Unexpected diastereoselective one-pot assembly of hexahydroazulenones from 2-alkylcyclohexanones and arylacetylenes in KOH/DMSO suspension

Article abstract of DOI:10.1016/j.tetlet.2011.06.019

2-Alkylcyclohexanones react with arylacetylenes (KOH/DMSO, 100 °C, 1 h) to afford unexpectedly hexahydroazulenones in 34-50% yields and ca. 100% diastereoselectivity (instead of the expected acetylenic alcohols), the minor products being isomeric arylethe

Full text of DOI:10.1016/j.tetlet.2011.06.019

Tetrahedron Letters 52 (2011) 4285–4287
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Unexpected diastereoselective one-pot assembly of hexahydroazulenones
from 2-alkylcyclohexanones and arylacetylenes in KOH/DMSO suspension
Boris A. Trofimov a, , Elena Yu. Schmidt a, Elena V. Skitaltseva a, Nadezhda V. Zorina a, Nadezhda I. Protsuk a,
⇑
Igor A. Ushakov a, Albina I. Mikhaleva a, Oleg A. Dyachenko b, Olga N. Kazheva b, Grigorii G. Aleksandrov c
a A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky Str., Irkutsk 664033, Russian Federation
b Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 Acad. Semenov Av., Chernogolovka, Moscow Region 142432, Russian Federation
c N. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 31 Leninsky Prp., Moscow 119991, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
2-Alkylcyclohexanones react with arylacetylenes (KOH/DMSO, 100 °C, 1 h) to afford unexpectedly hexa-
hydroazulenones in 34–50% yields and ca. 100% diastereoselectivity (instead of the expected acetylenic
alcohols), the minor products being isomeric arylethenyl ketones.
Received 17 March 2011
Revised 24 May 2011
Accepted 3 June 2011
Available online 21 June 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Azulenones
2-Alkylcyclohexanones
Arylacetylenes
Vinyl ketones
The development of new CAC bond forming reactions remains a
fundamental challenge of organic chemistry.1 Particular endeavors
in this area are directed to discover reactions that allow the
creation of several carbonAcarbon bonds in one synthetic opera-
tion leading to the construction of important polycyclic structures
with desired regio- and stereochemical control.1a Among such
structures the azulene scaffold, especially that of azulenone, has
attracted attention due to its theoretical,2 biological3 and pharma-
ceutical4 significance. These structures are abundant in nature and
represent rewarding synthetic objectives. Approaches toward
enantio- or diastereoselective construction of the azulenone
skeleton are limited by the intramolecular cyclization of b-aryl-
yield along with a mixture of minor products, arylethenyl ketones
14–19, in trace amounts in 24% yield (Scheme 1).9
The structures of azulenones 8–13 follow unambiguously from
single-crystal X-ray diffraction of compound 8 (Fig. 1) as a typical
representative of this series.10 The cycloheptene counterpart of
molecule 8 has the bath conformation. The cyclopentane ring
adopts the sofa conformation with the C(7) atom deviated by
0.61 Å from the average, almost an ideal plane formed by the
remaining carbon atoms. The dihedral angle between the averaged
planes of the benzene rings is 124.0°. Thus, the X-ray data provide
evidence that azulenones 8–13 are formed stereoselectively as sin-
gle diastereomers.
a
-diazaketones (Büchner reaction) in the presence of rhodium
The 1H and 13C NMR spectra of compounds 8–13 were in agree-
ment with the azulenone structure. In the 1H NMR spectra of
azulenones 8–13, doublets due to the 5-CH2 (3.36–3.40 and
3.69–3.71 ppm, 2J = 18.3 Hz) and 8-CH2 (2.54–2.55 and 2.75–
2.79 ppm, 2J = 14.2 Hz) protons were present. The CH2 protons
(positions 1, 2 and 3) were represented as complex multiplets
(1.39–2.31 ppm). Assignments of the 13C signals were based on
2D HSQC and HMBC spectra (Fig. 2). The configurations of carbon
atoms 8a and 3a were determined using 2D NOESY spectra, where
a correlation between the alkyl group protons and H3a was
observed.
Ketones 14–19 are the products of C-vinylation of 2-alkylcyclo-
hexanones 1 and 2. Ketones 14a–c, which were identified by 1H
NMR, GLC, and MS, were obtained in the ratio 14a:14b:14c =
3:1:2, were formed via vinylation of 2-methylcyclohexanone (1)
at positions 2 and 6.
complexes5 or rhodium salts,6 and by the cycloaddition of
2-phenyl-2-acylketenes with alkynyl ethers.2a In addition, the
base-catalyzed condensation of cyclopentadienes with phorone
to give hexahydroazulenones containing no asymmetric carbons
has been reported.7
In this Letter, we report our serendipitous finding that 2-alkyl-
cyclohexanones 1 and 2 when allowed to react with arylacetylenes
3–6 in KOH/DMSO suspension (alkylcyclohexanone:arylacety-
lene:KOH molar ratio = 1:1:1) at 100 °C for 1 h gave, instead of
the expected acetylenic alcohols 7,8 (3aR,8aR)-8a-alkyl-6,7-dia-
ryl-1,2,3,3a,8,8a-hexahydroazulen-4(5H)-ones 8–13 in 34–50%
⇑
Corresponding author. Tel.: +7 395251 19 26; fax: +7 395241 93 46.
E-mail address: boris_trofimov@irioch.irk.ru (B.A. Trofimov).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.06.019

4286
B. A. Trofimov et al. / Tetrahedron Letters 52 (2011) 4285–4287
R1
R2
HO
7
x
KOH/DMSO
100 oC, 1 h
+
R1
R2
R2
R2
O
3, R2 = H
+
+
R1
1, R1 = Me
2, R1 = Et
+
4, R2 = 4-Me
5, R2 = 3-F
6, R2 = 4-Ph
R1
R1
R1
R2
R2
O
O
H
O
14-19c
14-19a
14-19b
R2
O
14a:14b:14c = 3:1:2, 24% total yield (R1 = Me, R2 = H)
15a, 18%; 15b,c, traces (R1 = Me, R2 = 4-Me)
16a-c, traces (R1 = Me, R2 = 3-F)
8, 37% (R1 = Me, R2 = H)
9, 34% (R1 = Me, R2 = 4-Me)
10, 44% (R1 = Me, R2 = 3-F)
11, 37% (R1 = Me, R2 = 4-Ph)
12, 39% (R1 = Et, R2 = H)
13, 50% (R1 = Et, R2 = 3-F)
17a, 11%, 17b,c, traces (R1 = Me, R2 = 4-Ph)
18a-c, traces (R1 = Et, R2 = H)
19a-c, traces (R1 = Et, R2 = 3-F)
Scheme 1. Reaction of 2-alkylcyclohexanones 1 and 2 with arylacetylenes 3–6 in KOH/DMSO suspension.
The yields and stereochemistry of these vinyl ketones were
sensitive toward the substituents present on the starting
arylacetylenes 3–6 (Scheme 1). With tolylacetylene (4) and
4-phenylphenylacetylene (6), only vinyl ketones 15a and 17a of
Z-configuration were formed, while in the case of 3-fluorophenyl-
acetylene (5), no vinyl ketone was detected.
Initial attempts to optimize the reaction (using a two-fold
excess of arylacetylene, lower or higher temperature) only margin-
ally altered the product yields and ratios, though systematic opti-
mization may further improve the characteristics of this
synthetically interesting one-pot assembly.
In conclusion, a highly unexpected diastereoselective one-pot
assembly of diarylazulenones from 2-alkylcyclohexanones and
arylacetylenes in KOH/DMSO suspension has been described. The
process represents a new reaction which involves the formation
of four CAC bonds and yields biologically and synthetically impor-
tant condensed bicyclic systems in a single operation. Further
investigations are intended to define the scope and limitations of
the reaction by extending it to other cyclic ketones and substituted
acetylenes.
Acknowledgment
Figure 1. X-ray structure of azulenone 8.
This work was carried out using financial support from the Rus-
sian Foundation of Basic Research (Grant 11-03-00270).
References and notes
R2
1. (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624; (b)
Karimi, B.; Behzadna, H.; Elhamifar, D.; Akhavan, P. F.; Esfahani, F. K. Synthesis
2010, 1399; (c) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem. Int.
Ed. 2009, 48, 5094; (d) Li, C.-J. Acc. Chem. Res. 2009, 42, 335.
2. (a) Brown, D. G.; Hoye, T. R.; Brisbois, R. G. J. Org. Chem. 1998, 63, 1630; (b)
Wang, H.; Michalak, K.; Michalak, M.; Jimenez-Oses, G.; Wicha, J.; Houk, K. N. J.
Org. Chem. 2010, 75, 762.
3. Epstein, O. L.; Cha, J. K. Angew. Chem. Int. Ed. 2005, 44, 121.
4. (a) Fujiwara, M.; Ijichi, K.; Tokuhisa, K.; Katsuura, K.; Wang, G.-Y.-S.; Uemura,
D.; Shigeta, S.; Konno, K.; Yokota, T.; Baba, M. Antiviral Chem. Chemother. 1996,
7, 230; (b) Fujiwara, M.; Ijichi, K.; Tokuhisa, K.; Katsuura, K.; Shigeta, S.; Konno,
K.; Wang, G. Y. S.; Uemura, D.; Yokota, T.; Baba, M. Antimicrob. Agents
Chemother. 1996, 40, 271.
5. O’Keeffe, S.; Harrington, F.; Maguire, A. R. Synlett 2007, 2367.
6. (a) Maguire, A. R.; O’Leary, P.; Harrington, F.; Lawrence, S. E.; Blake, A. J. J. Org.
Chem. 2001, 66, 7166; (b) Maguire, A. R.; Buckley, N. R.; O’Leary, P.; Ferguson, G.
J. Chem. Soc., Perkin Trans. 1 1998, 4077; (c) Padwa, A.; Krumpe, K. E.; Gareau, Y.;
Chiacchiot, U. J. Org. Chem. 1991, 56, 2523.
H8'
H8
H1
NOESY
HMBC
R1
Ho
7
8
H1'
1
H
8a
2
6
3
3a
5
4
H5'
R2
H5
O
Figure 2. Characteristic NOESY and HMBC correlations of azulenones 8–13.

B. A. Trofimov et al. / Tetrahedron Letters 52 (2011) 4285–4287
4287
2
2
0
7. Ivchenko, C. B.; Ivchenko, P. V.; Nifant’ev, I. E.; Kashulin, L. A.; Taidakov, L. V.;
Kuz’mina, L. G. Russ. Chem. Bull. 2000, 49, 724.
1H, JH5–H5 = 18.1 Hz, H50), 2.97–2.94 (m, 1H, H3a), 2.69 (d, 1H, JH8–
2
= 14.0 Hz, H8), 2.62 (d, 1H, JH8–H8 = 14.0 Hz, H80), 2.28, 1.80 (m, 2H, H3,
0
H80
8. (a) Favorsky, A. E. Zh. Ross. Khim. Obshch. 1906, 37, 643; (b) Smith, M.; March, J.
March’s Advanced Organic Chemistry, 6th ed.; Wiley: New York, 2007. p 1360.
9. General procedure for the synthesis of azulenones 8–13 [an example of the reaction
of 2-methylcyclohexanone (1) with phenylacetylene 3]: A mixture of ketone 1
(2.00 g, 17.8 mmol), phenylacetylene 3 (1.82 g, 17.8 mmol), and KOHꢀ0.5H2O
(1.16 g, 17.8 mmol) in DMSO (20 mL) was heated (100 °C) and stirred for 1 h.
The reaction mixture, after cooling (20–22 °C), was diluted with H2O (50 mL),
neutralized (NH4Cl), and extracted with Et2O (10 mL ꢁ 4). The organic extract
obtained was washed with H2O (10 mL ꢁ 3) and dried (K2CO3) overnight. After
removal of the solvent, the crude residue (3.34 g) was purified by column
H30), 1.89, 1.74 (m, 2H, H2, H20), 1.64, 1.53 (m, 2H, H1, H10), 1.34, 0.90 (m, 2H,
CH2-Me), 0.45 (t, 3H, JCH2–Me = 7.7 Hz, Me). 13C NMR (101.61 MHz, CDCl3,
3
0
ppm): d 210.8 (C@O), 144.0 (Ci ), 142.5 (Ci), 138.7 (C7), 132.8 (C6), 129.4, 129.2
0
0
0
(Cm, Cm ), 127.9, 127.8 (Co, Co ), 126.3, 126.0 (Cp, Cp ), 61.4 (C3a), 55.5 (C8a), 50.9
(C5), 41.0 (C8), 34.9 (C1), 30.2 (C8a-CH2-Me), 25.4 (C3), 23.3 (C2), 8.2 (C8a-CH2-
Me).
(3aR,8aR)-6,7-Bis(3-fluorophenyl)-8a-ethyl-1,2,3,3a,8,8a-hexahydroazulen-4(5H)-
one (13): Yield 50%. Yellow oil. Anal. Calcd for C24H24F2O (366.44): C, 78.66; H,
6.60; F, 10.37. Found: C, 78.87; H, 6.54; F, 10.21. IR (film, cmꢂ1
) mmax: 3069,
3037, 2964, 2936, 2877, 2866, 1703, 1610, 1582, 1485, 1461, 1436, 1381, 1347,
chromatography (SiO2, benzene) to give azulenone
mixture of vinyl ketones 14a–c (0.92 g, 24%).
8
(2.09 g, 37%) and
a
1265, 1153, 1076, 964, 911, 872, 785, 734, 702, 648, 522. 1H NMR (400.13 MHz,
2
0
0
0
CDCl3, ppm): d 7.02–6.68 (m, 8H, Ho, Ho , Hm, Hm , Hp, Hp ), 3.69 (d, 1H, JH5–
2
0
H50
Azulenones 9–13 and ketones 15a,17a were obtained analogously.
= 18.0 Hz, H5), 3.34 (d, 1H, JH5–H5 = 18.0 Hz, H50), 2.94–2.91 (m, 1H, H3a),
(3aR,8aR)-8a-Methyl-6,7-diphenyl-1,2,3,3a,8,8a-hexahydroazulen-4(5H)-one (8):
White crystals (mp 90–92 °C). Anal. Calcd for C23H24O (316.44): C, 87.30; H,
2.63 (m, 2H, H8, H80), 2.27, 1.73 (m, 2H, H3, H30), 1.90, 1.67 (m, 2H, H2, H20),
3
1.53, 1.38 (m, 2H, H1, H10), 1.24, 0.84 (m, 2H, C8a-CH2-Me), 0.45 (t, 3H, JCH2–
7.64. Found: C, 87.38; H, 7.24. IR (KBr, cmꢂ1
)
m
max: 3080, 3057, 2926, 2864,
Me = 7.4 Hz, C8a-CH2-Me). 13C NMR (101.61 MHz, CDCl3, ppm): d 210.8 (C@O),
0
0
1696, 1599, 1492, 1442, 1379, 1338, 1278, 1255, 1209, 1152, 1134, 1120, 1068,
163.4 (d, J = 246.7 Hz, C3, C3 ), 146.8 (d, J = 7.6 Hz, C1 ), 145.2 (d, J = 7.6 Hz, C1),
139.4 (C7), 133.7 (C6), 130.5, 130.4 (d, J = 8.4 Hz, C5, C5 ), 125.9, 125.8 (d,
J = 2.7 Hz, C6, C6 ), 117.0, 116.8 (d, J = 21.7 Hz, C2, C2 ), 114.6, 114.3 (d,
J = 21.3 Hz, C4, C4 ), 62.3 (C3a), 56.4 (C8a), 51.5 (C5), 41.7 (C8), 35.8 (C1), 31.0
1030, 975, 912, 764, 700, 565, 530, 502. 1H NMR (400.13 MHz, CDCl3, ppm): d
0
2
0
0
0
0
0
0
7.10–6.97 (m, 10H, Ho, Ho , Hm, Hm , Hp, Hp ), 3.71 (d, 1H, JH5–H5 = 18.3 Hz, H5),
2
2
3.40 (d, 1H, JH5–H5 = 18.3 Hz, H50), 3.00–2.98 (m, 1H, H3a), 2.78 (d, 1H, JH8–
0
0
2
= 14.2 Hz, H8), 2.55 (d, 1H, JH8–H8 = 14.2 Hz, H80), 2.28, 1.77 (m, 2H, H3,
(C8a-CH2-Me), 26.3 (C3), 24.2 (C2), 9.2 (C8a-CH2-Me).
0
H80
H30), 1.87, 1.72 (m, 2H, H2, H20), 1.50, 1.39 (m, 2H, H1, H10), 1.05 (s, 3H, Me). 13C
Vinyl ketones 14a–c as a mixture: Yield 24%. Yellow oil. Anal. Calcd for C15H18
O
0
NMR (101.61 MHz, CDCl3, ppm): d 210.6 (C@O), 144.4 (Ci ), 142.7 (Ci), 139.0
(214.30): C, 84.07; H, 8.47. Found: C, 84.33; H, 8.61. IR (film, cmꢂ1
) m
max: 3058,
0
0
0
(C7), 132.9 (C6), 129.4 (Cm, Cm ), 128.0, 127.8 (Co, Co ), 126.4, 126.1 (Cp, Cp ), 60.9
(C3a), 51.9 (C8a), 51.2 (C5), 45.3 (C8), 39.3 (C1), 26.9 (C8a-Me), 24.9 (C3), 23.3
(C2).
3026, 2931, 2861, 1949, 1776, 1707, 1616, 1601, 1494, 1450, 1373, 1309, 1232,
1144, 1126, 1074, 1029, 966, 764, 748, 699. 1H NMR (400.13 MHz, CDCl3, ppm)
for 14a: d 7.16–7.14 (m, 2H, Hm), 7.12–7.10 (m, 1H, Hp), 7.04–7.02 (m, 2H, Ho),
6.51 (d, 1H, 3JH –Hb = 12.5 Hz, H ), 5.64 (d, 1H, 3JH –Hb = 12.5 Hz, Hb), 2.26, 1.82
(3aR,8aR)-8a-Methyl-6,7-di-p-tolyl-1,2,3,3a,8,8a-hexahydroazulen-4(5H)-one (9):
Yield 34%. White crystals (mp 86–88 °C). Anal. Calcd for C25H28O (344.49): C,
a
a
a
(m, 2H, H6, H60), 1.93, 1.45 (m, 2H, H3, H30), 1.85, 1.48 (m, 2H, H5, H50), 1.75,
87.16; H, 8.19. Found: C, 87.14; H, 8.27. IR (KBr, cmꢂ1
) mmax: 3019, 2956, 2923,
1.53 (m, 2H, H4, H40), 1.22 (s, 3H, Me). 13C NMR (101.61 MHz, CDCl3, ppm) for
2861, 1703, 1511, 1488, 1460, 1450, 1404, 1377, 1344, 1273, 1212, 1182, 1131,
14a: d 213.3 (C@O), 137.1 (C ), 136.3 (Ci), 131.0 (Cb), 128.8 (Co), 127.9 (Cm),
a
1076, 1042, 957, 949, 817, 724. 1H NMR (400.13 MHz, CDCl3, ppm): d 6.94–6.86
127.8 (Cp), 52.1 (C2), 44.9 (C3), 39.8 (C6), 29.1 (C5), 24.3 (Me), 22.2 (C4). 1H
2
2
0
0
0
(m, 8H, Ho, Ho , Hm, Hm ), 3.69 (d, 1H, JH5–H5 = 18.3 Hz, H5), 3.37 (d, 1H, JH5–
NMR (400.13 MHz, CDCl3, ppm) for 14b: d 7.30 (m, 2H, Ho), 7.21 (m, 1H, Hp),
2
= 18.3 Hz, H50), 2.99–2.97 (m, 1H, H3a), 2.75 (d, 1H, JH8–H8 = 14.0 Hz, H8),
7.19 (m, 2H, Hm), 6.42 (dd, 1H, 3JH –Hb = 16.1 Hz, 3JH –H6 = 7.3 Hz, H
a), 6.22 (d,
H50
a a
1H, 3JH –Hb = 16.1 Hz, Hb), 3.07 (m, 1H, H6), 2.38 (m, 1H, H2), 2.14, 1.60 (m, 2H,
0
2
2.55 (d, 1H, JH8–H8 = 14.0 Hz, H80), 2.031, 1.78 (m, 2H, H3, H30), 2.27 (s, 6H, Cp-
0
a
0
Me, Cp -Me), 1.92, 1.76 (m, 2H, H2, H2 ), 1.53, 1.43 (m, 2H, H1, H1 ), 1.05 (s, 3H,
H5, H50), 2.06, 1.39 (m, 2H, H3, H30), 1.62, 1.25 (m, 2H, H4, H40), 0.99 (d, 3H,
0
C8a-Me). 13C NMR (101.61 MHz, CDCl3, ppm): d 210.4 (C@O), 141.4 (Ci ), 139.9
3J = 6.5 Hz, Me). 13C NMR (101.61 MHz, CDCl3, ppm) for 14b: d 211.3 (C@O),
0
0
0
(Ci), 138.2 (C7), 135.7, 135.3 (Cp, Cp ), 132.2 (C6), 129.2 (Cm, Cm ), 128.7, 127.6
(Co, Co ), 60.5 (C3a), 51.8 (C8a), 51.5 (C5), 45.4 (C8), 39.5 (C1), 27.3 (C8a-Me),
137.2 (Ci), 130.9 (Cb), 128.5 (Cm), 128.1 (C ), 127.6 (Cp), 126.3 (Co), 54.0 (C6),
a
45.5 (C2), 36.9 (C3), 35.8 (C5), 25.3 (C4), 14.6 (Me). 1H NMR (400.13 MHz,
0
0
25.1 (C3), 23.5 (C2), 21.4 (Cp-Me, Cp -Me).
CDCl3, ppm) for 14c: d 7.23 (m, 2H, Hm), 7.18 (m, 1H, Hp), 7.10 (m, 2H, Ho), 6.60
(3aR,8aR)-6,7-Bis(3-fluorophenyl)-8a-methyl-1,2,3,3a,8,8a-hexahydroazulen-
(m, 1H, H ), 3.37 (m, 2H, CH2-Ph), 2.28 (m, 1H, H2), 2.75, 2.35 (m, 2H, H5), 2.27,
a
4(5H)-one (10): Yield 44%. Yellow oil. Anal. Calcd for C23H22F2O (352.42): C,
1.72 (m, 2H, H4), 1.97, 1.48 (m, 2H, H3), 1.09 (d, 3H, 3J = 6.4 Hz, Me). 13C NMR
(101.61 MHz, CDCl3, ppm) for 14c: d 202.9 (C@O), 138.7 (Ci), 137.3 (C6), 135.8,
78.39; H, 6.29; F, 10.78. Found: C, 78.33; H, 6.25; F, 10.81. IR (film, cmꢂ1
) mmax:
3068, 2960, 2937, 2868, 1704, 1610, 1582, 1485, 1462, 1437, 1343, 1265, 1191,
(C ), 128.7 (Cm), 128.6 (Co), 125.9 (Cp), 44.1 (C2), 34.0 (CH2-Ph), 31.9 (C3), 27.2
(C5), 24.7 (C4), 16.2 (Me).
a
1131, 1075, 1001, 973, 907, 872, 785, 703, 522. 1H NMR (400.13 MHz, CDCl3,
2
0
0
0
ppm):
H50
d
7.10–6.71 (m, 8H, Ho, Ho
,
0
Hm
,
Hm
,
Hp, Hp ), 3.69 (d, 1H, JH5–
(Z)-2-Methyl-2-(4-methylstyryl)cyclohexanone (15a): Yield 18%. Yellow oil. Anal.
Calcd for C16H20O (228.33): C, 84.16; H, 8.83. Found: C, 84.11; H, 8.91. IR (film,
2
= 18.3 Hz, H5), 3.36 (d, 1H, JH5–H5 = 18.3 Hz, H50), 3.00–2.98 (m, 1H, H3a),
2
2
2.79 (d, 1H, JH8–H8 = 13.9 Hz, H8), 2.54 (d, 1H, JH8–H8 = 13.9 Hz, H80), 2.28,
1.78 (m, 2H, H3, H30), 1.92, 1.75 (m, 2H, H2, H20), 1.51, 1.44 (m, 2H, H1, H10),
1.08 (s, 3H, C8a-Me). 13C NMR (101.61 MHz, CDCl3, ppm): d 208.9 (C@O), 162.5
cmꢂ1
) mmax: 3020, 2930, 2861, 1709, 1610, 1512, 1490, 1449, 1407, 1373, 1337,
0
0
1308, 1254, 1212, 1182, 1148, 1117, 1084, 1040, 1021, 980, 960, 950, 949, 818,
741, 533.1H NMR (400.13 MHz, CDCl3, ppm) d 7.04–7.01 (m, 2H, Hm), 6.97–6.95
(m, 2H, Ho), 6.52 (d, 1H, 3JH –Hb = 12.5 Hz, Hb), 5.66 (d, 1H, 3JH –Hb = 12.5 Hz,
0
0
(d, J = 246.5 Hz, C3, C3 ), 146.2 (d, J = 7.3 Hz, C1 ), 144.4 (d, J = 7.3 Hz, C1), 138.7
(d, J = 2.2 Hz, C7), 133.0 (d, J = 2.2 Hz, C6), 129.6, 129.5 (d, J = 7.3 Hz, C5, C5 ),
125.0 (d, J = 2.9 Hz, C6, C6 ), 116.1 (d, J = 21.3 Hz, C2, C2 ), 113.8, 113.5 (d,
a
a
H ), 2.31, 1.86 (m, 2H, H6, H60), 1.98, 1.49 (m, 2H, H3, H30), 1.91, 1.51 (m, 2H,
0
a
H5, H50), 1.77, 1.57 (m, 2H, H4, H40), 2.29 (s, 3H, Cp-Me), 1.25 (s, 3H, C2-Me). 13C
0
0
0
J = 21.3 Hz, C4, C4 ), 60.8 (C3a), 51.8 (C8a), 50.9 (C5), 45.2 (C8), 39.3 (C1), 27.0
NMR (101.61 MHz, CDCl3, ppm) d 214.0 (C@O), 137.0 (Cp), 136.7 (C ), 133.2 (Ci),
a
(C8a-Me), 24.9 (C3), 23.3 (C2).
(3aR,8aR)-6,7-Di(biphenyl-4-yl)-8a-methyl-1,2,3,3a,8,8a-hexahydroazulen-4(5H)-
131.1 (Cb), 128.9 (Co), 128.7 (Cm), 52.4 (C2), 45.2 (C3), 40.0 (C6), 29.3 (C5), 24.3
(Me), 22.3 (C4), 21.3 (Cp-Me).
one (11): Yield 37%. White crystals (mp 162 °C). Anal. Calcd for C35H32
O
(Z)-2-[2-(Biphenyl-4-yl)vinyl]-2-methylcyclohexanone (17a) in a mixture with 11:
(468.63): C, 89.70; H, 6.88. Found: 89.68; H, 6.91. IR (film, cmꢂ1
)
mmax: 3029,
Yield 11%. White powder. 1H NMR (400.13 MHz, CDCl3, ppm): d 7.56–7.55,
2960, 2932, 2865, 1701, 1602, 1518, 1486, 1461, 1448, 1403, 1377, 1343, 1262,
7.48–7.47, 7.40–7.38, 7.28–7.23, 7.16–7.14 (m, 9H,
Harom), 6.56 (d,
a
1130, 1076, 1007, 909, 840, 766, 733, 697, 648. 1H NMR (400.13 MHz, CDCl3,
3JH –Hb = 12.5 Hz, 1H; Hb), 5.73 (d, 3JH –Hb = 12.5 Hz, 1H; H ), 2.27, 1.83 (m,
a
a
2
ppm): d 7.49–7.47, 7.34–7.30, 7.08–7.05 (m, 18H, Harom), 3.73 (d, 1H, JH5–
2H; H6,60) 1.97, 1.44 (m, 2H; H3,30), 1.86, 1.49 (m, 2H; H5,50), 1.79, 1.53 (m, 2H;
H4,40), 1.28 (s, 3H, Me). 13C NMR (101.61 MHz, CDCl3, ppm): d 212.4 (C@O),
140.9, 140.0, 135.3, 129.1, 128.8, 127.7, 127.4, 127.2, 127.0 (12Carom), 137.5
2
= 18.2 Hz, H5), 3.42 (d, 1H, JH5–H5 = 18.2 Hz, H50), 2.99–2.96 (m, 1H, H3a),
0
H50
2
2
2.79 (d, 1H, JH8–H8 = 13.9 Hz, H8), 2.59 (d, 1H, JH8–H8 = 13.9 Hz, H80), 2.26,
1.83 (m, 2H, H3, H30), 1.87, 1.71 (m, 2H, H2, H20), 1.52, 1.42 (m, 2H, H1, H10),
1.06 (s, 3H, C8a-Me). 13C NMR (101.61 MHz, CDCl3, ppm): d 210.4 (C@O),
143.3–126.5 (24Carom), 139.1 (C7), 132.6 (C6), 61.0 (C3a), 51.9 (C8a), 51.0 (C5),
45.3 (C8), 39.3 (C1), 27.0 (C8a-Me), 25.0 (C3), 23.2 (C2).
0
0
(Ca), 130.6 (Cb), 54.3 (C2), 45.7 (C3), 37.1 (C6), 29.8 (C5), 22.7 (C4), 25.4 (C2-
Me).
10. Atomic coordinates, bond lengths, bond angles, and thermal parameters have
been deposited at the Cambridge Crystallographic Data Centre (CCDC). These
data can be obtained free of charge via www.ccdc.cam.uk.conts/retrieving.html
or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336
033; e-mail: deposit@ccdc.cam.ac.uk). Any request to the CCDC for data
should quote the full literature citation and CCDC reference number CCDC
826323.
(3aR,8aR)-8a-Ethyl-6,7-diphenyl-1,2,3,3a,8,8a-hexahydroazulen-4(5H)-one
(12):Yield 39%. White crystals (mp 91–93 °C). Anal. Calcd for C24H26O (330.46):
C, 87.23; H, 7.93. Found: C, 87.29; H, 8.05. IR (film, cmꢂ1
) mmax: 3055, 3021,
2961, 2938, 2875, 1701, 1599, 1492, 1460, 1443, 1380, 1345, 1265, 1130, 1069,
1029, 965, 911, 765, 700, 544. 1H NMR (400.13 MHz, CDCl3, ppm): d 7.09–6.96
2
0
0
0
0
(m, 10H, Ho, Ho , Hm, Hm , Hp, Hp ), 3.72 (d, 1H, JH5–H5 = 18.1 Hz, H5), 3.40 (d,