The Journal of Organic Chemistry
Article
Trifluoromethanesulfonic anhydride (0.037 mL, 0.27 mmol) was
added dropwise over 10 min, and the resulting mixture was stirred for
3 h. Water (2 mL) was added, and the mixture was warmed to 25 °C.
The mixture was extracted with CH2Cl2 (3 × 1 mL). The combined
organic layers were dried over Na2SO4 and concentrated. The resulting
oil was purified by flash chromatography (hexanes:EtOAc = 96:4) to
MS ES+) m/z calcd for C20H32NaO3Si (M + Na)+ 371.2013, found
371.2013.
Silyl Ether 3. To a solution of silyl peroxide 17 (0.056 g, 0.16
mmol) in toluene (0.40 mL) was added triphenylphosphine (0.059 g,
0.22 mmol). The mixture was heated to 100 °C and stirred for 24 h.
Upon cooling to 25 °C, H2O (2 mL) was added, and the mixture was
extracted with EtOAc (3 × 2 mL). The combined organic layers were
dried over Na2SO4 and concentrated. The resulting oil was purified by
flash chromatography (hexanes/Et2O = 80:20) to afford silyl ether 3
(0.042 g, 79%) as a clear colorless oil. Characterization was performed
on an inseparable 60:40 mixture of diastereomers: 1H NMR (600
MHz, CDCl3) δ 7.51 (d, J = 8.3, 0.6H), 7.49 (d, J = 8.4, 0.4H), 7.06−
7.08 (m, 1H), 6.78 (s, 0.4H), 6.69 (s, 0.6H), 3.81−3.82 (m, 0.6H),
3.68 (t, J = 6.5, 0.4H), 2.29 (s, 1.2H), 2.27 (s, 1.8H), 2.18−2.29 (m,
1H), 2.12 (s, 1.2H), 2.11 (s, 1.8H), 1.88−2.06 (m, 2.6H), 1.77−1.81
(m, 0.4H), 1.56 (s, 1.8H), 1.53 (s, 1.2H), 0.88−0.91 (m, 9H), 0.46−
0.58 (m, 6H); 13C NMR (150 MHz, CDCl3) δ 210.9 (C), 210.7 (C),
141.8 (C), 141.3 (C), 136.8 (C), 136.7 (C), 132.2 (C), 131.9 (C),
129.5 (CH), 128.7 (CH), 128.4 (CH), 128.3 (CH), 127.1 (CH),
127.0 (CH), 72.8 (C), 72.4 (C), 54.3 (CH), 53.7 (CH), 37.7 (CH2),
37.3 (CH2), 32.5 (CH3), 31.9 (CH3), 27.8 (CH3), 27.5 (CH3), 23.9
(CH2), 23.1 (CH2), 21.14 (CH3), 21.13 (CH3), 7.24 (CH3), 7.26
(CH3), 6.84 (CH2), 6.79 (CH2); IR (ATR) 2952, 2875, 1707, 1159,
904, 733 cm−1; HRMS (TOF MS ES+) m/z calcd for C20H32NaO2Si
(M + Na)+ 355.2064, found 355.2070.
Olefin 18. To ketone 3 (0.011 g, 0.034 mmol) was added a
solution of Cp2TiMe2 (5% w/v in THF/toluene, 0.4 mL, 0.1 mmol).
The mixture was heated at 65 °C and stirred for 24 h. Upon cooling to
25 °C, the mixture was filtered through a plug of silica eluted with
CH2Cl2 (8 mL). The filtrate was concentrated to afford olefin 18 (9.6
mg, 86%) as a clear colorless oil. Characterization was performed using
on an inseparable 60:40 mixture of diastereomers: 1H NMR (600
MHz, CDCl3) δ 7.46 (dd, J = 8.0, 1.0, 0.6H), 7.44 (dd, J = 8.0, 0.9,
0.4H), 6.99−7.00 (m, 1H), 6.85−6.86 (m, 1H), 4.91−4.92 (m, 1H),
4.81(m, 0.6H), 4.57 (m, 0.4H), 3.52 (dd, J = 10.2, 6.0, 0.6H), 3.40 (t, J
= 6.4, 0.4H), 2.27 (s, 1.2H), 2.26 (s, 1.8H), 1.90−2.07 (m, 2.6H),
1.78−1.85 (m, 1H), 1.72−1.76 (m, 0.4H), 1.70 (s, 1.2H), 1.58 (s,
1.8H), 1.52 (d, J = 1.4, 1.2H), 1.50 (d, J = 1.1, 1.8H), 0.87−0.92 (m,
9H), 0.46−0.57 (m, 6H); 13C NMR (150 MHz, CDCl3) δ 149.3 (C),
148.5 (C), 142.4 (C), 141.3 (C), 136.7 (C), 136.2 (C), 136.1 (C),
136.0 (C), 129.5 (CH), 128.4 (CH), 127.21 (CH), 127.19 (CH),
126.6 (CH), 126.5 (CH), 113.9 (CH2), 113.8 (CH2), 73.6 (C), 72.8
(C), 48.3 (CH), 47.3 (CH), 38.6 (CH2), 37.3 (CH2), 33.3 (CH3),
32.2 (CH3), 26.8 (CH2), 25.0 (CH2), 21.3 (CH3), 21.2 (CH3), 20.5
(CH3), 18.8 (CH3), 7.29 (CH3), 7.27 (CH3), 6.90 (CH2), 6.88
(CH2); IR (ATR) 2950, 2875, 1111, 1070, 1038, 1006, 743, 724 cm−1;
HRMS (TOF MS ES+) m/z calcd for C21H34NaOSi (M + Na)+
353.2271, found 353.2269.
Silyl Peroxide 19. A flask containing 1,2-dichloroethane (0.20
mL) was sparged with oxygen for 30 min. A separate flask containing
olefin 18 (0.013 g, 0.040 mmol) and Co(acac)2 (2 mg, 8 μmol) was
flushed with oxygen. The oxygenated solvent was added to the
reaction mixture. Triethylsilane (0.016 mL, 0.10 mmol) was added,
and the mixture was stirred for 15 h under a balloon of oxygen. The
mixture was concentrated, and the resulting residue was taken up in
CH2Cl2 and filtered through a plug of silica eluted with CH2Cl2 (25
mL). The filtrate was concentrated to afford silyl peroxide 19 (0.018 g,
95%) as a clear colorless oil. Characterization was performed on an
inseparable 60:40 mixture of diastereomers: 1H NMR (600 MHz,
CDCl3) δ 7.57−7.58 (m, 0.6H), 7.50 (m, 0.4H), 7.46 (d, J = 8.0,
0.6H), 7.40 (d, J = 8.0, 0.4H), 6.97−7.00 (m, 1H), 3.41 (dd, J = 10.1,
7.0, 0.6H), 3.34 (t, J = 7.1, 0.4H), 2.30 (s, 1.2H), 2.29 (s, 1.8H), 1.79−
2.04 (m, 3.4H), 1.69 (ddd, J = 13.3, 10.1, 3.8, 0.6H), 1.53 (s, 1.2H),
1.48 (s, 1.8H), 1.37 (s, 1.2H), 1.35 (s, 1.8H), 1.02−1.05 (m, 9H),
0.88−0.91 (m, 12H), 0.73−0.78 (m, 6H), 0.46−0.58 (m, 6H); 13C
NMR (150 MHz, CDCl3) δ 143.4 (C), 141.3 (C), 136.4 (C), 135.5
(C), 135.4 (C), 135.2 (C), 131.7 (CH), 130.9 (CH), 126.8 (CH),
126.7 (CH), 125.9 (CH), 125.8 (CH), 87.0 (C), 86.9 (C), 73.3 (C),
72.4 (C), 42.1 (CH), 42.0 (CH), 38.6 (CH2), 38.4 (CH2), 32.3
(CH3), 31.9 (CH3), 25.0 (CH3), 24.8 (CH3), 24.1 (CH2), 22.4 (CH2),
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afford triflate 4 (0.069 g, 97%) as a yellow oil: H NMR (600 MHz,
CDCl3) δ 7.19 (d, J = 8.4, 1H), 7.14 (dd, J = 8.4, 2.2, 1H), 7.07 (d, J =
2.2, 1H), 5.76 (ddt, J = 17.0, 10.2, 6.7, 1H), 4.97−5.02 (m, 2H), 4.05
(t, J = 7.2, 1H), 2.34 (s, 3H), 2.19 (dddd, J = 13.6, 8.9, 7.6, 6.0, 1H),
2.12 (s, 3H), 2.00−2.07 (m, 1H), 1.92−1.99 (m, 1H), 1.65−1.71 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 206.8 (C), 145.6 (C), 139.3
(C), 137.5 (CH), 131.7 (C), 129.87 (CH), 129.84 (CH), 121.5 (CH),
118.7 (q, J = 312, CF3), 115.6 (CH2), 50.6 (CH), 31.6 (CH2), 31.4
(CH3), 30.0 (CH2), 21.1 (CH3); 19F NMR (377 MHz, CDCl3) δ
−73.8 (s); IR (ATR) 2931, 1720, 1421, 1358, 1216, 1168, 1141 cm−1;
HRMS (TOF MS ES+) m/z calcd for C15H17F3NaO4S (M + Na)+
373.0692, found 373.0680. Anal. Calcd for C15H17F3O4S: C, 51.42; H,
4.89. Found: C, 51.44; H, 4.90.
Enones 16 and Δ9,10-16. To a sealed bomb were added K2CO3
(0.705 g, 5.10 mmol), triphenylphosphine (0.134 g, 0.510 mmol), and
palladium(II) acetate (0.038 mg, 0.17 mmol), followed by a solution of
triflate 4 (0.596 g, 1.70 mmol) in acetonitrile (22 mL). The sealed
bomb was heated at 80 °C for 20 h and then cooled to 25 °C. The
mixture was filtered through a plug of silica, eluted with CH2Cl2 (75
mL), and concentrated. The resulting oil was purified by flash
chromatography (hexanes:EtOAc = 85:15) to afford an inseparable
mixture of isomers 16 and Δ9,10-16 (20:3, 0.312 g, 91%) as a clear
colorless oil (note that isomeric ratios vary greatly in repeated
1
experiments). 16: H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.1,
1H), 7.16 (d, J = 8.1, 1H), 6.82 (s, 1H), 5.47 (m, 1H), 4.96 (m, 1H),
3.82 (t, J = 6.5, 1H), 2.56−2.63 (m, 1H), 2.43−2.50 (m, 1H), 2.31 (s,
3H), 2.11 (s, 3H), 2.10 (q, J = 6.3, 2H); 13C NMR (100 MHz, CDCl3)
δ 210.5 (C), 142.2 (C), 138.0 (C), 133.7 (C), 132.5 (C), 129.8 (CH),
128.4 (CH), 124.9 (C), 123.6 (CH), 122.7 (C), 108.3 (CH2), 54.5
(CH), 30.4 (CH2), 28.1 (CH3), 21.3 (CH3), 19.2 (CH2). Δ9,10-16: 1H
NMR (400 MHz, CDCl3) δ 7.17 (d, J = 7.8, 1H), 7.09 (d, J = 7.8, 1H),
7.00 (s, 1H), 5.72−5.73 (m, 1H), 3.53 (dd, J = 7.5, 3.7, 1H), 2.70−
2.77 (m, 1H), 2.47−2.54 (m, 1H), 2.34 (s, 3H), 2.04 (s, 3H), 2.00−
2.01 (m, 3H); 13C NMR (only diagnostic peaks reported, 100 MHz,
CDCl3) δ 129.7 (CH), 123.6 (C), 122.7 (CH), 52.2 (CH), 28.4
(CH2), 26.6 (CH2). Mixture: IR (ATR) 2932, 1704, 1353, 1152, 881,
821 cm−1; HRMS (TOF MS ES+) m/z calcd for C14H16NaO (M +
Na)+ 223.1099, found 223.1093. Anal. Calcd for C14H16O: C, 83.96;
H, 8.05. Found: C, 83.85; H, 7.90.
Silyl Peroxide 17. A flask containing 1,2-dichloroethane (12 mL)
was sparged with oxygen for 30 min. To a separate flask were added
isomers 16 and Δ9,10-16 (0.963 g, 4.81 mmol) and Co(acac)2 (0.247
mg, 0.962 mmol). The reaction flask was flushed with oxygen, and the
oxygenated solvent was added. Triethylsilane (1.92 mL, 12.0 mmol)
was added, and the mixture was stirred for 24 h under a balloon of
oxygen. The mixture was concentrated, and the resulting residue was
taken up in CH2Cl2 and filtered through a plug of silica eluted with
CH2Cl2 (125 mL). The filtrate was concentrated to afford silyl
peroxide 17 (1.42 g, 85%) as a clear colorless oil. Characterization was
1
performed using a 60:40 mixture of diastereomers: H NMR (600
MHz, CDCl3) δ 7.46 (d, J = 8.0, 0.4H), 7.43 (d, J = 8.0, 0.6H), 7.08−
7.09 (m, 1H), 6.80 (s, 0.4H), 6.78 (s, 0.6H), 3.80 (t, J = 5.8, 0.6H),
3.65 (dd, J = 7.7, 7.3, 0.4H), 2.52 (ddd, J = 13.9, 7.7, 3.3, 0.4H), 2.38
(ddd, J = 13.9, 7.6, 3.2, 0.6H), 2.30 (s, 1.2H), 2.29 (s, 1.8H), 2.16−
2.24 (m, 1H), 2.17 (s, 1.8H), 2.02 (s, 1.2H), 1.90−2.00 (m, 1H), 1.73
(ddd, J = 12.9, 10.8, 3.1, 0.6H), 1.60 (ddd, J = 13.7, 10.3, 3.2, 0.4H),
1.55 (s, 3H), 0.93−0.96 (m, 9H), 0.61−0.67 (m, 6H); 13C NMR (150
MHz, CDCl3) δ 211.4 (C), 210.4 (C), 138.0 (C), 137.6 (C), 136.1
(C), 135.7 (C), 134.7 (C), 134.5 (C), 129.6 (CH), 129.2 (CH), 128.3
(CH), 128.24 (CH), 128.22 (CH), 128.1 (CH), 80.99 (C), 80.96 (C),
54.7 (CH), 53.8 (CH), 31.2 (CH2), 30.5 (CH2), 28.5 (CH3), 27.3
(CH3), 26.4 (CH3), 25.8 (CH3), 22.84 (CH2), 22.80 (CH2), 21.21
(CH3), 21.19 (CH3), 6.90 (CH3), 6.89 (CH3), 3.99 (CH2), 3.97
(CH2); IR (ATR) 2955, 2877, 1709, 1164, 522 cm−1; HRMS (TOF
E
J. Org. Chem. XXXX, XXX, XXX−XXX