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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: [email protected]
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