 0.50 mmol) in dry dichloroethane (4

mL) was added dropwise to a solution containing 5-bromo-2-(prop-2-yn-1-yloxy)benzaldehyde

2c (130 mg, 0.55 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (5

mg, 5 mol%) at reflux conditions to afford 4d (126 mg, 61%) as a white solid according to

general procedure II. Rf = 0.29 (EtOAc/hexane = 1:4, v/v); mp 167-168

°C; IR (neat): νmax 2923, 1725, 1613, 1472, 1341, 1090, 744 cm−1; 1H

NMR (CDCl3, 400 MHz) δ = 0.99 (t, J = 7.4 Hz, 3H, CH3), 1.69-1.78

(m, 2H, CH2), 3.67 (t, J = 7.2 Hz, 2H, CH2), 4.96 (ABq distorted, 2H,

CH2), 5.60 (s, 1H, CH), 6.19 (s, 1H, CH), 6.78 (d, J = 8.8 Hz, 1H, ArH),

6.84 (d, J = 7.8 Hz, 1H, ArH), 6.92-6.94 (m, 1H, ArH), 6.97-7.01 (m,

1H, ArH), 7.29-7.33 (m, 2H, ArH), 7.46 (s, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ =

11.4, 20.7, 41.9, 63.8, 80.7, 92.7, 108.8, 113.5, 118.7, 122.5, 123.2, 125.6, 127.8, 128.0, 129.4,

130.6, 132.1, 138.8, 143.1, 151.9, 174.7 ppm; HRMS (ESI) Calculated for C21H1879BrNO3

(M+Na)+: 434.0368 found: 434.0364.

Synthesis of 7-nitro-1'-benzyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-

one (4e)


mL) was added dropwise to a solution containing 5-nitro-2-(prop-2-yn-1-yloxy)benzaldehyde 2d

(90 mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5

mol%) at reflux conditions to afford 4e (121 mg, 71%) as a white solid according to general

procedure II. Rf = 0.19 (EtOAc/hexane = 1.5:3.5, v/v); mp 199-200 °C; IR (neat): νmax 2981,

1718, 1612, 1465, 1357, 1213, 1088, 734 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.96 (s, 2H,

S7

4e

4f

4g

CH2), 5.16 (ABq, ΔδAB = 0.04, J = 13.2 Hz, 2H, CH2), 5.78 (s, 1H, CH), 6.31 (s, 1H, CH), 6.77

(d, J = 8 Hz, 1H, ArH), 6.91 -6.93 (m, 1H, ArH), 6.97-7.04 (m, 2H, ArH), 7.23-7.27 (m, 1H,

ArH), 7.33-7.42 (m, 5H, ArH), 8.17 (dd, J1 = 9.2 Hz, J2 = 2.8 Hz, 1H,

ArH), 8.34 (d, J = 2.8 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz)

δ = 44.1, 64.5, 80.1, 92.9, 109.7, 117.6, 123.42, 123.46, 123.6, 125.1,

125.3, 126.2, 127.3, 127.9, 129.0, 130.7, 135.2, 137.5, 142.0, 142.8,

158.0, 174.56 ppm; HRMS (ESI) Calculated for C25H18N2O5 (M+H)+:

427.1294 found: 427.1281.

Synthesis of 6-methoxy-1'-(prop-2-yn-1-yl)-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-

indol]-2'(1'H)-one (4f)

A solution of 3-diazo-1-(prop-2-yn-1-yl)indolin-2-one 1d (100 mg, 0.51 mmol) in dry

dichloroethane (4 mL) was added dropwise to a solution containing 3-methoxy-2-(prop-2-yn-1-

yloxy)benzaldehyde 2e (106 mg, 0.56 mmol) dissolved in dry DCE (5 mL)

and copper(I) thiophenecarboxylate (5 mg, 5 mol%) at reflux conditions to

afford 4f (119 mg, 65%) as a white solid according to general procedure II.

Rf = 0.13 (EtOAc/hexane = 1:4, v/v); mp 195-196 °C; IR (neat): νmax 3291,

2930, 1725, 1614, 1362, 1264, 1020, 733 cm−1; 1H NMR (CDCl3, 400

MHz) δ = 2.27 (s, 1H, CH), 3.90 (s, 3H, CH3), 4.49 (ABqd, ΔδAB = 0.13, J1

= 18 Hz, J2 = 2 Hz, 2H, CH2), 5.04 (ABq, ΔδAB = 0.08, J = 13.2 Hz, 2H,

CH2), 5.60 (s, 1H, CH), 6.26 (s, 1H, CH), 6.84-7.05 (m, 6H, ArH), 7.30-7.34 (m, 1H, ArH) ppm;

13C NMR (CDCl3, 100 MHz) δ = 29.6, 56.0, 64.0, 72.8, 76.6, 81.3, 92.6, 109.5, 110.9, 118.5,

121.3, 121.7, 123.7, 125.5, 126.6, 128.1, 130.5, 139.7, 141.7, 142.1, 148.2, 174.0 ppm; HRMS

(ESI) Calculated for C22H17NO4 (M+Na)+: 382.1053 found: 382.1049.

Synthesis of 5'-bromo-1'-benzyl-7-methoxy-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-

indol]-2'(1'H)-one (4g)

A solution of 1-benzyl-5-bromo-3-diazoindolin-2-one 1e (100 mg,

0.30 mmol) in dry dichloroethane (4 mL) was added dropwise to a

solution containing 4-methoxy-2-(prop-2-yn-1-

yloxy)benzaldehyde 2f (103 mg, 0.33 mmol) dissolved in dry DCE

(5 mL) and copper(I) thiophenecarboxylate (3 mg, 5 mol%) at

reflux conditions to afford 4g (102 mg, 70%) as a white solid

according to general procedure II. Rf = 0.30 (EtOAc/hexane = 1:4, v/v); mp 195-196 °C; IR

S8

4h

4i

(neat): νmax 2924, 1729, 1644, 1433, 1161, 1030, 809 cm−1; 1H NMR (CDCl3, 400 MHz) δ =

3.80 (s, 3H, CH3), 4.87 (s, 2H, CH2), 4.94 (ABq, ΔδAB = 0.04, J = 12.8 Hz, 2H, CH2), 5.62 (s,

1H, CH), 6.28 (s, 1H, CH), 6.45 (s, 1H, ArH), 6.54-6.59 (m, 2H, ArH), 7.06 (s, 1H, ArH), 7.23-

7.35 (m, 7H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.1, 55.4, 63.7, 81.3, 92.1, 101.7,

108.5, 111.0, 116.1, 117.6, 121.7, 127.3, 127.89, 127.98, 128.7, 129.0, 130.2, 133.2, 134.9,

140.7, 141.7, 153.9, 160.6, 174.7 ppm; HRMS (ESI) Calculated for C26H2079BrNO4 (M+H)

+:

490.0654 found: 490.0648.

Synthesis of 1'-methyl-4H,11cH-spiro[furo[2,3-d]naphtho[2,1-b]pyran-2,3'-indol]-2'(1'H)-

one (4h)

A solution of 3-diazo-1-methylindolin-2-one 1f (100 mg, 0.58 mmol) in dry dichloroethane (4

mL) was added dropwise to a solution containing 2-(prop-2-yn-1-yloxy)-

1-naphthaldehyde 2g (134 mg, 0.64 mmol) dissolved in dry DCE (5 mL)

and copper(I) thiophenecarboxylate (6 mg, 5 mol%) at reflux conditions

to afford 4h (171 mg, 83%) as a white solid according to general

procedure II. Rf = 0.39 (EtOAc/hexane = 1:4, v/v); mp 186-187 °C; IR

(neat): νmax 2254, 1720, 1617, 1466, 1088, 1015, 753 cm−1; 1H NMR

(CDCl3, 400 MHz) δ = 3.23 (s, 3H, CH3), 4.95 (ABq, ΔδAB = 0.13, J = 12 Hz, 2H, CH2), 5.76 (s,

1H, CH), 6.77-6.81 (m, 2H, ArH), 6.87-6.90 (m, 1H, ArH), 6.93-6.95 (m, 1H, ArH), 7.08 (d, J =

9.2 Hz, 1H, ArH), 7.23-7.27 (m, 1H, ArH), 7.31-7.35 (m, 1H, ArH), 7.40-7.44 (m, 1H, ArH),

7.71-7.75 (m, 2H, ArH), 8.21 (d, J = 8.4 Hz, 1H, ArH), ppm; 13C NMR (CDCl3, 100 MHz) δ

26.4, 63.9, 80.29, 92.0, 108.3, 116.8, 118.7, 123.3, 123.8, 123.9, 125.3, 125.6, 126.8, 128.0,

128.2, 129.4, 130.3, 130.4, 132.6, 140.2, 143.7, 151.8, 175.3 ppm; HRMS (ESI) Calculated for

C23H17NO3 (M+H)+: 356.1287 found: 356.1280.

Synthesis of 1'-ethyl-4H,11cH-spiro[furo[2,3-d]naphtho[2,1-b]pyran-2,3'-indol]-2'(1'H)-one

(4i)

A solution of 3-diazo-1-ethylindolin-2-one 1b (100 mg, 0.53 mmol) in

dry dichloroethane (4 mL) was added dropwise to a solution containing

2-(prop-2-yn-1-yloxy)-1-naphthaldehyde 2g (123 mg, 0.58 mmol)

dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (5 mg,

5 mol%) at reflux conditions to afford 4i (158 mg, 81%) as a white solid

according to general procedure II. Rf = 0.44 (EtOAc/hexane = 1:4, v/v);

S9

4j

mp 174-175 °C; IR (neat): νmax 2976, 1722, 1464, 1360, 1216, 1033, 754 cm−1; 1H NMR (CDCl3,

400 MHz) δ =1.33 (t, J = 7.2, 3H, CH3), 3.78 (q, J = 7.2 Hz, 2H, CH2), 4.95 (ABq, ΔδAB = 0.12, J

= 12 Hz, 2H, CH2), 5.76 (s, 1H, CH), 6.80-6.82 (m, 2H, ArH), 6.85-6.89 (m, 1H, ArH), 6.93-

6.96 (m, 1H, ArH), 7.08 (d, J = 9.2 Hz, 1H, ArH), 7.22-7.26 (m, 1H, ArH), 7.31-7.35 (m, 1H,

ArH), 7.41-7.45 (m, 1H, ArH), 7.71-7.75 (m, 2H, ArH), 8.23 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C

NMR (CDCl3, 100 MHz) δ 12.7, 34.9, 63.8, 80.32, 92.0, 108.5, 116.9, 118.7, 123.0, 123.9,

125.4, 125.7, 126.8, 128.0 128.5, 129.4, 130.24, 130.28, 130.29, 132.6, 140.1, 142.8, 151.8,

174.9 ppm; HRMS (ESI) Calculated for C24H19NO3 (M+Na)+: 370.1443 found: 370.1425.

Crystal data for compound (4i): (CCDC 1580080) C24H19NO3, white colour, diamond, M =

699.64, 0.28 × 0.19 × 0.11 mm, Triclinic, space group P-1 with a = 9.0014(13) Å, b =

9.5478(13) Å, c = 23.864(3) Å, α = 91.650(2) (2)°, β = 95.150(2) (2)°, γ = 113.925(2) (2)°, V =

1862.4(5) Å3, T = 150(2) K, R1 = 0.0465, wR2 = 0.1282 on observed data, z = 2, Dcalcd = 1.317

g/cm3, F(000) = 776, Absorption coefficient = 0.087 mm-1, λ = 0.71073 Å, 6462 reflections were

collected on a smart apex CCD single crystal diffractometer 5683 observed reflections (I≥2σ (I)).

The largest difference peak and hole = 0.249 and -0.226 e.Å-3, respectively. The structure was

solved by direct methods and refined by full-matrix least squares on F2 using SHELXL–97

software.

Synthesis of 1'-benzyl-4H,11cH-spiro[furo[2,3-d][1]naptho[2,1-b]pyran-2,3'-indol]-2'(1'H)-

one (4j)


mL) was added dropwise to a solution containing 2-(prop-2-yn-1-yloxy)-1-naphthaldehyde 2g

(92 mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I)

thiophenecarboxylate (4 mg, 5 mol%) at reflux conditions to afford 4j

(131 mg, 76%) as a white solid according to general procedure II. Rf =

0.34 (EtOAc/hexane = 1:4, v/v); mp 189-190 °C; IR (neat): νmax 2933,

1728, 1610, 1475, 1180, 1033, 699 cm−1; 1H NMR (CDCl3, 400 MHz) δ

= 4.74-4.77 (m, 1H, CH), 4.82-4.85 (m, 1H, CH), 4.93-4.98 (m, 2H,

CH2), 5.74 (s, 1H, CH), 6.61 (d, J = 7.6 Hz, 1H, CH), 6.77-6.80 (m, 2H, ArH), 6.88 (d, J = 6.8

Hz, 1H, ArH), 7.01-7.08 (m, 2H, ArH), 7.18-7.29 (m, 6H, ArH), 7.36-7.40 (m, 1H, ArH), 7.65-

7.69 (m, 2H, ArH), 8.18 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz ) δ 44.1,

63.8, 80.4, 92.0, 109.3, 116.7, 118.7, 123.3, 123.9, 124.0, 125.4, 125.6, 126.7, 127.5, 127.8,

S10

4k

4l

128.0, 128.3, 128.9, 129.4, 130.26, 130.3, 132.6, 135.5, 140.3, 142.8, 151.8, 175.5 ppm ; HRMS

(ESI) Calculated for C29H21NO3 (M+H)+: 432.1600 found: 432.1595.

Synthesis of 1'-benzyl-6,8-diiodo-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-

2'(1'H)-one (4k)


mL) was added dropwise to a solution containing 3,5-diiodo-2-(prop-2-yn-1-yloxy)benzaldehyde

2h (180 mg, 0.44 mmol) dissolved in dry DCE (5 mL) and copper(I) thiophenecarboxylate (4

mg, 5 mol%) at reflux conditions to afford 4k (189 mg, 75%) as a white solid according to

general procedure II. Rf = 0.09 (EtOAc/hexane = 1.5:3.5, v/v); mp 215-216 °C; IR (neat): νmax

2923, 1728, 1611, 1484, 1432, 1161, 667 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.94 (s, 2H,

CH2), 5.14 (ABq, ΔδAB = 0.05, J = 13.2 Hz, 2H, CH2), 5.72 (s, 1H, CH),

6.27 (s, 1H, CH), 6.76 (d, J = 8 Hz, 1H, ArH), 6.99-7.05 (m, 2H, ArH),

7.24-7.41 (m, 6H, ArH), 7.67 (s, 1H, ArH), 8.04 (s, 1H, ArH) ppm ; 13C

NMR (CDCl3, 100 MHz ) δ = 44.1, 64.6, 80.5, 84.1, 86.2, 93.0, 109.6,

122.9, 123.5, 125.5, 127.4, 127.6, 127.9, 128.3, 129.0, 130.7, 135.3, 135.5,

138.4, 142.8, 146.2, 151.8, 174.6 ppm; HRMS (ESI) Calculated for

C25H17I2NO3 (M+Na)+: 655.9196 found: 655.9193.

Synthesis of 5'-chloro-1'-benzyl-7,9-diiodo-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-

indol]-2'(1'H)-one (4l)

A solution of 1-benzyl-5-chloro-3-diazoindolin-2-one 1g (100 mg, 0.35 mmol) in dry

dichloroethane (4 mL) was added dropwise to a solution containing 3,5-diiodo-2-(prop-2-yn-1-

yloxy)benzaldehyde 2h (160 mg, 0.39 mmol) dissolved in dry DCE (5

mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%) at reflux

conditions to afford (189 mg, 81%) of 4l as a white solid according to

general procedure II. Rf = 0.48 (EtOAc/hexane = 1.5:3.5, v/v); mp 229-

230 °C; IR (neat): νmax 2933, 1724, 1614, 1500, 1159, 1022, 754 cm−1;

1H NMR (CDCl3, 400 MHz) δ = 4.88 (ABq, ΔδAB = 0.02, J = 16 Hz,

2H, CH2), 5.08 (ABq, ΔδAB = 0.06, J = 13.6 Hz, 2H, CH2), 5.67 (s, 1H, CH), 6.23 (s, 1H, CH),

6.62 (d, J = 8.4 Hz, 1H, ArH), 6.95 (s, 1H, ArH), 7.17 (d, J = 8.4 Hz, 1H, ArH), 7.27-7.34 (m,

5H, ArH), 7.61 (s, 1H, ArH), 8.00 (s, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.2,

64.5, 80.6, 84.3, 86.3, 92.6, 110.7, 122.3, 126.0, 127.3, 127.8, 128.0, 129.00, 129.04, 129.1,

S11

4m

4n

130.6, 134.8, 135.5, 139.1, 141.3, 146.4, 151.7, 174.2 ppm; HRMS (ESI) Calculated for

C25H1635ClI2NO3 (M+H)

+: 667.8986 found: 667.8979.

Synthesis of 3-benzyl-1'-methyl-4H,11cH-spiro[furo[2,3-d]naphtho[2,1-b]pyran-2,3'-indol]-

2'(1'H)-one (4m)

A solution of 3-diazo-1-methylindolin-2-one 1f (100 mg, 0.58 mmol) in dry dichloroethane (4

mL) was added dropwise to a solution containing 2-((3-phenylprop-2-yn-1-yl)oxy)-1-

naphthaldehyde 2i (183 mg, 0.64 mmol) dissolved in dry DCE (5 mL)

and copper(I) thiophenecarboxylate (6 mg, 5 mol%) at reflux

conditions to afford (210 mg, 84%) of 4m as a white solid according to

general procedure II. Rf = 0.25 (EtOAc/hexane = 1.5:3.5, v/v); mp 230-

231 °C; IR (neat): νmax 2923, 1728, 1611, 1433, 1341, 1166, 737 cm−1;

1H NMR (CDCl3, 400 MHz) δ = 3.08 (s, 3H, CH3), 4.93 (ABq, ΔδAB =

0.07, J = 12.1 Hz, 2H, CH2), 6.62 (d, J = 8 Hz, 1H, CH), 6.80-6.84 (m, 1H, ArH), 6.90-6.96 (m,

4H, ArH), 7.08 (d, J = 8.8 Hz, 1H, ArH), 7.13-7.21 (m, 4H, ArH), 7.29-7.33 (m, 1H, ArH), 7.39-

7.43 (m, 1H, ArH), 7.69-7.74 (m, 2H, ArH), 8.26 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C NMR

(CDCl3, 100 MHz) δ = 26.4, 63.1, 80.5, 94.4, 108.4, 117.2, 118.8, 123.3, 123.9, 125.5, 125.8,

126.8, 128.0, 128.04, 128.4, 128.6, 128.7, 129.4, 130.3, 130.4, 130.9, 132.7, 135.1, 136.5, 144.1,

152.0, 175.3 ppm; HRMS (ESI) Calculated for C29H21NO3 (M+Na)+: 454.1419 found: 454.1409.

Synthesis of 5'-bromo-3-(4-nitrophenyl)-1'-benzyl-4H,9bH-spiro[furo[3,2-c][1]benzopyran-

2,3'-indol]-2'(1'H)-one (4n)


mL) was added dropwise to a solution containing 2-((3-(4-nitrophenyl)prop-2-yn-1-

yl)oxy)benzaldehyde 2j (124 mg, 0.44 mmol) dissolved in dry DCE

(5 mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%) at reflux

conditions to afford (163 mg, 81%) of 4n as a white solid according

to general procedure II. Rf = 0.44 (EtOAc/hexane = 1.5:3.5, v/v); mp

248-249 °C IR (neat): νmax 2923, 1705, 1601, 1457, 1335, 1166, 744

cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.57 (d, 1H, J = 15.6 Hz,

CH), 4.86 (d, J = 13.6 Hz, 1H, CH), 5.01-5.09 (m, 2H, CH2), 6.45 (s, 1H, OCH), 6.67 (d, 1H, J =

7.6 Hz, ArH), 6.91-7.05 (m, 8H, ArH), 7.13-7.29 (m, 4H, ArH), 7.43 (d, J = 7.6 Hz, 1H, ArH),

7.96 (d, J = 9.2 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 43.9, 62.8, 81.8, 94.7,

S12

4o

4p

109.7, 116.8, 121.8, 123.7, 123.74, 125.6, 126.0, 126.6, 127.2, 127.4, 127.9, 128.7, 129.38,

129.44, 131.0, 132.7, 135.0, 137.3, 137.6, 142.9, 147.8, 152.7, 174.5 ppm; HRMS (ESI)

Calculated for C29H21NO3 (M+Na)+: 525.1426 found: 525.1427.

Synthesis of 3-(4-nitrophenyl)-4H,9bH-spiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-

one (4o)

A solution of 3-diazoindolin-2-one 1h (100 mg, 0.63 mmol) in dry dichloroethane (4 mL) was

added dropwise to a solution containing 2-((3-(4-nitrophenyl)prop-2-yn-1-yl)oxy)benzaldehyde

2j (195 mg, 0.69 mmol) dissolved in dry DCE (5 mL) and copper(I)

thiophenecarboxylate (6 mg, 5 mol%) at reflux conditions to afford

(203 mg, 78%) of 4o as a white solid according to general procedure

II. Rf = 0.76 (EtOAc/hexane = 2:3, v/v); mp 230-231 °C; IR (neat):

νmax 3004, 2253, 1441, 1377, 1039, 918, 743 cm−1; 1H NMR (CDCl3,

400 MHz) δ = 4.94 (ABq, ΔδAB = 0.18, J = 13.4 Hz, 2H, CH2 6.38 (s,

1H, CH), 6.82 (d, J = 7.6 Hz, 1H, ArH), 6.91-7.06 (m, 5H, ArH), 7.23-7.28 (m, 3H, ArH), 7.40

(d, J = 7.6 Hz, 1H, ArH), 8.05 (d, J = 8.8 Hz, 2H, ArH), 8.27 (br s, 1H, NH) ppm; 13C NMR

(CDCl3, 100 MHz) δ = 62.9, 81.8, 94.8, 110.7, 116.9, 121.8, 123.8, 123.9, 125.9, 126.0, 126.5,

127.9, 129.1, 129.5, 131.1, 132.2, 137.4, 138.1, 140.9, 147.8, 152.6, 176.6 ppm; HRMS (ESI)

Calculated for C24H16N2O5 (M-H)+: 411.0986 found: 411.0976.

Synthesis of 1'-benzyl-3-(4-iodophenyl)-4H,11cH-spiro[furo[2,3-d]naphtho[2,1-b]pyran-

2,3'-indol]-2'(1'H)-one (4p)


mL) was added dropwise to a solution containing 2-((3-(4-iodophenyl)prop-2-yn-1-yl)oxy)-1-

naphthaldehyde 2k (181 mg, 0.44 mmol) dissolved in dry DCE (5

mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%) at reflux

conditions to afford (210 mg, 83%) of 4p as a white solid according

to general procedure II. Rf = 0.41 (EtOAc/hexane = 1.5:3.5, v/v);

mp 245-246 °C; IR (neat): νmax 2924, 1722, 1613, 1469, 1353, 1216,

952, 753 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.43 (d, J = 16 Hz,

1H, CH2), 4.92 (ABq, ΔδAB = 0.02, J = 12.2 Hz, 2H, CH2), 5.16 (d, J = 15.7, 1H, CH2), 6.52-6.57

(m, 3H, ArH), 6.82-6.87 (m, 3H, ArH), 6.96-7.00 (m, 2H, ArH), 7.07-7.11 (m, 2H, ArH), 7.17-

7.24 (m, 3H, ArH), 7.33-7.37 (m, 1H, ArH), 7.44-7.50 (m, 3H, ArH), 7.72-7.77 (m, 2H, ArH),

S13

4q

8.29 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 43.7, 62.9, 80.8, 94.6, 95.2,

109.6, 117.0, 118.7, 123.4, 124.0, 125.4, 125.7, 126.8, 126.9, 127.6, 127.7, 128.1, 128.8, 129.4,

130.1, 130.4, 130.6, 132.6, 135.0, 135.4, 135.9, 137.8, 143.0, 151.8, 175.2 ppm; HRMS (ESI)

Calculated for C35H24INO3 (M+H)+: 634.0879 found: 634.0874.

Synthesis of 1'-benzyl-3-(6-bromopyridin-2-yl)-7-methoxy-4H,9bH-spiro[furo[3,2-

c][1]benzopyran-2,3'-indol]-2'(1'H)-one (4q)


mL) was added dropwise to a solution containing 2-((3-(6-bromopyridin-2-yl)prop-2-yn-1-

yl)oxy)-4-methoxybenzaldehyde 2l (152 mg, 0.44 mmol) dissolved in

dry DCE (5 mL) and copper(I) thiophenecarboxylate (4 mg, 5 mol%)

at reflux conditions to afford (186 mg, 82%) of 4q as a white solid

according to general procedure II. Rf = 0.40 (EtOAc/hexane = 1.5:3.5,

v/v); mp 226-227 °C; IR (neat): νmax 2924, 1725, 1611, 1436, 1259,

1159, 1116, 1029, 748 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.80 (s,

3H CH3), 4.98 (ABq, ΔδAB = 0.10, J = 15.6 Hz, 2H, CH2), 5.25-5.29 (m, 1H, CH2), 5.66 (d, J =

15.2 Hz, 1H, CH2), 6.35 (s, 1H, CH), 6.51-6.61 (m, 3H, ArH), 6.79-6.81 (m, 1H, ArH), 6.87-6.94

(m, 2H, ArH), 7.12-7. 37 (m, 9H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.3, 55.5, 65.4,

81.5, 92.7, 102.2, 108.5, 109.6, 119.7, 119.8, 123.5, 125.4, 126.2, 126.7, 127.75, 127.8, 128.4,

128.9, 129.0, 130.6, 135.7, 138.6, 141.5, 143.0, 143.5, 151.1, 154.0, 160.4, 174.9 ppm; HRMS

(ESI) Calculated for C31H2379BrN2O4 (M+Na)

+: 589.0739 found: 589.0724.

Procedure for the synthesis of compound 5

Synthesis of 2,2'-((1,4-phenylenebis(prop-2-yne-3,1-diyl))bis(oxy))dibenzaldehyde (5)

To a mixture of compound 2a (1 g, 6.24 mmol), 1,4-diiodobene (1.029 g, 3.12 mmol) in dry

triethylamine / dichloromethane (4:1) (5 mL) under a nitrogen atmosphere were added

[Pd(PPh3)2Cl2] (175 mg, 0.25 mmol) and CuI (24 mg, 0.12 mmol) successively. The reaction

mixture was stirred at room temperature for 6 h. After that, the solvent was removed under

reduced pressure, added water and extracted with dichloromethane. The crude product was

S14

6

5

purified by column chromatography using silica gel to afford the bis-aldehyde derivative (1.4 g,

58%) of 5 as a white solid. Rf = 0.19 (EtOAc/hexane = 1:4, v/v); mp 153-154 °C; IR (neat): νmax

2861, 1681, 1594, 1455, 1212, 1007, 834, cm−1; 1H NMR (CDCl3, 400 MHz) δ = 5.05 (s, 2H,

CH2), 7.09 (t, J = 7.6 Hz, 1H, ArH), 7.17 (d, J = 8.4 Hz, 1H, ArH), 7.36 (s, 2H, ArH), 7.56-7.60

(m, 1H, ArH), 7.87 (dd, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H, ArH) 10.52 (s, 1H, CH) ppm; 13C NMR

(CDCl3, 100 MHz) δ = 57.25, 85.03, 87.41, 113.39, 121.69, 122.43, 125.59, 128.65, 131.74,

135.77, 159.98, 189.65 ppm; HRMS (ESI) Calculated for

C26H18O4 (M+Na)+: 417.1103 found: 417.1098.

Synthesis of 1'-methyl-3-[4-(1'-methyl-2'-oxo-1',2',3'a,7'a-

tetrahydro-4H,9bH-spiro[furo [3,2-c][1]benzopyran-2,3'-indol]-3-

yl)phenyl]9a,9bdihydro4H,5aHspiro[furo[3,2-c][1]benzopyran-2,3'-indol]-2'(1'H)-one (6)

A solution of 1-methyl-3-diazoindolin-2-one 1f (100 mg, 0.58 mmol) in dry dichloroethane (4

mL) was added dropwise to a solution containing 2,2'-((1,4-phenylenebis(prop-2-yne-3,1-

diyl))bis(oxy))dibenzaldehyde 5 (115 mg, 0.029 mmol)

dissolved in dry DCE (5 mL) and copper(I)

thiophenecarboxylate (6 mg, 5 mol%) at reflux conditions to

afford 6 (157 mg, 79%) as a white solid according to general

procedure II. Rf = 0.06 (EtOAc/hexane = 1.5:3.5, v/v); mp

231-232 °C; IR (neat): νmax 2923, 1716, 1608, 1471, 1215,

1109, 755 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.09 (s, 3H,

CH3), 4.79-4.84 (m, 1H, CH2), 4.94-5.00 (m, 1H, CH2), 6.31 (s, 1H, CH), 6.57 (s, 1H, CH), 6.23

(s, 1H, CH), 6.74 (t, J = 8.4 Hz, 1H, ArH), 6.85-6.91 (m, 2H, ArH), 6.93-6.99 (m, 2H, ArH),

7.20-7.35 (m, 3H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 26.5, 63.2, 81.2, 94.3, 108.7,

116.7, 121.5, 123.5, 125.6, 126.4, 126.5, 126.6, 128.2, 128.3, 129.2, 130.7, 131.1, 133.5, 135.5,

144.0, 152.7, 174.8 ppm (due to the C2 Symmetry we observed half-half the signal); HRMS

(ESI) Calculated for C44H32N2O6 (M+Na)+: 685.2339 found: 685.2337.

Synthesis of dimethyl 1'-benzyl-2'-oxo-5-(2-(prop-2-yn-1-yloxy)phenyl)-5H-spiro[furan-

2,3'-indoline]-3,4-dicarboxylate (7)

To a mixture of spiro-indolooxirane 3a (100 mg, 0.26 mmol) and dimethyl

acetylenedicarboxylate (41 mg, 0.29 mmol) in dry toluene (5 mL) was stirred at reflux conditions

for 32 hours to afford 7 (90 mg, 66%) as a colorless liquid. Rf = 0.13 (EtOAc/hexane = 1:4, v/v);

S15

8

7

IR (neat): νmax 3282, 2952, 2123(w), 1723, 1611, 1259, 1022, 754. cm−1;

1H NMR (CDCl3, 400 MHz) δ = 2.52 (s, 1H, ≡CH), 3.48 (s, 3H, CH3),

3.75 (s, 3H, CH3), 4.63-4.74 (m, 3H, CH2), 5.07 (d, J = 16 Hz, 1H, CH2),

6.68 (d, J = 7.6 Hz, 1H, CH), 6.91 (s, 1H, ArH), 7.00-7.07 (m, 3H,

ArH), 7.18-7.42 (m, 8H, ArH), 7.56 (d, J = 7.2 Hz, 1H, ArH) ppm; 13C

NMR (CDCl3, 100 MHz) δ = 44.1, 52.4, 52.7, 56.1, 76.02, 78.4, 83.7,

89.5, 109.6, 112.1, 121.8, 123.2, 125.3, 126.2, 127.3, 127.4, 127.7,

128.2, 128.8, 130.1, 130.9, 135.5, 143.8, 147.3, 155.1, 161.0, 163.1, 173.8 2 ppm; HRMS (ESI)

Calculated for C31H25NO7 (M+H)+: 524.1709 found: 524.1712.

Synthesis of 1'-ethyl-5-phenyl-3-(2-(prop-2-yn-1-yloxy)phenyl)-3a,6a-dihydrospiro[furo

[3,4-c]pyrrole-1,3'-indoline]-2',4,6(3H,5H)-trione (8)

To a mixture of spiro-indolooxirane 3a (100 mg, 0.26 mmol) and N-phenylmaleimide (50 mg,

0.30 mmol) in dry toluene (5 mL) was stirred at reflux conditions for

27 hours to afford 8 (94 mg, 65%) as a white solid. Rf = 0.13

(EtOAc/hexane = 1:4, v/v); mp 186-187 °C; IR (neat): νmax 3289,

2923, 2125(w), 1714, 1614, 1339, 1267, 1006, 734 cm−1; 1H NMR

(CDCl3, 400 MHz) δ = 2.55 (t, J = 2.4 Hz, 1H, ≡CH), 3.87 (d, J = 8

Hz, 1H, CH), 4.45 (t, J = 8.1 Hz, 1H, CH), 4.83-4.87 (m, 3H, CH2),

4.98 (d, J = 15.6 Hz, 1H, CH2), 6.54 (d, J = 8 Hz, 1H, ArH), 6.78 (d, J

= 8 Hz, 1H, ArH), 6.99-7.12 (m, 5H, ArH), 7.24-7.41 (m, 11H, ArH), 7.47 (d, J = 7.6 Hz, 1H,

ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 43.8, 49.5, 52.0, 56.4, 75.7, 78.7, 83.9, 109.8,

111.6, 121.3, 123.1, 123.4, 125.1, 125.5, 126.1, 126.7, 127.3, 127.9, 128.6, 129.0, 129.2, 131.0,

131.6, 135.1, 143.4, 154.9, 172.9, 173.1, 175.8 ppm; HRMS (ESI) Calculated for C31H26N2O5

(M+Na)+: 577.1739 found: 577.1734.

Synthesis of dimethyl 1'-ethyl-2'-oxo-5-(2-(prop-2-yn-1-yloxy)phenyl)-5H-spiro[furan-2,3'-

indoline]-3,4-dicarboxylate (9)

A solution of 3-diazo-1-ethylindolin-2-one 1b (100 mg, 0.53 mmol) in dry dichloroethane or

toluene (4 mL) was added dropwise to a mixture of solution containing 2-[(prop-2-yn-1-

yl)oxy]benzaldehyde 2a (93 mg, 0.58 mmol), dimethyl acetylenedicarboxylate (83 mg, 0.58

mmol) and copper(I) thiophenecarboxylate (5 mg, 5 mol%) at reflux conditions for 1 hour to

afford 9 (164 mg, 67%) as a colorless liquid. Rf = 0.09 (EtOAc/hexane = 1:4, v/v); IR (neat): νmax

S16

9

3281, 2923, 2123, 1720, 1610, 1257, 1018, 742 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.33 (t, J

= 7.2 Hz, 3H, CH3), 2.57 (t, J = 2.4 Hz, 1H, ≡CH), 3.60 (s, 3H, CH3), 3.71-3.78 (m, 1H, CH),

3.81 (s, 3H, CH3), 3.84-3.93 (m, 1H, CH), 4.72 (ABqd, ΔδAB = 0.06, J1 =

15.8 Hz, J2 = 2.3 Hz, 2H, CH2), 6.88-6.91 (m, 2H, ArH), 7.07-7.13 (m,

3H, ArH), 7.37-7.45 (m, 3H, ArH), 7.58-7.60 (m, 1H, ArH) ppm; 13C

NMR (CDCl3, 100 MHz) δ = 12.3, 34.9, 52.3, 52.6, 56.1, 75.9, 78.4,

83.7, 89.5, 108.5, 112.1, 121.8, 122.9, 125.4, 126.3, 127.5, 128.2, 130.1,

130.8, 132.1, 143.7, 146.8, 155.1, 160.9, 163.1, 173.2 ppm; HRMS (ESI)

Calculated for C26H23NO7 (M+Na)+: 484.1372 found: 484.1377.

S17

Copies of 1H and 13C NMR spectra

1H NMR spectrum of 3a

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.57

7

2.40

1

2.40

7

2.41

2

4.57

0

4.57

5

4.60

9

4.61

5

4.62

5

4.63

0

4.66

5

4.67

0

4.80

5

4.82

9

4.84

5

4.84

9

4.88

9

6.76

4

6.78

4

6.99

2

7.01

3

7.06

7

7.08

6

7.10

5

7.12

8

7.14

7

7.23

8

7.24

8

7.26

0

7.26

6

7.27

5

7.28

9

7.29

3

7.31

1

7.33

1

7.33

4

7.35

1

7.37

0

1.00

2.27

3.34

1.07

1.06

2.22

7.31

1.23

1.06

apr-25 bn PROTON CDCl3 17/8/2018

3a

S18

13C NMR spectrum of 3a

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.04

55

.95

61

.49

63

.98

75

.69

76

.73

77

.04

77

.36

78

.37

10

9.5

7

11

1.5

0

12

1.0

6

12

1.5

7

12

1.9

3

12

2.6

4

12

3.7

1

12

7.4

1

12

7.6

5

12

8.7

7

12

9.0

2

12

9.6

2

12

9.9

4

13

5.6

2

14

3.8

3

15

5.4

5

17

0.2

7

3a

S19

1H NMR spectrum of 3b

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.2

06

1.2

24

1.2

42

1.5

88

2.4

10

2.4

16

2.4

22

3.6

58

3.6

76

3.6

94

3.7

07

3.7

12

3.7

25

3.7

43

3.7

61

4.5

90

4.5

95

4.6

01

4.7

39

6.8

99

6.9

10

6.9

21

6.9

30

7.0

93

7.1

12

7.1

30

7.1

31

7.2

33

7.2

51

7.2

60

7.2

66

7.2

81

7.2

88

7.3

69

7.3

72

7.3

88

7.3

91

7.4

07

7.4

10

7.7

42

3.3

0

1.0

0

2.3

0

1.9

8

1.0

1

2.1

4

1.1

0

2.2

8

1.1

1

0.9

9

apr-54a PROTON CDCl3 14/09/2016

3b

S20

13C NMR spectrum of 3b

3b

S21

1H NMR spectrum of 3e

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.58

1

2.50

8

2.51

4

2.52

0

4.72

6

4.73

1

4.73

6

4.79

3

4.82

9

4.84

8

4.88

7

6.79

4

6.81

3

7.08

4

7.08

9

7.09

0

7.10

7

7.12

7

7.12

8

7.22

9

7.24

8

7.25

4

7.25

8

7.27

4

7.28

0

7.29

2

7.29

7

7.30

0

7.31

0

7.31

4

7.31

9

7.32

2

8.24

4

8.25

1

1.00

1.95

3.23

1.09

2.23

8.18

1.08

0.97

apr 58 PROTON CDCl3 4/10/2016

3e

S22

13C NMR spectrum of 3e

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.09

56

.55

61

.36

62

.51

76

.75

77

.07

77

.39

10

9.8

4

11

1.3

9

12

2.1

4

12

2.8

2

12

2.9

1

12

5.4

9

12

5.6

9

12

7.3

4

12

7.8

0

12

8.8

6

13

0.4

6

13

5.3

3

14

1.8

0

14

3.9

3

15

9.7

5

16

9.7

2

3e

S23

1H NMR spectrum of 4a

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.63

1

4.85

4

4.89

3

4.91

1

4.95

0

4.97

9

5.62

2

6.30

0

6.68

6

6.70

6

6.89

2

6.91

1

6.92

4

6.95

6

6.97

5

6.99

3

7.15

3

7.16

2

7.16

8

7.17

4

7.18

1

7.18

7

7.19

5

7.20

7

7.22

7

7.25

4

7.27

3

7.28

4

7.29

4

7.30

5

7.32

7

2.00

2.34

1.14

1.32

1.12

4.34

4.09

3.96

apr-25 bn PROTON CDCl3 16/08/2018

4.854.904.955.005.05 ppm

4.85

4

4.89

3

4.91

1

4.95

0

4.97

9

4a

S24

13C NMR spectrum of 4a

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.06

63

.70

76

.75

77

.06

77

.38

81

.39

92

.66

10

9.4

5

11

6.7

7

12

1.4

6

12

1.8

3

12

3.3

7

12

5.4

9

12

5.9

9

12

6.8

3

12

7.4

0

12

7.8

0

12

8.3

1

12

8.9

0

12

9.1

8

13

0.3

8

13

5.4

2

13

9.8

7

14

2.6

8

15

2.7

8

17

5.2

2

4a

S25

1H NMR spectrum of 4b

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.28

5

1.30

3

1.32

1

1.57

8

3.68

4

3.70

1

3.71

9

3.73

7

3.75

0

3.75

5

3.76

7

3.77

2

3.78

5

3.80

3

3.82

1

3.83

9

4.96

2

5.59

4

6.18

9

6.82

1

6.83

7

6.84

3

6.85

7

6.92

0

6.93

6

6.93

9

6.97

2

6.99

1

7.01

0

7.15

2

7.15

9

7.17

4

7.18

1

7.26

2

7.29

4

7.29

8

7.31

5

7.31

7

7.32

1

7.33

3

3.13

2.23

2.00

1.00

0.98

1.96

0.94

1.03

0.98

2.07

apr-54 c PROTON CDCl3 16/9/2016

4b

S26

13C NMR spectrum of 4b

200 180 160 140 120 100 80 60 40 20 0 ppm

12

.60

35

.02

63

.81

76

.74

77

.05

77

.37

80

.77

92

.74

10

8.6

3

11

8.2

3

12

2.3

8

12

3.2

0

12

5.5

8

12

6.2

8

12

6.4

2

12

7.3

6

12

8.1

5

12

9.1

7

13

0.6

0

13

8.8

4

14

2.7

2

15

1.3

5

17

4.3

6

4b

S27

1H NMR spectrum of 4c

9 8 7 6 5 4 3 2 1 0 ppm

4.90

9

4.95

0

4.98

9

5.02

2

5.05

6

5.69

0

6.27

5

6.74

7

6.76

6

6.87

6

6.89

8

6.97

4

6.98

9

7.00

7

7.02

5

7.20

4

7.20

9

7.22

6

7.24

4

7.26

1

7.30

3

7.32

4

7.33

6

7.34

4

7.37

4

7.38

6

2.02

2.09

1.00

1.00

1.03

1.01

2.06

2.13

6.31

apr-88 PROTON CDCl3 22/02/2017

4c

S28

13C NMR spectrum of 4c

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.07

63

.82

76

.76

77

.07

77

.39

80

.86

92

.76

10

9.5

5

11

8.2

8

12

2.3

5

12

3.4

6

12

5.4

8

12

6.3

3

12

6.4

7

12

7.3

1

12

7.3

8

12

7.8

4

12

7.9

4

12

8.9

3

12

9.2

3

13

0.5

6

13

5.3

3

13

9.0

8

14

2.7

2

15

1.3

7

17

4.9

4

1

4c

S29

H NMR spectrum of 4d

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

0.9

73

0.9

92

1.0

10

1.2

52

1.6

59

1.6

92

1.7

11

1.7

29

1.7

47

1.7

66

1.7

84

3.6

49

3.6

67

3.6

86

4.9

25

4.9

62

4.9

96

5.5

99

6.1

93

6.7

71

6.7

93

6.8

29

6.8

49

6.9

22

6.9

40

6.9

73

6.9

91

7.0

10

7.2

65

7.2

92

7.2

98

7.3

09

7.3

12

7.3

20

7.3

27

7.4

60

3.3

2

2.1

9

2.1

7

2.0

0

1.0

2

1.0

2

1.0

2

1.0

8

1.0

4

1.1

2

2.3

7

1.0

1

apr-106 b PROTON CDCl3 5/6/2017

4d

S30

13C NMR spectrum of 4d

200 180 160 140 120 100 80 60 40 20 0 ppm

11

.40

20

.66

29

.72

41

.85

63

.82

80

.68

92

.72

10

8.7

9

11

3.5

4

11

8.6

9

12

2.5

2

12

3.1

8

12

5.5

5

12

7.8

3

12

8.0

4

12

9.4

1

13

0.5

7

13

2.0

7

13

8.7

6

14

3.1

1

15

1.8

9

17

4.7

4

4d

S31

1H NMR spectrum of 4e

9 8 7 6 5 4 3 2 1 0 ppm

1.6

29

4.9

58

5.1

14

5.1

47

5.1

64

5.1

97

5.7

78

6.3

07

6.7

56

6.7

76

6.9

07

6.9

26

6.9

71

6.9

89

7.0

08

7.0

21

7.0

44

7.2

34

7.2

53

7.2

72

7.3

03

7.3

33

7.3

40

7.3

54

7.3

61

7.3

80

7.3

96

7.4

17

8.1

58

8.1

65

2.0

0

2.0

6

1.0

6

1.0

6

1.0

4

1.0

2

2.1

3

1.0

5

5.3

6

1.0

8

1.0

3


4e

S32

13C NMR spectrum of 4e

200 180 160 140 120 100 80 60 40 20 0 ppm

-0.0

0

44

.11

64

.53

76

.70

77

.02

77

.34

80

.09

92

.93

10

9.6

6

11

7.5

9

12

3.4

2

12

3.4

6

12

3.5

5

12

5.1

1

12

5.3

4

12

6.2

2

12

7.3

3

12

7.8

7

12

8.9

5

13

0.7

4

13

5.2

3

13

7.4

6

14

2.0

2

14

2.8

1

15

7.9

5

17

4.5

5

4e

S33

1H NMR spectrum of 4f

9 8 7 6 5 4 3 2 1 0 ppm

-0.000

1.702

2.268

3.902

4.398

4.402

4.442

4.446

4.532

4.536

4.576

4.581

4.985

5.018

5.070

5.103

5.597

6.257

6.839

6.857

6.917

6.930

6.933

6.947

6.973

6.992

7.011

7.027

7.046

7.266

7.302

7.321

7.341

0.9

0

3.0

0

1.9

7

1.9

8

0.9

2

0.8

6

5.9

2

1.1

8

4f

S34

13C NMR spectrum of 4f

200 180 160 140 120 100 80 60 40 20 0 ppm

29

.56

56

.00

64

.04

72

.78

76

.78

77

.10

77

.42

81

.28

92

.55

10

9.5

0

11

0.9

0

11

8.4

5

12

1.2

8

12

1.7

0

12

3.7

0

12

5.5

4

12

6.5

5

12

8.0

8

13

0.4

7

13

9.6

7

14

1.6

8

14

2.0

6

14

8.2

2

17

4.0

4

4f

S35

1H NMR spectrum of 4g

9 8 7 6 5 4 3 2 1 0 ppm

1.6

33

3.7

95

4.8

72

4.8

93

4.9

25

4.9

46

4.9

78

5.6

17

6.2

75

6.4

51

6.5

43

6.5

65

6.5

72

6.5

88

6.5

94

7.0

61

7.2

33

7.2

55

7.2

77

7.2

95

7.3

15

7.3

31

7.3

51

3.0

0

2.1

9

1.8

5

1.0

0

1.0

0

1.0

1

2.0

6

0.9

8

7.4

2


4g

S36

13C NMR spectrum of 4g

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.10

55

.40

63

.68

76

.76

77

.08

77

.39

81

.34

92

.13

10

1.6

6

10

8.4

6

11

1.0

1

11

6.1

1

11

7.6

4

12

1.7

2

12

7.3

2

12

7.8

9

12

7.9

8

12

8.6

7

12

9.0

0

13

0.2

2

13

3.2

2

13

4.9

1

14

0.7

0

14

1.7

3

15

3.9

3

16

0.6

2

17

4.7

2

4g

S37

1H NMR spectrum of 4h

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.6

54

3.2

25

4.8

68

4.8

98

4.9

97

5.0

27

5.7

56

6.7

69

6.7

89

6.8

07

6.8

13

6.8

67

6.8

86

6.9

04

6.9

33

6.9

36

6.9

51

6.9

54

7.0

73

7.0

96

7.2

27

7.2

30

7.2

46

7.2

50

7.2

65

7.2

69

7.3

06

7.3

08

7.3

26

7.3

43

7.3

46

7.4

01

7.4

04

7.4

22

3.0

0

0.9

7

0.9

5

0.9

4

1.9

4

0.9

5

0.9

4

0.9

4

1.2

1

0.9

7

0.9

9

1.9

6

0.9

6


4h

S38

13C NMR spectrum of 4h

200 180 160 140 120 100 80 60 40 20 0 ppm

26

.42

63

.86

76

.76

77

.08

77

.40

80

.29

91

.97

10

8.3

2

11

6.7

8

11

8.6

6

12

3.2

6

12

3.8

1

12

3.9

4

12

5.3

3

12

5.5

6

12

6.8

1

12

7.9

9

12

8.2

2

12

9.3

8

13

0.2

7

13

0.3

8

13

2.6

1

14

0.2

4

14

3.6

7

15

1.8

2

17

5.3

2

4h

S39

1H NMR spectrum of 4i

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

04

1.30

9

1.32

7

1.34

5

1.56

4

3.75

0

3.76

8

3.78

6

3.80

4

4.86

9

4.89

9

4.99

5

5.02

5

5.75

9

6.79

7

6.80

6

6.81

5

6.85

4

6.85

6

6.87

3

6.87

4

6.89

2

6.89

3

6.93

4

6.93

7

6.95

2

6.95

5

7.07

2

7.09

5

7.21

7

7.22

0

7.23

6

7.24

0

7.25

3

7.25

9

7.30

9

7.32

9

7.34

6

7.34

9

7.41

0

7.41

2

7.43

0

7.44

8

7.70

6

7.72

9

7.74

9

8.22

2

8.24

3

3.05

2.09

1.03

1.05

1.00

1.98

1.05

0.99

1.01

1.08

1.03

1.05

2.08

1.04


4i

S40

13C NMR spectrum of 4i

200 180 160 140 120 100 80 60 40 20 0 ppm

12

.70

34

.98

63

.84

76

.77

77

.08

77

.40

80

.32

92

.03

10

8.4

5

11

6.8

5

11

8.6

5

12

3.0

3

12

3.9

3

12

5.3

8

12

5.7

4

12

6.8

1

12

7.9

7

12

8.4

7

12

9.3

8

13

0.2

4

13

0.2

9

13

2.6

2

14

0.0

9

14

2.7

6

15

1.8

0

17

4.9

2

4i

S41

COSY spectrum of 4i

ppm

1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5 ppm

2

3

4

5

6

7

8

apr-53 COSYGPSW CDCl3

4i

S42

HSQC spectrum of 4i

ppm

1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5 ppm

140

120

100

80

60

40

20

0

apr-53 HSQCGP CDCl3

4i

S43

1H NMR spectrum of 4j

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.18

2

1.57

1

4.73

6

4.77

4

4.81

9

4.84

8

4.93

3

4.94

6

4.97

2

4.97

5

5.74

1

6.60

3

6.62

2

6.76

5

6.78

3

6.80

2

6.87

6

6.89

3

7.01

0

7.03

2

7.04

2

7.04

5

7.06

1

7.06

4

7.08

0

7.08

3

7.18

4

7.20

0

7.21

2

7.22

2

7.23

3

7.24

3

7.25

3

7.27

3

7.28

3

7.29

3

7.36

1

1.00

1.04

1.94

0.99

1.03

2.00

0.97

2.02

6.35

0.90

2.05

1.00


4j

S44

13C NMR spectrum of 4j

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.08

63

.84

76

.76

77

.08

77

.39

80

.42

92

.04

10

9.3

3

11

6.7

6

11

8.6

6

12

3.2

9

12

3.8

8

12

3.9

7

12

5.3

6

12

5.6

4

12

6.8

6

12

7.4

5

12

7.8

2

12

8.0

0

12

8.2

5

12

8.9

2

12

9.3

9

13

0.2

6

13

0.3

0

13

2.6

1

13

5.5

3

14

0.3

1

14

2.7

5

15

1.8

2

17

5.4

9

4j

S45

1H NMR spectrum of 4k

9 8 7 6 5 4 3 2 1 0 ppm

4.94

4

5.09

2

5.12

5

5.15

4

5.18

7

5.72

4

6.26

8

6.75

3

6.77

3

6.98

7

7.00

6

7.02

7

7.04

5

7.23

8

7.24

2

7.25

8

7.27

5

7.27

8

7.30

4

7.31

5

7.32

4

7.32

9

7.34

0

7.34

5

7.37

0

7.38

5

7.40

5

7.67

3

2.00

2.08

0.99

0.98

1.03

2.05

6.47

1.00

0.97

APR-66 PROTON CDCl3 24/01/2017

4k

S46

13C NMR spectrum of 4k

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.09

64

.58

76

.77

77

.08

77

.40

80

.47

84

.10

86

.16

92

.99

10

9.6

2

12

2.8

6

12

3.5

1

12

5.5

3

12

7.3

7

12

7.6

2

12

7.8

7

12

8.3

1

12

8.9

5

13

0.7

1

13

5.2

6

13

5.4

7

13

8.3

6

14

2.7

5

14

6.2

0

15

1.7

5

17

4.6

4

4k

S47

1H NMR spectrum of 4l

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.25

5

1.62

9

4.83

3

4.87

3

4.88

0

4.92

0

5.03

2

5.06

6

5.09

9

5.13

3

5.66

6

6.22

7

6.61

2

6.63

3

6.94

7

7.16

0

7.18

1

7.27

4

7.29

1

7.32

1

7.33

7

7.61

4

8.00

4

2.00

1.99

0.93

0.94

0.96

0.92

0.88

4.79

0.95

0.92


4l

S48

13C NMR spectrum of 4l

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.18

64

.48

76

.77

77

.09

77

.40

80

.59

84

.25

86

.30

92

.63

11

0.7

0

12

2.2

9

12

5.9

8

12

7.2

9

12

7.7

5

12

8.0

4

12

9.0

0

12

9.0

4

12

9.1

4

13

0.6

4

13

4.8

0

13

5.4

6

13

9.0

8

14

1.2

7

14

6.4

0

15

1.7

4

17

4.2

2

4l

S49

1H NMR spectrum of 4m

9 8 7 6 5 4 3 2 1 0 ppm3

.08

37

4.8

73

1

4.9

03

4

4.9

51

3

4.9

81

6

6.6

13

4

6.6

32

8

6.8

00

0

6.8

18

7

6.8

37

4

6.8

99

8

6.9

18

6

6.9

34

6

6.9

43

6

6.9

62

4

7.0

68

0

7.0

90

4

7.1

26

3

7.1

45

7

7.1

61

8

7.1

79

6

7.1

95

4

7.2

13

4

7.2

87

9

7.3

06

3

7.3

25

0

7.3

89

0

7.4

08

7

7.4

26

9

7.6

92

3

2.9

4

2.0

0

0.9

7

1.0

0

3.8

9

1.0

0

3.9

4

0.9

8

0.9

9

1.9

7

0.9

7


4m

S50

13C NMR spectrum of 4m

200 180 160 140 120 100 80 60 40 20 0 ppm

26

.37

63

.06

76

.84

77

.16

77

.47

80

.45

94

.42

10

8.3

8

11

7.1

8

11

8.7

5

12

3.2

7

12

3.9

4

12

5.4

7

12

5.7

5

12

6.8

2

12

7.9

8

12

8.0

4

12

8.3

8

12

8.5

9

12

8.6

6

12

9.4

3

13

0.2

6

13

0.4

3

13

0.9

4

13

2.6

9

13

5.0

9

13

6.5

1

14

4.0

7

15

2.0

1

17

5.3

1

4m

S51

1H NMR spectrum of 4n

9 8 7 6 5 4 3 2 1 0 ppm

-0.000

4.555

4.594

4.847

4.881

5.013

5.053

5.087

5.088

5.293

6.452

6.658

6.677

6.909

6.920

6.926

6.930

6.943

6.947

6.968

6.987

7.000

7.012

7.015

7.031

7.033

7.050

7.052

7.131

7.133

7.138

7.151

7.155

7.170

7.191

7.196

7.207

7.213

7.227

7.233

0.9

9

1.0

0

1.9

9

0.2

8

0.9

5

0.9

9

7.9

0

3.9

6

1.0

0

1.8

9

4n

S52

13C NMR spectrum of 4n

200 180 160 140 120 100 80 60 40 20 0 ppm

43

.92

62

.81

76

.75

77

.07

77

.38

94

.73

10

9.7

4

11

6.8

4

12

1.7

9

12

3.7

0

12

3.7

4

12

5.6

3

12

6.0

0

12

6.5

8

12

7.1

7

12

7.4

2

12

7.8

7

12

8.7

1

12

9.3

8

12

9.4

4

13

1.0

0

13

2.7

0

13

5.0

1

13

7.3

4

13

7.5

5

14

2.9

4

14

7.8

1

15

2.6

5

17

4.5

3

4n

S53

1H NMR spectrum of 4o

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

2

1.2

59

4

1.7

16

5

4.8

60

9

4.8

94

4

5.0

40

3

5.0

74

1

6.3

82

9

6.8

10

5

6.8

30

0

6.9

07

5

6.9

28

1

6.9

42

9

6.9

62

7

6.9

82

1

7.0

01

1

7.0

08

5

7.0

28

0

7.0

35

9

7.0

57

8

7.2

31

1

7.2

35

5

7.2

48

9

7.2

53

8

7.2

61

9

7.2

82

6

7.3

85

7

7.4

04

7

8.0

29

1

8.0

50

9

1.2

0

1.1

5

1.0

3

1.0

8

5.1

8

3.0

2

1.2

3

2.2

8

1.0

0


4o

S54

13C NMR spectrum of 4o

200 180 160 140 120 100 80 60 40 20 0 ppm

62

.85

76

.74

77

.06

77

.38

81

.77

94

.81

11

0.7

4

11

6.8

5

12

1.8

4

12

3.8

0

12

3.8

9

12

5.9

4

12

6.0

0

12

6.5

2

12

7.8

6

12

9.1

4

12

9.4

7

13

1.1

0

13

2.2

3

13

7.3

7

13

8.1

1

14

0.8

8

14

7.7

8

15

2.6

1

17

6.6

1

4o

S55

1H NMR spectrum of 4p

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

002

1.65

87

4.41

42

4.45

36

4.88

10

4.91

16

4.91

87

4.94

92

5.14

52

5.18

45

5.26

35

6.51

52

6.53

49

6.54

78

6.56

84

6.81

68

6.83

37

6.84

89

6.86

78

6.96

16

6.97

99

6.99

80

7.07

07

7.09

28

7.11

27

7.16

65

7.18

33

7.20

18

7.21

37

7.23

20

7.23

51

7.33

02

7.34

83

7.36

70

7.43

50

7.45

38

0.97

2.00

1.02

3.02

2.92

1.98

2.07

3.21

1.06

3.00

2.09

0.93


4p

S56

13C NMR spectrum of 4p

200 180 160 140 120 100 80 60 40 20 0 ppm

43

.78

62

.86

76

.80

77

.12

77

.44

80

.82

94

.60

95

.16

10

9.5

5

11

6.9

6

11

8.6

8

13

0.5

6

13

2.5

8

13

5.0

1

13

5.3

5

13

5.9

2

13

7.7

8

14

3.0

3

15

1.8

4

17

5.2

4

4p

S57

1H NMR spectrum of 4q

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.65

9

3.79

6

4.90

6

4.94

5

5.00

9

5.04

8

5.24

7

5.28

5

5.29

4

5.63

6

5.67

4

6.35

1

6.51

1

6.52

9

6.54

4

6.54

9

6.58

3

6.58

9

6.60

4

6.61

0

6.78

5

6.80

5

6.87

0

6.88

8

6.90

6

6.92

2

6.93

7

6.94

0

7.12

3

7.14

2

7.16

1

7.18

2

7.20

8

7.22

4

7.22

8

7.28

2

3.00

0.80

0.91

0.98

0.95

0.81

2.99

0.91

1.93

9.08


4q

S58

13C NMR spectrum of 4q

200 180 160 140 120 100 80 60 40 20 0 ppm

44

.28

55

.45

65

.39

76

.76

77

.08

77

.40

81

.50

92

.72

10

2.2

0

10

8.4

7

10

9.5

9

11

9.6

7

11

9.8

2

12

3.4

7

12

5.3

7

12

6.1

9

12

6.6

5

12

7.7

5

12

7.8

3

12

8.4

3

12

8.8

5

12

9.0

3

13

0.5

8

13

5.6

5

13

8.6

3

14

1.5

0

14

3.0

0

14

3.4

6

15

1.1

3

15

3.9

7

16

0.3

6

17

4.8

8

4q

S59

1H NMR spectrum of 5

11 10 9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.6

65

5.0

49

7.0

73

7.0

92

7.1

11

7.1

64

7.1

85

7.2

63

7.3

60

7.5

58

7.5

62

7.5

80

7.5

97

7.6

01

7.8

59

7.8

63

7.8

78

7.8

82

10

.51

8

2.0

0

0.9

5

0.9

5

1.8

9

0.9

6

0.9

0

0.9

1

5

S60

13C NMR spectrum of 5

200 180 160 140 120 100 80 60 40 20 0 ppm

57

.25

76

.75

77

.06

77

.38

85

.03

87

.41

11

3.3

9

12

1.6

9

12

2.4

3

12

5.5

9

12

8.6

5

13

1.7

4

13

5.7

7

15

9.9

8

18

9.6

5

5

S61


9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.60

5

3.09

1

4.78

6

4.80

6

4.81

9

4.83

8

4.93

9

4.96

3

4.97

1

4.99

7

5.29

8

6.30

7

6.57

1

6.62

5

6.71

6

6.73

7

6.75

8

6.84

7

6.85

5

6.86

6

6.87

5

6.88

3

6.90

2

6.91

3

6.93

1

6.94

1

6.95

1

6.95

9

6.97

1

6.98

9

7.19

7

7.21

6

7.23

6

7.27

5

7.29

5

3.00

0.95

0.97

0.89

1.80

1.02

2.00

1.81

3.38

APR161 PROTON CDCl3 9/10/2017

6

S62


200 180 160 140 120 100 80 60 40 20 0 ppm

26

.47

63

.15

76

.73

77

.05

77

.37

81

.22

94

.33

10

8.6

7

11

6.6

8

12

1.5

0

12

3.4

6

12

5.5

5

12

6.3

6

12

6.4

8

12

6.5

6

12

8.1

6

12

8.3

4

12

9.1

8

13

0.7

3

13

1.0

9

13

3.5

1

13

5.5

3

14

3.9

5

15

2.6

8

17

4.7

6

6

S63


9 8 7 6 5 4 3 2 1 0 ppm

2.52

0

3.47

5

3.74

9

4.67

3

4.67

8

4.69

8

4.70

3

4.73

7

5.04

5

5.08

5

6.67

0

6.68

9

6.90

6

7.00

4

7.02

4

7.04

1

7.05

0

7.06

9

7.18

0

7.19

9

7.21

1

7.21

9

7.22

8

7.24

6

7.27

0

7.29

0

7.31

1

7.33

7

7.34

6

7.36

4

7.39

7

7.41

5

1.00

3.05

3.40

2.92

1.06

1.06

0.88

3.36

8.41

1.12


7

S64


200 180 160 140 120 100 80 60 40 20 0 ppm

44

.11

52

.40

52

.70

56

.11

76

.02

76

.79

77

.11

77

.43

78

.35

83

.73

89

.48

10

9.5

9

11

2.1

1

12

1.8

2

12

3.2

3

12

5.3

0

12

6.1

7

12

7.2

7

12

7.4

1

12

7.6

9

12

8.2

4

12

8.8

0

13

0.1

4

13

0.8

5

13

1.7

8

13

5.4

9

14

3.7

9

14

7.3

3

15

5.0

7

16

0.9

9

16

3.0

9

17

3.8

1

apr-328 C13CPD CDCl3 23/08/2018

7

S65


9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

2

1.5

73

1

2.5

40

5

2.5

46

3

2.5

52

0

3.8

61

6

3.8

82

3

4.4

25

3

4.4

45

6

4.4

65

8

4.8

33

8

4.8

39

6

4.8

66

9

4.9

59

1

4.9

98

3

6.5

31

3

6.5

51

1

6.7

69

0

6.7

88

6

6.9

87

8

7.0

06

5

7.0

25

2

7.0

41

7

7.0

64

9

7.0

86

1

7.0

98

9

7.1

17

1

7.2

35

4

7.2

57

1

7.2

68

8

7.2

88

0

7.3

02

9

7.3

28

9

7.3

37

2

7.3

74

1

7.3

93

6

7.4

07

0

7.4

11

3

1.0

0

0.9

6

1.0

1

3.0

7

1.1

0

0.9

5

0.9

9

5.1

1

11

.01

1.2

0


8

S66


200 180 160 140 120 100 80 60 40 20 0 ppm

43

.81

49

.45

52

.04

56

.43

75

.69

78

.70

83

.89

10

9.7

8

11

1.5

8

12

1.3

3

12

3.0

8

12

3.4

3

12

5.1

1

12

5.5

0

12

6.1

4

12

6.6

5

12

7.3

1

12

7.9

1

12

8.6

2

12

8.9

9

12

9.1

6

13

1.0

1

13

1.6

1

13

5.0

9

14

3.4

3

15

4.8

5

17

2.9

1

17

3.1

0

17

5.7

5

8

S67


9 8 7 6 5 4 3 2 1 0 ppm

1.31

43

1.33

23

1.35

02

1.65

99

2.56

10

2.56

65

2.57

23

3.60

07

3.70

74

3.72

55

3.74

33

3.76

09

3.77

88

3.80

78

3.84

31

3.86

11

3.87

91

3.89

67

3.91

45

3.93

23

4.70

86

4.71

44

4.74

82

4.75

39

4.77

89

4.78

46

4.81

84

4.82

42

6.88

22

6.90

24

6.90

80

7.06

73

7.08

87

7.10

84

7.12

72

7.30

34

7.36

59

7.38

60

7.40

01

7.40

49

7.43

30

7.45

13

7.58

21

7.58

49

3.00

0.85

2.90

0.96

2.99

1.07

2.04

1.95

3.05

3.09

1.02


9

S68


200 180 160 140 120 100 80 60 40 20 0 ppm

12

.32

34

.92

52

.28

52

.60

56

.11

75

.93

78

.36

83

.70

89

.54

10

8.5

5

11

2.1

2

12

1.7

9

12

2.9

2

12

5.4

3

12

6.3

3

12

7.4

7

12

8.2

4

13

0.0

5

13

0.8

4

13

2.1

1

14

3.7

4

14

6.7

6

15

5.0

9

16

0.9

4

16

3.0

7

17

3.1

9

9

S69

Solid-state arrangements of compound 4i

A unit cell contains two asymmetric units of 4i. The solid-state arrangements of compound 4i

divulged a number of close intermolecular links between the molecules, which are associated via

intermolecular five C-H---O hydrogen bonding interactions that are described as given below:

For C(14)–H(14)---O(4): H(14)---O(4) = 2.480 Å and < C(14)–H(14)---O(4) = 134.75o

For C(20)-H(20)---O(3): H(42)---O(3) = 2.360 Å and < C(20)-H(20)---O(3) = 162.77o

For C(28)-H(28)---O(6): H(28)---O(6) = 2.689 Å and < C(28)-H(28)---O(6) = 147.28 o



The three C–H···π interactions that are described as given below:

1. C(35)-H(35B)---Cg(1); H(35B)---Cg(1) = 2.586 Å and

S70

Figure 3. A partial packing view of 4i showing hydrogen bondings

Figure 4. The molecular arrangement of compound 4i viewed through b-axis.

S71

Figure 5. Energy minimization based on MM2 calculations for 3a and 4a

==============

7klvs4 4a 3e 76.1, 77.9, 108.8, 112.9, 122.1, 122.5, 123.4, 123.5, 126.3, 129.1, 129.3, 130.2,...

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