1274
C. N. Slattery et al. / Tetrahedron: Asymmetry 24 (2013) 1265–1275
4.21. General procedure for the C–H insertion reactions of
diazo-b-keto sulfones 23–28
a
-
2.49–2.70 [3H, m, C(5)H2, one of C(4)H2], 3.91 [1H, d, J 7.5,
C(2)HSO2], 4.05–4.14 [1H, m, C(3)HPh], 7.12–7.16 (2H, m, aromatic
H), 7.20–7.32 (3H, m, aromatic H), 7.47–7.53 (2H, m, aromatic H),
7.59–7.65 (1H, m, aromatic H), 7.77–7.83 (2H, m, aromatic H).
The CuCl2-L⁄-NaBARF catalyst was generated in situ from a mix-
ture of CuCl2 (5 mol %), bis(oxazoline) ligand (6 mol %) and NaBARF
(6 mol %) in DCM (15 mL). This catalytic mixture was stirred under
4.21.6. trans-2-Phenylsulfonyl-3-benzylcyclopentanone 3425
White solid, mp 83–85 °C; m
max(KBr)/cm–1 1750 (C@O), 1307,
nitrogen at 40 °C for 1.5 h. Next,
a-diazo-b-keto sulfone 23–28
(150 mg, 1 equiv) was added dropwise in DCM (15 mL) over 0.5 h
to the refluxing solution. The progress of the reaction was moni-
tored by IR spectroscopy, where reaction completion was indicated
by the disappearance of the characteristic diazo peak at 2110–
2126 cm–1. Upon reaction completion, evaporation of the reaction
solvent at reduced pressure gave the crude product. Purification
by flash chromatography on silica gel, employing ethyl acetate in
hexane as eluent, gave the pure cyclopentanone products 29–34.
1142 (SO2); dH (400 MHz) 1.57–1.68 [1H, m, one of C(4)H2],
2.10–2.27 [1H, m, one of C(4)H2], 2.28–2.42 [2H, m, C(5)H2], 2.78
[1H, dd, HA of ABC, J 13.6, 8.8, one of CH2Ph], 3.06 [1H, dd, HB of
ABC, J 13.2, 5.2, one of CH2Ph], 3.14–3.24 [1H, m, HC of ABC,
C(3)HBn], 3.49 [1H, d, J 7.2, C(2)HSO2], 7.14–7.20 (2H, m, aromatic
H), 7.22–7.34 (3H, m, aromatic H), 7.54–7.61 (2H, m, aromatic H),
7.65–7.71 (1H, m, aromatic H), 7.82–7.88 (2H, m, aromatic H).
4.22. General procedure for the aromatic addition reactions of
4.21.1. trans-2-Phenylsulfonyl-3-methylcyclopentanone 2925
a-diazo ketone 35–39 and 45
White solid, mp 123–125 °C; m
max(KBr)/cm–1 1744 (C@O), 1305,
1141 (SO2); dH (400 MHz) 1.29 (3H, d, J 6.8, CH3), 1.45–1.59 [1H, m,
one of C(4)H2], 2.25–2.40 [3H, m, C(5)H2, one of C(4)H2], 2.95–3.04
[1H, m, C(3)HCH3] 3.34 [1H, d, J 8.0, C(2)HSO2], 7.56–7.60 (2H, m,
aromatic H), 7.66–7.71 (1H, m, aromatic H), 7.87–7.90 (2H, m, aro-
matic H).
Diazo ketone 35–39 and 45 (100 mg, 1 equiv) in DCM (75 mL)
was added dropwise over 1 h to
a refluxing solution of
[Cu(MeCN)4]PF6 (6 mol %) and bis(oxazoline) ligand (6 mol %) in
DCM (75 mL). The progress of the reaction was monitored by TLC
and was found generally to be complete upon diazo ketone addi-
tion. Evaporation of the solvent at reduced pressure gave the crude
product. A 1H NMR spectrum of the crude material was recorded in
order to determine the efficiency of the cyclisation. Purification by
flash chromatography on silica gel employing ethyl acetate in hex-
ane as eluent, gave the pure azulenones 40–44, 46.
4.21.2. trans-2-Phenylsulfonyl-3-ethylcyclopentanone 3025
White solid, mp 79–81 °C; m
max(KBr)/cm–1 1743 (C@O), 1308,
1147 (SO2); dH (300 MHz) 0.98 (3H, t, J 7.5, CH3), 1.39–1.60 [2H,
m, one of CH2CH3, one of C(4)H2], 1.74–1.88 (1H, m, one of
CH2CH3), 2.28–2.50 [3H, m, C(5)H2, one of C(4)H2], 2.82–2.94
[1H, m, C(3)H], 3.39 [1H, d, J 6.9, C(2)HSO2], 7.54–7.61 (2H,
m, aromatic H), 7.65–7.72 (1H, m, aromatic H), 7.85–8.00 (2H,
m, aromatic H).
4.22.1. 3,8a-Dihydro-3,3,8a-trimethylazulen-1(2H)-one 407
Pale yellow oil;
m
max/cmꢀ1 (film) 1748 (CO), 1716 (CO); dH
(300 MHz) 0.75 [3H, s, C(8a)CH3], 1.14, 1.31 [2 ꢂ 3H, 2ꢂ s,
C(3)(CH3)2], 2.20 [1H, A of ABq, JAB 17.3, one of C(2)H2], 2.28 [1H,
B of ABq, JAB 17.3, one of C(2)H2], 4.15 [1H, d, J 7.9, C(8)H], 6.10
[1H, overlapping dd appears as t, J 7.6, 7.6, C(7)H], 6.21–6.44 [3H,
m, C(4)H, C(5)H, C(6)H].
4.21.3. trans-2-Phenylsulfonyl-3-iso-propylcyclopentanone 31
White solid, (Found C, 63.06; H, 6.79. C14H18O3S requires C,
63.13; H, 6.81%); mp 96–98 °C;
m
max(KBr)/cm–1 1746 (C@O),
1302, 1140 (SO2), dH (400 MHz) 0.91 [3H, d, J 6.8, one of CH(CH3)2],
0.97 [3H, d, J 6.8, one of CH(CH3)2], 1.65–1.76 [1H, m, one of
C(4)H2], 1.85–1.97 [1H, sym m, J 6.7, CH(CH3)2], 2.19–2.36 [2H,
m, one of C(4)H2, one of C(5)H2], 2.44–2.54 [1H, m, one of
C(5)H2], 2.86–2.94 [1H, sym m, J 6.7, C(3)Hi-Pr], 3.51 [1H, d, J 5.2,
C(2)HSO2], 7.56–7.62 (2H, m, aromatic H), 7.66–7.72 (1H, m, aro-
matic H), 7.84–7.88 (2H, m, aromatic H); dC(75.5 MHz) 18.1 [CH3,
one of CH(CH3)2], 20.5 [CH3, one of CH(CH3)2], 22.1 [CH2, C(4)H2],
31.0 [CH, CH(CH3)2], 38.4 [CH2, C(5)H2], 43.2 (CH, CHi-Pr), 73.0
(CH, CHSO2Ph), 129.1 (CH, 4ꢂ aromatic CH), 134.1 (CH, aromatic
CH), 134.0 (C, aromatic C), 207.6 (C, CO); m/z (ES+) 267.0
[(M+H)+, 100%], 284.1 [(M+H2O)+, 72%], 552.4 (89%).
4.22.2. 3,8a-Dihydro-3,3,6,8a-tetramethylazulen-1(2H)-one 41
Clear oil; m
max/cmꢀ1 (film) 1749 (CO), 1716 (CO); dH (300 MHz)
0.68 [3H, s, C(8a)CH3], 1.08, 1.26 [2 ꢂ 3H, 2ꢂ s, C(3)(CH3)2], 1.95
[3H, apparent d, J 0.8, C(6)CH3], 2.08 [1H, A of ABq, JAB 17.3, one
of C(2)H2], 2.16 [1H, B of ABq, JAB 17.3, one of C(2)H2], 3.49 [1H,
d, J 6.8, C(8)H], 5.82 [1H, dq, J 7.0, 1.1, C(7)H], 6.15–6.20 [2H, m,
C(4)H, C(5)H]; dC(75.5 MHz) 8.8 [CH3, C(8a)CH3], 22.2 [CH3,
C(6)CH3], 27.1 [CH3, one of C(3)(CH3)2], 27.8 [CH3, one of
C(3)(CH3)2], 35.1, 38.0 [2ꢂ C, C(3), C(8a)], 48.9 [CH2, C(2)H2], 66.9
br [CH, C(8)H], 84.7 [C, C(3a)], 120.9, 122.6, 127.8 [C(4)H, C(5)H,
C(6)H, C(7)H], 134.5 [C, C(6)], 218.0 (C, CO); HRMS (ES+): Exact
mass calculated for C14H19O [(M+H)+], 203.1436. Found 203.1434.
m/z (ES+) 203 [(M+H)+, 100%].
4.21.4. trans-2-Phenylsulfonyl-3-tert-butylcyclopentanone 32
White solid, (Found C, 64.21; H, 7.27. C15H20O3S requires C,
64.26; H, 7.19%); mp 93–96 °C;
m
max(KBr)/cm–1 1743 (C@O),
1306, 1142 (SO2); dH (300 MHz) 0.89 [9H, s, 3ꢂ C(CH3)], 1.87–
1.99 [1H, m, one of C(4)H2], 2.20–2.36 [2H, m, one of C(4)H2, one
of C(5)H2], 2.55–2.71 [1H, m, one of C(5)H2], 2.86–2.94 [1H, m,
C(3)H], 3.55 [1H, bd, J 3.6, C(2)H], 7.55–7.63 (2H, m, aromatic H),
7.66–7.30 (1H, m, aromatic H), 7.82–7.88 (2H, m, aromatic H);
dC(75.5 MHz) 21.5 [CH2, C(4)H2], 27.1 (CH3, 3ꢂ CH3), 33.6 [C,
C(CH3)3], 37.9 [CH2, C(5)H2], 46.3 [CH, C(3)H], 73.0 [CH, C(2)H],
129.0 (CH, aromatic CH), 129.18 (CH, aromatic CH), 129.39 (CH,
aromatic CH), 134.20 (CH, aromatic CH), 137.7 (C, aromatic C),
208.6 (C, CO); m/z (ES+) 281.2 [(M+H)+, 43%].
4.22.3. 3,8a-Dihydro-6-chloro-3,3,8a-trimethylazulen-1(2H)-
one 42
Pale yellow oil;
m
max/cmꢀ1 (film) 1750 (CO), 1720 (CO); dH
(300 MHz) 0.86 [3H, s, C(8a)CH3], 1.14, 1.33 [2 ꢂ 3H, 2ꢂ s,
C(3)(CH3)2], 2.21 [1H, A of ABq, JAB 17.3, one of C(2)H2], 2.39 [1H,
B of ABq, JAB 17.3, one of C(2)H2], 4.54 [1H, d, J 8.9, C(8)H], 6.14
[1H, dd, J 9.0, 1.4, C(7)H], 6.23 [1H, d, J 7.9, C(4)H], 6.52 [1H, dd, J
8.0, 1.6, C(5)H]; dC(75.5 MHz) 13.7 [CH3, C(8a)CH3], 28.9 [CH3,
one of C(3)(CH3)2], 29.7 [CH3, one of C(3)(CH3)2], 38.7, 44.9 [2ꢂ
C, C(3), C(8a)], 50.7 [CH2, C(2)H2], 101.4 [CH, C(8)H], 118.9 (CH),
123.3 [C, C(3a)], 125.6, 127.4 (2 x CH), 131.8 [C, C(6)], 217.0 (C,
CO); HRMS (ES+): Exact mass calculated for C13H16OCl [(M+H)+],
222.0811. Found 222.0809.
4.21.5. trans-2-Phenylsulfonyl-3-phenylcyclopentanone 3325
White solid, mp 96–99 °C;
1150 (SO2); dH (400 MHz) 1.92–2.07 [1H, m, one of C(4)H2],
m
max(KBr)/cm–1 1743 (C@O), 1306,