Metal-catalyzed formation of 1,3-cyclohexadienes: A catalyst-dependent reaction

Article abstract of DOI:10.1039/c4ob01922a

A metal-dependent and complementary catalytic method to synthesize the cyclohexadienes has been developed. When gold or indium salts were used as catalysts, 1,3-cyclohexadiene (1,3-CHD) could be obtained; when Cu(OTf)₂ was used as the catalyst,

Full text of DOI:10.1039/c4ob01922a

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Metal-catalyzed formation of 1,3-cyclohexadienes:
a catalyst-dependent reaction†
Cite this: DOI: 10.1039/c4ob01922a
Shifa Zhu,*a Xiaobing Huang,a Tian-Qi Zhao,b Tongmei Maa and Huanfeng Jianga
Received 10th September 2014,
Accepted 15th November 2014
A metal-dependent and complementary catalytic method to synthesize the cyclohexadienes has been
developed. When gold or indium salts were used as catalysts, 1,3-cyclohexadiene (1,3-CHD) could be
obtained; when Cu(OTf)2 was used as the catalyst, however, another isomer 2,4-cyclohexadiene (2,4-
CHD) was furnished instead.
DOI: 10.1039/c4ob01922a
www.rsc.org/obc
Introduction
1,3-Cyclohexadiene (1,3-CHD) is the core structure of many
naturally occurring and biologically active substances, such as
α-terpinene,1 α-phellandrene,2 gabaculine3 and safranal4
(Scheme 1). Among them, both α-terpinene and α-phell-
andrene are monoterpenoids, which are the raw materials of
many flavors and fragrances.1,2 Gabaculine, a naturally occur-
ring neurotoxin which was first isolated from the bacteria
Streptomyces toyacaensis, is a potent and irreversible GABA
transaminase inhibitor.3 For safranal, it is the main constitu-
ent responsible for the aroma of saffron.4 However, due to the
easy rearrangement of the double bonds and difficulties in iso-
lation of the isomers of CHD, it would be a great challenge to
selectively and efficiently synthetize 1,3-CHD and its isomers
in organic chemistry.5
Scheme 2 Metal-catalyzed 1,3-cyclohexadiene.
Results and discussion
Initial efforts were made to systematically investigate different
metal catalysts for the reaction of enynal 1a with styrene 2a in
DCE at 50 °C (Table 1). It was found that this reaction is highly
catalyst-dependent; four cyclic-products 3a–6a could be
afforded selectively when different metal salts were applied.
For example, 1,3-cyclohexadiene 3a could be obtained in 45%
yield when Cu(OTf)2 was employed (entry 1). The low yield
could be attributed to the isomerization of the starting
material 1a, as trans-1a was detected after the reaction. When
NHC-AuCl/Selectfluor6,7 and InCl3 were used as the catalysts8
instead, another cyclohexadiene 4a, which is the isomer of 3a,
could be obtained in 80% and 79% yields, respectively (entries
2 and 3). The salts of ZnI2, AgSbF6 and AgF could also be
served as the catalysts of choice. In these cases, cyclohexenol
5a was furnished in 58–74% yields (entries 4–6). It is supposed
that trace amount of adventitious water in the system could
mediate the reactions. Intriguingly, the catalysts CuCl2·2H2O
and AgNO3 afforded the furyl ketone 6a in 61% and
67% yields, respectively (entries 7 and 8).
To this end, we would like to report a metal-dependent
method to selectively synthesize the isomers of CHD from the
intermediate B, which was generated through metal-catalyzed
reaction of enynals and alkenes (Scheme 2).6
Scheme 1
aSchool of Chemistry and Chemical Engineering, South China University of
Technology, Guangzhou City, Guangdong Province 510640, China.
E-mail: zhusf@scut.edu.cn; Fax: +86-20-87112906
bDepartment of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong
†Electronic supplementary information (ESI) available: Experimental procedure
and spectral data. CCDC 1014190. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c4ob01922a
As shown in Table 1, the reaction is highly dependent on
the catalysts. The conditions of entries 1–3 could lead to the
1,3-CHD 3a and 4a selectively. Although gold and indium
showed similar reaction results in producing 1,3-CHD 4a,
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Table 1 Optimization of reaction conditionsa
Entry
Cat.
Add.
3a
4a
5a
6a
Conv.
1b
2c,d
3
4
5
6
7
8
Cu(OTf)2
IMes-AuCl
InCl3
ZnI2
AgSbF6
AgF
—
45%
—
—
—
—
—
—
—
—
—
—
—
64%
74%
58%
—
—
—
—
—
—
—
61%
67%
>99%
>99%
>99%
>99%
>99%
>99%
>99%
>99%
Selectfluor
80%
79%
—
—
—
—
—
—
—
—
—
CuCl2·2H2O
AgNO3
—
—
—
a Unless otherwise noted, the reactions were performed in DCE at 50 °C for 24 h using 10 mol% catalyst under N2, 1/2 = 1 : 3. [1] = 0.25 M. The
yield refers to isolated yield. IMes: 1,3-dimesityl-imidazol-2-ylidene. The stereochemistry of products 3a and 5a were determined by the NOE
spectrum. b trans-1a could be detected (32%) after reaction. c 80 °C. d 5 mol% IMes-AuCl, 15 mol% Selectfluor.
however, the indium showed better reaction scope and repro- tives, the yields were typically higher than 60% (4a–4i). The
ducibility to prepare 1,3-CHD 4a in most cases (see ESI†). electron-deficient 4-CF3-styrene and bulky 2,5-dimethyl styrene
Therefore, the substrate scope was then examined with InCl3 gave the products 4g and 4h in 55% and 69%, respectively,
as the catalyst. As summarized in Table 2, the catalytic process both of which were slightly lower than their analogues 4a–4c.
could be successfully applied to various enynals 1 and alkenes 2. However, for the extremely electron-deficient 2,3,4,5,6-penta-
For example, in addition to styrene 2a, different styrene deriva- fluorostyrene, only a trace product 4j was detected. However,
tives could be effectively reacted with enynal 1a as well the combination of IMes-AuCl/Selectfluor could enable the for-
(Table 2, 4a–4j). The reaction was not very sensitive to the elec- mation of 4j in 28% yield. In addition to the styrene deriva-
tronic properties and steric hindrance of the alkenes. For tives, the aliphatic alkenes could be served as good substrates
example, for the alkyl- or halogen-substituted styrene deriva- as well and it could give the desired 1,3-CHDs 4k–4m with
yields ranging from 70% to 92%. Besides enynal 1a, different
derivatives could also react with styrene. For example, the
Table 2 Substrate scopea
enynals having substituents on the CvC double bonds gave
the products in moderate yields (4n, 4o). For the enynals with
different substituents (electron-donating, electron-withdraw-
ing, and alkyl groups) on the CuC triple bonds, the reactions
proceeded smoothly as well, furnishing the desired products
4p–4t with yields ranging from 41% to 95%.
Having established the indium-catalyzed reaction of
enynals and alkenes as a reliable and efficient synthetic
process to construct the 1,3-CHD 4, our attention was then
turned to the Cu(OTf)2-catalyzed formation of 2,4-CHD 3. With
enynal 1a as the standard substrate, the reactions functioned
well for different styrene derivatives giving the desired 2,4-
CHDs 3a–3d in moderate yields (Scheme 3). It is worth noting
that all the products 3 are formed in trans-isomer.
Interestingly, when enynone 1t and the intramolecular sub-
strate enynal 8 were subjected to the same reaction conditions
a The reactions were performed at 50 °C for 24 h using 10 mol% cat.
under N2, 1/2 = 1 : 3. [1] = 0.25 M, isolated yield. b 5 mol% IMes-AuCl,
15 mol% Selectfluor was used instead.
Scheme 3 Cu(OTf)2-catalyzed reaction of 1a with 2.
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Scheme 7 The control reaction.
Furthermore, the controlled experiment also indicated that
2,4-CHD 3 was not formed by the dehydration of cyclohexenol
5. For example, cyclohexenol 5a remained unchanged upon
treatment with Cu(OTf)2 in DCE at 50 °C for 12 h. Therefore,
the formation of 3a is not from the dehydration of 5a
(Scheme 7).
Scheme 4 InCl3-catalyzed cyclopropanation of enynals.
in Table 2, the cyclopropanation products 7 and 9 could be
obtained instead in moderate to good yields (Scheme 4). These
results could be attributed to the formation of a carbene
intermediate.
Furthermore, when an electron-deficient dienophile (tetra-
cyanoethylene, TCE) was added to trap the 1,3-cyclohexadiene
4, the reaction occurred in one-pot, three-component manner,
affording the bridged product 10 (Scheme 5). The structure
and stereochemistry of the products were further confirmed by
the X-ray diffraction analysis of 10a (see ESI†).
It seems that 1,3-CHD 4 is more stable than its isomer 3, as
the CvC double bond in the former molecule is conjugated
with the carbonyl group.9 One may expect that the formation
of product 4 is by the metal-catalyzed isomerization of its
isomer 3. To elucidate the potential relationship between 3
and 4, a controlled reaction was then conducted. As shown in
Scheme 6, 2,4-CHD 3a remained unchanged upon treatment
with InCl3 in DCE at 50 °C for 24 h, which indicated that the
formation of 4a is not from the isomerization of 3a, but is
directly from the catalytic process.
To gain more information about the reaction mechanism,
additional D2O was added in the reaction of 1c and styrene.
The olefinic carbon atom in product 4q did not have the deu-
terium label. Instead, 65% incorporation of deuterium was
found at the position of the alkyl group of 3e (Scheme 8).
A plausible mechanism was then proposed, as shown in
Scheme 9 based on the above controlled reaction results. The
coordination of the triple bond of enynal 1 to [M] enhanced
the electrophilicity of alkyne, and the subsequent nucleophilic
attack of the carbonyl oxygen to the electron-deficient alkyne
would form the 6-endo-dig-intermediate pyrylium10 A or 5-exo-
dig-intermediate C. A Diels–Alder reaction between pyrylium A
and alkene 2 was followed to furnish the intermediate B. From
the intermediate B, three different ways occurred: the break-
ing of the C–O bond could lead to the enolate allyl cation E
(path a, M = Cu(OTf)2) or the allyl cation E′ with C–M being
intact (path b, M = [Au] or InCl3). β-Deprotonation elimination
of E or demetalation of E′ selectively afforded the isomers of
1,3-cyclohexadienes 3 and 4. In addition, the intermediate B
could also be trapped by the adventitious H2O to give the
cyclohexenol 5 (path c). The 5-exo-dig-intermediate C is equili-
brium with furan carbene D. The carbine intermediate D can
be oxidized into furyl ketone 6 (path d) or trapped by CvC to
form furyl cyclopropanes 7 (path e) or 9 (path f). We believed
that the formation of intermediates A–D is reversible and com-
petitive with each other. The metals/catalysts could control the
reaction pathway, thus furnished different products.
Scheme 5 Three-component reaction.
Scheme 6 The control reaction.
Scheme 8 Deuterium-labeling experiments.
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Scheme 9 Proposed mechanism.
and enynals (1, 0.3 mmol), and the reaction mixture was
stirred at 50 °C unless otherwise noted. The reaction was
Conclusions
In summary, a metal-dependent and complementary catalytic monitored by TLC, then the solvent was evaporated under
method to synthesize the cyclohexadienes has been developed. reduced pressure and the residue was purified by flash chrom-
When gold or indium was used as the catalyst, 1,3-cyclohexa- atography on silica gel (Hex–EtOAc = 20/1) to afford product 3.
diene (1,3-CHD) could be obtained. While Cu(OTf)2 was
(1,2-Dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone
(3a).
applied as the catalyst, another isomer 2,4-cyclohexadiene (2,4- Pale yellow oil; yield: 45% (35 mg); Rf = 0.38; IR (KBr) νmax
CHD) was furnished instead. In addition to cyclohexadienes 3 3056.49, 2957.19, 2858.46, 1686.72, 1596.71, 1537.84, 1386.63,
1
and 4, cyclohexenol 5, furyl ketone 6, furyl cyclopropanes 7 or 1210.16, 947.53, 702.17; H NMR (400 MHz, CDCl3) δ 7.79 (d,
9 could be selectively formed as well. We believe that the J = 7.3 Hz, 2H), 7.45 (t, J = 6.8 Hz, 1H), 7.34 (t, J = 7.3 Hz, 2H),
metal-dependent reaction mechanism would render useful 7.25 (d, J = 6.9 Hz, 2H), 7.22–7.17 (m, 2H), 7.13 (d, J = 6.6 Hz,
information to the organometallic chemists in understanding 1H), 5.98 (s, 2H), 5.82 (d, J = 8.2 Hz, 1H), 5.54 (d, J = 7.6 Hz,
the catalytic behavior of different transition metals.
1H), 4.35 (d, J = 8.6 Hz, 1H), 4.27 (d, J = 9.9 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 198.82, 144.12, 135.91, 133.07, 130.61,
128.69, 128.64, 128.24, 126.81, 125.14, 122.30, 121.86, 50.47,
40.88; HRMS (EI) calcd for C19H14O [M − H2]+: 258.1045,
Found: 258.1043.
Experimental
General information
(4′-(tert-Butyl)-1,2-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)metha-
none (3b). Brown yellow oil; yield: 48% (45 mg); Rf = 0.36;
IR (KBr) νmax 3057.07, 2958.49, 2855.18, 1692.35, 1596.86,
1517.61, 1223.71, 932.67, 815.21, 708.78; 1H NMR (400 MHz,
CDCl3) δ 7.79 (d, J = 7.4 Hz, 2H), 7.45 (t, J = 7.4 Hz, 1H), 7.34
(t, J = 7.6 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.17 (t, J = 6.1 Hz,
2H), 5.97 (dd, J = 14.5, 6.6 Hz, 2H), 5.83 (dd, J = 8.7, 3.8 Hz,
1H), 5.54 (dd, J = 8.6, 4.1 Hz, 1H), 4.38–4.29 (m, 1H), 4.26–4.18
(m, 1H), 1.21 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 198.90,
149.58, 140.93, 136.06, 132.92, 130.74, 128.63, 128.61, 127.77,
125.49, 125.14, 122.06, 121.89, 50.47, 40.37, 34.40, 29.70;
HRMS (EI) calcd for C23H24O [M]: 316.1827, Found: 316.1831.
(4′-Fluoro-1,2-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone
(3c). Pale yellow oil; yield: 62% (51 mg); Rf = 0.33; IR (KBr)
νmax 3049.15, 2928.07, 2854.30, 1661.55, 1596.03, 1443.43,
1250.46, 953.71, 724.50, 697.93; 1H NMR (400 MHz, CDCl3)
δ 7.79 (d, J = 7.9 Hz, 2H), 7.47 (t, J = 7.3 Hz, 1H), 7.36 (t, J =
7.5 Hz, 2H), 7.21 (dd, J = 7.9, 6.3 Hz, 2H), 6.88 (t, J = 8.5 Hz,
2H), 6.07–5.91 (m, 2H), 5.85–5.74 (m, 1H), 5.61–5.48 (m, 1H),
4.36–4.20 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 198.73, 161.75
(d, JC–F = 243.0 Hz), 139.88, 135.90, 133.12, 130.55, 129.72 (d,
JC–F = 7.9 Hz), 128.64 (d, JC–F = 12.1 Hz), 125.07, 122.50, 121.89,
Unless specified, all reactions were carried out under an inert
atmosphere of dry N2 in Schlenk tube; the solvents were puri-
fied by the standard method. 1H, 13C, 19F NMR spectra were
recorded on a Bruker AVANCE 400 spectrometer (400 MHz for
1
1H; 100 MHz for 13C; 376 MHz for 19F); H NMR and 13C NMR
chemical shifts were determined relative to the internal stan-
dard TMS at δ 0.0 and 19F NMR chemical shifts were deter-
mined relative to CFCl3 as the external standard. Chemical
shifts (δ) are reported in ppm, and coupling constants (J) are
in hertz (Hz). The following abbreviations were used to explain
the multiplicities: s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, br = broad. Infrared (IR) spectra are
recorded on a Nicolet 210 spectrophotometer. All reagents
were used as received from commercial sources, unless speci-
fied otherwise, or prepared as described in the literature.
General procedure for copper-catalyzed tandem reaction of
enynals with olefins
To a dichloroethane (DCE, 2 ml) suspension of Cu(OTf)2
(10.8 mg, 0.03 mmol) in Schlenk tube with a magnetic bar
under a nitrogen atmosphere was added olefin (2, 0.6 mmol)
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115.44, 115.23, 50.70, 40.24; 19F NMR (376 MHz, CDCl3) 129.09, 128.12, 127.15, 123.87, 35.01, 32.17, 21.06; HRMS (EI)
δ −116.27; HRMS (EI) calcd for C19H13FO [M − H2]+: 276.0950, calcd for C20H18O [M]: 274.1358, Found: 274.1360.
Found: 276.0954.
(4′-(tert-Butyl)-1,6-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)metha-
(4′-Chloro-1,2-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone none (4c). Yellow oil; yield: 81% (76 mg); Rf = 0.32; IR (KBr)
(3d). Brown yellow oil; yield: 45% (39 mg); Rf = 0.35; IR (KBr) νmax 3058.13, 2959.27, 2856.56, 1723.10, 1567.19, 1455.90,
1
νmax 3042.12, 2921.44, 2854.81, 1660.30, 1528.62, 1401.66, 1404.68, 1269.77, 1018.41, 705.42; H NMR (400 MHz, CDCl3)
1384.31, 1105.97, 699.84, 619.39; 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.3 Hz, 1H), 7.33 (t, J =
δ 7.79 (d, J = 7.3 Hz, 2H), 7.47 (t, J = 7.4 Hz, 1H), 7.36 (t, J = 7.5 Hz, 2H), 7.22–7.14 (m, 4H), 6.73 (d, J = 5.2 Hz, 1H),
7.6 Hz, 2H), 7.20–7.14 (m, 4H), 6.06–5.95 (m, 2H), 5.77 (dd, J = 6.13–6.00 (m, 2H), 4.23 (dd, J = 10.2, 2.5 Hz, 1H), 2.89–2.77 (m,
10.1, 2.7 Hz, 1H), 5.59–5.49 (m, 1H), 4.33–4.22 (m, 2H); 13C 1H), 2.61 (ddd, J = 18.5, 5.2, 2.7 Hz, 1H), 1.20 (s, 9H); 13C NMR
NMR (100 MHz, CDCl3) δ 198.48, 142.67, 135.82, 133.14, (100 MHz, CDCl3) δ 196.92, 149.20, 139.94, 138.81, 137.62,
132.53, 130.21, 129.63, 128.71, 128.68, 128.58, 125.06, 122.66, 137.04, 133.14, 131.34, 129.09, 128.08, 126.84, 125.30, 123.82,
121.86, 50.51, 40.31; HRMS (EI) calcd for C19H13ClO [M − H2]+: 34.66, 34.35, 32.01, 31.38; HRMS (EI) calcd for C23H22O
292.0655, Found: 292.0657.
[M − H2]+: 314.1671, Found: 314.1668.
(4-Chlorophenyl)(2-deuterio-1,2-dihydro-[1,1′-biphenyl]-2-yl)-
(4′-Fluoro-1,6-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone
methanone (3e). Pale yellow oil; yield: 35% (23 mg); Rf = 0.33 (4d). Pale yellow oil; yield: 73% (60 mg); Rf = 0.35; IR (KBr)
(Hex–EtOAc = 20/1); IR (KBr) νmax 3054.27, 2918.95, 2850.03, νmax 3054.37, 2923.59, 2857.00, 1634.52, 1505.76, 1269.07,
1679.28, 1588.17, 1489.53, 1384.00, 1109.57, 701.39, 618.86; 1229.19, 1163.58, 830.49, 705.44; 1H NMR (400 MHz, CDCl3)
1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.3 Hz, 2H), 7.32 (d, δ 7.52 (d, J = 7.1 Hz, 2H), 7.41 (t, J = 6.9 Hz, 1H), 7.33 (t, J = 7.1
J = 8.3 Hz, 3H), 7.22 (s, 6H), 7.14 (d, J = 7.5 Hz, 2H), 6.00 (t, J = Hz, 2H), 7.20 (s, 2H), 6.85 (t, J = 8.2 Hz, 2H), 6.74 (d, J = 4.1 Hz,
9.2 Hz, 2H), 5.83 (s, 1H), 5.50 (d, J = 9.0 Hz, 1H), 4.28 (s, 0.3H), 1H), 6.08 (d, J = 11.2 Hz, 2H), 4.21 (d, J = 10.1 Hz, 1H), 2.84
4.22 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 197.82, 143.88, (dd, J = 18.2, 10.4 Hz, 1H), 2.55 (d, J = 18.2 Hz, 1H); 13C NMR
139.50, 134.31, 131.04, 130.61, 129.99, 128.96, 128.64, 128.16, (100 MHz, CDCl3) δ 196.79, 161.70 (d, JC–F = 242.6 Hz), 138.89,
126.88, 126.06, 125.38, 122.31, 121.49, 50.54, 41.10; HRMS (EI) 138.59, 137.35, 137.19, 132.97, 131.52, 129.02, 128.68 (d, JC–F
=
calcd for C19H14DClO [M]+: 295.0874, Found: 295.0877.
7.8 Hz), 128.18, 123.93, 115.20 (d, JC–F = 21.3 Hz), 34.67, 32.09;
19F NMR (376 MHz, CDCl3) δ −116.67; HRMS (EI) calcd for
C19H15FO [M]: 278.1107, Found: 278.1106.
(4′-Chloro-1,6-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone
(4e). Pale yellow oil; yield: 68% (59 mg); Rf = 0.35; IR (KBr)
General procedure for indium-catalyzed tandem reaction of
enynals with olefins
To a dichloroethane (DCE, 2 ml) suspension of InCl3 (6.5 mg, νmax. 3075.12, 2924.85, 2850.42, 1731.58, 1560.59, 1487.96,
0.03 mmol) in Schlenk tube with a magnetic bar under a nitro- 1274.70, 1034.23, 928.91, 702.59; 1H NMR (400 MHz, CDCl3)
gen atmosphere was added olefin (2, 0.9 mmol) and enynals δ 7.53 (d, J = 7.5 Hz, 2H), 7.42 (t, J = 7.4 Hz, 1H), 7.33 (t, J = 7.6
(1, 0.3 mmol), and the reaction mixture was stirred at 50 °C Hz, 2H), 7.16 (q, J = 8.5 Hz, 4H), 6.75 (d, J = 5.3 Hz, 1H),
unless otherwise noted. The reaction was monitored by TLC, 6.14–6.02 (m, 2H), 4.20 (dd, J = 10.3, 2.5 Hz, 1H), 2.85 (dd, J =
then the solvent was evaporated under reduced pressure and 18.6, 10.3 Hz, 1H), 2.55 (ddd, J = 18.6, 5.4, 2.7 Hz, 1H); 13C
the residue was purified by flash chromatography on silica gel NMR (100 MHz, CDCl3) δ 196.69, 141.68, 138.52, 137.27,
(Hex–EtOAc = 20/1) to afford product 4.
137.07, 132.91, 132.29, 131.52, 128.99, 128.61, 128.55, 128.17,
(1,6-Dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone (4a).11 123.94, 34.91, 31.91; HRMS (EI) calcd for C19H15ClO [M]:
Pale yellow oil; yield: 79% (61 mg); Rf = 0.33; 1H NMR 294.0811, Found: 294.0810.
(400 MHz, CDCl3) δ 7.54 (d, J = 7.5 Hz, 2H), 7.40 (d, J = 6.9 Hz,
(4′-Bromo-1,6-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone
1H), 7.34 (d, J = 7.5 Hz, 2H), 7.25 (d, J = 7.5 Hz, 2H), 7.19–7.15 (4f). Yellow oil; yield: 85% (86 mg); Rf = 0.36; IR (KBr) νmax
(m, 2H), 7.11 (d, J = 7.3 Hz, 1H), 6.73 (d, J = 5.0 Hz, 1H), 3056.78, 2924.64, 2858.43, 1719.93, 1656.25, 1589.77, 1483.95,
1
6.14–6.01 (m, 2H), 4.30–4.20 (m, 1H), 2.86 (dd, J = 18.6, 10.4 1271.98, 1070.10, 704.30; H NMR (400 MHz, CDCl3) δ 7.52 (d,
Hz, 1H), 2.65–2.55 (m, 1H); 13C NMR (100 MHz, CDCl3) J = 7.5 Hz, 2H), 7.42 (t, J = 7.2 Hz, 1H), 7.31 (dd, J = 19.7,
δ 196.86, 143.17, 138.71, 137.48, 137.07, 133.01, 132.07, 131.41, 7.7 Hz, 4H), 7.12 (d, J = 7.9 Hz, 2H), 6.75 (d, J = 5.1 Hz, 1H),
129.05, 128.43, 128.11, 127.23, 126.59, 123.84, 35.34, 32.03.
6.08 (d, J = 11.5 Hz, 2H), 4.18 (d, J = 9.7 Hz, 1H), 2.85 (dd, J =
(4′-Methyl-1,6-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone 18.3, 10.3 Hz, 1H), 2.54 (d, J = 18.1 Hz, 1H); 13C NMR
(4b). Pale yellow oil; yield: 71% (58 mg); Rf = 0.30; IR (KBr) (100 MHz, CDCl3) δ 196.64, 142.23, 138.51, 137.29, 136.99,
νmax 3035.60, 2922.95, 2860.17, 1639.78, 1564.76, 1508.48, 132.89, 131.52, 131.51, 129.02, 128.99, 128.18, 123.96, 120.39,
1271.00, 812.09, 742.08, 702.71; 1H NMR (400 MHz, CDCl3) 35.00, 31.85; HRMS (EI) calcd for C19H15BrO [M]: 338.0306,
δ 7.68 (d, J = 7.4 Hz, 2H), 7.53 (t, J = 7.3 Hz, 1H), 7.45 (t, J = Found: 338.0301.
7.4 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 7.12 (d, J = 7.7 Hz, 2H),
Phenyl(4′-(trifluoromethyl)-1,6-dihydro-[1,1′-biphenyl]-2-yl)-
6.85 (d, J = 5.1 Hz, 1H), 6.25–6.12 (m, 2H), 4.35 (d, J = 8.7 Hz, methanone (4g). Pale yellow oil; yield: 55% (54 mg); Rf = 0.31;
1H), 2.97 (dd, J = 18.5, 10.3 Hz, 1H), 2.71 (ddd, J = 18.5, 4.9, 2.7 IR (KBr) νmax 3061.76, 2924.22, 2848.49, 1726.27, 1565.95,
Hz, 1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 196.88, 1452.10, 1324.47, 1274.43, 1121.20, 702.98; 1H NMR (400 MHz,
140.16, 138.79, 137.69, 136.93, 136.10, 133.02, 131.40, 129.17, CDCl3) δ 7.54 (d, J = 7.5 Hz, 2H), 7.44 (d, J = 7.8 Hz, 3H),
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7.35 (d, J = 7.1 Hz, 4H), 6.81 (d, J = 5.2 Hz, 1H), 6.25–5.98 (m, 26.42, 26.29; HRMS (EI) calcd for C20H24O [M]: 280.1827,
2H), 4.28 (d, J = 9.9 Hz, 1H), 2.88 (dd, J = 18.5, 10.4 Hz, 1H), Found: 280.1825.
2.57 (d, J = 18.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 196.56,
Phenyl(2,3,3a,7a-tetrahydro-1H-inden-4-yl)methanone (4l).
147.23, 138.39, 137.75, 136.62, 132.92, 131.61, 129.00, 128.22, Pale yellow oil; yield: 75% (50 mg); Rf = 0.38; IR (KBr) νmax
127.56, 125.42 (m, JC–F = 3.8 Hz), 124.06, 35.51, 31.83, 22.13; 2957.05, 2925.60, 2852.12, 1640.62, 1561.97, 1447.15, 1383.94,
19F NMR (376 MHz, CDCl3) δ −62.37; HRMS (EI) calcd for 1104.89, 701.34, 619.20; 1H NMR (400 MHz, CDCl3) δ 7.59–7.52
C20H15F3O [M]: 328.1075, Found: 328.1079.
(m, 2H), 7.42 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.4 Hz, 2H),
(2′,5′-Dimethyl-1,6-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)metha- 6.44–6.38 (m, 1H), 5.85 (dd, J = 3.3, 1.8 Hz, 2H), 3.08 (dt, J =
none (4h). Brown yellow oil; yield: 69% (59 mg); Rf = 0.32; IR 11.3, 8.9 Hz, 1H), 2.99–2.89 (m, 1H), 2.18 (ddd, J = 12.1, 7.2,
(KBr) νmax 3051.19, 2921.71, 2856.98, 1725.05, 1566.51, 3.5 Hz, 1H), 2.09 (dt, J = 14.0, 7.8 Hz, 1H), 1.61 (ddd, J = 12.4,
1451.59, 1272.30, 929.16, 733.08, 701.74; 1H NMR (400 MHz, 9.9, 6.2 Hz, 1H), 1.49–1.41 (m, 2H), 1.39–1.30 (m, 1H); 13C
CDCl3) δ 7.56 (d, J = 7.4 Hz, 2H), 7.43–7.37 (m, 1H), 7.32 (t, J = NMR (100 MHz, CDCl3) δ 197.94, 139.20, 139.12, 139.03,
7.5 Hz, 2H), 7.02–6.92 (m, 2H), 6.81 (d, J = 6.0 Hz, 2H), 6.10 (s, 134.53, 131.19, 128.96, 128.04, 120.72, 38.74, 36.12, 34.42,
1H), 5.97 (d, J = 4.2 Hz, 1H), 4.43 (dd, J = 11.1, 2.9 Hz, 1H), 34.37, 22.98; HRMS (EI) calcd for C16H16O [M]: 224.1201,
2.82 (dd, J = 18.3, 11.4 Hz, 1H), 2.40 (d, J = 19.0 Hz, 1H), 2.35 Found: 224.1202.
(s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 196.71,
(1,2,3,4,4a,8a-Hexahydro-1,4-methanonaphthalen-5-yl)(phenyl)-
140.84, 138.71, 137.93, 137.24, 135.03, 132.63, 132.00, 131.36, methanone (4m). Pale yellow oil; yield: 92% (69 mg); Rf = 0.30;
130.67, 129.02, 128.09, 127.19, 127.15, 123.60, 31.44, 31.14, IR (KBr) νmax 3054.12, 2952.00, 2873.57, 1641.71, 1569.84,
21.25, 19.26; HRMS (EI) calcd for C20H18O [M]: 288.1514, 1451.32, 1265.82, 928.55, 729.37, 702.49; 1H NMR (400 MHz,
Found: 288.1516.
CDCl3) δ 7.57–7.51 (m, 2H), 7.42 (t, J = 7.4 Hz, 1H), 7.33 (t, J =
(3′-Bromo-1,6-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)methanone 7.4 Hz, 2H), 6.24 (d, J = 5.9 Hz, 1H), 5.78 (dd, J = 9.5, 4.2 Hz,
(4i). Pale yellow oil; yield: 59% (60 mg); Rf = 0.32; IR (KBr) 1H), 5.68 (ddd, J = 9.5, 5.9, 1.7 Hz, 1H), 3.11 (d, J = 12.3 Hz,
νmax. 3055.73, 2922.94, 2854.50, 1631.83, 1560.93, 1460.08, 1H), 2.66 (dd, J = 12.2, 3.2 Hz, 1H), 2.11 (d, J = 8.0 Hz, 2H),
1271.60, 1068.59, 735.47, 695.80; 1H NMR (400 MHz, CDCl3) 1.70 (d, J = 9.7 Hz, 1H), 1.55–1.47 (m, 3H), 1.43–1.38 (m, 1H),
δ 7.58–7.50 (m, 2H), 7.43 (dd, J = 13.0, 5.5 Hz, 1H), 7.35 (dd, J = 1.24 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 198.27, 139.27,
14.6, 7.0 Hz, 3H), 7.24 (d, J = 7.9 Hz, 1H), 7.18–7.14 (m, 1H), 136.61, 136.39, 135.50, 131.28, 128.91, 128.05, 120.85, 45.60,
7.04 (t, J = 7.8 Hz, 1H), 6.78 (d, J = 5.4 Hz, 1H), 6.21–5.97 (m, 45.55, 44.88, 41.21, 34.81, 30.67, 30.36; HRMS (EI) calcd for
2H), 4.20 (dd, J = 10.3, 2.5 Hz, 1H), 2.85 (ddt, J = 18.3, 10.3, C18H18O [M]: 250.1358, Found: 250.1359.
2.6 Hz, 1H), 2.56 (ddd, J = 18.6, 5.6, 2.6 Hz, 1H); 13C NMR
Phenyl(2-phenyl-2,3,5,6,7,8-hexahydronaphthalen-1-yl)metha-
(100 MHz, CDCl3) δ 196.55, 145.51, 138.51, 137.60, 136.69, none (4n). Yellow oil; yield: 52% (49 mg); Rf = 0.36; IR (KBr)
132.92, 131.52, 130.26, 130.02, 129.74, 129.00, 128.19, 126.00, νmax 3026.36, 2926.19, 2857.48, 1668.87, 1597.36, 1384.34,
1
124.01, 122.50, 35.19, 31.90; HRMS (EI) calcd for C19H15BrO 1242.73, 1096.58, 700.51, 618.42; H NMR (400 MHz, CDCl3) δ
[M]: 338.0306; Found: 338.0309.
7.67 (d, J = 7.6 Hz, 2H), 7.40 (t, J = 7.3 Hz, 1H), 7.30 (t, J = 7.5
(2′,3′,4′,5′,6′-Pentafluoro-1,6-dihydro-[1,1′-biphenyl]-2-yl)(phenyl)- Hz, 2H), 7.14–7.08 (m, 4H), 7.03 (d, J = 6.5 Hz, 1H), 5.75 (s,
methanone (4j). Brown yellow oil; yield: 28% (29 mg); Rf = 1H), 3.89 (s, 1H), 2.43–2.27 (m, 2H), 2.20 (d, J = 15.1 Hz, 1H),
0.29; IR (KBr) νmax 3056.28, 2924.44, 2864.21, 1642.90, 1501.48, 2.15–2.02 (m, 4H), 1.80 (dt, J = 11.3, 5.3 Hz, 1H), 1.67–1.55 (m,
1
1401.21, 1274.77, 1126.44, 705.11, 619.38; H NMR (400 MHz, 2H); 13C NMR (100 MHz, CDCl3) δ 199.86, 142.96, 137.86,
CDCl3) δ 7.64 (d, J = 7.4 Hz, 2H), 7.46 (t, J = 7.4 Hz, 1H), 7.36 (t, 136.55, 133.63, 133.07, 132.68, 129.01, 128.62, 128.44, 128.10,
J = 7.6 Hz, 2H), 6.63 (d, J = 3.8 Hz, 1H), 6.25–6.16 (m, 1H), 126.29, 44.32, 31.66, 28.68, 27.49, 25.87, 23.02; HRMS (EI)
6.16–6.07 (m, 1H), 4.50 (dd, J = 14.3, 10.4 Hz, 1H), 2.69–2.45 calcd for C23H23O [M + H]+: 315.1743, Found: 315.1734.
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 195.78, 137.37, 136.86,
135.83, 132.76, 132.20, 129.42, 128.29, 123.78, 30.25, 30.05; 19
(1′,6′-Dihydro-[1,1′:3′,1″-terphenyl]-2′-yl)(phenyl)methanone
(4o). Yellow oil; yield: 52% (52 mg); Rf = 0.33; IR (KBr) νmax
F
NMR (376 MHz, CDCl3) δ −141.16, −141.18, −141.21, −141.23, 3058.80, 2924.45, 2851.59, 1642.72, 1578.39, 1492.40, 1238.46,
1
−157.59, −157.65, −157.70, −162.51, −162.53, −162.57, 1073.31, 736.70, 698.22; H NMR (400 MHz, CDCl3) δ 7.40 (d,
−162.58, −162.62, −162.64; HRMS (EI) calcd for C19H11F5O J = 7.9 Hz, 2H), 7.28 (d, J = 7.6 Hz, 2H), 7.18–7.06 (m, 7H), 6.98
[M]: 350.0730, Found: 350.0735.
(t, J = 7.3 Hz, 4H), 6.25 (d, J = 9.7 Hz, 1H), 6.09–5.98 (m, 1H),
(6-(Cyclohexylmethyl)cyclohexa-1,3-dien-1-yl)(phenyl)metha- 4.11 (dd, J = 9.6, 5.2 Hz, 1H), 2.98–2.85 (m, 1H), 2.63 (dt, J =
none (4k). Pale yellow oil; yield: 70% (59 mg); Rf = 0.32; IR 18.1, 5.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 199.84, 142.83,
(KBr) νmax. 3057.48, 2922.03, 2851.58, 1663.01, 1588.05, 139.68, 139.35, 137.84, 134.31, 131.89, 129.11, 129.07, 128.42,
1
1449.13, 1266.32, 1072.80, 928.32, 705.01; H NMR (400 MHz, 128.33, 128.03, 127.75, 127.68, 127.67, 126.72, 41.17, 31.64;
CDCl3) δ 7.56 (d, J = 7.6 Hz, 2H), 7.43 (t, J = 7.2 Hz, 1H), 7.34 (t, HRMS (MALDI/DHB) calcd for C25H21O [M + H]+: 337.1586
J = 7.2 Hz, 2H), 6.46 (d, J = 4.4 Hz, 1H), 6.01 (s, 2H), 3.06 (s, 0.002, Found: 337.15869.
1H), 2.44–2.28 (m, 2H), 1.76 (d, J = 12.8 Hz, 1H), 1.68–1.49 (m,
(1,6-Dihydro-[1,1′-biphenyl]-2-yl)(p-tolyl)methanone
(4p).
5H), 1.37–1.25 (m, 2H), 1.18–1.00 (m, 5H); 13C NMR (100 MHz, Pale yellow oil; yield: 95% (78 mg); Rf = 0.33; IR (KBr) νmax
CDCl3) δ 197.29, 140.50, 139.02, 136.07, 132.91, 131.22, 129.01, 3050.66, 2924.10, 2858.77, 1639.84, 1565.86, 1449.24, 1270.24,
1
128.04, 123.57, 38.43, 34.81, 34.20, 32.64, 27.78, 26.66, 26.61, 1178.22, 742.54, 704.81; H NMR (400 MHz, CDCl3) δ 7.46 (d,
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J = 8.0 Hz, 2H), 7.24 (s, 1H), 7.13 (dt, J = 16.8, 7.9 Hz, 6H), 6.71 (Hex–EtOAc = 5/1); IR (KBr) νmax 3604.83, 3027.12, 2921.47,
(d, J = 5.3 Hz, 1H), 6.11–5.98 (m, 2H), 4.23 (dd, J = 10.3, 2.9 Hz, 2848.98, 1685.77, 1597.62, 1493.23, 1284.34, 959.84, 698.81; 1H
1H), 2.85 (ddd, J = 15.7, 9.0, 5.2 Hz, 1H), 2.58 (ddd, J = 18.5, 5.3, NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.9 Hz, 2H), 7.42 (t, J =
3.1 Hz, 1H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 196.63, 7.3 Hz, 1H), 7.29 (t, J = 7.6 Hz, 2H), 7.16 (t, J = 9.2 Hz, 4H), 7.05
143.29, 142.07, 137.65, 136.30, 135.92, 132.61, 129.30, 128.80, (t, J = 6.8 Hz, 1H), 6.03 (dd, J = 6.3, 3.5 Hz, 1H), 5.78 (d, J = 9.9
128.41, 127.25, 126.54, 123.83, 35.58, 32.03, 21.53; HRMS (EI) Hz, 1H), 4.27 (d, J = 8.9 Hz, 1H), 4.21 (d, J = 3.0 Hz, 1H), 3.55
calcd for C20H18O [M]: 274.1358, Found: 274.1362.
(dd, J = 16.3, 8.1 Hz, 1H), 2.06 (dd, J = 7.7, 3.5 Hz, 2H); 13C
(4-Chlorophenyl)(1,6-dihydro-[1,1′-biphenyl]-2-yl)methanone NMR (100 MHz, CDCl3) δ 200.50, 143.88, 136.31, 133.18,
(4q). White solid (m.p. 83 °C); yield: 71% (62 mg); Rf = 0.35; IR 130.68, 128.61, 128.50, 128.15, 127.55, 126.60, 63.73, 51.14,
(KBr) νmax 3056.43, 2920.63, 2856.42, 1682.32, 1583.12, 37.68, 37.18; HRMS (EI) calcd for C19H18NaO2 [M + Na]+:
1
1481.11, 1396.18, 1099.04, 751.11, 615.01; H NMR (400 MHz, 301.1204, Found: 301.1199.
CDCl3) δ 7.48 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 7.22
2-(1,2-Diphenylcyclopropyl)-5-phenylfuran (7). Pale yellow
(d, J = 7.3 Hz, 2H), 7.16 (t, J = 7.3 Hz, 2H), 7.12–7.07 (m, 1H), oil; yield: 38% (38 mg); dr (Z : E) = 84 : 16; Rf = 0.4 (Hex–EtOAc
6.69 (d, J = 4.3 Hz, 1H), 6.07 (s, 2H), 4.21 (d, J = 8.5 Hz, 1H), = 50/1); IR (KBr) νmax 2957.38, 2923.42, 2850.31, 1461.67,
2.84 (dd, J = 18.6, 10.4 Hz, 1H), 2.59 (d, J = 18.1 Hz, 1H); 13C 1385.26, 1277.84, 913.14, 746.40, 697.89, 632.96; 1H NMR
NMR (100 MHz, CDCl3) δ 195.52, 143.10, 137.76, 137.36, (400 MHz, CDCl3) δ 7.55 (d, J = 7.6 Hz, 2H), 7.30 (t, J = 7.5 Hz,
136.98, 136.94, 133.35, 130.49, 128.50, 128.45, 127.19, 126.69, 2H), 7.18–7.14 (m, 1H), 7.10 (s, 5H), 6.98 (t, J = 8.1 Hz, 3H),
123.73, 35.47, 32.01; HRMS (EI) calcd for C19H15ClO [M]: 6.76 (d, J = 7.4 Hz, 2H), 6.45–6.40 (m, 1H), 5.69–5.64 (m, 1H),
294.0811, Found: 294.0813.
1-(1,6-Dihydro-[1,1′-biphenyl]-2-yl)heptan-1-one
3.00 (t, J = 7.7 Hz, 1H), 2.06 (dd, J = 8.7, 5.6 Hz, 1H), 1.91 (t, J =
(4r). Pale 5.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 154.50, 152.46,
yellow oil; yield: 56% (45 mg); Rf = 0.35; IR (KBr) νmax 2958.92, 143.82, 138.04, 131.61, 131.03, 128.48, 128.42, 128.20, 127.83,
2926.43, 2856.19, 1659.59, 1565.79, 1493.39, 1275.19, 1182.05, 126.75, 126.60, 126.23, 123.49, 110.78, 105.50, 77.37, 77.05,
751.25, 697.83; 1H NMR (400 MHz, CDCl3) δ 7.14 (d, J = 3.7 Hz, 76.73, 32.89, 32.67, 19.53; HRMS (EI) calcd for C25H20NaO2
4H), 7.06 (d, J = 5.5 Hz, 2H), 6.15–6.06 (m, 1H), 6.04–5.95 (m, [M + Na]+: 359.1412, Found: 359.1406.
1H), 4.07 (d, J = 10.2 Hz, 1H), 2.75 (dd, J = 18.3, 10.4 Hz, 1H),
Procedure for intramolecular reaction of tethered alkenyl
enynals
2.53 (dt, J = 18.5, 6.6 Hz, 3H), 1.51–1.43 (m, 2H), 1.16 (s, 6H),
0.78 (t, J = 6.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 200.57,
143.02, 137.63, 133.06, 132.90, 128.29, 127.24, 126.48, 123.93, To a dichloroethane (DCE, 2 ml) suspension of InCl3 (6.3 mg,
77.38, 77.06, 76.74, 37.37, 34.35, 32.05, 31.66, 29.02, 24.86, 0.03 mmol) in Schlenk tube with a magnetic bar under a nitro-
22.52, 14.05; HRMS (EI) calcd for C16H16O [M]: 269.1905, gen atmosphere was added olefin (8, 0.3 mmol) and the reac-
Found: 269.1900.
tion mixture was stirred at 50 °C unless otherwise noted. The
Cyclopropyl(1,6-dihydro-[1,1′-biphenyl]-2-yl)methanone (4s). reaction was monitored by TLC, then the solvent was evapor-
Pale yellow oil; yield: 80% (54 mg); Rf = 0.32; IR (KBr) νmax ated under reduced pressure and the residue was purified by
3068.52, 2920.54, 2854.64, 1733.21, 1555.45, 1457.14, 1263.94, flash chromatography on silica gel (Hex–EtOAc = 5/1) to afford
1
1207.13, 1023.88, 741.92; H NMR (400 MHz, CDCl3) δ 7.22 (d, product 9.
J = 5.5 Hz, 1H), 7.17–7.14 (m, 3H), 7.11–7.06 (m, 1H), 6.14
1-(Furan-2-yl)-3-tosyl-3-azabicyclo[3.1.0]hexane (9a). Brown
(ddd, J = 8.9, 5.5, 3.1 Hz, 1H), 6.07–5.93 (m, 1H), 4.08 (dd, J = yellow solid (m.p. 89 °C); yield: 85% (80 mg); Rf = 0.34; IR
10.2, 1.6 Hz, 1H), 2.82–2.70 (m, 1H), 2.51 (ddd, J = 18.4, 6.0, (KBr) νmax 3056.45, 2922.68, 2851.24, 1734.39, 1598.32,
1.4 Hz, 1H), 2.34–2.25 (m, 1H), 0.96–0.87 (m, 2H), 0.78–0.69 1462.51, 1349.00, 1165.19, 1101.18, 740.74; 1H NMR (400 MHz,
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 199.78, 142.94, 138.26, CDCl3) δ 7.63 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 7.15
133.04, 132.75, 128.32, 127.24, 126.46, 124.08, 34.83, 32.14, (s, 1H), 6.19 (s, 1H), 5.90 (d, J = 2.8 Hz, 1H), 3.69 (d, J = 9.0 Hz,
16.01, 10.81, 10.54; HRMS (EI) calcd for C16H16O [M]: 1H), 3.54 (d, J = 9.3 Hz, 1H), 3.25 (d, J = 9.0 Hz, 1H), 3.12 (dd, J
224.1201, Found: 224.1197.
= 9.2, 3.6 Hz, 1H), 2.37 (s, 3H), 1.69 (dt, J = 8.1, 4.2 Hz, 1H),
1-(1,6-Dihydro-[1,1′-biphenyl]-2-yl)-2,2-dimethylpro-pan-1-one 1.14–1.08 (m, 1H), 0.97 (t, J = 4.8 Hz, 1H); 13C NMR (100 MHz,
(4t). Pale yellow oil; yield: 41% (30 mg); Rf = 0.35; IR (KBr) νmax CDCl3) δ 153.45, 143.66, 141.11, 133.42, 129.73, 127.59, 110.40,
2958.58, 2924.85, 2851.36, 1647.09, 1564.74, 1453.18, 1268.55, 104.91, 51.23, 49.80, 25.70, 24.19, 21.55, 14.75; HRMS (EI)
1
1147.64, 749.96, 701.09; H NMR (400 MHz, CDCl3) δ 7.25 (d, calcd for C16H17NO3S [M]: 303.0929, Found: 303.0925.
J = 3.7 Hz, 4H), 7.19 (d, J = 4.2 Hz, 1H), 7.09 (d, J = 5.4 Hz, 1H),
1-(3-Phenylfuran-2-yl)-3-tosyl-3-azabicyclo[3.1.0]hexane (9b).
6.18 (s, 1H), 6.01 (s, 1H), 4.14 (d, J = 9.9 Hz, 1H), 2.85 (dd, J = Brown yellow solid (m.p. 124 °C); yield: 43% (49 mg); Rf = 0.30;
17.8, 10.0 Hz, 1H), 2.58 (d, J = 18.2 Hz, 1H), 1.26 (s, 9H); IR (KBr) νmax 2955.99, 2919.67, 2848.53, 1737.17, 1564.40,
1
13C NMR (100 MHz, CDCl3) δ 205.85, 142.17, 134.98, 130.31, 1446.96, 1346.64, 1162.84, 745.48, 700.54; H NMR (400 MHz,
130.03, 127.23, 126.24, 125.35, 122.60, 76.31, 76.00, 75.68, CDCl3) δ 7.59 (d, J = 7.9 Hz, 2H), 7.26 (d, J = 7.9 Hz, 2H), 7.20
42.80, 35.30, 31.11, 27.63; HRMS (EI) calcd for C17H20NaO (s, 6H), 6.39 (s, 1H), 3.72 (d, J = 9.2 Hz, 1H), 3.54 (d, J = 9.3 Hz,
[M + Na]+: 263.1412, Found: 263.1406.
1H), 3.15 (dd, J = 9.3, 3.7 Hz, 1H), 3.10 (d, J = 9.2 Hz, 1H), 2.39
(5-Hydroxy-1,2,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)(phenyl)- (s, 3H), 1.63 (dt, J = 8.1, 4.0 Hz, 1H), 1.02 (t, J = 4.8 Hz, 1H),
methanone (5a). Pale yellow oil; yield: 73% (61 mg); Rf = 0.23 0.92–0.85 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 147.61,
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143.63, 141.15, 133.02, 132.91, 129.71, 128.38, 127.90, 127.64,
1-Benzoyl-1,4,4a,5,6,7,8,8a-octahydro-1,4-ethano-5,8-metha-
126.95, 123.73, 111.65, 52.62, 49.89, 24.48, 24.31, 21.58, 15.09; nonaphthalene-10,10,11,11-tetracarbonitrile
(10d). Brown
HRMS (EI) calcd for C22H21NO3S [M]: 379.1242, Found: yellow solid (m.p. 150 °C); yield: 45% (51 mg); Rf = 0.30;
379.1246.
IR (KBr) νmax 3031.51, 2964.92, 2878.06, 2225.50, 1668.95,
1596.01, 1383.62, 1094.63, 785.28, 618.12; H NMR (400 MHz,
CDCl3) δ 7.84 (d, J = 8.0 Hz, 2H), 7.62 (t, J = 7.3 Hz, 1H), 7.50 (t,
J = 7.7 Hz, 2H), 6.92 (d, J = 8.5 Hz, 1H), 6.75–6.65 (m, 1H), 3.72
1
General procedure for indium-catalyzed tandem reaction of
enynals with olefins and tetracyanoethylene
To a dichloroethane (DCE, 2 ml) suspension of InCl3 (6.3 mg, (d, J = 6.2 Hz, 1H), 2.55 (d, J = 8.4 Hz, 1H), 2.43 (d, J = 8.3 Hz,
0.03 mmol) in Schlenk tube with a magnetic bar under a nitro- 1H), 2.28 (d, J = 11.6 Hz, 2H), 2.07 (d, J = 10.7 Hz, 1H),
gen atmosphere, was added olefin (2, 0.9 mmol) and enynals 1.57–1.50 (m, 1H), 1.48–1.41 (m, 1H), 1.29 (dd, J = 16.8, 9.9 Hz,
(1, 0.3 mmol) and tetracyanoethylene (0.6 mmol), and the reac- 1H), 1.03 (d, J = 10.7 Hz, 1H); 13C NMR (100 MHz, CDCl3)
tion mixture was stirred at 80 °C unless otherwise noted. The δ 196.92, 134.42, 134.40, 133.67, 131.88, 130.22, 129.02,
reaction was monitored by TLC, then the solvent was evapor- 111.69, 111.52, 111.41, 111.37, 61.33, 47.41, 47.02, 46.58,
ated under reduced pressure and the residue was purified by 43.82, 41.70, 41.04, 40.92, 34.59, 30.82, 30.60; HRMS (EI) calcd
flash chromatography on silica gel (Hex–EtOAc = 5/1) to afford for C24H19ON4 [M + H]+: 379.1553, Found: 379.1543.
product 10.
1-Benzoyl-7-phenylbicyclo[2.2.2]oct-5-ene-2,2,3,3-tetracarbo-
nitrile (10a). CCDC number 1014190, brown yellow solid
(m.p. 159 °C); yield: 70% (81 mg); Rf = 0.30; IR (KBr) νmax
Acknowledgements
3057.09, 2925.18, 2856.70, 2232.62, 1715.02, 1620.45, 1380.52, We are grateful to the funding from the National Basic
1
1096.28, 701.68, 620.75; H NMR (400 MHz, CDCl3) δ 7.31 (t, Research Program of China (973) (2011CB808600), the NNSFC
J = 7.4 Hz, 1H), 7.18 (d, J = 4.6 Hz, 3H), 7.10 (t, J = 7.8 Hz, 2H), (21172077,
21372086,
21422204),
Guangdong
NSF
7.06–6.99 (m, 2H), 6.98–6.91 (m, 1H), 6.80 (d, J = 8.5 Hz, 1H), (10351064101000000), and, SRF for ROCS, State Education
6.67 (d, J = 7.6 Hz, 2H), 4.05 (dd, J = 9.7, 5.0 Hz, 1H), 3.86–3.72 Ministry and “The Fundamental Research Funds for the
(m, 1H), 2.84 (dd, J = 14.3, 10.7 Hz, 1H), 2.19–2.07 (m, 1H); 13
C
Central Universities (SCUT)”.
NMR (100 MHz, CDCl3) δ 200.21, 138.25, 135.92, 134.54,
132.54, 132.07, 129.60, 129.28, 128.97, 128.28, 127.94, 111.64,
111.31, 111.27, 111.18, 61.30, 47.22, 45.95, 43.17, 40.80, 28.61;
HRMS (EI) calcd for C25H17ON4 [M + H]+: 389.1397, Found:
389.1386.
Notes and references
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1-Benzoyl-7-(p-tolyl)bicyclo[2.2.2]oct-5-ene-2,2,3,3-tetracarbo-
nitrile (10b). Brown solid (m.p. 162 °C); yield: 72% (87 mg);
Rf = 0.28; IR (KBr) νmax 3037.09, 2919.97, 2858.13, 2225.52,
1745.70, 1630.45, 1384.52, 1096.80, 700.68, 618.31; 1H NMR
(400 MHz, CDCl3) δ 7.32 (t, J = 7.3 Hz, 1H), 7.11 (t, J = 7.6 Hz,
2H), 6.98 (d, J = 7.8 Hz, 2H), 6.92 (dd, J = 13.2, 7.9 Hz, 3H),
6.78 (d, J = 8.6 Hz, 1H), 6.69 (d, J = 7.9 Hz, 2H), 4.02 (dd, J =
9.6, 5.0 Hz, 1H), 3.78 (s, 1H), 2.82 (dd, J = 15.1, 9.9 Hz, 1H),
2.20 (s, 3H), 2.13–2.05 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 200.30, 139.03, 135.94, 135.16, 134.43, 132.50, 132.12,
129.87, 129.43, 128.21, 128.08, 111.67, 111.33, 111.29, 111.23,
61.37, 47.16, 45.95, 42.83, 40.82, 28.60, 20.93; HRMS (EI) calcd
for C26H19ON4 [M + H]+: 403.1546, Found: 403.1553.
1-Benzoyl-7-(4-chlorophenyl)bicyclo[2.2.2]oct-5-ene-2,2,3,3-tetra-
carbonitrile (10c). Brown solid (m.p. 167 °C); yield: 46%
(58 mg); Rf = 0.25; IR (KBr) νmax 3040.58, 2935.20, 2859.07,
2228.41, 1760.13, 1642.45, 1388.52, 1099.57, 702.26, 619.82; 1H
NMR (400 MHz, CDCl3) δ 7.47 (t, J = 7.4 Hz, 1H), 7.32–7.23 (m,
4H), 7.06 (d, J = 8.1 Hz, 3H), 6.94 (d, J = 8.6 Hz, 1H), 6.87 (d, J =
7.8 Hz, 2H), 4.12 (dd, J = 9.8, 5.1 Hz, 1H), 3.90 (s, 1H), 2.95
(dd, J = 14.5, 10.0 Hz, 1H), 2.21–2.08 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 199.62, 136.74, 135.69, 135.18, 134.77,
132.88, 131.91, 130.84, 129.38, 128.46, 128.02, 111.51, 111.18,
111.14, 110.99, 61.09, 47.20, 45.83, 42.53, 40.67, 28.79; HRMS
(EI) calcd for C25H16ON4Cl [M + H]+: 423.1007, Found:
423.0995.
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