A copper(II)-mediated regioselective cyclization-acetoxylation of 6,8-Dien-1-ones for the synthesis of functionalized cyclopentanes

Article abstract of DOI:10.1021/jo100413p

This paper describes a copper(II) acetate-mediated cyclization- acetoxylation of 6,8-dien-1-ones in the presence of sodium acetate as base. A variety of functionalized cyclopentanes containing synthetic useful allylic alcohol moieties with three contiguou

Full text of DOI:10.1021/jo100413p

pubs.acs.org/joc
Various metal salts such as Mn(III), Fe(III), Ce(IV), and
A Copper(II)-Mediated Regioselective
Cyclization-Acetoxylation of 6,8-Dien-1-ones for
the Synthesis of Functionalized Cyclopentanes
V(V) are efficient oxidants and have been widely used in the
radical cyclization of carbonyl compounds.3-8 Copper(II)
salts are inexpensive and used as co-oxidants to terminate the
radical species in most cases.3 However, directly oxidizing
carbonyl compounds, especially for monoketones, to gen-
erate reactive R-keto radicals with copper(II) salts have
seldom been reported, and which still remains as a chal-
lenge.3,9-11 In 1996, Snider and co-workers reported a
successful free radical cyclization of unsaturated ketones
by the Mn(III)-based oxidative generation of R-keto radicals
directly from ketones with acetic acid as solvent.9 Recently,
Baran and co-workers reported a copper(II)-promoted cy-
clization of an enolate tethered with alkene to afford the
cyclopentane product as isomeric mixture in 28% yield.12
Yazhou Wang and Haifeng Du*
Beijing National Laboratory of Molecular Sciences,
CAS Key Laboratory of Molecular Recognition and Function,
Institute of Chemistry, Chinese Academy of Sciences,
Beijing 100190, China
haifengdu@iccas.ac.cn
Received March 5, 2010
€
Very recently, Kundig and Taylor reported independently an
efficient oxindole synthesis with copper(II) salts as oxidants
in the presence of strong bases.13 Employing inexpensive
copper(II) salts as oxidants for the radical cyclization of
6,8-dien-1-ones 1 for the synthesis of cyclopentane deriva-
tives attracts our interest for the following curiosities: (a)
whether the relatively unstable R-keto radicals 2 can be
formed; (b) whether the radicals 2 are active enough to react
with conjugated dienes; and (c) what will occur to the allyl
radicals 3, forming diene like most reported oxidative radi-
cal cyclization processes3 or trapping with other reagents
(Scheme 1). Herein, we wish to report our results on this
subject.
This paper describes a copper(II) acetate-mediated cycli-
zation-acetoxylation of 6,8-dien-1-ones in the presence
of sodium acetate as base. A variety of functionalized
cyclopentanes containing synthetic useful allylic alcohol
moieties with three contiguous stereogenic centers were
synthesized in moderate to good yields with moderate to
high regioselectivities.
(4) For leading references on Mn(III)-mediated cyclizations, see:
(a) References 3a-c and references cited there. (b) C-als-kan, R.; Fadelalla,
M. A.; S-ahin, E.; Watson, W. H.; Balci, M. J. Org. Chem. 2007, 72, 3353.
(c) Alvarez-Manzaneda, E.; Chahboun, R.; Cabrera, E.; Alvarez, E.; Alvarez-
Manzaneda, R.; Lachkar, M.; Messouric, I. Synlett 2007, 2425. (d) Heinrich,
M. R. Tetrahedron Lett. 2007, 48, 3895. (e) Curry, L.; Hallside, M. S.; Powell,
L. H.; Sprague, S. J.; Burton, J. W. Tetrahedron 2009, 65, 10882. (f) Tsubusaki,
T.; Nishino, H. Tetrahedron 2009, 65, 9448.
(5) For leading references on Fe(III)-mediated radical cyclizations, see:
(a) Jahn, U.; Hartmann, P.; Dix, I.; Jones, P. G. Eur. J. Org. Chem. 2002, 718.
(b) Bolm, C.; Legros, J.; Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217 and
references cited there.
(6) For leading references on Ce(IV)-mediated radical cyclizations, see:
(a) Nair, V.; Mathew, J.; Prabhakaran, J. Chem. Soc. Rev. 1997, 26, 127.
(b) Nair, V.; Balagopal, L.; Rajan, R.; Mathew, J. Acc. Chem. Res. 2004, 37,
21. (c) Nair, V.; Deepthi, A. Tetrahedron 2009, 65, 1074 and references cited
there.
Functionalized cyclopentanes are very important sub-
structures which are present in many biologically active
natural products, such as prostaglandins (PGs),1 and have
also been used as chiral ligands in asymmetric synthesis.2
Metal-mediated radical cyclization of alkenes provides a
powerful approach for the synthesis of highly functionalized
cyclic compounds.3 Metal oxidants play a crucial role in the
cyclization process: producing radicals and/or interaction
with intermediate radicals for subsequent transformations.3
(7) For leading references on V(V)-mediated cyclizations, see: Hirao, T.
Pure Appl. Chem. 2005, 77, 1539 and references cited there.
(8) For recent radical cyclization examples, see: (a) Yuan, W.; Du, H.;
Zhao, B. G.; Shi, Y. Org. Lett. 2007, 9, 2589. (b) Zhao, B.; Du, H.; Shi, Y.
J. Am. Chem. Soc. 2008, 130, 7220. (c) Powell, L. H.; Docherty, P. H.;
Hulcoop, D. G.; Kemmitt, P. D.; Burton, J. W. Chem. Commun. 2008, 2559.
(d) Beauseigneur, A.; Ericsson, C.; Renaud, P.; Schenk, K. Org. Lett. 2009,
11, 3778. (e) Taniguchi, T.; Ishibashi, H. Org. Lett. 2010, 12, 124.
(9) (a) McCarthy Cole, B.; Han, L.; Snider, B. B. J. Org. Chem. 1996, 61,
7832. (b) Snider, B. B.; Kiselgof, E. Y. Tetrahedron 1996, 52, 6073. (c) O’Neil,
S. V.; Quickley, C. A.; Snider, B. B. J. Org. Chem. 1997, 62, 1970.
(10) For leading references on the generation of R-keto radicals via
halogen atom-transfer processes, see: (a) Curran, D. P.; Chang, C.-T.
J. Org. Chem. 1989, 54, 3140. (b) Yang, D.; Yan, Y.-L.; Zheng, B.-F.;
Gao, Q.; Zhu, N.-Y. Org. Lett. 2006, 8, 5757. (c) Fang, X.; Liu, K.; Li, C.
J. Am. Chem. Soc. 2010, 132, 2274.
(1) For leading reviews, see: (a) Collins, P. W.; Djuric, S. W. Chem. Rev.
ꢀ
Rev. 2007, 107, 3286. (c) Jahn, U.; Galano, J.-M.; Durand, T. Angew. Chem.,
Int. Ed. 2008, 47, 5894.
(2) For a leading review, see: (a) Dahlenburg, L. Eur. J. Inorg. Chem.
1993, 93, 1533. (b) Das, S.; Chandrasekhar, S.; Yadav, J. S.; Gree, R. Chem.
€
2003, 2733. For leading references, see: (b) Cunningham, A. F., Jr.; Kundig,
E. P. J. Org. Chem. 1988, 53, 1823. (c) Zhu, G.; Cao, P.; Jiang, Q.; Zhang, X.
J. Am. Chem. Soc. 1997, 119, 1799. (d) Dahlenburg, L.; Kaunert, A. Eur. J.
Inorg. Chem. 1998, 885. (e) Mastranzo, V. M.; Quintero, L.; Anaya de
Parrodi, C.; Juaristi, E.; Walsh, P. J. Tetrahedron 2004, 60, 1781.
(3) For leading reviews on metal-mediated radical cyclizations, see:
(a) Melikyan, G. G. Synthesis 1993, 833. (b) Snider, B. B. Chem. Rev.
1996, 96, 339. (c) Melikyan, G. G. Org. React. 1997, 49, 427. (d) Renaud,
P.; Sibi, M. P. Radicals in Organic Synthesis; Wiley-VCH: Weinheim, Germany,
2001. (e) Clark, A. J. Chem. Soc. Rev. 2002, 31, 1. (f) Zard, S. Z. Radical
Reaction in Organic Synthesis; Oxford University Press: Oxford, UK, 2003.
(g) Studer, A. Chem. Soc. Rev. 2004, 33, 267. (h) Pintauer, T.; Matyjaszewski, K.
Chem. Soc. Rev. 2008, 37, 1087. (i) Majumdar, K. C.; Basu, P. K.; Gonzalez, A.
Curr. Org. Chem. 2009, 13, 599.
(11) For leading reviews on atom transfer radical reactions, see: (a) Ref-
erence 3e. (b) Pintauer, T.; Matyjaszewski, K. Chem. Soc. Rev. 2008, 37, 1087.
(12) DeMartino, M. P.; Chen, K.; Baran, P. S. J. Am. Chem. Soc. 2008,
130, 11546.
€
(13) (a) Jia, Y.-X.; Kundig, E. P. Angew. Chem., Int. Ed. 2009, 48, 1636.
(b) Perry, A.; Taylor, R. J. K. Chem. Commun. 2009, 3249.
DOI: 10.1021/jo100413p
r
Published on Web 04/02/2010
J. Org. Chem. 2010, 75, 3503–3506 3503
2010 American Chemical Society

Wang and Du
JOCNote
SCHEME 1
TABLE 2. Copper(II) Acetate-Mediated Cyclization-Acetoxylation
of 1a-ha
SCHEME 2. Initial Studies on Cyclization-Acetoxylation of 1a
entry
R1
time (h)b 6/7c total yield of 6/60 (dr)e, f
6 and 7 (%)d
1
2
3
4
5
6
Ph (1a)
12
16
9
7
8
6
12
96
91/9
80
82
75
79
68
84
40
50
1.8/1.0
1.9/1.0
2.0/1.0
1.9/1.0
1.6/1.0
2.1/1.0
1.1/1.0
1.0/1.0
4-MeO-C6H4 (1b)
3,5-Me2-C6H3 (1c)
2-Me-C6H4 (1d)
2-naphthyl (1e)
4-F-C6H4 (1f)
82/18
82/18
78/22
81/19
87/13
75/25
64/36
7g 4-CF3-C6H4 (1g)
8
Cyclohexyl (1h)
aAll the reactions were carried out with the substrate (0.30 mmol),
TABLE 1. Optimization of Reaction Conditions for Copper(II)
Acetate-Mediated Cyclization-Acetoxylation of 1aa
Cu(OAc)2 (0.75 mmol), and NaOAc (0.75 mmol) in DMSO (3.0 mL) at
80 °C under argon for the time indicated unless otherwise stated. bTime
for the first step. cThe ratio was determined by 1H NMR of the isomeric
entry
Cu(OAc)2
(equiv)
base (equiv)
yield (%)b
(6aþ6a0)/
(7aþ7a0)c
e
mixture. dThe average yield for two experiments. The diastereomeric
ratio was determined by 1H NMR of the isomeric mixture. fPure 6a-h
can be obtained while 6a0-h0 cannot be separated from 7. gThe reaction
was carried out at 60 °C.
1
2
3
4
1.0
1.0
2.5
3.0
2.5
2.5
2.5
2.5
2.5
NaOAc (1.0)
none
58
NDd
NRe
80
NaOAc (2.5)
NaOAc (3.0)
NaOAc (2.5)
NaOAc (2.5)
NaHCO3 (2.5)
pyrrolidine (2.5)
ethylenediamine (2.5)
91/9
ND
ND
ND
ND
96/4
83/17
74
57
76
56
64
39
effective bases for the current reaction in the presence of
4 A molecular sieves, and up to 96/4 regioselectivity was
obtained (Table1, entries 8 and 9).
5 f
6 g
7
8h
The substrate scope was then investigated with Cu(OAc)2
(2.5 equiv) as oxidant and NaOAc (2.5 equiv) as base. As
shown in Table 2, all the reactions of arylketone substrates
(1a-g) went efficiently to give the desired cyclopentanes in
moderate to good yields (40-84%) with good regioselec-
tivities (75/25-91/9). However, the diastereoselectivities of 6
were very poor (Table 2, entries 1-7). Moreover, the reac-
tion of cyclohexylketone substrate 1h can also give the
corresponding cyclopentanes in a reasonable yield for a
longer time (Table 2, entry 8). In most cases, only pure
stereoisomers 6a-g can be isolated from the isomeric
mixtures.
The effect of substituents on conjugated dienes was then
studied, and the results are summarized in Table 3. For the
reactions of 1i-m, all stereoisomers (6i-m, 6i0-m0, and
7k-m) can be isolated as pure compounds. It was found
that the regioselectivity could be reached to >97/3 for the
cyclization-acetoxylation of substrate 1i bearing 1,1-di-
phenyl substituents (Table 3, entry 1). Terminal dienes were
also effective for the cyclization-acetoxylation to give mode-
rate yields and good regioselectivities (Table 3, entries 3 and
4). However, when substrates bearing monoalkenes were
subjected to this reaction, no desired products were ob-
tained, which suggested that 1,3-diene moieties were neces-
sary for current transformations.15 The stereochemistry of 6l
was determined by the X-ray structure of 8, which was
derived from 6l (see the Supporting Information). The
relative stereochemistry between hydroxyl and cyclopentyl
9h
aAll the reactions were carried out with 1a (0.30 mmol), Cu(OAc)2,
and base in DMSO (3.0 mL) at 80 °C under argon for 12 h unless
otherwise stated. bTotal yield for the isomeric mixture. cThe ratio of
(6a þ 6a0)/(7a þ 7a0) was determined by 1H NMR of the isomeric
f
mixture. dNot determined. eNo reaction. DMF was used as solvent.
gCu(OAc)2 H2O was used. h4 A MS (500 mg/mmol) was added.
3
The initial studies were carried out with 1,9-diphenylnona-
6,8-dien-1-one (1a) (mixture of E and Z) as substrate with
1.0 equiv of Cu(OAc)2 as oxidant and 1.0 equiv of NaOAc as
base. We were pleased to find that the R-keto radicals 2 can
be generated efficiently even in such a weak basic condition,
and the reaction went smoothly in DMSO at 80 °C for 12 h
via a cyclization-acetoxylation process to give 1,2-trans-
cyclopentanes 4 and 5 which were further converted to 6 and
7 by the deprotection of acetyl groups in 58% yield for two
steps with a good regioselectivity (Scheme 2).14
Encouraged by this promising result, the reaction condi-
tions were further optimized in order to improve the yields,
and some results are summarized in Table 1. It was found
that no desired products were observed without base
(Table 1, entry 2). When the amount of Cu(OAc)2 and
NaOAc was increased to 2.5 equiv, the total yield for the
mixture of all isomers can be improved to 80% with a high
regioselectivity (Table 1, entry 1 vs 3). Copper(II) acetate
hydrate can also be used as oxidant with only a slightly lower
yield. The reaction proceeded well with NaHCO3 as base to
give the desired product in a reasonable yield (Table 1, entry
7). Primary and secondary amines were also found to be
(15) Two substrates bearing mono-alkenes (1-phenylhept-6-en-1-one and
1,7-diphenylhept-6-en-1-one) were subjected to this reaction, and no desired
products were observed, which may be relevant to the radical stabilities. For
a theoretical perspective on radical stability, see: Zipse, H. Top. Curr. Chem.
2006, 263, 163.
(14) 1,2-cis-Cyclopentanes were barely detected by GC-MS and 1H NMR
of the crude reaction mixture if there was any.
3504 J. Org. Chem. Vol. 75, No. 10, 2010

Wang and Du
JOCNote
TABLE 3. Copper(II) Acetate-Mediated Cyclization-Acetoxylation
of 1i-ma
electronic, steric hindrance factors, and/or the radical and
cation stabilities.
In conclusion, we have discovered a facile 5-exo-cycli-
zation/acetoxylation of readily available 6,8-dien-1-ones
mediated by inexpensive copper(II) acetate as efficient oxi-
dant and sodium acetate as base. A variety of 1,2-trans-
cyclopentanes containing synthetic useful allylic alcohol
moieties with three contiguous stereogenic centers can be
afforded in moderate to good yields with moderate to high
regioselectivities.
entry
R1/R2/R3/R4
time (h)b
6/7c
total yield of 6/60 (dr)f
6 and 7 (%)d,e
Experiment Section
1
2
3
4
5
4-F-C6H4/Ph/Ph/H (1i)
4-F-C6H4/Ph/Me/H (1j)
4-F-C6H4/H/H/H (1k)
Ph/H/H/H (1l)
6
8
8
7
8
>97/3
95/5
39
56
66
59
67
2.1/1.0
2.0/1.0
1.7/1.0
1.6/1.0
3.7/1.0
All cyclization-acetoxylation products are new compounds
and give satisfactory spectroscopic characterization.
87/13
85/15
57/43
General Procedure for the Cyclization-Acetoxylation of 6,8-
Dien-1-ones. To a Schlenk tube charged with the substrate
1 (0.30 mmol), Cu(OAc)2 (0.136 g, 0.75 mmol), and NaOAc
(0.062 g, 0.75 mmol) was added degassed DMSO (3.0 mL) under
Argon. The resulting mixture was immersed into an oil bath
(80 °C) and stirred until the reaction was complete as monitored
by TLC. After cooling to room temperature, water (50 mL) was
added and the mixture was extracted with EtOAc (2 ꢀ 25 mL).
The combined organic layers were washed with brine and dried
over anhydrous Na2SO4. After removal of solvents, the residue
was treated with K2CO3 (0.065 g, 0.47 mmol) and MeOH
(2.5 mL) and stirred at room temperature for 1 h, and then
concentrated. The residue was purified by flash column chro-
matography (silica gel, petroleum ether/ethyl acetate = 15/1-
5/1) to yield the corresponding isomeric mixture of 6 and 7.
Further careful isolation by flash chromatography on silica gel
gave pure separable isomers.
Ph/H/H/Me (1m)
aAll the reactions were carried out with the substrate (0.30 mmol),
Cu(OAc)2 (0.75 mmol), and NaOAc (0.75 mmol) in DMSO (3.0 mL) at
80 °C under argon for the time indicated. bTime for the first step. cThe
ratio was determined by 1H NMR of the isomeric mixture. dThe average
yield for two experiments. eAll stereoisomers can be separated by flash
chromatography, while 7i and 7j (entries 1 and 2) cannot be obtained due
to the trace amounts. f The diastereomeric ratio was determined by 1H
NMR of the isomeric mixture.
SCHEME 3. Proposed Mechanism for Copper(II) Acetate-
Mediated Cyclization-Acetoxylation
Table 2, entry 1 (6a): colorless oil, Rf 0.12 (petroleum ether/
ethyl acetate = 15/1); IR (film) 3462, 1676 cm-1; 1H NMR (400
MHz, CDCl3) δ 8.00 (d, J = 7.2 Hz, 2H), 7.51 (dd, J = 7.6, 7.2
Hz, 1H), 7.41 (dd, J = 7.6, 7.2 Hz, 2H), 7.28-7.23 (m, 4H),
7.22-7.21 (m, 1H), 6.54 (d, J = 15.6 Hz, 1H), 6.20 (dd, J = 15.6,
6.4 Hz, 1H), 4.14 (dd, J = 7.2, 6.8 Hz, 1H), 3.85-3.79 (m, 1H),
2.89-2.81 (m, 1H), 2.57 (br s, 1H), 2.16-2.08 (m, 1H),
1.93-1.87 (m, 1H), 1.78-1.70 (m, 3H), 1.60-1.53 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 203.9, 137.1, 136.8, 132.8, 131.7,
130.6, 128.6, 128.5, 128.5, 127.6, 126.5, 76.1, 49.4, 48.6, 32.4,
29.5, 25.7; HRMS (EI) calcd for C21H22O2 (M) 306.1620, found
306.1623.
Inseparable mixture of 6a0, 7a, and 7a0: colorless oil, Rf 0.08
(petroleum ether/ethyl acetate = 15/1); IR (film) 3454, 1676
cm-1. 6a0: 1H NMR (400 MHz, CDCl3) δ 7.94-7.89 (d, J = 7.6
Hz, 2H), 7.58-7.18 (m, 8H), 6.52 (d, J = 16.0 Hz, 1H), 6.17 (dd,
J = 16.0, 6.8 Hz, 1H), 4.28 (dd, J = 6.4, 6.0 Hz, 1H), 3.73 (m,
1H), 2.91-2.82 (m, 1H), 2.25 (br s, 1H), 2.18-1.50 (m, 6H). 7a
(major epimer of 7): 1H NMR (400 MHz, CDCl3) δ 7.94-7.89
(d, J = 7.6 Hz, 2H), 7.58-7.18 (m, 8H), 5.77 (dd, J = 15.6,
7.6 Hz, 1H), 5.64 (dd, J = 15.6, 6.4 Hz, 1H), 5.10 (d, J =
6.4 Hz, 1H), 3.56-3.49 (m, 1H), 3.06-2.96 (m, 1H), 2.18-1.50
(m, 6H).
moieties of 6a-m and 6a0-m0 was tentatively assigned by
NOE studies and NMR spectra comparison with 6l and 6l0
(see the Supporting Information).
A plausible mechanism is proposed in Scheme 3 on the
basis of the observed experiment results. R-Keto radicals 2
are generated by the oxidation of 1 with Cu(OAc)2 as single
electron oxidant under the assistance of NaOAc. Due to the
relatively weak acidic R-CH2 of monoketones, it is not easy
to form anion with such a weak base (NaOAc or NaHCO3)
alone. Hence, Cu(OAc)2 is supposed to act as a Lewis acid to
activate the carbonyl group. Further 5-exo radical addition
to the double bond gives allyl radical intermediate 3. Radical
species 3 will be further oxidized to cation intermediate 9
followed by the addition of acetate to afford products 6
and 7. Alternatively, a Kharasch-Sosnovsky pathway in-
volving trivalent copper intermediates16 generated by the
interaction of Cu(OAc)2 with allyl radicals 3 is also possible.
The observed regioselectivities may be relevant with the
Table 3, entry 1 (6i): colorless oil, Rf 0.25 (petroleum ether/
ethyl acetate = 10/1); IR (film) 3462, 1676, 1597 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.99 (dd, J = 8.8, 5.6 Hz, 2H), 7.40-7.34
(m, 3H), 7.28-7.18 (m, 7H), 7.09 (dd, J = 8.8, 8.4 Hz, 2H), 6.04
(d, J = 9.6 Hz, 1H), 4.01 (dd, J = 9.2, 8.8 Hz, 1H), 3.67-3.62
(m, 1H), 2.84-2.76 (m, 1H), 2.06-2.00 (m, 1H), 1.92-1.86 (m,
2H), 1.76-1.67 (m, 2H), 1.65-1.59 (m, 1H), 1.42-1.33 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 202.3, 165.8 (d, JC-F = 252.7
Hz), 144.5, 141.9, 139.6, 133.6 (d, JC-F = 2.6 Hz), 131.5 (d,
(16) For leading references on Kharasch-Sosnovsky reactions, see: (a)
Kharasch, M. S.; Sosnovsky, G. J. Am. Chem. Soc. 1958, 80, 756. (b) Andrus,
M. B.; Lashley, J. C. Tetrahedron 2002, 58, 845. (c) Eames, J.; Watkinson, M.
JC-F = 9.1 Hz), 130.4, 123.1, 123.0, 128.4, 127.9, 127.6, 115.7
(d, JC-F = 21.6 Hz), 73.3, 49.8, 49.5, 32.1, 29.6, 25.7; HRMS
(EI) calcd for C27H25FO2 (M) 400.1839, found 400.1843.
Angew. Chem., Int. Ed. 2001, 40, 3567. (d) Mayoral, J. A.; Rodrı
Rodrıguez, S.; Salvatella, L. Chem.;Eur. J. 2008, 14, 9274.
´
´
guez-
J. Org. Chem. Vol. 75, No. 10, 2010 3505

Wang and Du
JOCNote
6i0: colorless oil, Rf 0.21 (petroleum ether/ethyl acetate =
1.92-1.85 (m, 1H), 1.76-1.68 (m, 4H), 1.65-1.58 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 201.7, 165.9 (d, JC-F = 252.9
Hz), 139.9, 133.8 (d, JC-F = 2.8 Hz), 131.2 (d, JC-F = 9.2 Hz),
115.7 (d, JC-F = 23.5 Hz), 74.8, 48.5, 47.5, 32.6, 27.6,
25.6; HRMS (EI) calcd for C15H17FO2 (M) 248.1213, found
248.1215.
10/1); IR (film) 3460, 1676, 1597 cm-1; H NMR (400 MHz,
1
CDCl3) δ 7.93 (dd, J = 8.8, 5.6 Hz, 2H), 7.32-7.31 (m, 3H),
7.21-7.19 (m, 3H), 7.07-7.03 (m, 6H), 5.98 (d, J = 10.0 Hz,
1H), 4.11 (dd, J = 9.6, 6.8 Hz, 1H), 3.46-3.40 (m, 1H),
2.88-2.80 (m, 1H), 2.04-1.98 (m, 2H), 1.75-1.60 (m, 5H);
13C NMR (100 MHz, CDCl3) δ 201.4, 165.8 (d, JC-F = 252.8
Hz), 144.2, 141.9, 134.1, 133.7 (d, JC-F = 2.6 Hz), 131.3 (d,
7k: colorless oil, Rf 0.12 (petroleum ether/ethyl acetate =
10/1); IR (film) 3337, 1677, 1597 cm-1; H NMR (400 MHz,
1
J
C-F = 9.2 Hz), 130.2, 123.1, 128.5, 128.3, 127.8, 127.7, 127.6,
CDCl3) δ 7.98-7.95 (m, 2H), 7.12 (dd, J = 11.2, 8.4 Hz, 2H),
5.71-5.57 (m, 1H), 4.04 (d, J = 5.2 Hz, 1H), 3.49-3.43 (m, 1H),
3.07-3.00 (m, 1H), 2.13-2.04 (m, 1H), 2.02-1.96 (m, 1H),
1.88-1.71 (m, 3H), 1.59-1.49 (m, 1H), 1.30 (br s, 1H); 13C
NMR (100 MHz, CDCl3) δ 200.7, 165.9 (d, JC-F = 253.1 Hz),
135.0, 133.7 (d, JC-F = 2.8 Hz), 131.3 (d, JC-F = 9.1 Hz), 129.1,
115.8 (d, JC-F = 21.7 Hz), 63.6, 52.7, 45.8, 33.4, 31.3, 25.2;
HRMS (ESI) calcd for C15H17FO2Na (M þ Na) 271.1105,
found 271.1107.
115.7 (d, JC-F = 21.6 Hz), 72.4, 49.0, 48.9, 32.4, 28.8, 25.8;
HRMS (ESI) calcd for C27H25FO2Na (M þ Na) 423.1731,
found 423.1726.
Table 3, entry 3 (6k): colorless oil, Rf 0.21 (petroleum ether/
ethyl acetate =10/1); IR (film) 3462, 1676, 1598 cm-1; 1H NMR
(400 MHz, CDCl3) δ 8.01 (dd, J = 8.4, 5.2 Hz, 2H), 7.11 (dd,
J = 8.4, 7.2 Hz, 2H), 5.84 (ddd, J = 17.2, 10.4, 6.4 Hz, 1H), 5.19
(d, J = 17.2 Hz, 1H), 5.06 (d, J = 10.4 Hz, 1H), 3.95 (s, 1H),
3.72-3.66 (m, 1H), 2.75-2.67 (m, 1H), 2.12-2.04 (m, 1H),
1.91-1.83 (m, 1H), 1.79-1.65 (m, 4H), 1.52-1.43 (m, 1H); 13
C
Acknowledgment. We are grateful to the generous finan-
cial support from the Ministry of Science and Technology
(2009ZX09501-018) and Institute of Chemistry, Chinese
Academy of Sciences (CAS).
NMR (100 MHz, CDCl3) δ 202.2, 165.8 (d, JC-F = 252.6 Hz),
140.4, 133.6 (d, JC-F = 2.7 Hz), 131.4 (d, JC-F = 9.2 Hz), 115.7
(d, JC-F = 21.8 Hz), 115.4, 76.8, 49.4, 48.1, 32.5, 29.6, 25.8;
HRMS (EI) calcd for C15H17FO2 (M) 248.1213, found
248.1215.
6k0: colorless oil, Rf 0.16 (petroleum ether/ethyl acetate =
Supporting Information Available: The procedure for pre-
paration of 1a and copper(II)-mediated cyclization-acetoxyla-
tion of 6,8-dien-1-ones 1, characterization of 1a, 6, 7, and 8,
X-ray structure of 8, NOE studies of 6a, 6a0, 6j, 6j0, 6l, and 6l0,
along with NMR spectra of 6 and 7. This material is available
free of charge via the Internet at http://pubs.acs.org.
10/1); IR (film) 3457, 1673, 1600 cm-1; H NMR (400 MHz,
1
CDCl3) δ 8.00 (dd, J = 8.8, 5.6 Hz, 2H), 7.12 (dd, J = 8.0, 5.6
Hz, 2H), 5.89-5.80 (ddd, J = 17.2, 10.4, 6.4 Hz, 1H), 5.20 (d,
J = 17.2 Hz, 1H), 5.08 (d, J = 10.4 Hz, 1H), 4.11 (s, 1H),
3.67-3.61 (m, 1H), 2.80-2.73 (m, 1H), 2.11-2.05 (m, 1H),
3506 J. Org. Chem. Vol. 75, No. 10, 2010