Job/Unit: O30200
/KAP1
Date: 27-03-13 19:15:48
Pages: 12
W. Ying, J. W. Herndon
27.7, 24.6, 19.1 ppm. IR (neat): ν˜ = 3060, 2936, 2852, 1659, 1592,
FULL PAPER
ganic extracts were washed with brine, dried with sodium sulfate,
and concentrated on a rotary evaporator. The residue was purified
by silica gel flash chromatography (dichloromethane) to give com-
–
1
1506, 1460, 1408, 1370, 1257, 1213, 1167, 1033 cm . HRMS: calcd.
for C28
28 2 4
H N O
SBr [M + H]+ 567.0948; found 567.0948.
2
0
pound 10d (2.103 g, 92%) as a colorless oil. [α]
D
= +28.1 (c =
): δ = 7.70 (dd, J = 1.3,
.1 Hz, 2 H, Ptz-H, o to S), 7.31 (dd, J = 1.3, 7.5 Hz, 2 H, Ptz-H,
Data for 13d: [α]2
CDCl ): δ = 7.74 (d, J = 8.1 Hz, 2 H, Ptz-H, o to S), 7.31 (dd, J =
.5, 7.8 Hz, 2 H, Ptz-H, o to N), 7.23 (dd, J = 1.2, 7.5 Hz, 2 H,
Ptz-H, m to N), 7.11 (dt, J = 0.6, 7.5 Hz, 2 H, Ptz-H, m to S), 7.02
s, 1 H, Ar-H, o to Br), 6.72 (s, 1 H, Ar-H, o to alkyl), 4.82 (t, J =
.8 Hz, 1 H, CORCH-N), 4.10–3.55 (m, 3 H, ArCH CO and
RCH -N), 3.87 (s, 3 H, OCH ), 3.86 (s, 3 H, OCH ), 3.14 (dt, J =
3.3, 13.6 Hz, 1 H, RCH -N), 2.16–2.02 (m, 1 H), 1.80–1.05 (m, 5
H) ppm. 13C NMR (75 MHz, CDCl
): δ = 205.5, 158.5, 148.7,
48.3, 141.2, 128.8, 127.6, 127.5, 125.9, 125.2, 122.6, 115.3, 114.8,
14.3, 62.0, 56.13, 56.05, 46.7, 45.2, 25.8, 24.1, 20.9 ppm. IR (neat):
0
1
1
D 3
= +3.4 (c = 1.18, CHCl ). H NMR (300 MHz,
1
8
3 3
1.06, CHCl ). H NMR (300 MHz, CDCl
3
1
o to N), 7.24 (dt, J = 1.3, 7.5 Hz, 2 H, Ptz-H, m to N), 7.10 (dt, J
1.3, 7.5 Hz, 2 H, Ptz-H, m to S), 5.26 (br. s, 1 H, R CH-N),
.69–3.57 (m, 1 H, equatorial RCH -N), 2.91 (dt, J = 3.0, 13.2 Hz,
H, axial RCH -N), 2.30 (d, J = 2.1 Hz, 1 H, ϵC-H), 1.85–1.52
CH CH -R), 1.51–1.35 (m, 1 H, R-CH CH CH
R), 1.30–1.05 (m, 1 H, R-CH -R) ppm. C NMR
75 MHz, CDCl ): δ = 157.0, 141.2, 128.8, 127.5, 127.4, 125.0,
22.3, 80.9, 72.8, 45.3, 43.2, 30.1, 24.8, 19.7 ppm. IR (neat): ν˜ =
293, 3060, 2942, 2861, 1662, 1460, 1401, 1320, 1252, 1168, 1129,
=
2
(
4
3
1
2
2
2
2
3
3
(
m, 4 H, R-CH
2
2
2
2
2
2
-
13
2
2
2 2
CH CH
3
(
3
1
1
1
3
1
–1
+
ν˜ = 3060, 2955, 2934, 2856, 1726, 1659, 1508, 1460, 1406, 1309,
19 2
033 cm . HRMS: calcd. for C20H N OS [M + H] 335.1213;
–
1
1
258, 1219, 1166, 1033 cm .
found 335.1224.
Preparation of Alkyne Ketone 5d by Sonogashira Coupling of Bromo
Ketone 12d and Trimethylsilylacetylene: A procedure analogous to
that for 5a was used, starting from bromo ketone 12d (1 equiv.,
Preparation of Alkynylproline 11d by Sonogashira Coupling of Alk-
yne Urea 10d with 1-Bromo-2-iodo-4,5-dimethoxybenzene: A pro-
cedure analogous to that for 11a was used, starting from alkyne
5
5
67 mg, 1 mmol), trimethylsilylacetylene (5 equiv., 0.712 mL,
mmol), Pd(PPh Cl (0.3 equiv., 211 mg, 0.3 mmol), tri-
1
(
0
0d (1.35 equiv., 1.002 g, 2.218 mmol), bromide-iodide
1.0 equiv., 761 mg, 2.995 mmol), Pd(PPh (0.05 equiv., 128 mg,
.111 mmol), and copper(I) iodide (0.1 equiv., 42 mg, 0.222 mmol).
9
3
)
2
2
3 4
)
phenylphosphane (0.6 equiv., 157 mg, 0.6 mmol), and copper(I)
iodide (0.12 equiv., 23 mg, 0.12 mmol). After final chromato-
graphic purification, alkyne-ketone 5d (485 mg, 83%) was obtained
After final chromatographic purification, alkyne-bromide 11d
2
0
(
+
(
2
D
1.134 g, 93%) was obtained as a pale yellow semi-solid. [α] =
2
0
1
1
as a pale yellow semi-solid. [α]
NMR (300 MHz, CDCl ): δ = 7.59 (dd, J = 0.9, 7.5 Hz, 2 H, Ptz-
H, o to S), 7.30 (s, 1 H, Ar-H, o to C=O), 7.21 (dd, J = 1.2, 7.5 Hz,
H, Ptz-H, o to N), 7.13 (dt, J = 1.5, 7.5 Hz, 2 H, Ptz-H, m to
N), 7.01 (dt, J = 0.9, 7.5 Hz, 2 H, Ptz-H, m to S), 6.93 (s, 1 H, Ar-
H, o to alkyne), 5.05–4.91 (m, 1 H, R CH-N), 3.92 (s, 3 H, OCH ),
.90 (s, 3 H, OCH ), 3.88 (br. d, J = 13.2 Hz, 1 H, equatorial
RCH -N) 3.67 (dd, J = 7.8, 16.5 Hz, 1 H, COCH -R), 3.35 (dd, J
6.0, 16.5 Hz, 1 H, COCH -R), 2.86 (dt, J = 2.4, 13.2 Hz, 1 H,
axial RCH -N), 1.69–1.13 (m, 6 H, R-CH CH CH -R), 0.21 [s, 9
H, Si(CH ] ppm. C NMR (75 MHz, CDCl ): δ = 198.1, 157.1,
D 3
= +1.8 (c = 0.47, CHCl ). H
44.6 (c = 2.90, CHCl
dd, J = 1.3, 8.1 Hz, 2 H, Ptz-H, o to S), 7.30 (dd, J = 1.3, 7.5 Hz,
H, Ptz-H, o to N), 7.20 (dt, J = 1.5, 7.8 Hz, 2 H, Ptz-H, m to
3 3
). H NMR (300 MHz, CDCl ): δ = 7.73
3
2
N), 7.08 (dt, J = 1.5, 7.5 Hz, 2 H, Ptz-H, m to S), 7.01 (s, 1 H, Ar-
H, o to Br), 6.89 (s, 1 H, Ar-H, o to alkyne), 5.57–5.45 (m, 1 H,
2
3
R
1
RCH
2
CH-N), 3.88 (s, 3 H, OCH
H, equatorial RCH -N), 3.09 (dt, J = 3.0, 13.2 Hz, 1 H, axial
-N), 2.01–1.83 (m, 2 H, R-CH CH CH -R), 1.73 (td, J = 4.5,
-R), 1.69–1.57 (m, H, R-
-R), 1.56–1.44 (m, 1 H, R-CH CH CH -R), 1.33–
-R) ppm. 1 C NMR (75 MHz,
3 3
), 3.86 (s, 3 H, OCH ), 3.75–3.65 (m,
3
3
2
2
2
2
2
2
2
=
2
12.9 Hz,
1
CH
H, R-CH
2
CH
2
CH
2
1
2
2
2
2
CH
2
CH
2
2
2
2
2
1
3
3
3
)
3
3
1.15 (m, 1 H, R-CH
2
CH
2
CH
2
1
1
1
51.2, 149.2, 141.5, 133.6, 128.4, 127.4, 127.1, 124.7, 121.6, 116.2,
15.1, 111.3, 104.6, 99.8, 56.0, 55.9, 49.7, 42.3, 41.8, 28.2, 24.8,
9.2, –0.2 ppm. IR (neat): ν˜ = 3061, 2956, 2934, 2856, 2145, 1727,
CDCl
3
): δ = 156.8, 149.7, 148.0, 141.3, 128.6, 127.54, 127.47, 125.0,
1
3
1
22.1, 117.0, 116.7, 115.2, 115.0, 89.6, 83.7, 56.2, 56.1, 46.3, 43.4,
0.5, 25.0, 20.1 ppm. IR (neat): ν˜ = 3062, 2939, 2856, 1663, 1508,
–
1
–
1
1664, 1591, 1510, 1460, 1407, 1266, 1252, 1219, 1124 cm . HRMS:
calcd. for C33
460, 1440, 1401, 1321, 1254, 1231, 1206, 1168, 1031, 1008 cm .
SiS [M + H]+ 585.2238; found 585.2241.
+
37 2 4
H N O
HRMS: calcd. for C28
49.0838.
26 2 3
H N O SBr [M + H] 549.0842; found
5
Formation of Phenanthrene 17d by Coupling of Ketone Alkyne 5d
with Carbene Complex 6 Followed by Dehydrogenation: A procedure
analogous to that for 17a was used, starting from alkyne-ketone
Preparation of Bromo Ketone 12d by Hydration of Alkyne 11d: A
procedure analogous to that for 12a was used, starting from bromo-
alkyne 11d (1 equiv., 136 mg, 0.248 mmol), mercuric trifluoro-
acetate (1.2 equiv., 127 mg, 0.297 mmol), and red mercuric oxide
12d (1 equiv., 593 mg, 1.014 mmol), carbene complex 6 (1.5 equiv.,
441 mg, 290 mmol), and palladium on carbon (10%; 0.25 equiv.,
270 mg, 0.253 mmol). After final chromatographic purification,
(2.4 equiv., 129 mg, 0.594 mmol). Chromatographic purification
compound 17d (412 mg, 69% over two steps) was obtained as a
gave two fractions, desired bromo ketone 12d (98 mg, 70%) as a
pale yellow oil, and undesired regioisomeric bromo ketone 13d
2
0
1
pale yellow semi-solid. [α]
D 3
= –31.5 (c = 2.66, CHCl ). H NMR
(
300 MHz, CDCl ): δ = 8.03 (br. s, 1 H, Ar-H, C-ring), 7.90 (s, 1
3
(
11 mg, 8%) as a brown semi-solid.
Data for 12d: [α]20
= –3.3 (c = 2.54, CHCl ). H NMR (300 MHz,
3
H, Ar-H, bay region of A-ring), 7.83 (d, J = 2.1 Hz, 1 H, Ar-H,
bay region of B-ring), 7.72 (d, J = 9.0 Hz, 1 H, Ar-H, B-ring m to
OMe), 7.46 (d, J = 7.5 Hz, 2 H, Ptz-H, o to S), 7.39 (s, 1 H, Ar-
H, non-bay region of A-ring), 7.25–7.15 (m, 3 H, Ar-H, Ptz-H),
1
D
CDCl ): δ = 7.63 (d, J = 8.1 Hz, 2 H, Ptz-H, o to S), 7.26 (ddd, J
0.6, 1.2, 7.8 Hz, 2 H, Ptz-H, o to N), 7.19 (ddt, J = 0.6, 1.5,
3
=
7
7
.5 Hz, 2 H, Ptz-H, Ptz-H, m to N), 7.18 (s, 1 H, Ar-H, o to C=O), 7.09 (dt, J = 1.5, 7.5 Hz, 2 H, Ptz-H, m to N), 7.01 (dt, J = 1.5,
.06 (ddt, J = 0.6, 1.2, 7.5 Hz, 2 H, Ptz-H, m to S), 7.02 (s, 1 H, 7.5 Hz, 2 H, Ptz-H, m to S), 5.04–4.86 (m, 1 H, R CH-N), 4.30 (s,
CH-N), 3.92 (s, 6 H, 2 3 H, OCH ), 4.15 (s, 3 H, OCH ), 4.03 (s, 3 H, OCH ), 4.03–3.87
), 3.79 (br. d, J = 13.5 Hz, 1 H, equatorial RCH -N), 3.35 (m, 1 H, equatorial RCH -N), 3.50 (dd, J = 5.1, 13.2 Hz, 1 H,
dd, J = 9.0, 15.9 Hz, 1 H, COCH -R), 3.19 (dd, J = 4.8, 15.9 Hz, ArCH -R), 3.28 (dd, J = 10.2, 13.5 Hz, 1 H, ArCH -R), 3.16 (dt,
-R), 2.83 (dt, J = 2.7, 13.5 Hz, 1 H, axial RCH -N), J = 2.4, 13.5 Hz, 1 H, axial RCH -N), 1.93–1.33 (m, 6 H, R-
.75–1.05 (m, 6 H, R-CH CH CH CH CH ): δ = 157.8,
-R) ppm. 13C NMR (75 MHz, CH -R) ppm. 13C NMR (75 MHz, CDCl
): δ = 199.6, 157.5, 151.4, 148.2, 141.5, 132.2, 128.7, 127.6,
2
Ar-H, o to Br), 4.97–4.78 (m, 1 H, R
OCH
(
1
1
2
3
3
3
3
2
2
2
2
2
H, COCH
2
2
2
2
2
2
2
2
2
3
CDCl
3
157.2, 149.7, 148.7, 141.4, 130.6, 129.8, 129.6, 127.4, 127.3, 126.9,
126.0, 124.7, 124.5, 120.3, 115.2, 105.8, 103.9, 103.8, 56.5, 56.0,
127.3, 124.9, 121.8, 116.4, 112.7, 111.1, 56.3, 56.2, 49.7, 42.6, 42.1,
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0