Oxidative Rearrangement of Alkenes using In Situ Generated

Hypervalent Iodine(III)

Supplementary Material

Anees Ahmad,a Paulo Scarassati,a Nazli Jalalian,a,b Berit Olofsson,b Luiz F. Silva, Jr a*

a Instituto de Química - Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, CP

26077, CEP 05513-970 São Paulo SP, Brazil

b Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-

106 91 Stockholm, Sweden

E-mail: luizfsjr@iq.usp.br

Contents

Page

1. Experimental Section 2

2. Selected NMR Spectra 5

NMR of 2 5

NMR of 4 6

NMR of 5 7

NMR of 7 8

NMR of 9 9

NMR of 11 10

NMR of 13 11

NMR of 15 12

NMR of 17 13

1

1. Experimental Section

General information

All commercially available reagents were used without further purification unless otherwise noted.

All solvents used for reactions and chromatography were dried and purified by standard methods.

TLC analyses were performed using silica gel 60F 254 precoated plates, with detection by UV-

absorption (254 nm) and by spraying with p-anisaldehyde and phosphomolybdic acid solutions

followed by charring at ~150 °C for visualization. Flash column chromatography was performed

using silica gel 200-400 Mesh. All NMR analyses were recorded using CDCl3 as solvent and TMS as

internal standard. Chemical shifts are reported in ppm downfield from TMS with reference to internal

solvent. Preparation of substrates 1,1, 2 3,1, 3 6,2 8,1 10,1 12,2 14,4 and 165 were performed as described in

the literature.

(1,2,3,4-Tetrahydronaphthalen-4-yl)methanol (2). General Procedure A: In situ generation of

HTIB for Oxidative Rearrangement of Alkenes followed by reduction with NaBH4. To a stirred

solution of PhI (0.204 g, 0.114 mL, 1.00 mmol) in HFIP/CH2Cl2 (1:6, 3.5 mL) was added mCPBA

(77%, 0.224 g, 1.00 mmol), followed by TsOH.H2O (0.19 g, 1.0 mmol). The resulting solution was

stirred at rt for 30 min. H2O (0.40 mL, 22 mmol) and alkene 1 (0.115 g, 0.800 mmol) was added at 0

oC. After 2 min, NaBH4 (0.19 g, 5.0 mmol) was added. The mixture was stirred for 2 h. The reaction

was quenched with saturated solution of NaHCO3, extracted with EtOAc, washed with brine and dried

over anhydrous MgSO4. The solvent was evaporated under reduced pressure. The crude product was

purified by flash column chromatography (10-20%, EtOAc in hexane), giving alcohol 26 (0.920 g,

0.570 mmol, 71%) as colorless oil.

(3,4-Dihydro-2H-chromen-4-yl)methanol (7). The reaction was performed following General

Procedure A, using PhI (0.204 g, 0.114 mL, 1.00 mmol), mCPBA (77%, 0.224 g, 1.00 mmol) and

TsOH.H2O (0.19 g, 1.0 mmol) in HFIP/CH2Cl2 (1:6, 3.5 mL). After 30 min, H2O (0.40 mL, 22 mmol)

and alkene 6 (0.118 g, 0.810 mmol) was added at 0 oC. NaBH4 (0.19 g, 5.0 mmol) was added once the

starting material was finished. Purification by flash column chromatography (10-20% EtOAc in

hexane) gave compound 72 (0.11 g, 0.67 mmol, 83%) as colorless oil.

(2,3-Dihydro-1H-inden-1-yl)metanol (9). The reaction was performed following General Procedure

A, but using PhI (0.490 g, 0.274 mL, 2.40 mmol), mCPBA (77%, 0.538 g, 2.30 mmol) and

TsOH.H2O (0.456 g, 2.30 mmol) in HFIP/CH2Cl2 (1:6, 6 mL). After 30 min, H2O (0.40 mL, 22 mmol)

and alkene 8 (0.270 g, 2.08 mmol) was added at 0 oC. NaBH4 (0.19 g, 5.0 mmol) was added once the

2

starting material was finished. Purification by flash column chromatography (10-20% EtOAc in

hexane) gave alcohol 91 (0.202 g, 1.36 mmol, 65%) as colorless oil.

8,9-Dihydro-5H-benzo[7]annulen-6(7H)-one (15). General Procedure B: In situ generation of

HTIB for Oxidative Rearrangement of Alkenes. The reaction was performed, using PhI (0.204 g,

0.114 mL, 1.00 mmol), mCPBA (77%, 0.224 g, 1.00 mmol), and TsOH.H2O (0.19 g, 1.0 mmol) in

HFIP/CH2Cl2 (1:6, 5 mL). After 30 min, H2O (0.40 mL, 22 mmol) and alkene 14 (0.125 g, 0.870

mmol) was added at 0 oC. The reaction was quenched with saturated solution of NaHCO3, extracted

with EtOAc, washed with brine and dried over anhydrous MgSO4. Purification by flash column

chromatography (5-8% EtOAc in hexane) gave compound 157 (0.135 g, 0.840 mmol, 97%) as

colorless oil.

1-Phenylpropan-2-one (17). The reaction was performed following the General Procedure B, but

using PhI (0.204 g, 0.114 mL, 1.00 mmol), mCPBA (77%, 0.224 g, 1.00 mmol), and TsOH.H2O (0.19

g, 1.0 mmol) in HFIP/CH2Cl2 (1:6, 5 mL). After 30 min, H2O (0.40 mL, 22 mmol) and alkene 16

(0.094 g, 0.80 mmol) was added at 0 oC. Purification by flash column chromatography (5-8% EtOAc

in hexane) gave compound 175 (0.087 g, 0.65 mmol, 81%) as colorless oil.

1-(1,2,3,4-Tetrahydronaphthalen-4-yl)ethanone (11). General Procedure C: In situ Generation

of HTIB for Ring Contraction of Methyl Substituted Cyclic Alkenes. To a stirred solution of PhI

(0.204 g, 0.114 mL, 1.00 mmol) in TFE/CH2Cl2 (1:1, 5 mL) was added mCPBA (77%) (0.224 g, 1.00

mmol), followed by TsOH.H2O (0.19 g, 1.0 mmol). The resulting solution was stirred at rt for 30 min.

To this mixture alkene 10 (0.127 g, 0.800 mmol) was added at 0 oC. The reaction was quenched with

NaHCO3, extracted with EtOAc, washed with brine and dried over anhydrous MgSO4. The solvent

was evaporated under reduced pressure. The crude product was purified by flash column

chromatography (5-7%, EtOAc in hexane), giving ketone 111 (0.111 g, 0.640 mmol, 79%) as

colorless liquid.

1-(3,4-Dihydro-2H-chromen-4-yl)ethanone (13). The reaction was performed following General

Procedure C, but using PhI (0.204 g, 0.114 mL, 1.00 mmol), mCPBA (77%, 0.224 g, 1.00 mmol), and

TsOH.H2O (0.19 g, 1.0 mmol) in TFE/CH2Cl2 (1:1, 5 mL). After 30 min, alkene 12 (0.135 g, 0.840

mmol) was added at 0 oC. Purification by flash column chromatography (5-7% EtOAc in hexane)

gave ketone 132 (0.091 g, 0.51 mmol, 61%) as colorless oil.

1-(2,3-Dihydro-1H-inden-1-yl)ethanone (4) The reaction was performed following General

Procedure C, but using PhI (0.063 g, 0.035 mL, 0.31 mmol), mCPBA (77%, 0.070 g, 0.31 mmol), and

TsOH.H2O (0.060 g, 0.31 mmol) in TFE/CH2Cl2 (1:1, 5 mL). After 30 min, alkene 3 (0.044 g, 0.30

3

mmol) was added at 0 oC. Purification by flash column chromatography (5-7% EtOAc in hexane)

gave compound 41 (0.035 g, 0.22 mmol, 73%) as colorless oil.

1-Methyl-2-tetralone (5) To a stirred solution of 3 (0.115 g, 0.800 mmol) in TFE/CH2Cl2 (1:4, 5 mL)

at 0 oC was added mCPBA (77%, 0.224 g, 1.00 mmol), and TsOH.H2O (0.19 g, 1.0 mmol). After 20

min, the reaction was quenched with NaHCO3. Purification by flash column chromatography (7-10%

EtOAc in hexane) gave ketone 57 (0.104 g, 0.650 mmol, 81 %) as colorless oil.

Reaction of 6,7-dihydro-5H-benzo[7]annulene (1) with In situ generation of Iodine(III) from p-

C6H4I2. The reaction was performed using p-C6H4I2 (0.165 g, 0.500 mmol), mCPBA (77%, 0.224 g,

1.00 mmol), and TsOH.H2O (0.19 g, 1.0 mmol) in HFIP/CH2Cl2 (1:6, 5 mL). After 2 h, H2O (0.4 mL,

22 mmol) and alkene 1 (0.124 g, 0.860 mmol) were added at 0 oC. Purification by flash column

chromatography (10-20% EtOAc in hexane) gave alcohol 26 (0.089 g, 0.55 mmol, 63%) as colorless

oil.

Reaction of 6,7-dihydro-5H-benzo[7]annulene (1) with HTIB in HFIP/CH2Cl2/H2O followed by

in situ reduction. The reaction was performed, using alkene 1 (0.150 g, 1.04 mmol), HTIB (0.448g,

1.14 mmol) HFIP/CH2Cl2 (1:6, 6 mL) and H2O 22 equiv at 0 oC. NaBH4 was added in excess (5

equiv.). Purification by flash column chromatography (10-20% EtOAc in hexane) gave alcohol 26

(0.109 g, 0.672 mmol, 65%) as colorless oil.

References:

1. Siqueira, F. A.; Ishikawa, E. E.; Fogaca, A.; Faccio, A. T.; Carneiro, V. M. T.; Soares, R. R. S.; Utaka, A.; Tebeka, I. R. M.; Bielawski, M.; Olofsson, B.; Silva, L. F., Jr. J. Braz. Chem. Soc. 2011, 22, 1795.

2. Ahmad, A.; Silva, L. F., Jr. Synthesis 2012, 44, 3671.3. Silva, L. F., Jr.; Siqueira, F. A.; Pedrozo, E. C.; Vieira, F. Y. M.; Doriguetto, A. C. Org. Lett. 2007, 9, 1433.4. Phan, D. H. T.; Kou, K. G. M.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 16354.5. Justik, M. W.; Koser, G. F. Tetrahedron Lett. 2004, 45, 6159.6. Taylor, S. K.; Hockerman, G. H.; Karrick, G. L.; Lyle, S. B.; Schramm, S. B. J. Org. Chem. 1983, 48, 2449.7. Justik, M. W.; Koser, G. F. Molecules 2005, 10, 217.

4

Selected NMR Spectra

ppm (t1)0.000.501.001.502.002.503.003.504.004.505.005.506.006.507.007.50

7.2477.2257.2027.1697.1567.1387.1257.1097.0947.079

3.8153.7833.0072.9792.9502.7912.7622.7311.9481.9421.9161.8961.8861.8751.8521.8341.8221.8031.7951.7851.7651.7371.7261.6471.541

2.00

0.87

1.93

0.85

4.03

0.90

3.02

HO

1H-NMR of 2, 200 MHz, CDCl3

ppm (t1)0255075100125

138.150136.644

129.334128.682126.101125.670

77.63677.00076.365

67.121

40.279

29.685

25.173

19.761

HO

13C-NMR of 2, 50 MHz, CDCl3

5

1H-NMR of 4, 200 MHz, CDCl3

6

1H-NMR of 5, 200 MHz, CDCl3

13C-NMR of 5, 50 MHz, CDCl3

7

ppm (t1)0.000.501.001.502.002.503.003.504.004.505.005.506.006.507.007.508.008.509.00

7.2527.1817.1807.1797.1597.1567.1537.1527.1257.1227.1196.8996.8956.8746.8706.8426.8386.8156.8115.2874.2084.1944.1904.1874.170

3.9163.8993.8803.8633.8253.7983.7883.7623.0112.9932.9852.9672.1092.1002.0902.0832.0722.0672.0642.0512.0401.6940.000

1.00

1.21

2.15

1.92

0.95

0.98

1.96

1.02

1.03

ppm (t1)6.806.907.007.107.20

7.2527.1817.1807.1797.1597.1567.1537.1527.1257.1227.119

6.8996.8956.8746.8706.8426.8386.8156.811

0.95

0.98

1.96

ppm (t1)1.752.002.252.502.753.003.253.503.754.004.254.50

4.2084.1944.1904.1874.1703.9163.8993.8803.8633.8253.7983.7883.762

3.0112.9932.9852.967

2.1092.1002.0902.0832.0722.0672.0642.0512.0401.694

1.00

1.21

2.15

1.92

1.02

1.03

O

HO

1H-NMR of 7, 300 MHz, CDCl3

ppm (t1)255075100125150

155.286

129.161127.896122.055120.285117.074

77.42477.00076.576

66.41963.337

36.033

24.374

O

HO

13C-NMR of 7, 75 MHz, CDCl3

8

ppm (t1)0.000.501.001.502.002.503.003.504.004.505.005.506.006.507.007.508.00

7.3007.2777.2577.2497.2277.2177.2107.1957.1827.1697.150

3.8113.7803.4223.3923.3603.3523.3222.9862.9512.9112.8762.8302.3572.3242.3162.2922.2842.2752.2602.2522.2432.2202.2102.1782.0191.9881.9761.9561.9451.9241.9131.8921.8811.6541.525

2.00

0.87

1.97

0.89

0.89

0.78

0.32

4.20

HO

1H-NMR of 9, 200 MHz, CDCl3

ppm (t1)0255075100125

144.741143.774

126.963126.218124.753124.077

77.68677.04976.413

65.916

47.536

31.35628.430

-0.00000

HO

13C-NMR of 9, 50 MHz, CDCl3

9

ppm (t1)0.000.501.001.502.002.503.003.504.004.505.005.506.006.507.007.508.00

7.2517.2137.2087.2027.1857.1737.1547.1437.1327.1107.0026.9906.9786.9646.954

3.8293.788

2.8242.7922.7642.4662.1152.0352.0232.0182.0131.996

1.07

2.00

0.05

0.84

3.28

6.04

0.48

O

1H-NMR of 11, 200 MHz, CDCl3

10

ppm (t1)0.02.55.07.5

7.2587.2007.1987.1947.1927.1707.1677.0517.0497.0487.0467.0457.0437.0426.9156.9116.8916.8866.8706.8696.8686.8666.8436.8426.8406.8395.2894.2004.1924.1894.1754.1744.1714.1624.1584.1563.8163.7963.7762.3202.2742.2622.2552.2432.2362.2252.2022.2012.1542.1392.1332.1282.1192.1132.1072.0922.0461.648

2.11

1.02

1.05

1.20

1.15

3.00

1.12

0.84

1.04

ppm (t1)6.806.907.007.107.20

7.2007.1987.1947.1927.1707.1677.0517.0497.0487.0467.0457.0437.0426.9156.9116.8916.8866.8706.8696.8686.8666.8436.8426.8406.839

1.02

1.05

1.12

0.84

ppm (t1)2.002.252.502.753.003.253.503.754.004.25

4.2004.1924.1894.1754.1744.1714.1624.1584.1563.8163.7963.776

2.3202.2742.2622.2552.2432.2362.2252.2022.2012.1542.1392.1332.1282.1192.1132.1072.0922.046

2.11

1.20

1.15

3.00

1.04

O

O

1H-NMR of 13, 300 MHz, CDCl3

ppm (t1)0255075100125150175200

208.794

154.636

129.990128.654120.480118.999117.400

77.42477.00076.576

63.761

48.473

27.99124.502

O

O

13C-NMR of 13, 75 MHz, CDCl3

11

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.2557.2267.2117.2037.1997.1897.1827.1767.1677.1607.1527.131

3.726

2.9802.9492.9382.9162.6012.5662.5322.0542.0322.0212.0132.0011.9881.9771.954

2.00

2.05

1.90

2.09

4.11

O

1H-NMR of 15, 200 MHz, CDCl3

ppm (f1)050100150200

208.636

140.391133.513129.497129.143127.497127.045

77.63677.00076.364

50.097

43.617

32.943

26.209

O

13C-NMR of 15, 50 MHz, CDCl3

12

1H-NMR of 17, 200 MHz, CDCl3

13C-NMR of 17, 50 MHz, CDCl3

13