Supporting Information for BF3·OEt2 Catalyzed chemoselective C=C ...

S1

Supporting Information

for

BF3·OEt2 Catalyzed chemoselective C=C bond cleavage of α,β-enones:

An unexpected synthesis of 3-alkylated oxindoles and spiro-indolooxiranes

Sengodagounder Muthusamy,* and Ammasi Prabu

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

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

CONTENTS

General information S2

General procedure for 3-alkylated oxindoles 3 S2

Characterization of product 3 S3-S14




Optimization, characterization of products 9a, 10 S17-S22

General procedure and characterization of products 11-13 S22-S24

NMR-titration experiments S24-S28

1H and 13C NMR spectra of product 3 S29-S80

1H and 13C NMR spectra of products 6,7 S81-S88

1H and 13C NMR spectra of product 9a, 10, 11, 12, 13 S89-S108

References S109

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2021

mailto:[email protected]

S2

General information

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

solid compounds were crystalized using ethyl acetate and hexane as solvents. 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 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 the electrospray ionization (ESI) technique on a Thermo Exactive

Orbitrap mass spectrometer. All solvents are commercial grade(LR) without distillation. 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. Acetophenone, aldehyde and BF3·Et2O were

purchased from M/s Aldrich and M/s Alfa Aesar and used as provided. The diazoamides1 and

chalcones2 were prepared according to the literature.

Experimental Section

General experimental procedure for the synthesis of alkylated oxindoles 3

To a solution of diazoamide 1 (1.0 equiv) and chalcone 2 (1.0 equiv) in CHCl3 (5 mL) was added

10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under the open-air atmosphere

and monitored by TLC until the disappearance of the diazoamide. After the appropriate period,

the reaction mixture was diluted with CHCl3 (10 mL) and water (15 mL). The organic phase was

separated and the aqueous layer was washed with CHCl3 (10 mL). The concentration of the

combined organic layers under reduced pressure afforded the crude product, which was purified

by column chromatography using silica gel to afford the corresponding product 3.

S3

Synthesis of 1-benzyl-3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3a)

To a solution of 1-benzyl-3-diazo-1,3-dihydro-2H-indol-2-one (1a) (100 mg, 0.40 mmol) and

(2E)-1-(4-methylphenyl)-3-phenylprop-2-en-1-one (2a) (90 mg, 0.40 mmol) in CHCl3 (5 mL)

was added 10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under an open-air

atmosphere to afford 3a (103 mg, 73%) as a colorless crystalline solid according to general

procedure. Rf = 0.39 (EtOAc/hexane = 1:4, v/v); mp 146-147 °C; IR (neat):

νmax 2922, 1708, 1684, 1607, 1462, 1354, 745 cm−1; 1H NMR (CDCl3, 400

MHz) δ = 2.40 (s, 3H, CH3), 3.44 (dd, J1 = 18 Hz, J2 = 9 Hz, 1H, CH), 3.86

(dd, J1 = 18.1 Hz, J2 = 2.9 Hz, 1H, CH), 4.16 (dd, J1 = 8.8 Hz, J2 = 2.3 Hz,1H,

CH), 4.97 (s, 2H, CH2), 6.73 (d, J = 7.6 Hz, 1H, ArH), 6.92-6.96 (m, 1H, ArH),

7.12-7.15 (m, 1H, ArH), 7.23-7.37 (m, 8H, ArH), 7.89 (d, J = 8 Hz, 2H, ArH)

ppm; 13C NMR (CDCl3, 100 MHz) δ = 21.7, 40.0, 41.3, 44.0, 109.1, 122.5, 124.5, 127.4, 127.6,

128.0, 128.3, 128.8, 129.2, 129.4, 134.0, 135.0, 143,5, 144.4, 177.9, 196.5 ppm; HRMS (ESI)

Calculated for C24H21NO2 (M+H)+: 356.1651 found: 356.1644.

Synthesis of 1-methyl-3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3b)

To a solution of 3-diazo-1-methyl-1,3-dihydro-2H-indol-2-one (1b) (100 mg, 0.58 mmol) and

(2E)-1-(4-methylphenyl)-3-phenylprop-2-en-1-one (2a) (128, 0.58 mmol) in CHCl3 (5 mL) was

added 10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under an open-air

atmosphere to afford 3b (110 mg, 68%) as a colorless crystalline solid according to general

procedure. Rf = 0.25 (EtOAc/hexane = 1:4, v/v); mp 198-199 °C; IR (neat): νmax 2923, 1704,

1606, 1467, 1345, 1263, 1090, 735 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 2.40

(s, 3H, CH3), 3.26 (s, 3H, CH3), 3.36 (dd, J1 = 18 Hz, J2 = 9.2 Hz, 1H, CH),

3.80 (dd, J1 = 18 Hz, J2 = 2.8 Hz, 1H, CH), 4.07 (d, J = 9.2 Hz, 1H, CH), 6.85

(d, J = 7.6 Hz, 1H, ArH), 6.98 (t, J = 7.6 Hz, 1H, ArH), 7.25-7.29 (m,4H, ArH),

7.87 (d, J = 8 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 21.7, 26.4,

40.0, 41.2, 108.0, 122.5, 124.5, 128.1, 128.3, 129.2, 129.4, 133.9, 144.3, 144.4,

177.9, 196.6 ppm; HRMS (ESI) Calculated for C18H17NO2 (M+H)+: 280.1338

found: 280.1333.

Synthesis of 1-benzyl-3-(2-oxo-2-phenylethyl)-1,3-dihydro-2H-indol-2-one (3c)3

3a

3b

S4

To a solution of 1-benzyl-3-diazo-1,3-dihydro-2H-indol-2-one (1a) (100 mg,

0.40 mmol) and (2E)-1,3-diphenylprop-2-en-1-one (2b) (83 mg, 40 mmol) in

CHCl3 (5 mL) was added 10 mol% of BF3·OEt2. The reaction mixture was

stirred at 0 °C under an open-air atmosphere to afford 3c (99 mg, 73%) as a

colorless crystalline solid according to general procedure. Rf = 0.34

(EtOAc/hexane = 1:4, v/v); mp 162-163 °C; IR (neat): νmax 3057, 2914, 1702,

1605, 1356, 1216, 744 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.47 (dd, J1 = 27.2 Hz, J2 = 9.0

Hz, 1H, CH), 3.89 (dd, J1 = 18.4 Hz, J2 = 3.2 Hz, 1H, CH), 4.17 (dd, J1 = 8.8 Hz, J2 = 2.8 Hz,

1H, CH), 4.97 (s, 2H, CH2), 6.74 (d, J = 7.6 Hz, 1H, ArH), 6.95 (t, J = 7.6 Hz, 1H, ArH), 7.14 (t,

J = 7.6 Hz, 1H, ArH), 7.25-7.38 (m, 6H, ArH) 7.45-7.49 (m, 2H, ArH), 7.56-7.59 (m, 1H, ArH),

7.98-8.01 (m, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 40.1, 41.3, 44.0, 109.1, 122.6,

124.4, 127.4, 127.7, 128.1, 128.2, 128.8, 128.9, 129.1, 133.5, 136.0, 136.4, 143.5, 177.9, 196.9

ppm; HRMS (ESI) Calculated for C23H19NO2 (M+H)+: 342.1494 found: 342.1485.

Synthesis of 1-benzyl-3-[2-(4-methoxyphenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3d)4


(2E)-1-(4-methoxyphenyl)-3-phenylprop-2-en-1-one (2c) (95 mg, 0.40 mmol) in CHCl3 (5 mL)


atmosphere to afford 3d (105 mg, 71%) as a colorless crystalline solid

according to general procedure. Rf = 0.18 (EtOAc/hexane = 1:4, v/v); mp 166-

167 °C; IR (neat): νmax 2924, 1705, 1674, 1595, 1359, 1165 698 cm−1; 1H NMR

(CDCl3, 400 MHz) δ = 3.42 (dd, J1 = 18.0 Hz, J2 = 9.0 Hz, 1H, CH), 3.82 (d, J

= 2.8 Hz, 1H, CH), 3.87 (s, 3H, CH3), 4.17 (d, J = 7.6 Hz, 1H, CH), 4.97 (s, 2H,

CH2), 6.73 (d, J = 7.6 Hz, 1H, ArH), 6.93-6.97 (m, 3H, ArH), 7.14 (t, J = 7.6

Hz, 1H, ArH), 7.24-7.37 (m, 6H, ArH), 7.98 (d, J = 8.8 Hz, 2H, ArH) ppm; 13C NMR (CDCl3,

100 MHz) δ = 39.7, 41.4, 44.0, 55.5, 109.0, 113.9, 122.5, 124.5, 127.4, 127.6, 128.0, 129.3,

129.5, 130.5, 136.0, 143.4, 163.8, 178.0, 195.3 ppm; HRMS (ESI) Calculated for C24H21NO3

(M+H)+: 372.1600 found: 372.1594

Synthesis of 3-[2-([1,1'-biphenyl]-4-yl)-2-oxoethyl]-1-benzyl-1,3-dihydro-2H-indol-2-one

(3f)5


(2E)-1-([1,1'-biphenyl]-4-yl)-3-phenylprop-2-en-1-one (2d) (114 mg, 0.40 mmol) in CHCl3 (5

3d

3c

S5

mL) was added 10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under an open-

air atmosphere to afford 3f (105 mg, 63%) as a colorless crystalline solid according to general


νmax 2921, 1707, 1605, 1481, 1353, 1273, 753 cm−1; 1H NMR (CDCl3, 400

MHz) δ = 3.43 (dd, J1 = 18.1 Hz, J2 = 9.0 Hz, 1H, CH), 3.85 (dd, J1 = 18.1 Hz,

J2 = 3.0 Hz, 1H, CH), 4.12 (dd, J1 = 8.8 Hz, J2 = 2.5 Hz, 1H, CH), 4.91 (s, 2H,

CH2), 6.67 (d, J = 7.6 Hz, 1H, ArH), 6.89 (t, J = 7.6 Hz, 1H, ArH), 7.08 (t, J =

7.6 Hz, 1H, ArH), 7.17-7.41 (m, 9H, ArH), 7.54-7.63 (m, 4H), 8.00 (d, J = 8.4

Hz, 2H, ArH) ) ppm; 13C NMR (CDCl3, 100 MHz) δ = 40.1, 41.3, 44.0, 109.1, 122.6, 124.5,

127.3, 127.7, 128.1, 128.4, 128.8, 129.0, 129.1, 135.1, 135.9, 139.8, 143.5, 146.2, 177.9, 196.5

ppm; HRMS (ESI) Calculated for C29H23NO2 (M+Na)+: 440.1626 found: 440.1621.

Synthesis of 1-benzyl-3-[2-oxo-2-(2,4,6-trimethylphenyl)ethyl]-1,3-dihydro-2H-indol-2-one

(3g)


(2E)-3-phenyl-1-(2,4,6-triisopropylphenyl)prop-2-en-1-one (2e) (134 mg, 0.40 mmol) in CHCl3

(5 mL) was added 10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under an

open-air atmosphere to afford 3g (106 mg, 57%) as a colorless amorphous solid according to

general procedure. Rf = 0.51 (EtOAc/hexane = 1.5:3.5, v/v); mp 116-117 °C;

IR (neat): νmax 2961, 1706, 1610, 1461, 1354, 1211, 1008, 741 cm−1; 1H NMR

(CDCl3, 400 MHz) δ = 1.06-1.16 (m, 18H, CH3), 2.56-2.65 (m, 2H, CH2),

2.76-2.83 (m, 1H, CH), 3.14 (dd, J1 = 19.0 Hz, J2 = 8.2 Hz, 1H, CH), 3.50 (dd,

J1 = 18.6 Hz, J2 = 3.0 Hz, 1H, CH), 3.97-3.99 (m, 1H, CH), 4.87 (ABq, ΔδAB =

0.08, J = 15.7 Hz, 2H, CH2), 6.66 (d, J = 7.6 Hz, 1H,ArH), 6.91-6.94 (m, 3H,

ArH), 7.06-7.28 (m, 7H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 24.0, 30.8, 34.4, 41.1,

44.0, 47.3, 109.2, 121.2, 122.3, 124.1. 127.4, 127.6, 128.1, 128.8, 136.0, 136.5, 143.7, 143.9,

149.9, 177.5, 207.5 ppm; HRMS (ESI) Calculated for C32H37NO2 (M+H)+: 468.2903 found:

468.2897.

Synthesis of 1-benzyl-3-[2-(4-fluorophenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3i)


(2E)-1-(4-fluorophenyl)-3-phenylprop-2-en-1-one (2f) (90 mg, 0.40 mmol) in CHCl3 (5 mL) was


3g

3f

S6

atmosphere to afford 3i (90 mg, 63%) as a colorless crystalline solid according to general


1601, 1354, 1221, 1160, 841, 739 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.45

(dd, J1 = 18.2 Hz, J2 = 8.8 Hz, 1H, CH), 3.86 (dd, J1 = 18.2 Hz, J2 = 3.1 Hz, 1H,

CH), 4.16 (dd, J1 = 8.8 Hz, J2 = 2.7 Hz, 1H, CH), 4.98 (s, 2H, CH2), 6.75 (d, J =

7.6 Hz, 1H, ArH), 6.96 (t, J = 7.6 Hz, 1H, ArH), 7.13-7.18 (m, 3H, ArH), 7.23-

7.37 (m, 6H, ArH), 8.01-8.05 (m, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ

= 40.0, 41.3, 44.0, 109.1, 115.9 (d, J = 22 Hz), 122.6, 124.4, 127.4, 127.8, 128.1,

128.8, 129.0, 130.9 (d, J = 10 Hz), 132.8 (d, J = 2 Hz), 135.9, 143.5, 166 (d, J =

254 Hz), 177.7, 195.3 ppm; HRMS (ESI) Calculated for C23H18FNO2 (M+H)+: 360.1400 found:

360.1390.

Synthesis of 3-[2-(4-chlorophenyl)-2-oxoethyl]-1-ethyl-1,3-dihydro-2H-indol-2-one (3j)

To a solution of 3-diazo-1-ethyl-1,3-dihydro-2H-indol-2-one (1c) (100 mg, 0.53 mmol) and

(2E)-1-(4-chlorophenyl)-3-phenylprop-2-en-1-one (2g) (130 mg, 0.53 mmol) in CHCl3 (5 mL)


atmosphere to afford 3j (109 mg, 65%) as a colorless amorphous solid according

to general procedure. Rf = 0.32 (EtOAc/hexane = 1:4, v/v); mp 151-152 °C; IR

(neat): νmax 2920, 1705, 1609, 1487, 1356, 1219, 748 cm−1; 1H NMR (CDCl3,

400 MHz) δ = 1.31 (t, J = 7.6 Hz, 3H, CH3), 3.36 (dd, J1 = 18.4 Hz, J2 = 9.2 Hz,

1H, CH), 3.76-3.85 (m, 3H, CH2/CH), 4.04 (dd, J1 = 9 Hz, J2 = 2.9 Hz, 1H, CH),

6.88 (d, J = 7.6 Hz, 1H, ArH), 6.96-7.00 (m, 1H, ArH), 7.23-7.29 (m, 2H, ArH),

7.43-7.45 (m, 2H, ArH), 7.91 (d, J = 8.8 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ =

12.7, 34.9, 40.0, 41.2, 108.2, 122.3, 124.5, 128.1, 129.0, 129.2, 129.6, 134.7, 139.9, 143.4, 177.1,

195.8 ppm; HRMS (ESI) Calculated for C18H1635ClNO2 (M+H)+: 314.0948 found: 314.0931.

Synthesis of 3-[2-(2-bromophenyl)-2-oxoethyl]-1-methyl-1,3-dihydro-2H-indol-2-one (3k)

To a solution of 3-diazo-1-methyl-1,3-dihydro-2H-indol-2-one (1b) (100 mg,

0.58 mmol) and (2E)-1-(2-bromophenyl)-3-phenylprop-2-en-1-one (2h) (115

mg, 0.58 mmol) in CHCl3 (5 mL) was added 10 mol% of BF3·OEt2. The reaction

mixture was stirred at 0 °C under an open-air atmosphere to afford 3k (120 mg,

60%) as a colorless crystalline solid according to general procedure. Rf = 0.40


3j

3k

3i

S7

1609, 1353, 1215, 1104, 735 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.30 (s, 3H, CH3), 3.50 (dd,

J1 = 18.4 Hz, J2 = 8.8 Hz, 1H, CH), 3.91 (dd, J1 = 18.4 Hz, J2 = 3.2 Hz, 1H, CH), 4.10 (dd, J1 =

18.4 Hz, J2 = 3.2 Hz, 1H, CH), 6.90-7.05 (m, 2H, ArH), 7.26-7.34 (m, 2H, ArH), 7.73 (t, J = 8

Hz, 1H, ArH), 8.32-8.47 (m, 2H, ArH), 8.81-8.82 (m, 1H, ArH) ppm; 13C NMR (CDCl3, 100

MHz) δ = 26.5, 40.2, 41.0, 108.3, 122.6, 123.1, 124.2, 127.7, 128.4, 128.6, 130.1, 133.7, 137.5,

144.4, 148.5, 177.3, 195.09 ppm; HRMS (ESI) Calculated for C17H1479BrNO2 (M+H)+: 344.0286

found: 344.0282.

Synthesis of 1-benzyl-3-[2-(4-bromophenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3l)4


(2E)-1-(4-bromophenyl)-3-phenylprop-2-en-1-one (2i) (115 mg, 0.40 mmol) in CHCl3 (5 mL)


atmosphere to afford 3l (106 mg, 63%) as a colorless crystalline solid according

to general procedure. Rf = 0.46 (EtOAc/hexane = 1:4, v/v); mp 132-133 °C; IR


400 MHz) δ = 3.44 (dd, J1 = 18 Hz, J2 = 8.8 Hz, 1H, CH), 3.85 (dd, J1 = 18 Hz,

J2 = 3 Hz, 1H, CH), 4.15 (dd, J1 = 8.4 Hz, J2 = 2,4 Hz, 1H, CH), 4.97 (s, 2H,

CH2), 6.75 (d, J = 7.6 Hz, 1H, ArH), 6.96 (t, J = 7.6 Hz, 1H, ArH), 7.14-7.37 (m,

7H, ArH), 7.62 (d, J = 8.4 Hz, 2H, ArH), 7.86 (d, J = 8.8 Hz, 2H, ArH) ppm; 13C

NMR (CDCl3, 100 MHz) δ = 40.0, 41.2, 44.0, 109.2, 122.6, 124.3, 127.4, 127.7, 128.1, 128.78,

128.84, 129.7, 132.1, 135.0, 135.9, 143.5, 177.7, 195.9 ppm; HRMS (ESI) Calculated for

C23H1879BrNO2 (M-H)+: 418.0448 found: 418.0451.

Synthesis of 1-methyl-3-[2-(4-nitrophenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3m)

To a solution of 3-diazo-1-methyl-1,3-dihydro-2H-indol-2-one (1b) (100 mg, 0.58 mmol) and

(2E)-1-(4-nitrophenyl)-3-phenylprop-2-en-1-one (2j) (101 mg, 0.58 mmol) in CHCl3 (5 mL) was

added 10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under an

open-air atmosphere to afford 3m (91 mg, 51%) as a colorless crystalline solid

according to general procedure. Rf = 0.18 (EtOAc/hexane = 1.5:3.5, v/v); mp

131-132 °C; IR (neat): νmax 2928, 1696, 1610, 1468, 1347, 1215, 1091, 749 cm−1;

1H NMR (CDCl3, 400 MHz) δ = 3.13 (s, 3H, CH3), 3.24 (dd, J1 = 18.4 Hz, J2 =

8.8 Hz, 1H, CH), 3.62 (dd, J1 = 18.4 Hz, J2 = 3.6 Hz, 1H, CH), 3.97 (dd, J1 = 8.7

Hz, J2 = 3.4 Hz, 1H, CH), 6.91-6.95 (m, 1H, ArH), 7.17-7.35 (m, 5H, ArH), 7.48-7.50 (m, 1H,

3m

3l

S8

ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 26.5, 41.4, 43.7, 108.2, 118.4, 122.6, 124.5, 127.6,

128.3, 128.6, 128.9, 132.0, 133.9, 140.6, 144.3, 177.2, 200.9 ppm; HRMS (ESI) Calculated for

C17H14N2O4 (M+H)+: 311.1032 found: 311.1043.

Synthesis of 3-[2-(3-bromo-4-nitrophenyl)-2-oxoethyl]-1-ethyl-1,3-dihydro-2H-indol-2-one

(3n)


(2E)-1-(3-bromo-4-nitrophenyl)-3-phenylprop-2-en-1-one (2k) (176 mg, 0.53 mmol) in CHCl3

(5 mL) was added 10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under an

open-air atmosphere to afford 3n (71 mg, 33%) as a colorless crystalline solid


201-202 °C; IR (neat): νmax 2929, 1695, 1604, 1535, 1353, 1217, 1029,738

cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.32 (t, J = 7.2 Hz, 3H, CH3), 3.41 (dd,

J1 = 18.4 Hz, J2 = 8.4 Hz, 1H, CH), 3.78-3.85 (m, 3H, CH2/CH), 4.03 (dd, J1 =

8.4 Hz, J2 = 3.2 Hz, 1H, CH), 6.90 (d, J = 7.6 Hz, 1H, ArH), 7.00 (t, J = 7.6 Hz,

1H, ArH), 7.21-7.31 (m, 2H, ArH), 7.88 (d, J = 7.9 Hz, 1H, ArH), 7.98-8.01

(m, 1H, ArH), 8.4 (d, J = 1.6 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 12.6, 35.0,

40.1, 41.0, 108.4, 120.2, 122.5, 124.3, 125.1, 128.4, 128.6, 131.9, 135.8, 136.2, 143.5, 150.1,

176.7, 194.1 ppm; HRMS (ESI) Calculated for C18H1579BrN2O4 (M+H)+: 403.0293 found:

403.0285.

Synthesis of 1-benzyl-5-methyl-3-(2-oxo-2-phenylethyl)-1,3-dihydro-2H-indol-2-one (3p)3

To a solution of 1-benzyl-3-diazo-5-methyl-1,3-dihydro-2H-indol-2-one (1d) (100 mg, 0.38

mmol) and (2E)-1,3-diphenylprop-2-en-1-one (2b) (176 mg, 0.38 mmol) in CHCl3 (5 mL) was

added 10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under

an open-air atmosphere to afford 3p (100 mg, 74%) as a colorless crystalline

solid according to general procedure. Rf = 0.39 (EtOAc/hexane = 1:4, v/v);

mp 161-162 °C; IR (neat): νmax 2913, 1698, 1599, 1493, 1445, 1353,

1185,728 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 2.29 (s, 3H, CH3), 3.53 (dd,

J1 = 18.2 Hz, J2 = 9 Hz, 1H, CH), 3.95 (dd, J1 = 18.2 Hz, J2 = 3.0 Hz, 1H,

CH), 4.20-4.22 (m, 1H, CH), 5.02 (s, 2H, CH2), 6.68 (d, J = 8 Hz, 1H, ArH),

7.00 (d, J = 8 Hz, 1H, ArH), 7.13 (s, 1H, ArH), 7.30-7.65 (m, 8H, ArH), 8.07 (d J = 8 Hz, 2H,


3n

3p

S9

127.6, 128.3, 128.76, 128.82, 129.2, 132.2, 133.5, 136.0, 136.4, 141.0, 177.8, 197.0 ppm; HRMS

(ESI) Calculated for C24H21NO2 (M+H)+: 356.1651 found: 356.1646.

Synthesis of 1-benzyl-5-methoxy-3-(2-oxo-2-phenylethyl)-1,3-dihydro-2H-indol-2-one (3q)

To a solution of 1-benzyl-3-diazo-5-methoxy-1,3-dihydro-2H-indol-2-one (1e) (100 mg, 0.36



atmosphere to afford 3q (96 mg, 72%) as a colorless crystalline solid according to general


νmax 2923, 1701, 1599, 1445, 1363, 1187, 1147, 725 cm−1; 1H NMR (CDCl3,

400 MHz) δ = 3.52 (dd, J1 = 18.2 Hz, J2 = 9.0 Hz,1H, CH), 3.74 (s, 3H,

CH3), 3.94 (dd, J1 = 18.2 Hz, J2 = 2.8 Hz, 1H, CH), 4.19-4.21 (m, 1H, CH),

5.00, (s, 2H, CH2), 6.66-6.73 (m, 2H, ArH), 6.95 (s, 1H, ArH), 7.30-7.40 (m,

5H, ArH), 7.52 (t, J = 7.6 Hz, 2H, ArH), 7.61-765 (m, 1H, ArH), 8.05 (d, J =

7.2 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 40.2, 41.7, 44.1, 55.8, 109.4, 112.0,

112.3, 127.3, 127.6, 128.2, 128.75, 128.82, 130.5, 133.5, 136.0, 136.3, 136.9, 155.9, 177.5, 196.9

ppm; HRMS (ESI) Calculated for C24H21NO3 (M+H)+: 372.1600 found: 372.1623.

Synthesis of 3-[2-([1,1'-biphenyl]-4-yl)-2-oxoethyl]-5-chloro-1-benzyl-1,3-dihydro-2H

-indol-2-one (3r)

To a solution of 1-benzyl-5-chloro-3-diazo-1,3-dihydro-2H-indol-2-one (1f) (100 mg, 0.35

mmol) and (2E)-1-([1,1'-biphenyl]-4-yl)-3-phenylprop-2-en-1-one (2d) (100 mg, 0.35 mmol) in

CHCl3 (10 mL) was added 10 mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under

an open-air atmosphere to afford 3r (108 mg, 68%) as a colorless crystalline

solid according to general procedure. Rf = 0.26 (EtOAc/hexane = 1.5:.3.5,

v/v); mp 178-179 °C; IR (neat): νmax 2919, 1707, 1681, 1601, 1483, 1352,

1263, 805 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.49-3.57 (m, 1H, CH),

3.94 (dd, J1 = 18.4 Hz, J2 = 2.8 Hz, 1H, CH), 4.15 (d, J = 5.6 Hz, 1H, CH),

4.97 (s, 2H, CH2), 6.33-6.65 (m, 1H, ArH), 7.12 (d, J = 6.8 Hz, 1H, ArH),

7.25-7.49 (m, 9H, ArH), 7.62-7.71 (m, 4H, ArH), 8.05-8.08 (m, 2H, ArH), ppm; 13C NMR

(CDCl3, 100 MHz) δ = 39.9, 41.2, 44.1, 110.0, 124.9, 127.30, 127.33, 127.4, 127.8, 127.95,

128.01, 128.4, 128.8, 128.9, 129.0, 130.8, 134.8, 135.5, 139.8, 142.1, 146.4, 177.3, 196.1 ppm;

HRMS (ESI) Calculated for C29H2235ClNO2 (M+Na)+: 474.1237 found: 474.1244.

3r

3q

S10

Synthesis of 1-benzyl-5-bromo-3-(2-oxo-2-phenylethyl)-1,3-dihydro-2H-indol-2-one (3s)

To a solution of 1-benzyl-5-bromo-3-diazo-1,3-dihydro-2H-indol-2-one (1g) (100 mg, 0.30



atmosphere to afford 3s (81 mg, 63%) as a colorless crystalline solid

according to general procedure. Rf = 0.46 (EtOAc/hexane = 1:4, v/v); mp 162-

163 °C; IR (neat): νmax 2917, 1707, 1602, 1483, 1350, 1289, 1217, 690 cm−1;

1H NMR (CDCl3, 400 MHz) δ = 3.55 (dd, J1 = 18.4 Hz, J2 = 8.8 Hz, 1H, CH),

3.95 (dd, J1 = 18.4 Hz, J2 = 2.4 Hz, 1H, CH), 4.18 (d, J = 8 Hz, 1H, CH), 5.00

(s, 2H, CH2), 6.64 (d, J = 8.4 Hz, 1H, ArH), 7.30-7.66 (m, 10H, ArH), 8.04 (d,

J = 7.6 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 39.9, 41.2, 44.1, 110.5, 115.3,

127.3, 127.6, 127.8, 128.3, 128.8, 128.9, 130.9, 131.1, 133.7, 135.4, 136.1, 142.5, 177.2, 196.5

ppm; HRMS (ESI) Calculated for C23H1879BrNO2 (M+Na)+: 442.0420 found: 442.0419

Synthesis of 5-bromo-1-methyl-3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-

one (3t)

To a solution of 5-bromo-3-diazo-1-methyl-1,3-dihydro-2H-indol-2-one (1h) (100mg, 0.40

mmol) and (2E)-1-(4-methylphenyl)-3-phenylprop-2-en-1-one (2a) (89 mg, 0.40 mmol) in


an open-air atmosphere to afford 3t (93mg, 65%) as a colorless crystalline

solid according to general procedure. Rf = 0.35 (EtOAc/hexane = 1:4, v/v);

mp 153-154 °C; IR (neat): νmax 2917, 1711, 1606, 1483, 1345, 1098, 806

cm−1; 1H NMR (CDCl3, 400 MHz) δ = 2.42 (s, 3H, CH3), 3.25 (s, 3H, CH3),

3.39 (dd, J1 = 18.4 Hz, J2 = 8.8 Hz, 1H, CH), 3.82 (dd, J1 = 18.3 Hz, J2 = 2.9

Hz, 1H, CH), 4.03-4.05 (m, 1H, CH), 6.73 (d, J = 8.4 Hz, 1H, ArH), 7.27-

7.41 (m, 4H, ArH), 7.87 (d, J = 8.4 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 21.7,

26.5, 39.8, 41.2, 109.4, 115.2, 127.7, 128.3, 129.4, 130.9, 131.2, 133.7, 143.4, 144.6, 177.2,

196.2 ppm; HRMS (ESI) Calculated for C18H1679BrNO2 (M+H)+: 358.0443 found: 358.0437.

Synthesis of 1-benzyl-5-bromo-3-[2-(4-bromophenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-

one (3u)

3t

3s

S11


mmol) and (2E)-1-(4-bromophenyl)-3-phenylprop-2-en-1-one (2i) (137 mg, 0.30 mmol) in


an open-air atmosphere to afford 3u (76mg, 51%) as a colorless crystalline solid according to

general procedure. Rf = 0.54 (EtOAc/hexane = 1:4, v/v); mp 148-149 °C; IR


400 MHz) δ = 3.39 (dd, J1 = 18.4 Hz, J2 = 8.4 Hz, 1H, CH), 3.77 (dd, J1 =

18.4 Hz, J2 = 3.2 Hz, 1H, CH), 4.00-4.02 (m, 1H, CH), 4.87 (ABq, ΔδAB =

0.02, J = 15.8 Hz, 2H, CH2), 6.51 (d, J = 8.4 Hz, 1H, ArH), 7.16-7.28 (m, 7H,

ArH), 7.54 (d, J = 8.4 Hz, 2H, ArH), 7.77 (d, J = 8.4 Hz, 2H, ArH) ppm; 13C

NMR (CDCl3, 100 MHz) δ = 39.8, 41.2, 44.1, 110.6, 115.4, 127.3, 127.5,

127.8, 128.9, 129.0, 129.7, 130.9, 131.0, 132.1, 134.8, 135.4, 142.5, 177.0, 195.5 ppm; HRMS

(ESI) Calculated for C23H1779Br81BrNO2 (M+H)+: 499.9684 found: 499.9683

Synthesis of 5-bromo-3-[2-(3,4-dimethoxyphenyl)-2-oxoethyl]-1-benzyl-1,3-dihydro-2H

-indol-2-one (3v)


mmol) and (2E)-1-(3,4-dimethoxyphenyl)-3-phenylprop-2-en-1-one (2l) (137 mg, 0.30 mmol) in


an open-air atmosphere to afford 3v (86mg, 60%) as a colorless amorphous

solid according to general procedure. Rf = 0.11 (EtOAc/hexane = 1.5:3.5,

v/v); mp 123-124 °C; IR (neat): νmax 2943, 1710, 1670, 1487, 1343, 1273,

730 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.64 (dd, J1 = 19 Hz, J2 = 8.1

Hz, 1H, CH), 3.83 (s, 3H, CH3), 3.92-3.98 (m, 4H, CH3/CH), 4.11 (dd, J1

= 7.6 Hz, J2 = 2.8 Hz, 1H, CH), 5.00 (ABq, ΔδAB = 0.08, J = 15.7 Hz, 2H,

CH2), 6.62 (d, J = 8 Hz, 1H, ArH), 6.96 (d, J = 8.8 Hz, 1H, ArH), 7.09-

7.12 (m, 1H, ArH), 7.28-7.42 (m, 8H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 41.8, 44.0,

44.8, 55.86, 55.92, 110.4, 113.2, 113.8, 115.2, 121.4, 126.7, 127.3, 127.7, 128.9, 130.6, 131.5,

135.6. 142.6, 153.5, 153.8, 177.5, 197.5 ppm; HRMS (ESI) Calculated for C25H2279BrNO4

(M+H)+: 480.0810 found: 480.0805.

Synthesis of 1-benzyl-5-iodo-3-(2-oxo-2-phenylethyl)-1,3-dihydro-2H-indol-2-one (3w)

3v

3u

S12

To a solution of 1-benzyl-3-diazo-5-iodo-1,3-dihydro-2H-indol-2-one (1i) (100 mg, 0.27 mmol)

and (2E)-1,3-diphenylprop-2-en-1-one (2b) (56 mg, 0.27 mmol) in CHCl3 (5 mL) was added 10

mol% of BF3·OEt2. The reaction mixture was stirred at 0 °C under an open-air atmosphere to

afford 3w (74 mg, 59%) as a colorless crystalline solid according to general


νmax 2918, 1705, 1598, 1483, 1351, 1215, 1175, 690 cm−1; 1H NMR (CDCl3,

400 MHz) δ = 3.56 (dd, J1 = 18.4 Hz, J2 = 8.4 Hz, 1H, CH), 3.94 (dd, J1 =

18.4 Hz, J2 = 2.8 Hz, 1H, CH), 4.15-4.17 (m, 1H, CH), 5.00 (s, 2H, CH2), 6.55

(d, J = 8 Hz, 1H, ArH), 7.30-7.67 (m, 10H, ArH), 8.04 (d, J = 7.6 Hz, 2H,


128.8, 128.9, 131.5, 133.1, 133.7, 135.5, 136.1, 136.9, 143.3, 177.0, 196.4 ppm; HRMS (ESI)

Calculated for C23H18INO2 (M+H)+: 468.0460 found: 468.0464.

Synthesis of 1-benzyl-3-[2-(naphthalen-1-yl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3x)


(2E)-1-(naphthalen-1-yl)-3-phenylprop-2-en-1-one (2m) (163 mg, 0.40 mmol) in CHCl3 (5 mL)


atmosphere to afford 3x (110 mg, 70%) as a colorless crystalline solid


161-162 °C; IR (neat): νmax 2919, 1703, 1608, 1355, 1217, 1170, 746 cm−1; 1H

NMR (CDCl3, 400 MHz) δ = 3.53 (dd, J1 = 18 Hz, J2 = 8.8 Hz, 1H, CH),

3.92-3.98 (m, 1H, CH), 4.24 (dd, J1 = 8.8 Hz, J2 = 2.8 Hz, 1H, CH), 5.03 (s,

2H, CH2), 6.79 (d, J = 7.6 Hz, 1H, ArH), 7.00 (t, J = 7.6 Hz, 1H, ArH), 7.20 (t,

J = 7.6 Hz, 1H, ArH), 7.29-7.65 (m, 11H, ArH), 8.04-8.06 (m, 2H, ArH), ppm; 13C NMR

(CDCl3, 100 MHz) δ = 40.1, 41.3, 44.0, 109.1, 122.6, 124.4, 127.4, 127.6, 128.0, 128.2, 128.75.

128.84, 129.1,133.5, 135.9, 136.4, 143.5, 177.9, 196.9 ppm; HRMS (ESI) Calculated for

C27H21NO2 (M+H)+: 392.1651 found: 392.1653.

Synthesis of 1-ethyl-3-[2-(naphthalen-2-yl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3y)


(2E)-1-(naphthalen-2-yl)-3-phenylprop-2-en-1-one (2n) (137 mg, 0.53 mmol) in CHCl3 (5 mL)


atmosphere to afford 3y (113mg, 65%) as a colorless amorphous solid according to general

3x

3w

S13


1609, 1462, 1358, 1227, 1133, 739 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.27

(t, J = 7.2 Hz, 3H, CH), 3.48 (dd, J1 = 17.9 Hz, J2 = 8.7 Hz, 1H, CH), 3.75-3.88

(m, 3H, CH/CH2), 4.13 (dd, J1 = 8.4 Hz, J2 = 3.2 Hz, 1H, CH), 6.84 (d, J = 7.6

Hz, 1H, ArH), 7.00 (t, J = 7.6 Hz, 1H, ArH), 7.24-7.59 (m, 5H, ArH), 7.83-

7.96 (m, 3H, ArH), 8.61 (d, J = 8.4 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100

MHz) δ = 12.7, 34.9, 41.8, 43.1, 108.3, 122.4, 124.4, 124.5, 125.8, 126.6,

128.07, 128.12, 128.2, 128.5, 129.3, 130.1, 133.1, 134.0, 135.1, 143.5, 177.2,

201.0 ppm; HRMS (ESI) Calculated for C22H19NO2 (M+H)+: 330.1494 found: 330.1486.

Synthesis of 3-[2-(anthracen-9-yl)-2-oxoethyl]-1-ethyl-1,3-dihydro-2H-indol-2-one (3z)


(2E)-1-(anthracen-9-yl)-3-phenylprop-2-en-1-one (2o) (163 mg, 0.53 mmol) in CHCl3 (5 mL)


atmosphere to afford 3z (106 mg, 53%) as a colorless amorphous solid


121-122 °C; IR (neat): νmax 2979, 1702, 1609, 1462, 1366, 1273, 737 cm−1; 1H

NMR (CDCl3, 400 MHz) δ = 1.34, (t, J = 7.2 Hz, 3H, CH3), 3.66 (dd, J1 = 19.6

Hz, J2 = 7.4 Hz, 1H, CH), 3.77-3.96 (m, 3H, CH/CH2) 4.07 (dd, J1 = 7.2 Hz, J2

= 3.2 Hz, 1H, CH), 6.95 (d, J = 7.6 Hz, 1H, ArH ), 7.16 (t, J = 7.6 Hz, 1H,

ArH), 7.36 (t, J = 7.6 Hz, 1H, ArH ) 7.44-7.53 (m, 5H, ArH), 7.78-7.80 (m, 2H, ArH), 7.98-8.01

(m, 2H, ArH), 8.46 (s, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 12.5, 35.0, 41.3, 46.7,

108.5, 122.30, 122.33, 124.1, 124.2, 125.6, 126.98, 127.03, 128.3, 128.8, 129.0, 131.0, 134.9,

144.0, 177.0, 207.0 ppm; HRMS (ESI) Calculated for C26H21NO2 (M+H)+: 380.1651 found:

380.1629.

Synthesis of methyl 2-(4-methylbenzoyl)-1,3-diphenylcyclopropane-1-carboxylate (3aa)6

To a solution of methyl 2-diazo-2-phenylacetate (1k) (100 mg, 0.57 mmol) and

(2E)-1-(4-methylphenyl)-3-phenylprop-2-en-1-one (2a) (126 mg, 0.57 mmol)

in CHCl3 (5 mL) was added 10 mol% of BF3·OEt2. The reaction mixture was

stirred at 0 °C under an open-air atmosphere to afford 6a (44 mg, 21%) as a

colorless amorphous solid according to general procedure. Rf = 0.8

(EtOAc/hexane = 0.5:4.5, v/v); mp 157-158 °C; IR (neat): νmax 2951, 1715,

3z

3aa

3y

S14

1670, 1445, 1263, 1180, 716 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 2.49 (s, 3H, CH3), 3.46 (s,

3H, CH3), 4.03 (d, J = 7.2 Hz, 1H, CH), 4.45 (d, J = 7.2 Hz, 1H, CH), 7.29-7.43 (m, 12H, ArH),

8.06 (d, J = 8 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 21.8, 35.2, 35.4, 48.7, 52.7,

127.3, 127.9, 128.3, 128.4, 128.6, 128.8, 129.5, 130.1, 134.8, 135.3, 135.5, 144.2, 170.0, 193.5

ppm; HRMS (ESI) Calculated for C25H23O3 (M+H)+: 371.1647 found: 371.1607.

Synthesis of 3,3'-(((butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis(2-oxoethane-2,1-

diyl))bis(1-benzylindolin-2-one) (6a)


(2E,2'E)-1,1'-((butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis(3-phenylprop-2-en-1-one) (5a)

(101 mg, 0.20 mmol) in CHCl3 (5 mL) was added 10 mol% of BF3·OEt2. The reaction mixture

was stirred at 0 °C under an open-air atmosphere to afford 6a (182

mg, 59%) as a colorless crystalline solid according to general

procedure. Rf = 0.28 (EtOAc/hexane = 1.5:3.5, v/v); mp 187-188 °C;

IR (neat): νmax 2927, 1707, 1672, 1599, 1454, 1356, 1291, 1236, 753

cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.73 (s, 1H, CH), 2.31-2.34

(m, 1H, CH ), 3.44 (dd, J1 = 18.4 Hz, J2 = 9.2 Hz, 1H, CH), 3.90 (dd,

J1 = 18.4 Hz, J2 = 3.2 Hz, 1H, CH), 4.12-4.28 (m, 3H, CH2), 4.86-

4.92 (m, 2H, CH2), 6.69 (d, J = 7.6 Hz, 1H, ArH), 6.88-6.99 (m, 3H,

ArH), 7.08-7.13 (m, 1H, ArH), 7.22-7.42 (m, 7H, ArH), 7.75 (d, J =

7.6 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 29.2, 41.7,

43.9, 45.3, 65.1, 109.0, 112.6, 121.0, 122.5, 124.4, 127.3, 127.5, 127.6, 127.9, 128.8, 129.3,

130.5, 134.1, 136.0, 143.4, 157.9, 177.9, 198.7 ppm (due to the C2 Symmetry we observed half-

half the signal); HRMS (ESI) Calculated for C50H44N2O6 (M+K)+: 807.2863 found: 807.2852.

Synthesis of (((hexane-1,6-diylbis(oxy))bis(2,1-phenylene))bis(2-oxoethane-2,1-diyl))bis(1-

benzylindolin-2-one) (6b)


(2E,2'E)-1,1'-((hexane-1,6-diylbis(oxy))bis(2,1-phenylene))bis(3-phenylprop-2-en-1-one) (5b)

(106 mg, 0.2 mmol) in CHCl3 (5 mL) was added 10 mol% of BF3·OEt2. The reaction mixture

was stirred at 0 °C under an open-air atmosphere to afford 6b (179 mg, 56%) as a colorless

crystalline solid according to general procedure. Rf = 0.30 (EtOAc/hexane = 1.5:3.5, v/v); mp

6a

S15

210-211 °C; IR (neat): νmax 2931, 1709, 1671, 1602, 1457, 1356, 753

cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.50 (s, 2H, CH2), 1.83 (s, 2H,

CH2), 3.54-3.60 (m, 1H, CH2), 3.90-3.60 (m, 4H, CH2), 4.88-5.02 (m, 2H,

CH2), 6.69-6.71 (m, 1H, ArH), 6.92-6.99 (m, 3H, ArH), 7.09-7.13 (m, 1H,

ArH), 7.21-7.30 (m, 6H, ArH), 7.41-7.45 (m, 1H, ArH), 7.77 (d, J = 7.6

Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 26.1, 29.1, 42.0,

44.0, 45.3, 68.5, 109.1, 112.4, 120.6, 122.6, 124.3, 127.2, 127.6, 127.8,

128.8, 129.6, 130.4, 130.7, 134.1, 135.8, 143.3, 158.6, 178.4, 198.5 ppm

(due to the C2 Symmetry we observed half-half the signal); HRMS (ESI)

Calculated for C52H48N2O6 (M+H)+: 797.3591 found: 797.3588.

Synthesis of 2-benzoyl-3-(4-chlorophenyl)-1'-ethylspiro[cyclopropane-1,3'-indol]-2'(1'H)-

one (7a)

To a solution of InCl3 (20 mol%) in 6:2 mL water and THF were added 1-benzyl-3-diazo-1,3-

dihydro-2H-indol-2-one (1a) (100 mg, 0.40 mmol) and (2E)-1-(4-chlorophenyl)-3-phenylprop-2-

en-1-one (2g) (97 mg, 0.40 mmol) under an air atmosphere. The reaction mixture was stirred at

ambient temperature for 24 h and extracted with ethyl acetate. The organic phase was dried over

Na2SO4 and concentrated in vacuo. The residue was purified by chromatographic purification

(Hexane/EtOAc) to afford the desired cyclopropane product 7a (154

mg, 83%) as a colorless crystalline solid. Rf = 0.31 (EtOAc/hexane =

1:4, v/v); mp 225-226 °C; IR (neat): νmax 3057, 1708, 1673, 1606,

1357, 1179, 1091, 739 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 4.13 (d,

J = 8 Hz, 1H, CH), 4.31 (d, J = 8.4 Hz, 1H, CH), 4.93 (ABq, ΔδAB =

0.06, J = 15.6 Hz, 2H, CH2), 6.76 (d, J = 7.6 Hz, 1H, ArH), 6.94 (t, J =

7.6 Hz, 1H, ArH), 7.11 (t, J = 7.6 Hz, 1H, ArH), 7.21-7.41 (m, 12H,

ArH), 7.51-7.55 (m, 1H, ArH), 7.93 (d, J = 7.6 Hz, 1H, ArH) ppm; 13C NMR (CDCl3, 100 MHz)

δ = 38.6, 41.4, 44.1, 109.2, 122.0, 122.6, 125.7, 127.3, 127.7, 128.4, 128.5, 128.8, 128.9, 130.7,

131.9, 133.5, 133.9, 136.0, 136.9, 142.9, 172.0, 192.7 ppm; HRMS (ESI) Calculated for

C30H2235ClNO2 (M+H)+: 464.1417 found: 464.1412.

Synthesis of 2-benzoyl-3-(4-chlorophenyl)-1'-methylspiro[cyclopropane-1,3'-indol]-2'(1'H)-

one (7b)

7a

6b

S16


dimethyl phosphite (40 μL, 0.44 mmol) in 2.0 mL THF was added to a flame-dried round bottom

flask equipped with a magnetic stirring bar under argon. The solution was cooled to -30 °C and

0.5 M KHMDS in toluene (110 μL, 0.48 mmol, 1.2 equiv) was added dropwise, after additional

10 min, a solution of (2E)-1-(4-chlorophenyl)-3-phenylprop-2-en-1-one (2g) (97 mg, 0.40 mmol)

in 1.0 mL THF was added dropwise. The reaction was allowed to proceed at the same

temperature and was monitored by TLC. Once the α,β-unsaturated ketone

was fully consumed the reaction mixture was quenched with saturated

aqueous ammonium chloride. After being warmed to ambient

temperature, the mixture was extracted with ethyl acetate. The organic

phase was dried over Na2SO4 and concentrated in vacuo. The residue was

purified by chromatographic purification (Hexane/EtOAc) to afford the

desired cyclopropane product 7b (132 mg, 71%) as a colorless crystalline

solid. Rf = 0.31 (EtOAc/hexane = 1:4, v/v); mp 196-197 °C; IR (neat): νmax 2922, 1706, 1605,

1459, 1353, 1175, 741 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.67 (d, J = 8.4 Hz, 1H, CH), 4.22

(d, J = 8.0 Hz, 1H, CH), 4.59 (d, J = 15.6 Hz, 1H, CH), 5.19 (d, J = 15.6 Hz, 1H, CH), 6.18 (d, J

= 7.6 Hz, 1H, ArH), 6.79-6.85 (m, 2H, ArH), 7.02 (d, J = 6.8 Hz, 1H, ArH), 7.02-7.39 (m, 11H,

ArH), 7.78 (d, J = 8.4 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 37.5, 39.3, 41.7,

44.0, 109.3, 121.3, 122.1, 125.2, 127.3, 127.7, 127.8, 128.0, 128.7, 129.2, 129.8, 129.9, 133.5,

134.8, 135.8, 139.9, 143.2, 172.5, 190.7 ppm; HRMS (ESI) Calculated for C30H2235ClNO2

(M+H)+: 464.1417 found: 464.1410.

Synthesis of 3-methoxy-1-methyl-1,3-dihydro-2H-indol-2-one (8)7

To a solution of 3-diazo-1-methyl-1,3-dihydro-2H-indol-2-one (1b) (100 mg, 0.58 mmol), (2E)-

1-(4-methylphenyl)-3-phenylprop-2-en-1-one (2a) (90 mg, 0.58 mmol) and methanol (23 μL,

0.58 mmol) in CHCl3 (5 mL) was added 10 mol% of BF3·OEt2. The reaction

mixture was stirred at 0 °C temperature to afford product 8 (88 mg, 86%) as a

light yellow amorphous solid. Rf = 0.46 (EtOAc/hexane = 1.5:3.5, v/v); mp

131-132 °C; IR (neat): νmax 2927, 1705, 1612, 1467, 1350, 1019, 752 cm−1; 1H

NMR (CDCl3, 400 MHz) δ = 3.19 (s, 3H, CH3), 3.52 (s, 3H, CH3), 4.86 (s, 1H, CH), 6.82 (d, J =

7.8 Hz, 1H, ArH), 7.10 (t, J = 7.6 Hz, 1H, ArH), 7.32-7.36 (m, 1H, ArH), 7.38-7.42 (m, 1H,

8

7b

S17

ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 26.0, 56.1, 76.7, 108.4, 122.9, 125.3, 130.0 144.3,

174.3 ppm.

Table 2. Optimization of reaction conditions of spiro-indolooxiranes 10a

Entry Catalyst Base Solvent Temp. (°C) Yieldb %

1 NiBr2 TEA PhMe rt 35

2 FeCl3 TEA PhMe rt 22

3 CuCl2 TEA PhMe rt 30

4 CuBr TEA PhMe rt 46

5 CuI TEA PhMe rt 61

6 CuI DBU PhMe rt 20

7 CuI DMAP PhMe rt 68

8 CuI DABCO PhMe rt nrc

9 CuI DMAP THF rt 39

10 CuI DMAP DMF rt 15

11 CuI DMAP Acetone rt 91

12 CuI DMAP DCM rt nrc

13 CuI DMAP Acetone 50 44

14d CuI DMAP Acetone rt nrc aReaction conditions: 10 mol% catalyst, 3a (0.13 mmol, 1.0 equiv.), base (0.13 mmol, 1.0 equiv.), solvent (4.0 mL), at room temperature, for 15 h under an open air

atmosphere. bIsolated yield. cThe reaction was conducted at 50 °C. dThe reaction

carried out under argon atmosphere.

Further to develop the synthesis of spiro-indolooxiranes, the required 3-alkylated oxindole 3a

was synthesized from diazoamide. The reaction of 3-alkylated oxindole 3a was initially studied

with triethylamine (TEA) in the presence of various catalysts, solvents and the results were

summarized in Table 2. Our initial investigation began with the epoxide formation of 3-alkylated

oxindole 3a dissolved in 4 mL of toluene at room temperature for 13 hours in the presence of 10

mol% of NiBr2 and 1.0 equiv. of trimethylamine the desired spiro-indolooxirane 10a was

isolated in 35% yield (Table 2, entry 1). Moreover, FeCl3 didn’t improve the yield of product 10a

(Table 2, entry 2). In order to optimize the reaction conditions, various copper catalysts, such as

S18

CuCl2, CuBr, or CuI, were examined; however, CuI enhanced the yield of product 10a (Table 2,

entry 5). Then optimize various bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 4-

Dimethylaminopyridine (DMAP), and 1,4-diazabicyclo[2.2.2]octane (DABCO). Among the

bases screening indicated that DMAP was optimal to give spiro-indolooxirane 10a in 68% yield

(Table 2, entry 7). Successively, the screening of solvents (Table 2, entries 9–12) revealed that

acetone was the optimum choice in terms of isolated yield of product 10a. The above reaction

was carried out at 50 °C afforded product 10a in 44% yield (Table 2, entry 13).

Scheme 8. Control experiments for 10a

The reaction was carried out under argon atmosphere however, the desired product 10a was not

formed (Table 2, entry 13). Thus, the optimized reaction conditions for the formation of product

10a were found to be 10 mol% of CuI and DMAP in acetone at room temperature, as indicated

in Table 2, entry 11.

To understand the reaction mechanism of this epoxidation transformation, few control

experiments were performed. When the reaction was carried out with 3-alkylated oxindole 3a at

room temperature in the presence of DMAP, the formation of oxindole-derived α,β-unsaturated

enamide 9a was successfully isolated in 86% yield. The oxindole-derived α,β-unsaturated

enamide 9a was converted into spiro-indolooxirane 10a (Scheme 8, eq 1). Similarly, the reaction

was carried out with CuI didn’t give the desired product 10a, but the subsequent addition of 1

S19

equiv of DMAP delivered the desired product 10a (Scheme 8, eq 2). In order to study

mechanistic pathway for the reaction, we examined the reaction between 3-alkylated oxindole 3a

(1 equiv) and CuI (0.1 equiv) in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)

did not afford the desired product 10a. This suggests a radical pathway for this transformation.

A plausible mechanism for the formation of spiro-indolooxiranes 10 from 3-alkylated oxindoles

3 is depicted in Scheme 9. Under mild basic conditions, the protons at the CHα and CHβ position

of 3 is amenable for oxidation to provide the intermediate A. Copper-bound dioxygen is able to

activate superoxide to insert into the α,β-unsaturated enamide B to form 2-oxyindolenylperoxo

radical intermediate C, which triggers the O-O bond cleavage reaction leading to spiro-

indolooxiranes 10.

Scheme 9. Plausible reaction mechanism for 10.

General experimental procedure for the synthesis of spiro-indolooxiranes 10

A mixture of DMAP (1.0 equiv) and copper iodide (0.1 equiv) in 4 mL acetone was stirred at

room temperature for 5 minutes. Then, 3-alkylated oxindole 3 (1.0 equiv) was added to the

reaction mixture and stirred for 15-24 h. The mixture was then quenched with water and

extracted with ethyl acetate (3×10 mL). The concentration of the combined organic layers under

reduced pressure afforded the crude product, which was purified by column chromatography

using silica gel to afford the corresponding product 10.

Synthesis of (3E)-1-benzyl-3-[2-(4-methylphenyl)-2-oxoethylidene]-1,3-

dihydro-2H-indol-2-one (9a)

To a solution of DMAP (0.14 mmol) in acetone (4 mL) was added 1-benzyl-

3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3a) (50 mg,

0.14 mmol) the reaction mixture was stirred at room temperature to afford 9a

(42 mg, 86%) as a colorless amorphous solid according to general procedure.

Rf = 0.46 (EtOAc/hexane = 1:4, v/v); mp 141-142 °C; IR (neat): νmax 2922, 1701, 1659, 1596,

9a

S20

1482, 1345, 1228, 692 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 2.33 (s, 3H, CH3), 5.00 (s, 2H,

CH2), 6.64 (d, J = 8 Hz, 1H, ArH), 7.11 (d. J = 8 Hz, 1H, ArH), 7.30-7.37 (m, 6H, ArH), 7.57-

7.61 (m, 2H, ArH), 7.67-6.68 (m, 1H, ArH), 7.98 (s, 1H, ArH), 8.16-8.19 (m, 3H, ArH) ppm; 13C

NMR (CDCl3, 100 MHz) δ = 21.1, 44.0, 109.03, 120.3, 126.4, 127.3, 127.7, 128.3, 128.85,

128.92, 132.4, 133.0, 133.8, 135.6, 136.8, 137.7, 143.0, 168.2, 191.3 ppm; HRMS (ESI)

Calculated for C24H19NO2 (M+H)+: 354.1494 found: 354.1504.

Synthesis of 1-benzyl-3'-(4-methylbenzoyl)spiro[indole-3,2'-oxiran]-2(1H)-one (10a)

To a solution of DMAP (17 mg, 0.14 mmol) and copper iodide (3 mg, 0.014 mmol) in acetone (4

mL) was added 1-benzyl-3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3a)

(50 mg, 0.14 mmol) the reaction mixture was stirred at room temperature to

afford 10a (49 mg, 95%) as a colorless crystalline solid according to

general procedure. Rf = 0.35 (EtOAc/hexane = 1:4, v/v); mp 198-199-174

°C; IR (neat): νmax 2923, 1701, 1599, 1445, 1363, 1187, 1147, 725 cm−1; 1H

NMR (CDCl3, 400 MHz) δ = 2.40 (s, 3H, CH3), 5.02 (d, J = 4.4 Hz, 3H,

NCH2/OCH), 6.77 (d, J = 8 Hz, 1H, ArH), 6.92 (t, J = 7.6 Hz, 1H, ArH),

7.12 (d, J = 7.6 Hz, 1H, ArH), 7.19-7.37 (m, 10H, ArH), 7.85 (d, J = 8.4

Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 21.9, 44.5, 60.9, 64.0, 110.0, 119.4, 123.3,

124.5, 127.3, 128.0, 128.5, 129.0, 129.7, 130.9, 132.7, 135.1, 144.5, 145.7, 170.5, 190.2 ppm;

HRMS (ESI) Calculated for C24H19NO3 (M+H)+: 370.1443 found: 370.1437.

Synthesis of 3'-benzoyl-1-benzyl-5-methoxyspiro[indole-3,2'-oxiran]-2(1H)-one (10b)


mL) was added 1-benzyl-3-diazonio-5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-ide (3q) (50 mg,

0.13 mmol) the reaction mixture was stirred at room temperature to

afford 10b (47 mg, 91%) as a colorless amorphous solid according to

general procedure. Rf = 0.23 (EtOAc/hexane = 1:4, v/v); mp 148-149

°C; IR (neat): νmax 2923, 1701, 1599, 1445, 1363, 1187, 1147, 725

cm−1; 1H NMR (CDCl3, 400 MHz) δ = 3.57 (s, 3H, CH3), 4.91 (s, 2H,

CH2), 4.97 (s, 1H, CH), 6.59-6.67 (m, 3H, ArH), 7.19-7.56 (m, 8H,

ArH), 7.88 (d, J = 7.6 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.6, 55.7, 61.2,

64.01, 110.7, 110.8, 116.4, 120.4, 127.3, 128.0, 128.4, 129.0, 129.1, 134.5, 135.15, 135.19,

10a

10b

S21

137.7, 156.2, 170.2, 190.70 ppm; HRMS (ESI) Calculated for C24H19NO4 (M+H)+: 386.1392

found: 386.1386.

Synthesis of 3'-([1,1'-biphenyl]-4-carbonyl)-1-benzylspiro[indole-3,2'-oxiran]-2(1H)-one

(10c)


mL) was added 3-[2-([1,1'-biphenyl]-4-yl)-2-oxoethyl]-1-benzyl-1,3-dihydro-2H-indol-2-one

(3f) (50 mg, 0.12 mmol) the reaction mixture was stirred at room temperature to afford 10c (45

mg, 87%) as a colorless crystalline solid according to general procedure. Rf

= 0.37 (EtOAc/hexane = 1:4, v/v); mp 210-211 °C; IR (neat): νmax 2923,

1701, 1599, 1445, 1363, 1187, 1147, 725 cm−1; 1H NMR (CDCl3, 400 MHz)

δ = 5.07 (s, 2H, CH2), 5.12 (s, 1H, CH), 6.96 (d, J = 0.8 Hz, 1H, ArH), 6.98-

7.00 (m, 1H, ArH), 7.19-7.21 (m, 1H, ArH), 7.25-7.29 (m, 1H, ArH), 7.33-

7.53 (m, 7H, ArH), 7.63-7.74 (m, 5H, ArH), 8.07 (d, J = 8.4 Hz, 2H, ArH)

ppm; 13C NMR (CDCl3, 100 MHz) δ = 44.5, 61.0, 64.1, 110.0, 119.4, 123.3,

124.6, 127.3, 127.4, 127.6, 128.0, 128.6, 129.0, 129.1, 131.0, 133.8, 135.1, 139.4, 144.6, 147.3,

170.5, 190.2 ppm; HRMS (ESI) Calculated for C29H21NO3 (M+Na)+: 454.1419 found: 454.1414.

Synthesis of 3'-(2-bromobenzoyl)-1-methylspiro[indole-3,2'-oxiran]-2(1H)-one (10d)


mL) was added 3-[2-(2-bromophenyl)-2-oxoethyl]-1-methyl-1,3-dihydro-2H-indol-2-one (3k)

(50 mg, 0.16 mmol) the reaction mixture was stirred at room temperature

to afford 10d (42 mg, 79%) as a colorless crystalline solid according to

general procedure. Rf = 0.31 (EtOAc/hexane = 1:4, v/v); mp 167-169 °C;

IR (neat): νmax 2923, 1701, 1599, 1445, 1363, 1187, 1147, 725 cm−1; 1H

NMR (CDCl3, 400 MHz) δ = 3.22 (s, 3H, CH3), 4.81 (s, 1H, CH), 6.81-

6.85 (m, 1H, ArH), 6.96 (t, J = 7.6 Hz, 1H, ArH), 7.24-7.34 (m, 4H, ArH),

7.48-7.53 (m, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 26.9, 62.7, 65.4, 109.0, 119.3,

120.5, 123.3, 124.8, 127.9, 131.0, 131.2, 133.7, 134.2, 137.8, 145.5, 170.1, 193.2 ppm; HRMS

(ESI) Calculated for C17H1279BrNO3 (M+H)+: 358.0079 found: 358.0083.

Synthesis of 1-ethyl-3'-(naphthalene-2-carbonyl)spiro[indole-3,2'-oxiran]-2(1H)-one (10e)


mL) was added 1-ethyl-3-[2-(naphthalen-2-yl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-one (3y) (50

mg, 0.15 mmol) the reaction mixture was stirred at room temperature to afford 10e (44 mg, 85%)

10d

10c

S22

as a colorless amorphous solid according to general procedure. Rf = 0.38


1445, 1363, 1187, 1147, 725 cm−1; 1H NMR (CDCl3, 400 MHz) δ = 1.40 (t, J

= 7.2 Hz, 3H, CH3), 3.82-3.98 (m, 2H, CH2), 4.99 (s, 1H, CH), 6.95-6.99 (m,

2H, ArH), 7.26-8.10 (m, 8H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ =

12.8, 35.6, 61.6, 65.0, 109.2, 119.6, 123.1, 124.4, 124.8, 125.5, 127.0, 128.7,

129.0, 130.1, 130.3, 131.1, 131.9, 134.0, 134.8, 144.6, 169.9, 193.2 ppm;


General experimental procedure for the synthesis of 11

A mixture of 3-alkylated oxindoles 3 (4.0 mmol) in dry MeOH (15 mL) was added NaBH4 (8.0

mmol) slowly at 0 °C under nitrogen atmosphere. The reaction mixture was allowed to stir for 5

hours at room temperature and the solvent was evaporated. The mixture was then quenched with

water and extracted with ethyl acetate (3×10 mL). The concentration of the combined organic

layers under reduced pressure afforded the crude product, which was purified by column

chromatography using silica gel to afford the corresponding product 11.

Synthesis of 3-[2-([1,1'-biphenyl]-4-yl)-2-hydroxyethyl]-1-benzyl-1,3-dihydro-2H-indol-2-

one (11a)

To the stirred solution of 3-[2-([1,1'-biphenyl]-4-yl)-2-oxoethyl]-1-benzyl-1,3-dihydro-2H-indol-

2-one (3f) (50 mg, 0.12 mmol) in dry MeOH (40 mL) was added NaBH4 (14 mg, 0.36 mmol)

slowly at 0 °C under nitrogen atmosphere. The reaction mixture was allowed to stir for 2 hours at

0 °C to afford corresponding alcohol 11a (47 mg, 95%) as a colorless crystalline solid. Rf = 0.15

(EtOAc/hexane = 1.5:3.5, v/v); mp 171-172 °C; IR (neat): νmax 3380, 2991,

1689, 1610, 1485, 1359, 1070, 739 cm−1; 1H NMR (CDCl3, 400 MHz) δ =

2.17-2.29 (m, 2H, CH2), 2.44-2.50 (m, 1H, CH), 3.63-3.77 (m, 1H, CH), 4.83-

4.85 (m, 2H, CH2), 5.14-5.17 (m, 1H, CH), 6.64-6.68 (m, 1H, ArH), 6.91-6.98

(m, 1H, ArH), 7.05-7.12 (m, 1H, ArH), 7.17-7.28 (m, 6H, ArH), 7.35 (t, J = 7.6

Hz, 2H, ArH), 7.44-7.52 (m, 6H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ =

39.3, 40.7, 42.6, 43.96, 43.98, 45.1, 71.1, 73.5, 109.3, 109.4, 122.8, 122.9, 123.7, 124.0, 126.1,

126.5, 127.11, 127.14, 127.25, 127.31, 127.37, 127.39, 127.7, 127.8, 128.0, 128.2, 128.8, 128.9,

130.0, 135.6, 135.7, 140.3, 140.6, 140.9, 141.0, 143.0, 143.2, 143.3, 143.5, 179.2 ppm; HRMS

(ESI) Calculated for C29H25NO2 (M+Na)+: 442.1783 found: 442.1783.

11a

10e

S23

Synthesis of 1-benzyl-3-[2-(4-bromophenyl)-2-hydroxyethyl]-1,3-dihydro-2H-indol-2-one

(11b)

To the stirred solution of 1-benzyl-3-[2-(4-bromophenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-2-

one (3l) (50 mg, 0.12 mmol) in dry MeOH (40 mL) was added NaBH4 (14 mg, 0.36 mmol)

slowly at 0 °C under nitrogen atmosphere. The reaction mixture was allowed to stir for 5 hours at

room temperature to afford corresponding alcohol 11b (44 mg, 89%) as a colorless crystalline

solid. Rf = 0.12 (EtOAc/hexane = 1.5:3.5 v/v); mp 167-168 °C; IR (neat): νmax

3401, 2923, 1691, 1611, 1485, 1364, 1071, 749 cm−1; 1H NMR (CDCl3, 400

MHz) δ = 2.16-2.34 (m, 2H, CH), 2.47-2.54 (m, 1H, CH), 3.70 (dd, J1 = 9.6

Hz, J2 = 3.6 Hz, 1H, CH), 3.84 (dd, J1 = 9.2 Hz, J2 = 4.8 Hz, 1H, CH), 4.32 (d,

J = 6.4 Hz, 1H, CH), 4.95-5.01 (m, 2H, CH2), 5.20 (d. J = 6.8 Hz, 1H, CH),

6.77-6.81 (m, 1H, ArH), 7.04-7.39 (m, 10H, ArH), 7.51-7.54 (m, 2H, ArH),

ppm; 13C NMR (CDCl3, 100 MHz) δ = 39.1, 40.7, 42.4, 43.97, 44.0145.2, 7.07,

73.3, 109.4, 109.5, 121.1, 121.3, 122.9, 123.0, 123.6, 123.9, 127.4, 127.5, 127.76, 127.84, 128.1,

128.3, 128.6, 128.8, 128.87, 128.92, 131.5, 131.6, 135.5, 135.6, 142.9, 143.17, 143.22, 143.5,

179.1, 179.2 ppm; HRMS (ESI) Calculated for C23H2081BrNO2 (M+H)+: 424.0735 found:

424.0764.

Synthesis of 3-tert-butoxy-1-benzyl-3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-

indol-2-one (12)

To a solution of FeCl3 (7 mg, 0.04 mmol) and TBHP (55 μL, 0.56 mmol) in acetonitrile (2 mL)

was added 1-benzyl-3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-

indol-2-one (3a) (50 mg, 0.14 mmol) and the reaction mixture was stirred at

room temperature to afford 12 (41 mg, 69%) as a colorless liquid according

to general procedure. Rf = 0.38 (EtOAc/hexane = 1:4, v/v); IR (neat): νmax

2923, 1730, 1684, 1611, 1465, 1358, 1181, 1007, 701 cm−1; 1H NMR

(CDCl3, 400 MHz) δ = 1.04 (s, 9H, C(CH3)3), 2.32 (s, 3H, CH3), 3.71-3.91

(m, 2H, CH2), 4.66 (d, J = 16 Hz, 1H, NCH), 5.26 (d, J = 16 Hz, 1H, NCH),

6.55 (d, J = 8 Hz, 1H, ArH), 6.85-6.89 (m, 1H, ArH), 7.07-7.33 (m, 10H, ArH), 7.73 (d, J = 8.4

Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ = 21.7, 26.4, 42.5, 43.9, 80.7, 82.4, 109.2,

122.0, 124.1, 127.1, 128.3, 128.6, 129.2, 129.7, 134.0, 135.9, 144.3, 144.5, 174.0, 194.2 ppm;


11b

12

S24

Synthesis of 1-benzyl-3-hydroxy-3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-indol-

2-one (13)

To a solution of 3-tert-butoxy-1-benzyl-3-[2-(4-methylphenyl)-2-oxoethyl]-1,3-dihydro-2H-

indol-2-one (12) (30 mg, 0.07 mmol) in acetonitrile (5 mL) was stirred at

reflux conditions for 6 hours to afford 13 (14 mg, 52%) as a colorless

crystalline solid. Rf = 0.13 (EtOAc/hexane = 1.5:3.5, v/v); mp 161-162 °C; IR

(neat): νmax 3364, 3059, 1680, 1608, 1349, 1174, 1000, 733 cm−1; 1H NMR

(CDCl3, 400 MHz) δ = 2.44 (s, 3H, CH3), 3.63 (d, J = 17.2 Hz, 1H of CH2),

3.91 (d, J = 17.2 Hz, 1H of CH2), 4.98 (ABq, ΔδAB = 0.06, J = 15.6 Hz, 2H,

CH2), 6.76 (d, J = 7.2 Hz, 1H, ArH), 7.01-7.04 (m, 1H, ArH), 7.20-7.45 (m,

9H, ArH), 7.84 (d, J = 7.6 Hz, 2H, ArH) ppm; 13C NMR (CDCl3, 100 MHz) δ

= 21.7, 44.0, 44.5, 74.6, 109.7, 123.1, 124.0, 127.3, 127.7, 128.4, 128.9, 129.4, 129.8, 130.2,

134.0, 135.6, 142.9, 144.8, 176.7, 197.8 ppm; HRMS (ESI) Calculated for C24H21NO3 (M+H)+:

372.1600 found: 372.1604.

13

S25

NMR-Titration experiments

The 13C NMR titration experiments were performed to investigate the interactions of chalcone 2a

with BF3·OEt2 and the results revealed the presence of binding (Figure S1).

(e)

(d)

(c)

(b)

(a)

S26

Figure S1. 13C-NMR spectra of chalcone 2a signals in CDCl3

(a) Chalcone 2a only.

(b) Chalcone 2a (20 mg) with BF3·OEt2 (4 μL)

(c) Chalcone 2a (20 mg) with BF3·OEt2 (6 μL)

(d) Chalcone 2a (20 mg) with BF3·OEt2 (8 μL)

(e) Chalcone 2a (20 mg) with BF3·OEt2 (10 μL)

Next, the 1H NMR experiments were performed at different time interval to follow the reaction

between diazoamide 1a and chalcone 2a in the presence of BF3·OEt2 to afford product 3a with

the by-product of benzoic acid determined using D2O exchange experiment as shown in Figure

S2.

(a) 2a only

(b) 2a+BF3·OEt2 (4 μL)

(c) 2a+BF3·OEt2 (6 μL)

(d) 2a+BF3·OEt2 (8 μL)

(e) 2a +BF3·OEt2 (10 μL)

S27

Figure S2. 1H-NMR spectra of reaction mixture 3a signals in CDCl3

(a) 1a

(b) 2a

(c) 1a+2a+BF3·OEt2

(10 μL) after 5 min.

(d) 1a+2a+BF3·OEt2

(10 μL) after 10

min.

(e) 1a+2a+BF3·OEt2

(10 μL)+D2O after

30 min.

(a) 1a

(b) 2a

(c) 1a+2a+BF3·OEt2

(10 μL) after 5 min.

(d) 1a+2a+BF3·OEt2

(10 μL) after 10

min.

(e) 1a+2a+BF3·OEt2

(10 μL)+D2O after

30 min.

S28

(a) Diazoamide 1a (10 mg).

(b) Chalcone 2a (10 mg).

(c) A mixture of diazoamide 1a (10 mg), chalcone 2a (10 mg) with BF3·OEt2 (10 μL) after 5 minutes.

(d) A mixture of diazoamide 1a (10 mg), chalcone 2a (10 mg) with BF3·OEt2 (10 μL) after 10 minutes.

(e) A mixture of diazoamide 1a (10 mg), chalcone 2a (10 mg) with BF3·OEt2 (10 μL) and 1 drop of D2O

after 30 minutes.

In order to determine the presence of benzoic acid as a byproduct during the formation of

product 3a, NMR experiments at different time interval were recorded between benzaldehyde

and BF3·OEt2 in CDCl3 as shown in Figure S3. The disappearance of aldehyde at 10.20 ppm with

the appearance of benzoic acid as a broad singlet at 11.32 ppm were observed and confirmed

with D2O exchange experiments.

Figure S3. 1H-NMR spectra of benzaldehyde signals in CDCl3

(a) Benzaldehyde only.

(b) Benzaldehyde (20 mg) with BF3·OEt2 (5 μL) after 5 minutes.

(c) Benzaldehyde (20 mg) with BF3·OEt2 (5 μL) after 10 minutes.

(d) Benzaldehyde (20 mg) with BF3·OEt2 (5 μL) after 20 minutes.

(e) A mixture of benzaldehyde, BF3·OEt2 (5 μL) and 1 drop of D2O after 30 minutes.

(a)

(b)

(c)

(d)

(e)

S29

Copies of 1H and 13C NMR spectra

1H NMR spectrum of 3a

9 8 7 6 5 4 3 2 1 0 ppm

2.40

21

3.40

68

3.42

93

3.45

20

3.47

46

3.83

65

3.84

39

3.88

17

3.88

91

4.15

01

4.15

62

4.17

25

4.17

83

4.96

82

6.71

97

6.73

92

6.91

87

6.93

75

6.95

63

7.11

49

7.13

43

7.15

35

7.23

42

7.24

97

7.26

90

7.30

66

7.32

59

7.34

49

7.36

61

7.88

38

7.90

41

3.00

1.00

1.04

1.02

1.99

1.02

1.04

1.07

8.34

2.00

apr-17 PROTON CDCl3 2/6/2019

3a

S30

13C NMR spectrum of 3a

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

21.7

1

39.9

8

41.3

2

44.0

0

76.7

8

77.1

0

77.4

2

109.

06

122.

54

124.

48

127.

36

127.

62

127.

98

128.

34

128.

82

129.

21

129.

41

133.

98

135.

98

143.

45

144.

35

177.

93

196.

46

apr-17 C13CPD CDCl3 2/6/2019

3a

S31

COSY spectrum of 3a

3.03.54.04.55.05.56.06.57.07.58.08.5ppm ppm

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

apr-17 COSYGPSW CDCl3 2/6/2019

3a

S32

HSQC spectrum of 3a

2.53.03.54.04.55.05.56.06.57.07.58.0ppm ppm

140

120

100

80

60

40

20

0

apr-17 HSQCGP CDCl3 2/6/2019

3a

S33

1H NMR spectrum of 3b

9 8 7 6 5 4 3 2 1 0 ppm

2.40

2

3.26

4

3.33

0

3.35

3

3.37

5

3.39

8

3.77

6

3.78

3

3.82

1

3.82

8

4.05

7

4.08

0

6.84

0

6.85

9

6.96

3

6.98

2

7.00

1

7.24

5

7.26

4

7.28

5

7.86

1

7.88

1

3.00

2.98

1.02

0.99

0.98

1.11

1.06

4.26

2.00


3b

S34

13C NMR spectrum of 3b

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

21

.70

26

.42

39

.96

41

.23

76

.78

77

.10

77

.41

10

8.0

2

12

2.5

2

12

4.4

7

12

8.0

7

12

8.2

7

12

9.2

2

12

9.3

9

13

3.8

9

14

4.2

8

14

4.3

5

17

7.8

7

19

6.6

2

apr-12 C13CPD CDCl3 31/12/2015

3b

S35

1H NMR spectrum of 3c

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.73

2

3.44

1

3.46

3

3.48

6

3.50

9

3.86

6

3.87

4

3.91

2

3.92

0

4.15

6

4.16

3

4.17

8

4.18

5

4.97

3

6.72

8

6.74

7

6.92

8

6.94

7

6.96

6

7.12

4

7.14

3

7.16

2

7.24

5

7.25

5

7.26

3

7.28

0

7.28

4

7.31

1

7.32

5

7.33

0

7.34

2

7.34

9

7.35

4

7.37

1

7.37

5

7.44

7

7.46

5

7.48

5

1.04

1.04

1.01

2.00

1.01

1.01

1.06

6.30

2.04

1.02

2.06


3c

S36

13C NMR spectrum of 3c

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

40

.10

41

.28

44

.01

76

.84

77

.15

77

.47

10

9.1

2

12

2.5

9

12

4.4

4

12

7.3

8

12

7.6

6

12

8.0

5

12

8.2

3

12

8.7

6

12

8.8

5

12

9.1

0

13

3.5

4

13

5.9

6

13

6.3

6

14

3.4

7

17

7.8

7

19

6.8

9

3c

S37

1H NMR spectrum of 3d

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.6

83

3.3

90

3.4

12

3.4

34

3.4

57

3.8

17

3.8

24

3.8

67

4.1

60

4.1

79

4.9

74

6.7

24

6.7

43

6.9

29

6.9

49

6.9

65

7.1

23

7.1

42

7.1

61

7.2

44

7.2

59

7.2

62

7.2

83

7.3

13

7.3

32

7.3

50

7.3

67

7.9

70

7.9

92

0.9

8

3.9

5

0.9

7

2.0

0

1.0

0

2.9

6

1.0

2

6.1

3

1.9

4


3d

S38

13C NMR spectrum of 3d

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

39

.73

41

.37

43

.98

55

.53

76

.75

77

.07

77

.27

77

.38

10

9.0

3

11

3.8

7

12

2.5

3

12

4.5

0

12

7.3

5

12

7.6

0

12

7.9

5

12

8.8

1

12

9.2

6

12

9.5

3

13

0.5

1

13

5.9

7

14

3.4

3

16

3.7

9

17

8.0

0

19

5.3

0

apr-348 C13CPD CDCl3 17/10/2018

3d

S39

1H NMR spectrum of 3f

9 8 7 6 5 4 3 2 1 0 ppm

3.3

99

3.4

22

3.4

45

3.4

67

3.8

23

3.8

31

3.8

69

3.8

76

4.1

09

4.1

16

4.1

31

4.1

38

4.9

10

6.6

62

6.6

81

6.8

66

6.8

85

6.9

04

7.0

60

7.0

79

7.0

98

7.1

74

7.1

83

7.2

01

7.2

13

7.2

44

7.2

64

7.2

82

7.3

04

7.3

25

7.3

43

7.3

77

7.3

96

7.4

14

7.5

41

7.5

60

1.0

0

1.0

0

0.9

8

2.0

3

0.9

8

1.0

5

1.0

5

9.2

8

4.1

6

1.9

5


3f

S40

13C NMR spectrum of 3f

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

40

.13

41

.32

44

.02

76

.76

77

.08

77

.39

10

9.1

2

12

2.6

0

12

4.4

6

12

7.3

3

12

7.3

7

12

7.6

5

12

8.0

5

12

8.3

7

12

8.8

4

12

9.0

2

12

9.1

1

13

5.0

5

13

5.9

3

13

9.7

8

14

3.4

6

14

6.1

9

17

7.9

0

19

6.4

6

apr-365 C13CPD CDCl3 10/12/2018

3f

S41

1H NMR spectrum of 3g

9 8 7 6 5 4 3 2 1 0 ppm

1.0

59

9

1.0

76

5

1.1

46

1

1.1

63

4

2.5

62

0

2.5

78

2

2.5

94

9

2.6

11

8

2.6

28

6

2.6

45

4

2.7

57

2

2.7

74

3

2.7

91

5

2.8

08

7

2.8

25

9

3.1

10

5

3.1

31

2

3.1

59

0

3.1

79

6

3.4

78

2

3.4

85

7

3.5

26

7

3.5

34

2

3.9

66

3

3.9

72

7

3.9

86

4

4.8

09

9

4.8

49

2

4.8

99

2

4.9

38

5

6.6

52

8

6.6

72

2

6.9

12

2

6.9

21

2

6.9

40

3

7.0

59

6

7.0

78

8

7.0

98

1

7.1

23

0

7.1

33

3

7.1

40

8

7.1

58

5

7.1

86

2

7.2

05

3

7.2

23

8

7.2

56

4

7.2

74

9

18

.20

2.0

1

1.0

1

0.9

9

1.0

0

0.9

9

2.0

0

0.9

6

2.9

9

7.1

8


3g

S42

13C NMR spectrum of 3g

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

24

.03

30

.83

34

.40

41

.14

44

.01

47

.27

76

.81

77

.13

77

.45

10

9.2

3

12

1.1

8

12

2.3

4

12

4.1

3

12

7.3

8

12

7.6

0

12

8.0

8

12

8.8

0

13

6.0

2

13

6.4

9

14

3.6

9

14

3.9

1

14

9.9

4

17

7.5

3

20

7.4

8

apr-384 C13CPD CDCl3 28/12/2018

3g

S43

1H NMR spectrum of 3i

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.6

32

3.4

20

3.4

42

3.4

65

3.4

87

3.8

37

3.8

45

3.8

83

3.8

90

4.1

42

4.1

48

4.1

64

4.1

70

4.9

76

6.7

37

6.7

56

6.9

41

6.9

60

6.9

79

7.1

25

7.1

46

7.1

57

7.1

68

7.1

76

7.2

32

7.2

51

7.2

58

7.2

72

7.2

89

7.3

17

7.3

36

7.3

53

7.3

71

8.0

11

8.0

25

8.0

33

0.9

9

1.0

0

0.9

7

2.0

0

0.9

7

1.0

1

2.9

8

6.3

4

1.9

5


3i

S44

13C NMR spectrum of 3i

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

39

.95

41

.25

44

.01

76

.77

77

.08

77

.40

10

9.1

4

11

5.7

7

11

5.9

9

12

2.5

9

12

4.3

7

12

7.3

6

12

7.6

5

12

8.0

9

12

8.8

3

12

8.9

6

13

0.8

4

13

0.9

4

13

2.8

0

13

2.8

3

13

5.8

9

14

3.4

6

16

4.7

1

16

7.2

5

17

7.7

4

19

5.2

7

apr-41 C13CPD CDCl3 13/9/2017

3i

S45

1H NMR spectrum of 3j

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

2

1.2

93

4

1.3

11

5

1.3

29

5

1.7

25

8

3.3

29

6

3.3

52

1

3.3

75

1

3.3

97

6

3.7

63

6

3.7

71

4

3.7

91

4

3.8

09

3

3.8

16

8

3.8

27

5

3.8

45

6

4.0

21

2

4.0

28

6

4.0

43

7

4.0

51

0

6.8

72

0

6.8

91

5

6.9

63

8

6.9

82

5

7.0

01

1

7.2

29

1

7.2

48

1

7.2

63

1

7.2

68

6

7.2

88

0

7.4

24

8

7.4

46

3

7.9

03

2

7.9

24

7

3.0

0

0.9

9

2.9

8

0.9

8

0.9

9

0.9

9

2.1

8

1.9

8

1.9

8


3j

S46

13C NMR spectrum of 3j

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

12

.65

34

.89

40

.03

41

.19

76

.76

77

.08

77

.40

10

8.2

2

12

2.3

2

12

4.5

2

12

8.1

2

12

9.0

3

12

9.1

9

12

9.5

7

13

4.7

4

13

9.9

2

14

3.4

4

17

7.1

3

19

5.8

0

Apr-151 C13CPD CDCl3 20/9/2017

3j

S47

1H NMR spectrum of 3k

9 8 7 6 5 4 3 2 1 0 ppm

3.30

4

3.47

0

3.49

2

3.51

6

3.53

8

3.88

2

3.89

0

3.92

8

3.93

6

4.08

2

4.08

9

4.10

3

4.11

1

6.89

9

6.91

8

7.01

6

7.03

4

7.05

3

7.25

8

7.27

6

7.30

3

7.32

1

7.34

1

7.70

5

7.72

5

7.74

5

8.31

8

8.33

8

8.44

4

8.44

7

8.44

9

8.46

3

8.46

5

8.46

8

3.00

1.07

0.90

0.90

1.98

2.07

0.95

1.95

0.90


3k

S48

13C NMR spectrum of 3k

220 200 180 160 140 120 100 80 60 40 20 ppm

26.4

8

40.2

3

41.0

3

76.8

1

77.1

3

77.4

5

108.

25

122.

64

123.

08

124.

20

127.

74

128.

38

128.

55

130.

09

133.

67

137.

48

144.

37

148.

48

177.

27

195.

01

apr-558 C13CPD CDCl3 2/12/2019

3k

S49

1H NMR spectrum of 3l

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.6

12

3.4

08

3.4

30

3.4

53

3.4

75

3.8

24

3.8

32

3.8

70

3.8

77

4.1

35

4.1

41

4.1

56

4.1

62

4.9

73

6.7

36

6.7

55

6.9

41

6.9

60

6.9

79

7.1

39

7.1

58

7.1

78

7.2

22

7.2

40

7.2

59

7.2

73

7.2

81

7.2

89

7.3

16

7.3

36

7.3

52

7.3

68

7.6

09

7.6

30

7.8

48

7.8

70

0.9

5

0.9

7

0.9

3

2.0

0

0.9

4

0.9

7

7.2

1

1.9

4

1.9

1


3l

S50

13C NMR spectrum of 3l

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

39

.98

41

.18

44

.01

76

.75

77

.07

77

.39

10

9.1

7

12

2.6

1

12

4.3

4

12

7.3

5

12

7.6

7

12

8.1

3

12

8.7

8

12

8.8

4

12

9.7

2

13

2.0

8

13

5.0

3

13

5.8

5

14

3.4

5

17

7.6

7

19

5.8

9

apr-45 C13CPD CDCl3 19/9/2017

3l

S51

1H NMR spectrum of 3m

9 8 7 6 5 4 3 2 1 0 ppm

3.1

30

3.2

07

3.2

28

3.2

52

3.2

75

3.5

95

3.6

04

3.6

41

3.6

50

3.9

55

3.9

63

3.9

76

3.9

85

6.7

35

6.7

55

6.9

13

6.9

32

6.9

49

6.9

51

7.1

65

7.1

68

7.1

73

7.1

86

7.1

91

7.2

06

7.2

11

7.2

26

7.2

43

7.2

58

7.2

61

7.2

77

7.2

79

7.3

30

7.3

35

7.3

49

7.3

54

7.4

81

3.0

0

1.2

3

1.0

3

1.0

7

1.0

6

1.1

3

5.3

6

1.2

5


3m

S52

13C NMR spectrum of 3m

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

26

.45

41

.37

43

.66

76

.89

77

.21

77

.53

10

8.1

7

11

8.8

4

12

2.6

3

12

4.5

0

12

7.5

6

12

8.2

7

12

8.5

5

12

8.8

5

13

2.0

3

13

3.8

9

14

0.5

8

14

4.2

9

17

7.2

2

20

0.8

9

apr-562 C13CPD CDCl3 2/12/2019

3m

S53

1H NMR spectrum of 3n

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.2

99

1.3

17

1.3

35

1.6

49

3.3

80

3.4

01

3.4

26

3.4

47

3.7

79

3.7

87

3.7

94

3.8

12

3.8

30

3.8

48

4.0

14

4.0

22

4.0

35

4.0

43

6.8

90

6.9

09

6.9

82

7.0

01

7.0

20

7.2

11

7.2

29

7.2

65

7.2

90

7.3

09

7.8

67

7.8

87

7.9

81

7.9

86

8.0

02

8.0

07

8.3

99

8.4

03

3.0

0

1.0

1

2.9

9

0.9

8

1.0

0

1.0

2

2.2

3

0.9

8

0.9

7

0.9

5


3n

S54

13C NMR spectrum of 3n

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

12

.63

34

.97

40

.08

41

.01

76

.74

77

.06

77

.37

10

8.4

1

12

0.1

5

12

2.4

5

12

4.3

3

12

5.0

5

12

8.3

8

12

8.6

0

13

1.8

5

13

5.8

3

13

6.2

3

14

3.4

7

15

0.0

9

17

6.7

2

19

4.1

4

apr-343 C13CPD CDCl3 11/10/2018

3n

S55

1H NMR spectrum of 3p

9 8 7 6 5 4 3 2 1 0 ppm

2.2

92

3.4

96

3.5

18

3.5

41

3.5

64

3.9

22

3.9

30

3.9

68

3.9

75

4.2

01

4.2

17

4.2

23

5.0

17

6.6

74

6.6

94

6.9

94

7.0

14

7.1

34

7.3

02

7.3

08

7.3

17

7.3

22

7.3

27

7.3

33

7.3

65

7.3

85

7.4

02

7.4

06

7.4

22

7.5

11

7.5

30

7.5

49

7.6

17

7.6

36

7.6

54

3.0

0

0.9

0

0.9

1

0.8

2

1.8

3

0.8

2

0.8

1

0.8

0

7.8

1

1.5

2


3p

S56

13C NMR spectrum of 3p

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

21

.14

40

.19

40

.24

41

.25

41

.32

44

.01

76

.82

77

.14

77

.46

10

8.8

5

12

5.2

8

12

5.3

3

12

7.3

5

12

7.6

0

12

8.2

6

12

8.7

6

12

8.8

2

12

9.1

8

13

2.1

6

13

3.5

3

13

6.0

3

13

6.3

6

14

1.0

2

17

7.8

4

19

6.9

7

apr566 C13CPD CDCl3 24/01/2020

3p

S57

1H NMR spectrum of 3q

9 8 7 6 5 4 3 2 1 0 ppm

3.4

89

3.5

11

3.5

34

3.5

57

3.7

36

3.9

17

3.9

24

3.9

63

3.9

70

4.1

89

4.1

94

4.2

11

5.0

01

6.6

58

6.6

79

6.7

05

6.7

10

6.7

26

6.7

31

6.9

45

7.3

03

7.3

14

7.3

21

7.3

30

7.3

62

7.3

82

7.3

97

7.5

00

7.5

19

7.5

38

7.6

09

7.6

28

7.6

46

8.0

40

1.0

1

3.0

0

1.0

3

0.9

8

1.9

7

1.9

9

0.9

4

5.1

4

2.0

1

1.0

0

1.9

8


3q

S58

13C NMR spectrum of 3q

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

40

.17

41

.65

44

.07

55

.76

76

.80

77

.11

77

.43

10

9.3

9

11

2.0

1

11

2.2

9

12

7.3

4

12

7.6

1

12

8.2

2

12

8.7

5

12

8.8

2

13

0.4

6

13

3.5

4

13

6.0

0

13

6.3

4

13

6.9

1

15

5.9

3

17

7.4

9

19

6.8

9

apr-378 C13CPD CDCl3 28/12/2018

3q

S59

COSY spectrum of 3q

ppm

3.54.04.55.05.56.06.57.07.58.0 ppm

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

apr-378 COSYGPSW CDCl3 28/12/2018

3q

S60

HSQC spectrum of 3q

ppm

3.54.04.55.05.56.06.57.07.58.0 ppm

140

120

100

80

60

40

20

0

apr-378 HSQCGP CDCl3 28/12/20118

3q

S61

1H NMR spectrum of 3r

9 8 7 6 5 4 3 2 1 0 ppm

3.48

6

3.50

0

3.50

7

3.52

2

3.53

1

3.54

6

3.55

3

3.56

7

3.91

0

3.91

7

3.95

6

3.96

3

4.14

0

4.15

4

4.97

0

6.61

7

6.63

1

6.65

1

7.10

9

7.12

6

7.25

1

7.26

1

7.28

1

7.29

2

7.30

3

7.32

7

7.34

0

7.35

1

7.38

9

7.40

5

7.42

1

7.44

2

7.45

7

7.47

4

7.49

2

7.62

1

7.63

8

7.67

9

1.00

1.01

0.99

1.93

0.99

0.97

9.44

4.05

1.97


3r

S62

13C NMR spectrum of 3r

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

39

.91

41

.36

44

.12

76

.75

77

.06

77

.38

10

9.9

8

12

4.9

3

12

7.3

0

12

7.3

3

12

7.4

0

12

7.7

9

12

7.9

5

12

8.0

1

12

8.3

9

12

8.8

4

12

8.9

1

12

9.0

2

13

0.7

6

13

4.8

3

13

5.5

2

13

9.7

5

14

2.0

6

14

6.3

5

17

7.3

4

19

6.0

5

apr-403 C13CPD CDCl3 9/7/2019

3r

S63

1H NMR spectrum of 3s

9 8 7 6 5 4 3 2 1 0 ppm

1.2

96

1.6

78

3.5

20

3.5

42

3.5

66

3.5

88

3.9

24

3.9

30

3.9

70

3.9

76

4.1

65

4.1

85

5.0

03

6.6

25

6.6

46

7.3

00

7.3

20

7.3

42

7.3

75

7.3

83

7.4

18

7.5

10

7.5

29

7.5

48

7.6

23

7.6

41

7.6

60

8.0

32

8.0

51

0.8

6

0.9

0

0.9

3

2.0

0

0.8

2

10

.46

2.1

3


3s

S64

13C NMR spectrum of 3s

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

39

.88

41

.23

44

.08

11

0.5

1

11

5.3

4

12

7.2

8

12

7.6

0

12

7.8

0

12

8.2

5

12

8.7

9

12

8.9

1

13

0.8

7

13

1.1

0

13

3.7

0

13

5.4

4

13

6.0

7

14

2.5

3

17

7.2

2

19

6.4

5

apr-522 C13CPD CDCl3 25/11/2021

3s

S65

1H NMR spectrum of 3t

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.66

2

2.41

7

3.25

4

3.35

6

3.37

8

3.40

2

3.42

4

3.79

3

3.80

0

3.83

8

3.84

6

4.02

7

4.04

4

4.05

0

6.72

1

6.74

2

7.26

5

7.28

1

7.38

2

7.40

7

7.41

0

7.86

0

7.88

1

3.00

3.01

1.11

0.98

0.98

0.91

4.19

1.93


3t

S66

13C NMR spectrum of 3t

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

21

.73

26

.54

39

.79

41

.20

76

.74

77

.06

77

.26

77

.38

10

9.3

8

11

5.2

3

12

7.6

6

12

8.3

0

12

9.4

4

13

0.9

1

13

1.2

1

13

3.6

5

14

3.4

3

14

4.5

6

17

7.2

4

19

6.2

1

apr-240 C13CPD CDCl3 21/3/2018

3t

S67

1H NMR spectrum of 3u

10 9 8 7 6 5 4 3 2 1 ppm

1.17

5

3.35

4

3.37

5

3.40

0

3.42

1

3.74

7

3.75

5

3.79

3

3.80

1

4.00

2

4.00

7

4.02

2

4.82

6

4.86

6

4.87

2

4.91

1

6.50

3

6.52

4

7.17

5

7.19

4

7.20

9

7.21

6

7.24

6

7.25

4

7.25

9

7.27

5

7.52

5

7.54

6

7.75

5

7.77

6

1.00

1.02

1.01

2.04

0.96

7.20

2.02

2.05


3u

S68

13C NMR spectrum of 3u

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

39

.76

41

.16

44

.09

76

.78

77

.10

77

.42

11

0.5

8

11

5.3

6

12

7.2

8

12

7.5

1

12

7.8

3

12

8.9

3

12

8.9

7

12

9.7

4

13

0.8

8

13

0.9

6

13

2.1

2

13

4.7

6

13

5.3

8

14

2.5

4

17

7.0

4

19

5.4

9

apr-523 C13CPD CDCl3 25/11/2019

3u

S69

1H NMR spectrum of 3v

9 8 7 6 5 4 3 2 1 0 ppm

3.6

08

3.6

29

3.6

56

3.6

76

3.8

29

3.9

24

3.9

35

3.9

75

3.9

83

4.0

97

4.1

04

4.1

16

4.1

23

4.9

46

4.9

86

5.0

15

5.0

54

6.6

09

6.6

29

6.9

52

6.9

74

7.0

91

7.0

99

7.1

14

7.1

22

7.2

77

7.2

99

7.3

08

7.3

16

7.3

23

7.3

30

7.3

41

7.3

53

7.3

73

7.3

79

7.3

86

7.4

09

0.9

3

2.8

9

4.0

6

1.0

3

2.0

0

0.9

2

0.9

4

0.9

1

8.1

3


3v

S70

13C NMR spectrum of 3v

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

41.8

1

44.0

0

44.8

1

55.8

6

56.0

1

76.8

4

77.1

6

77.4

8

110.

40

113.

20

113.

80

115.

16

121.

39

126.

69

127.

29

127.

72

128.

88

130.

59

131.

53

135.

61

142.

60

153.

48

153.

82

177.

46

197.

46

apr-559 C13CPD CDCl3 3/12/2019

3v

S71

1H NMR spectrum of 3w

9 8 7 6 5 4 3 2 1 0 ppm

1.71

6

3.52

6

3.54

7

3.57

2

3.59

3

3.91

6

3.92

3

3.96

2

3.96

9

4.15

1

4.16

6

4.17

2

4.99

9

6.53

7

6.55

7

7.30

3

7.30

9

7.32

3

7.33

5

7.34

4

7.35

6

7.37

6

7.38

6

7.49

5

7.51

3

7.53

2

7.55

1

7.58

3

7.62

6

7.64

4

7.66

3

8.03

4

8.05

3

0.94

0.92

0.92

2.00

0.99

10.2

1

1.99

trial-2 apr-368 PROTON CDCl3 22/12/2018

3w

S72

13C NMR spectrum of 3w

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

39

.85

41

.03

44

.03

76

.75

77

.07

77

.38

85

.29

11

1.1

1

12

7.2

8

12

7.7

9

12

8.2

5

12

8.7

8

12

8.9

0

13

1.4

5

13

3.0

6

13

3.6

7

13

5.4

5

13

6.1

1

13

6.8

8

14

3.2

5

17

7.0

4

19

6.4

2

trial-2 apr-368 C13CPD CDCl3 22/12/2018

3w

S73

1H NMR spectrum of 3x

9 8 7 6 5 4 3 2 1 0 ppm

3.4

98

3.5

20

3.5

43

3.5

65

3.9

23

3.9

30

3.9

68

3.9

76

4.2

12

4.2

19

4.2

34

4.2

41

5.0

30

6.7

85

6.8

04

6.9

85

7.0

04

7.0

23

7.1

81

7.2

00

7.2

19

7.2

94

7.3

02

7.3

12

7.3

19

7.3

32

7.3

36

7.3

40

7.3

67

7.3

86

7.4

06

7.4

10

7.4

27

7.5

03

7.5

21

7.5

41

0.9

8

0.9

9

0.9

4

2.0

0

0.9

7

0.9

7

1.0

0

10

.01

1.8

8


3x

S74

13C NMR spectrum of 3x

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

40

.09

41

.27

44

.01

76

.79

77

.11

77

.43

10

9.1

1

12

2.5

8

12

4.4

3

12

7.3

7

12

7.6

4

12

8.0

4

12

8.2

2

12

8.7

5

12

8.8

4

12

9.0

9

13

3.5

3

13

5.9

4

13

6.3

7

14

3.4

6

17

7.8

7

19

6.8

8

apr-564 C13CPD CDCl3 4/12/2019

3x

S75

1H NMR spectrum of 3y

9 8 7 6 5 4 3 2 1 0 ppm

1.2

52

1.2

70

1.2

88

1.9

38

3.4

49

3.4

71

3.4

94

3.5

15

3.7

54

3.7

72

3.7

90

3.8

08

3.8

29

3.8

38

3.8

74

3.8

82

4.1

12

4.1

20

4.1

33

4.1

41

6.8

35

6.8

54

6.9

95

7.0

14

7.2

36

7.2

53

7.2

73

7.3

21

7.3

39

7.4

23

7.4

43

7.4

62

7.5

04

7.5

22

7.5

24

7.5

48

7.5

51

7.5

69

7.5

72

7.8

26

7.8

46

7.8

67

7.8

85

7.9

44

7.9

64

8.5

99

8.6

20

3.0

0

1.0

0

3.1

1

0.9

3

0.9

7

1.0

2

5.3

9

3.1

4

0.9

6


3y

S76

13C NMR spectrum of 3y

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

12

.66

34

.89

41

.77

43

.08

76

.85

77

.17

77

.49

10

8.2

9

12

2.3

8

12

4.3

7

12

4.5

1

12

5.7

6

12

6.5

7

12

7.8

3

12

8.0

7

12

8.1

2

12

8.1

6

12

8.4

8

12

9.2

7

13

0.1

4

13

3.1

2

13

4.0

0

13

5.0

6

14

3.5

1

17

7.2

4

20

0.9

8

apr-337 C13CPD CDCl3 22/9/2018

3y

S77

1H NMR spectrum of 3z

9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.3

22

1.3

40

1.3

58

1.7

00

3.6

47

3.6

77

3.6

96

3.7

83

3.7

91

3.8

04

3.8

22

3.8

32

3.8

40

3.8

59

3.8

78

3.8

96

3.9

14

4.0

59

4.0

67

4.0

77

4.0

85

6.9

38

6.9

57

7.1

37

7.1

56

7.1

75

7.2

47

7.3

43

7.3

62

7.3

81

7.4

44

7.4

57

7.4

63

7.4

72

7.4

80

7.4

88

7.5

00

7.5

08

7.5

26

7.7

77

7.7

95

7.8

00

7.9

84

7.9

91

7.9

99

8.0

08

8.4

61

3.0

0

0.9

5

3.2

1

0.9

3

0.9

8

1.0

1

0.9

9

5.2

1

2.0

7

2.0

2

1.0

1


3z

S78

13C NMR spectrum of 3z

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

12

.52

34

.97

41

.34

46

.67

76

.76

77

.07

77

.39

10

8.5

3

12

2.3

0

12

2.3

3

12

4.0

9

12

4.1

8

12

5.5

5

12

5.5

7

12

6.9

8

12

7.0

1

12

7.0

3

12

8.2

8

12

8.5

0

12

8.7

7

12

8.9

6

13

1.0

0

13

4.9

2

14

3.9

8

17

7.0

4

20

6.9

7

apr-339 C13CPD CDCl3 8/10/2018

3z

S79

1H NMR spectrum of 3aa

3aa

S80

13C NMR spectrum of 3aa

3aa

S81


9 8 7 6 5 4 3 2 1 0 ppm

1.7

26

2.3

27

2.3

41

3.4

05

3.4

28

3.4

51

3.4

74

3.8

76

3.8

84

3.9

22

3.9

30

4.1

18

4.1

35

4.2

11

4.2

23

4.2

35

4.2

48

4.8

99

4.9

07

4.9

24

6.6

81

6.7

00

6.8

98

6.9

14

6.9

33

6.9

40

6.9

62

6.9

69

6.9

88

7.0

07

7.0

92

7.1

02

7.1

12

7.1

30

7.2

15

7.2

33

7.2

49

7.2

71

7.2

90

7.3

07

7.3

25

7.3

83

7.4

02

7.4

19

7.4

22

7.7

41

7.7

60

0.6

1

0.9

9

0.9

6

0.9

8

3.0

8

2.0

0

0.9

8

3.0

0

1.0

0

7.3

2

0.9

5


6a

S82


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

29

.22

41

.69

43

.86

45

.33

65

.07

76

.76

77

.08

77

.40

10

8.9

7

11

2.5

5

12

0.9

7

12

2.4

5

12

4.4

3

12

7.2

7

12

7.5

2

12

7.5

9

12

7.8

7

12

8.7

8

12

9.2

8

13

0.4

7

13

4.0

9

13

6.0

2

14

3.4

2

15

7.9

0

17

7.8

9

19

8.7

2

apr-489 C13CPD CDCl3 12/07/2019

6a

S83


9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.5

00

1.8

25

3.5

53

3.5

64

3.5

80

3.8

98

3.9

07

3.9

14

3.9

45

3.9

53

3.9

61

4.0

00

4.0

16

4.0

26

4.0

31

4.1

34

4.1

59

4.1

84

4.8

80

4.9

20

4.9

58

4.9

82

4.9

97

6.6

87

6.6

98

6.7

06

6.9

15

6.9

38

6.9

67

6.9

86

7.0

92

7.1

11

7.1

21

7.1

29

7.2

13

7.2

24

7.2

40

7.2

57

7.2

79

7.3

04

7.4

06

7.4

10

7.4

28

7.4

45

7.4

49

7.7

62

7.7

81

2.2

7

2.3

4

1.0

0

1.1

4

2.2

7

1.0

8

2.1

4

0.9

9

3.3

6

0.9

6

6.4

6

1.1

0

0.9

8


6b

S84


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

0.0

3

26

.06

29

.05

41

.99

44

.02

45

.33

68

.53

76

.74

77

.06

77

.37

10

9.1

0

11

2.4

1

12

0.5

7

12

2.5

5

12

4.2

7

12

7.2

3

12

7.5

5

12

7.7

9

12

8.7

6

12

9.5

7

13

0.4

1

13

0.6

9

13

4.1

3

13

5.8

3

14

3.3

1

15

8.5

6

17

8.3

9

19

8.5

4

apr-349 C13CPD CDCl3 30/10/2018

6b

S85


9 8 7 6 5 4 3 2 1 0 ppm

1.6

49

4.1

15

4.1

35

4.3

01

4.3

22

4.8

75

4.9

14

4.9

48

4.9

87

6.7

54

6.7

73

6.9

25

6.9

44

6.9

63

7.0

94

7.1

13

7.1

32

7.2

07

7.2

27

7.2

48

7.2

54

7.2

59

7.2

66

7.2

84

7.2

97

7.3

73

7.3

92

7.4

11

7.5

09

7.5

27

7.5

45

1.0

3

1.0

2

2.0

0

1.0

0

1.0

4

1.0

7

12

.01

1.1

2

2.1

9


7a

S86


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

38.6

1

41.4

1

41.4

7

44.1

0

76.8

1

77.1

3

77.4

5

109.

15

122.

02

122.

59

125.

65

127.

28

127.

74

128.

42

128.

50

128.

84

128.

85

130.

67

131.

91

133.

49

133.

86

135.

95

136.

87

142.

85

171.

99

192.

73

apr-488 C13CPD CDCl3 2/8/2019

7a

S87


9 8 7 6 5 4 3 2 1 0 ppm

1.6

93

3.6

63

3.6

84

4.2

12

4.2

32

4.5

72

4.6

11

5.1

71

5.2

10

6.1

73

6.1

92

6.7

89

6.8

08

6.8

29

6.8

50

7.0

07

7.0

24

7.1

64

7.1

83

7.1

98

7.2

01

7.2

15

7.2

33

7.2

51

7.2

69

7.2

97

7.3

04

7.3

08

7.3

15

7.3

45

7.3

67

7.3

86

0.9

8

0.9

3

1.0

1

1.0

0

1.0

0

2.0

4

1.8

8

11

.22

1.9

7

7b

S88


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

37.5

2

39.2

6

41.7

1

44.0

3

76.7

7

77.0

8

77.4

0

109.

25

121.

27

122.

11

125.

19

127.

34

127.

66

127.

84

127.

96

128.

65

129.

17

129.

76

129.

86

133.

50

134.

78

135.

75

139.

88

143.

19

172.

46

190.

74

APR-658 C13CPD CDCl3 14/12/2020

7b

S89


9 8 7 6 5 4 3 2 1 0 ppm

1.62

6

2.33

3

5.00

4

6.62

6

6.64

6

7.09

6

7.11

6

7.30

3

7.31

9

7.32

3

7.33

0

7.34

6

7.35

8

7.36

8

7.56

7

7.58

5

7.60

5

7.66

6

7.68

4

7.70

3

7.98

4

8.16

4

8.16

7

8.18

7

3.00

2.03

0.99

1.00

5.93

2.01

1.00

0.96

2.90

apr-679 a PROTON CDCl3 2/2/2021

9a

S90


220 200 180 160 140 120 100 80 60 40 20 0 ppm

21.0

8

43.9

5

76.7

1

77.0

3

77.3

5

109.

03

120.

27

126.

40

127.

26

127.

72

128.

30

128.

85

128.

92

132.

39

133.

01

133.

81

135.

60

136.

76

137.

72

143.

00

168.

15

191.

34

apr-679 a C13CPD CDCl3 2/2/2021

9a

S91


9 8 7 6 5 4 3 2 1 0 ppm

-0.0

00

1.5

90

2.4

02

5.0

11

5.0

22

6.7

63

6.7

83

6.8

96

6.9

15

6.9

34

7.1

09

7.1

28

7.1

85

7.1

88

7.2

05

7.2

07

7.2

24

7.2

27

7.2

48

7.2

62

7.2

68

7.2

95

7.3

01

7.3

12

7.3

17

7.3

22

7.3

25

7.3

37

7.3

50

7.3

53

3.0

0

2.7

9

0.9

5

0.9

3

0.8

8

9.2

9

1.6

9

Apr-512 PROTON CDCl3 6/9/2019

10a

S92


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

21

.86

44

.50

60

.88

64

.02

76

.73

77

.05

77

.36

10

9.9

8

11

9.3

8

12

3.3

0

12

4.5

2

12

7.3

3

12

7.9

9

12

8.5

0

12

8.9

8

12

9.7

3

13

0.9

2

13

2.7

0

13

5.0

6

14

4.4

9

14

5.7

4

17

0.5

2

19

0.1

7

apr-512 C13CPD CDCl3 6/9/2020

10a

S93


9 8 7 6 5 4 3 2 1 0 ppm

1.18

2

1.54

5

3.57

1

4.91

4

4.96

6

6.57

9

6.58

6

6.59

5

6.60

2

6.64

7

6.65

3

6.66

4

6.67

0

7.18

9

7.21

7

7.22

5

7.23

8

7.25

7

7.27

1

7.29

2

7.38

2

7.40

1

7.42

0

7.52

4

7.54

3

7.56

1

7.86

9

7.88

8

3.00

2.95

2.87

8.33

1.86


10b

S94


200 180 160 140 120 100 80 60 40 20 0 ppm4

4.5

8

55

.74

61

.22

64

.05

76

.72

77

.04

77

.36

11

0.6

8

11

0.8

0

11

6.3

9

12

0.4

0

12

7.3

2

12

7.9

7

12

8.3

8

12

8.9

6

12

9.0

5

13

4.5

0

13

5.1

5

13

5.1

9

13

7.7

4

15

6.1

9

17

0.1

9

19

0.7

3

apr-533 C13CPD CDCl3 11/10/2019

10b

S95

1H NMR spectrum of 10c

9 8 7 6 5 4 3 2 1 0 ppm

1.6

14

5.0

67

5.1

22

6.8

25

6.8

45

6.9

60

6.9

62

6.9

79

6.9

80

6.9

98

7.0

00

7.1

86

7.2

04

7.2

05

7.2

45

7.2

48

7.2

65

7.2

67

7.2

84

7.2

87

7.3

03

7.3

28

7.3

40

7.3

51

7.3

62

7.3

73

7.3

89

7.3

99

7.4

37

7.4

48

7.4

55

7.4

61

7.4

73

2.0

0

1.0

4

1.1

4

1.1

3

1.0

3

1.1

9

7.2

6

4.8

0

2.3

2


10c

S96

13C NMR spectrum of 10c

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

44

.54

60

.99

64

.05

76

.71

77

.03

77

.35

11

0.0

2

11

9.3

6

12

3.3

2

12

4.5

6

12

7.3

1

12

7.3

6

12

7.6

4

12

8.0

1

12

8.6

3

12

8.9

9

12

9.0

7

13

0.9

9

13

3.8

2

13

5.0

7

13

9.4

4

14

4.5

8

14

7.2

6

17

0.4

7

19

0.1

9

apr-538 C13CPD CDCl3 11/11/2019

10c

S97

1H NMR spectrum of 10d

9 8 7 6 5 4 3 2 1 0 ppm

3.2

23

4.8

09

6.8

10

6.8

32

6.8

52

6.9

36

6.9

55

6.9

74

7.1

93

7.2

40

7.2

59

7.2

69

7.2

82

7.2

87

7.3

00

7.3

06

7.3

17

7.3

19

7.3

23

7.3

33

7.3

37

7.4

75

7.4

80

7.4

93

7.4

98

7.5

07

7.5

10

3.0

0

0.9

6

1.3

5

1.1

5

3.9

5

2.3

6

APr-569(2) PROTON CDCl3 06/02/2020

10d

S98

13C NMR spectrum of 10d

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

26

.93

62

.72

65

.41

76

.77

77

.09

77

.41

10

8.9

5

11

9.2

8

12

0.4

5

12

3.2

6

12

4.7

9

12

7.8

5

13

0.9

5

13

1.2

1

13

3.7

2

13

4.2

3

13

7.7

8

14

5.5

2

17

0.0

7

19

3.1

6

APr-569(2) C13CPD CDCl3 6/2/2020

10d

S99

1H NMR spectrum of 10e

9 8 7 6 5 4 3 2 1 0 ppm

1.3

79

1.3

97

1.4

15

1.7

29

3.8

17

3.8

34

3.8

52

3.8

70

3.8

88

3.9

05

3.9

29

3.9

48

3.9

65

3.9

83

4.9

94

6.9

51

6.9

69

6.9

89

7.2

57

7.2

75

7.3

02

7.3

57

7.3

76

7.3

95

7.4

80

7.4

99

7.5

18

7.5

95

7.6

13

7.6

31

7.6

76

7.6

96

7.7

13

7.8

59

7.8

77

7.9

15

7.9

35

3.0

0

1.9

0

0.9

5

1.8

8

8.2

5

0.9

3


10e

S100

13C NMR spectrum of 10e

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

12

.76

35

.56

61

.57

65

.01

76

.75

77

.06

77

.38

10

9.1

7

11

9.6

2

12

3.0

8

12

4.3

6

12

4.8

1

12

5.5

0

12

7.0

1

12

8.7

0

12

8.9

7

13

0.0

7

13

0.3

2

13

1.1

0

13

1.9

4

13

4.0

1

13

4.7

9

14

4.5

7

16

9.8

9

19

3.2

3

apr-543 C13CPD CDCl3 30/10/2019

10e

S101


9 8 7 6 5 4 3 2 1 0 ppm

2.2

08

2.2

28

2.2

36

2.2

49

2.2

62

2.2

78

2.2

86

3.6

31

3.6

39

3.6

54

3.6

63

3.7

53

3.7

61

4.8

25

4.8

40

4.8

54

5.1

44

5.1

54

5.1

65

5.1

75

6.6

35

6.6

56

6.6

78

6.9

28

6.9

37

6.9

47

6.9

56

6.9

75

7.0

52

7.0

79

7.0

98

7.1

18

7.1

66

7.1

86

7.2

05

7.2

29

7.2

40

7.2

58

7.2

76

7.3

34

7.3

53

7.3

72

7.4

35

7.4

55

7.4

97

7.5

06

7.5

16

1.5

3

0.5

5

1.0

2

2.0

0

1.0

1

0.9

6

0.9

8

1.2

5

6.6

4

2.0

5

6.0

9

trial-3 PROTON CDCl3 22/12/2018

11a

S102


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

39

.25

40

.69

42

.55

43

.96

43

.98

45

.10

71

.12

73

.48

76

.76

77

.08

77

.39

10

9.2

7

10

9.3

7

12

2.7

5

12

2.9

3

12

3.6

7

12

3.9

6

12

6.1

4

12

6.4

7

12

7.1

1

12

7.1

4

12

7.2

5

12

7.3

1

12

7.3

7

12

7.3

9

12

7.7

3

12

7.7

9

12

7.9

7

12

8.1

7

12

8.8

0

12

8.8

5

12

8.8

9

12

8.9

9

13

5.5

9

13

5.7

3

14

0.3

2

14

0.5

7

14

0.8

8

14

0.9

5

14

3.0

0

14

3.1

6

14

3.2

6

14

3.4

7trial-3 C13CPD CDCl3 22/12/2018

11a

S103


9 8 7 6 5 4 3 2 1 0 ppm

1.79

5

2.21

9

2.28

0

2.29

0

2.29

9

2.30

8

2.31

7

2.33

3

4.31

5

4.33

1

4.94

6

4.96

9

4.99

1

4.99

5

5.00

8

5.19

2

5.20

9

6.76

8

6.79

2

6.81

2

7.06

0

7.06

8

7.07

9

7.08

7

7.10

6

7.16

6

7.18

6

7.20

6

7.20

8

7.21

2

7.23

2

7.25

1

7.28

2

7.30

3

7.31

6

7.32

4

7.33

0

7.33

8

7.34

2

7.35

2

7.35

7

7.36

8

7.39

0

7.50

7

7.52

0

7.52

7

7.53

6

7.54

1

1.57

0.52

1.04

0.51

2.43

1.00

1.02

10.4

9

2.25


11b

S104


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

39

.08

40

.65

42

.37

43

.97

44

.01

45

.18

70

.72

73

.25

76

.77

77

.09

77

.40

10

9.3

5

10

9.4

5

12

1.1

3

12

1.3

3

12

2.8

5

12

3.0

4

12

3.5

8

12

3.8

6

12

7.3

7

12

7.4

5

12

7.7

6

12

7.8

4

12

8.0

8

12

8.2

8

12

8.5

9

12

8.7

6

12

8.8

7

12

8.9

2

13

1.5

3

13

1.6

1

13

5.4

7

13

5.6

1

14

2.9

3

14

3.1

7

14

3.2

2

14

3.5

1

17

9.1

4

17

9.1

8

apr-695 C13CPD CDCl3 26/02/2021

11b

S105

1H NMR spectrum of 12

9 8 7 6 5 4 3 2 1 0 ppm

1.0

35

1.1

83

1.5

11

2.3

20

3.7

15

3.7

57

3.8

66

3.9

08

4.6

38

4.6

78

5.2

42

5.2

82

6.5

44

6.5

64

6.8

50

6.8

69

6.8

87

7.0

70

7.0

89

7.1

08

7.1

40

7.1

60

7.1

68

7.1

90

7.2

03

7.2

21

7.2

39

7.3

15

7.3

32

7.7

17

7.7

38

9.1

0

3.0

0

1.9

5

0.8

8

0.9

4

0.9

7

1.0

8

9.8

3

1.9

2


12

S106

13C NMR spectrum of 12

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

21

.66

26

.43

42

.48

43

.86

76

.71

77

.03

77

.34

80

.73

82

.39

10

9.1

7

12

2.0

2

12

4.0

9

12

7.0

9

12

8.3

3

12

8.5

5

12

9.2

2

12

9.7

4

13

4.0

1

13

5.9

2

14

4.2

8

14

4.5

0

17

3.9

6

19

4.2

4

apr-540 C13CPD CDCl3 5/11/2019

12

S107

1H NMR spectrum of 13

9 8 7 6 5 4 3 2 1 0 ppm

2.4

37

3.6

09

3.6

52

3.8

93

3.9

36

4.9

24

4.9

63

4.9

98

5.0

37

6.7

52

6.7

70

7.0

08

7.0

25

7.0

43

7.2

00

7.2

18

7.2

39

7.2

61

7.2

79

7.3

08

7.3

26

7.3

55

7.3

72

7.3

90

7.4

12

7.4

33

7.4

53

7.8

35

7.8

54

3.0

0

0.9

8

0.9

3

2.6

3

0.9

8

1.0

1

9.0

6

1.9

4


13

S108

13C NMR spectrum of 13

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

21

.73

43

.99

44

.52

74

.62

76

.78

77

.10

77

.41

10

9.7

0

12

3.1

1

12

4.0

3

12

7.3

4

12

7.6

6

12

8.3

9

12

8.8

5

12

9.4

1

12

9.8

2

13

0.2

2

13

4.0

1

13

5.5

7

14

2.9

3

14

4.8

1

17

6.7

0

19

7.7

8

apr-602 C13CPD CDCl3 8/1/2021

13

S109

References

1. Cava, M. P.; Little, R. L.; Naipier, D. R. J. Am. Chem. Soc. 1958, 80, 2257.

2. Kazi, I.; Guha, S.; Sekar, G. Org. Lett. 2017, 19, 1244 and references cited therein.

3. Cao, S-H.; Zhang, X-C.; Wei, Y.; Shi, M. Eur. J. Org. Chem. 2011, 2668.

4. Gandikota, N. M.; Bollaa, R. S.; Bandyopadhyay, A.; Viswanath, I. V. K. Russian Journal of Organic Chemistry, 2019, 55,

1197.

5. Tan, B.; Candeias, N. R.; Barbas, C. F. Nature Chem. 2011, 3, 473.

6. Shao, J.; Luo, Q.; Bi, H.; Wang, S. R. Org. Lett. 2021, 23, 459.

7. Empel, C.; Verspeek, D.; Jana, S.; Koenigs, R. M. Adv. Synth. Catal. 2020, 362, 4716.

Supporting Information for BF3·OEt2 Catalyzed chemoselective C=C ...

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