Palladium(0)-catalyzed [2 + 2 + 1] cyclization of 1,6-enynes with vinyl bromides: A highly diastereoselective synthesis of tetrahydro-1H-cyclopenta [c] furans bearing two quaternary carbon centers

Article abstract of DOI:10.1039/c7ob00768j

A new cascade process has been accomplished for the synthesis of tetrahydro-1H-cyclopenta[c]furans through palladium-catalyzed [2 + 2 + 1] cyclization of 1,6-enynes with vinyl bromides. Notably, the key feature of this transformation is the use of vinyl bromides as the C1 building block. Various functionalized tetrahydro-1H-cyclopenta[c]furans bearing two quaternary carbon centers could be obtained in good yields with excellent diastereoselectivities.

Full text of DOI:10.1039/c7ob00768j

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Palladium(0)-catalyzed [2+2+1] cyclization of 1,6-enynes with
vinyl bromides: a highly diastereoselective synthesis of terahydro-
1H-cyclopenta[c]furans bearing two quaternary carbon centers†
Received 00th January 20xx,
Accepted 00th January 20xx
Yunxia Diao, Zhijun Zuo, Hui Wang, Jingjing Liu* and Xinjun Luan*
DOI: 10.1039/x0xx00000x
A new cascade process has been accomplished for the synthesis of terahydro-1H-cyclopenta[c]furans through palladium-
catalyzed [2+2+1] cyclization of 1,6-enynes with vinyl bromides. Notably, the key feature of this transformation is the use
of vinyl bromides as the C1 building block. Various functionalized tetrahydro-1H-cyclopenta[c]furans bearing two
quaternary carbon centers could be obtained in good yields with excellent diastereoselectivities.
www.rsc.org/
structures.6 Remarkably, the majority of these transformations
were realized through [2+2+2] cyclizations of 1,6-enyens with
two-atom synthons, such as alkenes,7 alkynes,8 aryls,9 and
Introduction
carbonyls,10 providing a straightforward route to various [5,6]-
bicyclic rings. In contrast, the development of related [2+2+1]
cycloadditions for constructing [5,5]-bicyclic frameworks has
lagged dramatically. So far, Pauson-Khand reaction, which uses
CO as the one-carbon component, is the more common
approach for enabling the [2+2+1] cyclization with 1,6-enyens
(Scheme 1a).11 Moreover, isocyanide, an isoelectronic
counterpart of carbon monoxide, was applicable in the
cyclocarbonylation process as well.12 It is notable that these
processes often need to use very toxic agents to incorporate a
carbonyl group. Very recently, our group reported an
example of [2+2+1] cyclization between bromophenols and
1,6-diynes, which was initiated by Pd(0)-mediated oxidative
addition to C-Br, and terminated by arene dearomatization.13
Stimulated by these findings, we herein describe a novel
[2+2+1] cyclization of 1,6-enynes with some well-designed
The fused O-heterocycles have gained growing interest among
the synthetic community owing to their broad distribution in
natural products with remarkable pharmacological activities.1
In particular, the intriguing cyclopenta[c]furan scaffolds often
serve as the core structure of many biologically active natural
products (Fig. 1). For example, epoxydictymene, which was
isolated from Dictyota dichotoma, contains the sterically
congested cyclopenta[c]furan framework.2 Fusarisentin A, is
identified as a potent inhibitor for acinar morphogenesis as
well as cell migration and
Merrilactone possesses neurite outgrowth activity in
cultures of fetal rat cortical neurons,4 and anislactones B could
be treated as HBV inhibitor.5 As
consequence, the
invasion of cancer cells.3
A
a
exploration of more simple and efficient strategies for
accessing cyclopenta[c]furan derivatives from readily available
starting materials is of great significance.
vinyl bromides by using β-elimination as the final step, leading
H
O
H
H
to the formation of a new class of attractive terahydro-1H-
cyclopenta[c]furans bearing two quaternary carbon centers in
a highly diastereoselective fashion (Scheme 1b).
H
H
H
O
O
OH
H
O
O
H
H
O
OH
OH
O
O
O
HO
N
H
O
O
O
O
HO
Previous work:
Epoxydictymene
Fusarisetin A
Merrilactone A
Anislactones B
a)
Fig. 1 Selected examples bearing the cyclopenta[c]furan skeleton
.
Z
Z
R2
[M]
+
[CO]
R2
R1
Transition-metal-catalyzed [2+2+x] cycloadditions involving
1,6-enynes represents a powerful and versatile approach for
the assembly of a great number of carbo- and heterocyclic
M = Co, Ru
Rh, Ir
R1
O
O
This work:
b)
O
Br
R'
Me
H
[Pd0]
Me
Me
+
R1
R1
R'
Scheme 1 Development of [2+2+1] cyclizations with 1,6-enynes by a) using CO as
the C1 building block. b) using vinyl bromides as the C1 building block (this work).
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1,6-enynes (1a
proceeded smoothly to afford the corresponding tetrahydro-
1H-cyclopenta[c]furan derivatives 3a in moderate to good
-k) to react with 2a, and these reactions
Results and discussion
At the outset, we began the studies by using 1,6-enyne 1a
to react with (Z)-(1-bromoprop-1-en-1-yl)benzene (2a) that has
great potential to serve as a C1 synthon for [2+2+1] cyclizations,
and the experimental data are summarized in Table 1. To our
delight, the envisioned product 3a could be formed as a single
diastereomer in 35% yield when the reaction was carried out
in the presence of 5.0 mol% of Pd(OAc)2, 10.0 mol% PPh3, 2.0
equivalents of K2CO3 in 1,4-dioxane at 100 °C for 48 h (entry 1).
Other solvents such as DCE, toluene and THF were then tested,
but none of them gave better results (entries 2-4). Next, a
survey of bases revealed that organic bases (DBU and Et3N)
were ineffective (entries 5-6), whereas most of inorganic bases
were applicable for the desired transformation (entries 7-9),
with K3PO4 showing the superior performance. Upon studies
on the palladium precursors, it indicated that neither Pd2dba3
nor PdCl2 was more beneficial for the process (entries 10-11).
Notably, it was found that Pd(PPh3)4 could greatly improve the
title reaction to give 3a in 67% yield (entry 12). Inspired by the
literature precedents that tetrabutylammonium (TBA) salts
often showed a positive influence on the palladium-catalyzed
cross-coupling reactions,14 we then attempted to use them as
additives (entries 13-15). Gratifyingly, the results disclosed
that the yield of terahydro-1H-cyclopenta[c]furan 3a could be
dramatically increased to 78% by using 1.1 equivalent of TBAI.
In the end, it should be noted that 3a was always formed as
one diastereomer under the above conditions.
-
k
yields with excellent diastereoselectivities (>19:1) (Table 2).
With respect to the substituent on the alkyne moiety, this
reaction allowed to tolerate various aromatic groups being
substituted with electron-neutral or electron-donating groups
such as methyl (1b,h
) and methoxy (1c,g) groups, and
electron-withdrawing groups such as fluoro (1d,i), chloro (1e),
and trifluoromethyl (1f) groups. Noteworthy, the sterically
more hindered substrates 1h-i containing an ortho-substituted
phenyl ring could undergo the envisioned [2+2+1] cyclizations,
leading to the formation of products 3h-i in 37% and 63% yield,
respectively. Moreover, 1,6-enyne 1j that bears a heterocyclic
group behaved quite well in the process to give compound 3j
in 80% yield. Besides the aromatic substituents, an aliphatic
group could be also incorporated into the 1,6-enyne substrate,
and the run with 1k was able to provide product 3k in 45%
isolated yield. Unfortunately, the limitation of this [2+2+1]
cyclization appeared when substrate 1l bearing an apparent
allyl group was tested. Presumably, the desired intermolecular
cyclization was dramatically hampered by the unwanted
β–
hydride elimination that occurred within the 1,6-enyne 1l. In
addition, it is necessary to mention that all the reactions led to
the formation of a single diastereomer, and the relative
stereochemistry of product 3a was assigned by 2D NOESY NMR
spectra (see the Supporting Information for details), which
showed rather clear NOE correlation between the vinyl and
methyl protons, indicating a cis relationship of these substituents.
Moreover, the structural assignment was further confirmed by a
single-crystal X-ray diffraction studies for 3h (Fig. 2).15 In the end,
Table 1 Optimization of the reaction conditionsa
Table 2 Scope with respect to 1,6-enynes for the [2+2+1] cyclization
Entry
[Pd]/L
Base
Solvent
yield (%)b
1
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd2(dba)3/PPh3
PdCl2/PPh3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
1,4-dioxane
DCE
35
<5
21
23
<5
<5
<5
38
41
10
29
67
56
70
78
2
3
toluene
4
THF
5
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
6
DBU
7
Na2CO3
Cs2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
8
9
10
11
12
13c
14d
15e
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
aReactions were conducted with 0.20 mmol of 2a. bIsolated yield. c1.1 equiv. of
TBAC was used. d1.1 equiv. of TBAB was used. e1.1 equiv. of TBAI was used.
Under the optimal reaction conditions, we first explored
the generality of this new transformation by using a variety of
2 | J. Name., 2012, 00, 1-3
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addition of vinyl bromide 2a to Pd0 species, which is followed
by intermolecular carbopalladation of the C-C triple bond from
1a to generate alkenylpalladium intermediate
coordination and migratory insertion of the C-C double bond
from the allylic moiety to produce an alkylpalladium species
B. Subsequently,
C
.
Afterwards, an intramolecular 5-exo-trig cyclization proceeds
through diastereoselective migratory insertion of the vinyl
fragment from the sterically less encumbered face of alkene,
leading to the formation of bicyclic Pd(II) intermediate
D.
Fig. 2 ORTEP plot of the crystal structure of 3h (at 30% probability level)
Finally, β-hydride elimination takes place to give the desired
product 3a and a hydridopalladium complex, from which the
active Pd0 species is regenerated via reductive elimination.
it was found the N-tethered 1,6-enyne 1m could undergo the
title [2+2+1] cyclization with 2a, affording a diastereomeric
mixture (6:1 dr) of 3m in 64% yield, and the relative
stereochemistry of its major diastereomer was consistent with
O
Br
Me
H
Me
[Pd0]
Ph
Ph
products 3a
-
k
(see the Supporting Information for details).
2a
Ph
3a
β-elimination
We next turned our attention to study on the reaction
scope of vinyl bromides (Table 3). The results indicated that
vinyl bromides (2b-e) that contain electronically differentiated
aromatic substituents could participate very well in the
[2+2+1] reaction to give tetrahydro-1H-cyclopenta[c]furans
3a′-d′ as single diastereomeric products in 58-72% yields.
O
BrPd
Ph
Me
Me
PdBr
H
Ph
A
O
Ph
D
Me
carbopalladation
Me
carbopalladation
Moreover, the vinyl bromide 2f bearing
a heterocyclic
Ph
1a
Ph
O
substituent such as 2-thienyl group could undergo the [2+2+1]
cyclization with 1a quite efficiently, affording compound 3e′ in
69% isolated yield. Satisfactorily, the alkyl substituent of vinyl
bromides was not limited to a methyl group and longer
aliphatic substituents, such as an ethyl group, was also
accommodated to generate the envisioned product 3f′ as a 5:1
mixture of E and Z isomers in 66% yield. It should be noted
that E-configured (1-bromoprop-1-en-1-yl)benzene was
inapplicable for the [2+2+1] reaction, and no desired products
were observed when cyclic vinyl bromides (2h-i) were tested.
O
Me
Ph
PdBr
Me
Ph
Ph
Me
PdBr
Me
carbopalladation
B
C
Scheme 2 Proposed mechanism
Conclusions
In summary, we have developed a facile and efficient
Pd(0)-catalyzed [2+2+1] intermolecular cyclization by using
easily accessible vinyl bromides, a C1-synthon, and 1,6-enynes
to generate tetrahydro-1H-cyclopenta[c]furans containing two
quanternary carbon centers in good yields with excellent
diastereoselectivities. Further extension of the current method
and the application of these cyclization transformations in
synthesizing complex molecules are in progress.
Table 3 Scope with respect to vinyl bromides for the [2+2+1] cyclization
O
O
Pd(PPh3)4 (5.0 mol%)
K3PO4 (2.0 equiv.)
TBAI (1.1 equiv.)
Br
R'
R''
Me
+
Me
H
Ph
1,4-dioxane, 100 °C, 48 h
Ph
1a
R'
3a'-h'
R''
2b-i
O
O
O
O
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Experimental
General Information
MeO
F
Me
Cl
3d' 63%
3a' 58%
3b'
3c'
72%
67%
All reactions were carried out under an argon atmosphere
using standard Schlenk-Lines or a glovebox. All solvents were
distilled and dried before used. Analytical thin-layer
chromatography was performed with 0.25 mm coated
commercial silica gel plates (TLC Silica Gel 60 F254); visualization
of the developed chromatogram was performed by
fluorescence. Flash chromatography was performed with silica
gel (300−400 mesh). Proton nuclear magnetic resonance (1H
NMR) data and Carbon-13 nuclear magnetic resonance (13C
NMR) data were acquired at 400, 100 MHz, respectively, in
CDCl3 with TMS as internal standard. Infrared (IR) data were
recorded as films on potassium bromide plates on FT-IR
spectrometer. Absorbance frequencies are reported in
O
O
O
O
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Me
S
3e'
3f'
3g' <5%
3h' <5%
69%
66% (E/Z = 5/1)
Based on the catalytic cycles put forth for related literature
reports,16 a plausible mechanism for this Pd-catalyzed [2+2+1]
cyclization, using substrates 1a and 2a for illustrative purposes,
is depicted in Scheme 2. The reaction is initiated by oxidative
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reciprocal centimeter (cm−1). High resolution mass spectra
1-Fluoro-2-(3-((2-methylallyl)oxy)prop-1-yn-1-yl)benzene
were acquired on a Bruker Daltonics MicroTof-Q II (ESI) or an (1i). Yellow liquid (547 mg, 67% yield). 1H NMR (400 MHz,
Agilent GC-MS (EI) mass spectrometer. Compounds 1a-b,17a CDCl3): δ 7.44 (td, J = 7.6, 1.8 Hz, 1H), 7.34-7.26 (m, 1H), 7.12-
1c,17b 1g,17b 1k,17c 2a,18a 2b,18b 2c,18c 2f,18d 2g,18e 2h,18f and 2i,18a 7.03 (m, 2H), 5.05 (d, J = 0.9 Hz, 1H), 4.96 (s, 1H), 4.39 (s, 2H),
were prepared according to literature methods.
4.06 (s, 2H), 1.79 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 162.9 (d,
J = 251.6 Hz), 141.5, 133.6 (d, J = 1.2 Hz), 130.2 (d, J = 7.9 Hz),
123.9 (d, J = 3.8 Hz), 115.5 (d, J = 20.9 Hz), 113.2, 11.2 (d, J =
General procedure for the preparation of enynes17a
To a solution of arylpropargyl alcohol (4.0 mmol) in freshly 15.7 Hz), 90.5 (d, J = 3.2 Hz), 79.6, 73.7, 57.7, 19.6. IR (KBr):
distilled THF (8 mL) was added NaH (6.0 mmol, freshly pre- 3078, 2918, 2852, 2236, 1654, 1492, 1449, 1371, 1355, 1257,
washed with dry hexane) portionwise under nitrogen 1106, 1033, 904, 757, 702, 574 cm-1. HRMS (ESI) m/z
atmosphere at 0 °C. The white suspension was slowly warmed calculated for C13H13FONa [M+Na]+ 227.0848, found 227.0848.
to room temperature and stirred for 2 hours. The reaction
2-(3-((2-Methylallyl)oxy)prop-1-yn-1-yl)thiophene
(1j).
mixture was then cooled to 0 °C and 3-bromo-2-methyl-1- Yellow liquid (637 mg, 83% yield). 1H NMR (400 MHz, CDCl3): δ
propene (8.0 mmol) was added dropwise. After complete 7.27-7.21 (m, 2H), 6.97 (dd, J = 5.2, 3.6 Hz, 1H), 5.03 (d, J = 0.6
addition, the reaction was warmed to room temperature and Hz, 1H), 4.96 (s, 1H), 4.37 (s, 2H), 4.03 (s, 2H), 1.78 (s, 3H). 13C
further stirred for 2 hours. Water (10 mL) was slowly added NMR (100 MHz, CDCl3): δ 141.3, 132.3, 127.2, 126.8, 122.4,
and the aqueous layer was extracted with diethyl ether (3 × 20 113.0, 89.1, 79.3, 73.6, 57.7, 19.5. IR (KBr): 3077, 2915, 2847,
mL). The combined organic layers were washed with water, 2220, 1655, 1451, 1374, 1359, 1190, 1087, 904, 849, 703 cm-1.
brine and dried over anhydrous Mg2SO4 and concentrated HRMS (ESI) m/z calculated for C11H12OSNa [M+Na]+ 215.0507,
under vacuum. The crude product was purified by flash found 215.0509.
chromatography on silica gel to afford desired product.
General procedure for the preparation of vinyl bromides18a
1-Fluoro-4-(3-((2-methylallyl)oxy)prop-1-yn-1-yl)benzene
(1d). Yellow liquid (595 mg, 73% yield). 1H NMR (400 MHz, To a cold solution of triphenyl phosphite (1.85 ml, 7.0 mmol) in
CDCl3): δ 7.46-7.39 (m, 2H), 7.04-6.93 (m, 2H), 5.02 (s, 1H), anhydrous dichloromethane (20 mL) maintained at -60 °C
4.94 (s, 1H), 4.33 (s, 2H), 4.03 (s, 2H), 1.77 (s, 3H). 13C NMR under Ar flow, bromine (400 μL, 7.7 mmol) was dropped in.
(100 MHz, CDCl3): δ 162.4 (d, J = 249.5 Hz), 141.4, 133.6 (d, J = Anyhdrous triethylamine (1.2 mL, 8.4 mmol) and ketone (6.4
8.4 Hz), 118.7 (d, J = 3.5 Hz), 115.5 (d, J = 22.1 Hz), 113.0, 85.0, mmol) were added to the faint orange solution. The reaction
84.81 (d, J = 1.3 Hz), 73.6, 57.6, 19.5. IR (KBr): 3077, 2977, mixture was stirred for 18 h, while warming to rt, and heated
2918, 2853, 2243, 1657, 1507, 1381, 1093, 740, 705, 531 cm-1. to reflux for a further 2 h. The crude product was purified by
HRMS (ESI) m/z calculated for C13H13FONa [M+Na]+ 227.0848, flash chromatography on silica gel to afford desired product.
found 227.0849.
(Z)-1-(1-Bromoprop-1-en-1-yl)-4-fluorobenzene (2d). Yellow
1
liquid (730 mg, 53% yield). H NMR (400 MHz, CDCl3): δ 7.51-
1-Chloro-4-(3-((2-methylallyl)oxy)prop-1-yn-1-yl)benzene
(1e). Yellow liquid (759 mg, 86% yield). 1H NMR (400 MHz, 7.44 (m, 2H), 7.01 (t, J = 8.7 Hz, 2H), 6.21 (q, J = 6.6 Hz, 1H),
CDCl3): δ 7.39-7.35 (m, 2H), 7.31-7.26 (m, 2H), 5.03 (s, 1H), 1.94 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 162.6 (d, J
4.96 (s, 1H), 4.34 (s, 2H), 4.03 (s, 2H), 1.78 (s, 3H). 13C NMR = 248.0 Hz), 136.4 (d, J = 3.2 Hz), 129.2 (d, J = 8.2 Hz), 126.3,
(100 MHz, CDCl3): δ 141.4, 134.5, 133.0, 128.7, 121.2, 113.2, 125.3, 115.1 (d, J = 21.7 Hz), 18.1. IR (KBr): 2918, 2854, 1689,
86.2, 85.0, 73.8, 57.7, 19.6. IR (KBr): 3077, 2919, 2851, 2241, 1505, 1376, 952, 839, 760, 711, 545 cm-1. HRMS (EI) m/z
1653, 1489, 1397, 1090, 828, 752, 526 cm-1. HRMS (ESI) m/z calculated for C9H8BrF 213.9793, found 213.9788.
calculated for C13H13ClONa [M+Na]+ 243.0553, found 243.0553.
(Z)-1-(1-Bromoprop-1-en-1-yl)-4-chlorobenzene (2e). Light
yellow liquid (851 mg, 58% yield). 1H NMR (400 MHz, CDCl3): δ
1-(3-((2-Methylallyl)oxy)prop-1-yn-1-yl)-4-(trifluoromethy-
l)benzene (1f). Yellow liquid (762 mg, 75% yield). 1H NMR (400 7.45 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 6.28 (q, J = 6.4
MHz, CDCl3): δ 7.59-7.53 (m, 4H), 5.04 (s, 1H), 4.97 (s, 1H), 4.37 Hz, 1H), 1.94 (d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ
(s, 2H), 4.04 (s, 2H), 1.79 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 138.5, 134.0, 128.7, 128.4, 127.0, 125.3, 18.2. IR (KBr): 3008,
141.3, 131.9, 130.1 (q, J = 32.7 Hz), 126.5 (q, J = 1.3 Hz), 125.1 2918, 2852, 1669, 1507, 1375, 1095, 750, 702, 541 cm-1. HRMS
(q, J = 3.7 Hz), 123.8 (q, J = 272.2 Hz), 113.1, 87.8, 84.7, 73.9, (EI) m/z calculated for C9H8BrCl 229.9498, found 229.9502.
57.5, 19.4. IR (KBr): 3079, 2977, 2852, 2231, 1616, 1516, 1323,
1168, 1017, 842, 747, 716, 597 cm-1. HRMS (ESI) m/z
calculated for C14H13F3ONa [M+Na]+ 277.0816, found 277.0815.
General procedure for Pd(0)-Catalyzed [2+2+1] cyclization of 1,6-
enynes with vinyl bromides.
1-Methyl-2-(3-((2-methylallyl)oxy)prop-1-yn-1-yl)benzene
(1h). Yellow liquid (523 mg, 65% yield). 1H NMR (400 MHz, charged with Pd(PPh3)4 (11.6 mg, 0.01 mmol), K3PO4 (84.9 mg,
CDCl3): δ 7.43 (d, J = 7.5 Hz, 1H), 7.25-7.17 (m, 2H), 7.16-7.10 0.40 mmol), TBAI (81.3 mg, 0.22 mmol), substrate (0.20
(m, 1H), 5.04 (s, 1H), 4.96 (s, 1H), 4.41 (s, 2H), 4.07 (s, 2H), 2.45 mmol), and (0.24 mmol), followed by sequential addition of
In a glovebox, a 5.0 mL vial equipped with a stir bar was
1
2
(s, 3H), 1.79 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 141.5, 140.2, 1,4-dioxane (1.2 mL). The vial was sealed with a Teflon screw
132.0, 129.3, 128.3, 125.4, 122.4, 113.0, 88.9, 85.0, 73.4, 57.7, cap and then the reaction mixture was heated at 100 °C for 48
20.6, 19.5. IR (KBr): 3073, 2919, 2851, 2233, 1655, 1485, 1455, h. After the reaction vessel was cooled to room temperature,
1374, 1354, 1260, 1084, 902, 758, 716 cm-1. HRMS (ESI) m/z the mixture was extracted with ethyl acetate, dried over
calculated for C14H16ONa [M+Na]+ 223.1099, found 223.1100.
anhydrous Mg2SO4 and concentrated under vacuum. The
4 | J. Name., 2012, 00, 1-3
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residue was then purified on silica gel to afford the desired
product.
6-(4-Chlorophenyl)-3a-methyl-5-phenyl-5-vinyl-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3e). Yellow oil (44.5 mg,
66% yield). 1H NMR (400 MHz, CDCl3): δ 7.38-7.35 (m, 2H), 7.31 (t,
3a-Methyl-5,6-diphenyl-5-vinyl-3,3a,4,5-tetrahydro-1H-
cyclopenta[c]furan (3a). Yellow oil (45.4 mg, 75% yield). 1H J = 7.6 Hz, 2H), 7.22 (t, J = 7.1 Hz, 1H), 7.05 (d, J = 8.7 Hz, 2H),
NMR (400 MHz, CDCl3): δ 7.39 (d, J = 7.9 Hz, 2H), 7.30 (t, J = 7.6 6.67 (d, J = 8.7 Hz, 2H), 6.52 (dd, J = 17.5, 10.8 Hz, 1H), 5.30 (d,
Hz, 2H), 7.26-7.19 (m, 1H), 7.12-7.04 (m, 3H), 6.79-6.73 (m, 2H), J = 11.7 Hz, 1H), 5.16 (d, J = 17.5 Hz, 1H), 4.68 (d, J = 13.7 Hz,
6.53 (dd, J = 17.5, 10.8 Hz, 1H), 5.29 (d, J = 10.7 Hz, 1H), 5.21 (d, J 1H), 4.58 (d, J = 13.7 Hz, 1H), 3.81 (d, J = 7.5 Hz, 1H), 3.49 (d, J
= 17.5 Hz, 1H), 4.71 (d, J = 13.6 Hz, 1H), 4.61 (d, J = 13.6 Hz, = 7.5 Hz, 1H), 2.33 (q, J = 13.4 Hz, 2H), 1.37 (s, 3H). 13C NMR
1H), 3.81 (d, J = 7.4 Hz, 1H), 3.49 (d, J = 7.2 Hz, 1H), 2.40-2.27 (100 MHz, CDCl3): δ 153.0, 148.2, 141.8, 133.4, 132.8, 132.6,
(m, 2H), 1.38 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.2, 129.8, 128.7, 128.2, 126.9, 126.5, 115.3, 78.7, 68.5, 65.0, 55.2,
148.6, 141.9, 134.9, 133.9, 128.6, 128.5, 128.0, 127.0, 126.7, 51.6, 23.6. IR (KBr): 3082, 2958, 2805, 1598, 1490, 1371, 1265,
126.2, 115.0, 78.7, 68.5, 65.0, 55.0, 51.4, 23.6. IR (KBr): 3083, 1235, 1025, 861, 746, 702 cm-1. HRMS (ESI) m/z calculated for
2961, 2929, 2852, 1635, 1598, 1494, 1372, 1265, 1025, C22H21ClONa [M+Na]+ 359.1179, found 359.1178.
920,700 cm-1. HRMS (ESI) m/z calculated for C22H22ONa
[M+Na]+ 325.1568, found 325.1580.
3a-Methyl-5-phenyl-6-(4-(trifluoromethyl)phenyl)-5-vinyl-
3,3a,4,5-tetrahydro-1H-cyclopenta[c]furan (3f). Colorless oil
1
3a-Methyl-5-phenyl-6-(p-tolyl)-5-vinyl-3,3a,4,5-tetrahydro- (45.2 mg, 61% yield). H NMR (400 MHz, CDCl3): δ 7.40 -7.29
1H-cyclopenta[c]furan (3b). Light yellow oil (46.2 mg, 73% (m, 6H), 7.26-7.20 (m, 1H), 6.85 (d, J = 8.2 Hz, 2H), 6.54 (dd, J =
yield). 1H NMR (400 MHz, CDCl3): δ 7.41-7.36 (m, 2H), 7.30 (t, J 17.4, 10.7 Hz, 1H), 5.31 (d, J = 10.7 Hz, 1H), 5.15 (d, J = 17.4 Hz,
= 7.6 Hz, 2H), 7.21 (t, J = 7.2 Hz, 1H), 6.90 (d, J = 8.2 Hz, 2H), 1H), 4.74 (d, J = 13.9 Hz, 1H), 4.62 (d, J = 13.9 Hz, 1H), 3.83 (d, J
6.65 (d, J = 8.2 Hz, 2H), 6.53 (dd, J = 17.5, 10.8 Hz, 1H), , 5.28 = 7.5 Hz, 1H), 3.52 (d, J = 7.5 Hz, 1H), 2.40-2.31 (m, 2H), 1.40 (s,
(dd, J = 10.7, 0.9 Hz, 1H), 5.20 (d, J = 17.5 Hz, 1H), 4.70 (d, J = 3H). 13C NMR (100 MHz, CDCl3): δ 155.3, 148.0, 141.7, 138.5 (q,
13.5 Hz, 1H), 4.61 (d, J = 13.5 Hz, 1H), 3.80 (d, J = 7.4 Hz, 1H), J = 1.0 Hz), 132.8, 128.7, 128.6, 128.4 (q, J = 32.6 Hz), 126.9,
3.48 (d, J = 7.4 Hz, 1H), 2.38-2.26 (m, 2H), 2.22 (s, 3H), 1.37 (s, 126.6, 124.9 (q, J = 3.7 Hz), 124.1 (q, J = 272.0 Hz), 115.4, 78.7,
3H). 13C NMR (100 MHz, CDCl3): δ 151.2, 148.7, 141.9, 136.5, 68.6, 65.0, 54.4, 51.7, 23.7. IR (KBr): 3084, 2963, 2853, 1616,
133.7, 132.0, 128.7, 128.5, 128.4, 126.9, 126.2, 114.9, 78.7, 1373, 1327, 1167, 1121, 1015, 844, 746, 702 cm-1. HRMS (ESI)
68.4, 65.1, 54.9, 51.4, 23.6, 21.0. IR (KBr): 3082, 2959, 2851, m/z calculated for C23H21F3ONa [M+Na]+ 393.1442, found
1635, 1514, 1446, 1371, 1264, 1023, 823, 763, 702 cm-1. HRMS 393.1451.
(ESI) m/z calculated for C23H24ONa [M+Na]+ 339.1725, found
339.1738.
6-(3-Methoxyphenyl)-3a-methyl-5-phenyl-5-vinyl-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3g). Yellow oil (47.2 mg, 71
1
% yield). H NMR (400 MHz, CDCl3): δ 7.42 (d, J = 8.0 Hz, 2H),
6-(4-Methoxyphenyl)-3a-methyl-5-phenyl-5-vinyl-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3c). Yellow oil (57.2 mg, 86 7.32 (t, J = 7.7 Hz, 2H), 7.21 (t, J = 7.3 Hz, 1H), 7.04 (t, J = 8.0
1
% yield). H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 7.6 Hz, 2H), Hz, 1H), 6.65 (d, J = 8.2 Hz, 1H), 6.52 (dd, J = 17.5, 10.8 Hz, 1H),
7.31 (t, J = 7.5 Hz, 2H), 7.22 (t, J = 7.2 Hz, 1H), 6.71-6.62 (m, 6.44 (d, J = 7.8 Hz, 1H), 6.19 (s, 1H), 5.30 (d, J = 10.8 Hz, 1H),
4H), 6.53 (dd, J = 17.4, 10.8 Hz, 1H), 5.29 (dd, J = 10.8, 1.2 Hz, 5.20 (d, J = 17.5 Hz, 1H), 4.70 (d, J = 13.7 Hz, 1H), 4.60 (d, J =
1H), 5.21 (dd, J = 17.5, 1.2 Hz, 1H), 4.69 (d, J = 13.4 Hz, 1H), 13.7 Hz, 1H), 3.81 (t, J = 6.7 Hz, 1H), 3.55 (d, J = 12.8 Hz, 1H),
4.60 (d, J = 13.4 Hz, 1H), 3.80 (d, J = 7.4 Hz, 1H), 3.71 (s, 3H), 3.42 (s, 3H), 2.41-2.30 (m, 2H), 1.38 (s, 3H). 13C NMR (100 MHz,
3.48 (d, J = 7.4 Hz, 1H), 2.42-2.23 (m, 2H), 1.37 (s, 3H). 13C NMR CDCl3): δ 158.9, 152.6, 148.6, 141.9, 136.3, 133.8, 128.8, 128.5,
(100 MHz, CDCl3): δ 158.2, 149.9, 148.8, 141.9, 133.4, 129.9, 127.1, 126.3, 121.4, 115.1, 113.2, 113.1, 78.7, 68.4, 65.0, 54.9,
128.5, 127.6, 127.0, 126.3, 115.0, 113.4, 78.8, 68.5, 65.1, 55.1, 54.7, 51.5, 23.6. IR (KBr): 3057, 2958, 2849, 1598, 1490, 1371,
54.9, 51.5, 23.7. IR (KBr): 3056, 2961, 2868, 1741, 1606, 1513, 1235, 1026, 892, 763, 702 cm-1. HRMS (ESI) m/z calculated for
1445, 1373, 1252, 1183, 1028, 835, 738, 703, 585 cm-1. HRMS C23H24O2Na [M+Na]+ 355.1674, found 355.1685.
(ESI) m/z calculated for C23H24O2Na [M+Na]+ 355.1674, found
355.1689.
3a-Methyl-5-phenyl-6-(o-tolyl)-5-vinyl-3,3a,4,5-tetrahydro-
1H-cyclopenta[c]furan (3h). Light yellow solid (23.4 mg, 37%
yield). 1H NMR (400 MHz, CDCl3): δ 7.28-7.18 (m, 5H), 7.11-
6-(4-Fluorophenyl)-3a-methyl-5-phenyl-5-vinyl-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3d). Yellow oil (46.1 mg, 72 7.03 (m, 2H), 6.89-6.81 (m, 1H), 6.57 (d, J = 7.7 Hz, 1H), 6.23
1
% yield). H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 7.5 Hz, 2H), (dd, J = 17.2, 11.1 Hz, 1H), 5.33-5.19 (m, 2H), 4.18 (d, J = 12.8
7.30 (t, J = 7.6 Hz, 2H), 7.21 (t, J = 7.2 Hz, 1H), 6.85-6.67 (m, Hz, 1H), 3.98 (d, J = 12.8 Hz, 1H), 3.89 (d, J = 7.4 Hz, 1H), 3.61
4H), 6.51 (dd, J = 17.5, 10.8 Hz, 1H), 5.29 (d, J = 10.7 Hz, 1H), (d, J = 7.4 Hz, 1H), 2.69 (d, J = 13.4 Hz, 1H), 2.44 (d, J = 13.4 Hz,
5.18 (d, J = 17.5 Hz, 1H), 4.67 (d, J = 13.5 Hz, 1H), 4.56 (d, J = 1H), 2.02 (s, 3H), 1.47 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
13.5 Hz, 1H), 3.81 (d, J = 7.5 Hz, 1H), 3.49 (d, J = 7.5 Hz, 1H), 150.7, 145.5, 143.7, 137.1, 134.9, 134.7, 129.9, 128.7, 128.0,
2.33 (q, J = 13.4 Hz, 2H), 1.37 (s, 3H). 13C NMR (100 MHz, 127.8, 127.2, 126.3, 124.8, 113.4, 79.9, 70.3, 64.0, 54.1, 46.9,
CDCl3): δ 161.4 (d, J = 247.7 Hz), 151.9 (d, J = 1.6 Hz), 148.2, 23.3, 20.0. IR (KBr): 3057, 2959, 2855, 1599, 1446, 1374, 1263,
141.8, 132.9, 131.1 (d, J = 3.4 Hz), 130.2 (d, J = 7.7 Hz), 128.6, 1019, 915, 881, 752, 702 cm-1. HRMS (ESI) m/z calculated for
126.9, 126.4, 115.1, 114.9 (d, J = 21.1 Hz), 78.7, 68.5, 64.8, 54.9, C23H24ONa [M+Na]+ 339.1725, found 339.1734.
51.5, 23.6. IR (KBr): 3083, 2961, 2851, 1601, 1446, 1372, 1236,
6-(2-Fluorophenyl)-3a-methyl-5-phenyl-5-vinyl-3,3a,4,5-
1162, 1026, 837, 739, 703, 573 cm-1. HRMS (ESI) m/z calculated tetrahydro-1H-cyclopenta[c]furan (3i). Yellow oil (40.4 mg, 63
for C22H21FONa [M+Na]+ 343.1474, found 343.1487.
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1
% yield). H NMR (400 MHz, CDCl3): δ 7.40 (d, J = 7.6 Hz, 2H), calculated for C29H29NO2SNa [M+Na]+ 478.1817, found
7.31 (t, J = 7.5 Hz, 2H), 7.24 (d, J = 7.7 Hz, 1H), 7.07 (dd, J = 12.9, 478.1814.
6.4 Hz, 1H), 7.00-6.91 (m, 1H), 6.67 (t, J = 7.5 Hz, 1H), 6.38 (dd,
3a-Methyl-6-phenyl-5-(p-tolyl)-5-vinyl-3,3a,4,5-tetrahydro-
J = 17.4, 10.8 Hz, 1H), 6.21 (t, J = 7.3 Hz, 1H), 5.37-5.22 (m, 2H), 1H-cyclopenta[c]furan (3a′). Yellow oil (36.7 mg, 58% yield). 1H
4.40 (dd, J = 13.4, 1.7 Hz, 1H), 4.24 (d, J = 13.4 Hz, 1H), 3.86 (d, NMR (400 MHz, CDCl3): δ 7.26 (d, J = 7.7 Hz, 2H), 7.10 (d, J =
J = 7.4 Hz, 1H), 3.60 (d, J = 7.4 Hz, 1H), 2.55 (d, J = 13.5 Hz, 1H), 7.5 Hz, 5H), 6.81- 6.75 (m, 2H), 6.51 (dd, J = 17.4, 10.8 Hz, 1H),
2.30 (d, J = 13.4 Hz, 1H), 1.44 (s, 3H). 13C NMR (100 MHz, 5.27 (d, J = 10.7 Hz, 1H), 5.18 (d, J = 17.5 Hz, 1H), 4.70 (d, J =
CDCl3): δ 160.0 (d, J = 247.1 Hz), 155.1 (d, J = 1.7 Hz), 146.8, 13.6 Hz, 1H), 4.60 (d, J = 13.6 Hz, 1H), 3.80 (d, J = 7.4 Hz, 1H),
143.0, 129.4 (d, J = 2.6 Hz), 128.7 (d, J = 8.7 Hz), 128.3, 127.7, 3.48 (d, J = 7.4 Hz, 1H), 2.37-2.24 (m, 5H), 1.37 (s, 3H). 13C NMR
126.6, 126.5, 123.2 (d, J = 3.6 Hz), 123.1 (d, J = 13.4 Hz), 115.5 (100 MHz, CDCl3): δ 152.1, 145.6, 142.1, 135.8, 135.0, 133.9,
(d, J = 24.3 Hz), 114.6, 79.6, 69.7, 64.5 (d, J = 12.4 Hz), 54.6, 129.2, 128.7, 128.0, 126.9, 126.7, 114.9, 78.8, 68.2, 65.1, 54.9,
50.3, 23.8. IR (KBr): 3058, 2960, 2861, 1636, 1489, 1447, 1372, 51.6, 23.7, 21.0. IR (KBr): 3053, 2959, 2850, 1635, 1508, 1444,
1263, 1208, 1026, 921, 798, 756, 702 cm-1. HRMS (ESI) m/z 1371, 1262, 1025, 917, 841, 764, 694 cm-1. HRMS (ESI) m/z
calculated for C22H21FONa [M+Na]+ 343.1474, found 343.1471.
calculated for C23H24ONa [M+Na]+ 339.1725 found 339.1736.
5-(4-Methoxyphenyl)-3a-methyl-6-phenyl-5-vinyl-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3b′). Yellow solid (44.5 mg,
3a-Methyl-5-phenyl-6-(thiophen-2-yl)-5-vinyl-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3j). Yellow oil (49.3 mg, 80
1
% yield). H NMR (400 MHz, CDCl3): δ 7.41 (d, J = 7.5 Hz, 2H), 67% yield). 1H NMR (400 MHz, CDCl3): δ 7.29 (d, J = 8.4 Hz, 2H),
7.31 (t, J = 7.5 Hz, 2H), 7.24 (t, J = 7.1 Hz, 1H), 7.06 (d, J = 5.0 7.09 (s, 3H), 6.85 (d, J = 8.3 Hz, 2H), 6.81-6.72 (m, 2H), 6.49
Hz, 1H), 6.78-6.73 (m, 1H), 6.52 (dd, J = 17.5, 10.8 Hz, 1H), 6.23 (dd, J = 17.4, 10.8 Hz, 1H), 5.26 (d, J = 10.8 Hz, 1H), 5.18 (d, J =
(d, J = 3.3 Hz, 1H), 5.32 (d, J = 10.7 Hz, 1H), 5.23 (d, J = 17.5 Hz, 17.5 Hz, 1H), 4.69 (d, J = 13.6 Hz, 1H), 4.58 (d, J = 13.6 Hz, 1H),
1H), 4.68 (d, J = 14.0 Hz, 1H), 4.57 (d, J = 14.0 Hz, 1H), 3.81 (d, J 3.80 (s, 4H), 3.48 (d, J = 7.4 Hz, 1H), 2.41-2.23 (m, 2H), 1.37 (s,
= 7.5 Hz, 1H), 3.49 (d, J = 7.5 Hz, 1H), 2.34 (q, J = 13.3 Hz, 2H), 3H). 13C NMR (100 MHz, CDCl3): δ 157.9, 152.0, 142.3, 140.7,
1.38 (s, 3H).13C NMR (100 MHz, CDCl3): δ 150.6, 147.2, 141.6, 135.1, 134.1, 128.7, 128.1, 128.1, 126.8, 114.9, 113.8, 78.8,
138.4, 128.9, 128.4, 127.8, 126.9, 126.7, 126.2, 125.1, 115.2, 67.9, 65.1, 55.3, 54.8, 51.6, 23.6. IR (KBr): 3054, 2957, 2849,
79.0, 69.0, 64.7, 55.4, 51.8, 23.2. IR (KBr): 3081, 2960, 2849, 1608, 1509, 1371, 1250, 1180, 1027, 918, 826, 765, 695 cm-1.
1598, 1446, 1372, 1264, 1024, 919, 888, 762, 700 cm-1. HRMS HRMS (ESI) m/z calculated for C23H24O2Na [M+Na]+ 355.1674
(ESI) m/z calculated for C20H20OSNa [M+Na]+ 331.1133 found found 355.1686.
331.1144.
3a,6-Dimethyl-5-phenyl-5-vinyl-3,3a,4,5-tetrahydro-1H-
5-(4-Fluorophenyl)-3a-methyl-6-phenyl-5-vinyl-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3c′). Yellow oil (46.1 mg,
1
cyclopenta[c]furan (3k). Colorless oil (21.6 mg, 45% yield). H 72% yield). 1H NMR (400 MHz, CDCl3): δ 7.38-7.31 (m, 2H), 7.11
NMR (400 MHz, CDCl3): δ 7.35-7.27 (m, 4H), 7.23-7.18 (m, 1H), (s, 3H), 6.99 (t, J = 8.4 Hz, 2H), 6.77 (s, 2H), 6.50 (dd, J = 17.4,
6.33 (dd, J = 17.5, 10.7 Hz, 1H), 5.31 (dd, J = 10.6, 1.3 Hz, 1H), 10.8 Hz, 1H), 5.30 (d, J = 10.7 Hz, 1H), 5.22 (d, J = 17.4 Hz, 1H),
5.19 (dd, J = 17.5, 1.3 Hz, 1H), 4.35 (d, J = 12.1 Hz, 1H), 4.28 4.71 (d, J = 13.6 Hz, 1H), 4.62 (d, J = 13.7 Hz, 1H), 3.82 (d, J =
(dd, J = 12.2, 1.5 Hz, 1H), 3.75 (d, J = 7.4 Hz, 1H), 3.43 (d, J = 7.4 7.3 Hz, 1H), 3.48 (d, J = 7.3 Hz, 1H), 2.38 (d, J = 13.4 Hz, 1H),
Hz, 1H), 2.23 (q, J = 13.4 Hz, 2H), 1.33 (s, 3H), 1.28 (s, 3H). 13C 2.24 (d, J = 13.4 Hz, 1H), 1.38 (s, 3H). 13C NMR (100 MHz,
NMR (100 MHz, CDCl3): δ 147.7, 146.4, 142.3, 131.5, 128.2, CDCl3): δ 161.3 (d, J = 245.2 Hz), 152.4, 144.3 (d, J = 3.1 Hz),
127.3, 126.1, 113.7, 79.8, 68.6, 63.0, 54.1, 50.2, 23.0, 12.3. IR 141.6, 134.6, 133.5, 128.5, 128.4 (d, J = 7.8 Hz), 128.0, 126.8,
(KBr): 3081, 2958, 2854, 1635, 1446, 1377, 1263, 1018, 914, 115.3, 115.2 (d, J = 15.4 Hz), 78.7, 68.0, 65.0, 54.9, 51.5, 23.5.
882, 760, 701 cm-1. HRMS (ESI) m/z calculated for C17H20ONa IR (KBr): 3056, 2962, 2868, 1600, 1506, 1373, 1225, 1161,
[M+Na]+ 263.1412 found 263.1417.
1025, 828, 764, 696 cm-1. HRMS (ESI) m/z calculated for
C22H21FONa [M+Na]+ 343.1474, found 343.1474.
3a-Methyl-5,6-diphenyl-2-tosyl-5-vinyl-1,2,3,3a,4,5-
hexahydrocyclopenta[c]pyrrole (3m). Compound 3m was
5-(4-Chlorophenyl)-3a-methyl-6-phenyl-5-vinyl-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3d′). Yellow oil (42.4 mg,
isolated by silica gel column chromatography as
a
diastereomeric mixture (dr = 6:1) in 64% yield (58.2 mg). The 63% yield). 1H NMR (400 MHz, CDCl3): δ 7.33-7.25 (m, 4H),
pure analytical sample of the major diastereomer of 3m was 7.14-7.08 (m, 3H), 6.81-6.74 (m, 2H), 6.49 (dd, J = 17.4, 10.8
1
obtained by preparative TLC on silica gel as a yellow solid. H Hz, 1H), 5.31 (d, J = 10.7 Hz, 1H), 5.22 (d, J = 17.4 Hz, 1H), 4.71
NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.2 Hz, 2H), 7.32 (d, J = (d, J = 13.8 Hz, 1H), 4.63 (d, J = 13.8 Hz, 1H), 3.81 (d, J = 7.4 Hz,
8.1 Hz, 2H), 7.25-7.19 (m, 3H), 7.18 -7.15 (m, 2H), 7.11-7.05 1H), 3.47 (d, J = 7.4 Hz, 1H), 2.37 (d, J = 13.4 Hz, 1H), 2.19 (d, J
(m, 3H), 6.69-6.65 (m, 2H), 6.37 (dd, J = 17.5, 10.8 Hz, 1H), 5.22 = 13.4 Hz, 1H), 1.37 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.6,
(d, J = 11.6 Hz, 1H), 5.11 (d, J = 16.9 Hz, 1H), 4.26 (d, J = 14.1 147.2, 141.2, 134.4, 133.2, 132.0, 128.6, 128.6, 128.3, 128.1,
Hz, 1H), 4.14 (d, J = 14.1 Hz, 1H), 3.50 (d, J = 8.9 Hz, 1H), 2.96 126.8, 115.5, 78.7, 68.1, 65.0, 55.1, 51.4, 23.6. IR (KBr): 3054,
(d, J = 9.0 Hz, 1H), 2.44 (s, 3H), 2.37 (d, J = 13.6 Hz, 1H), 2.22 (d, 2960, 2850, 1635, 1489, 1372, 1262, 1094, 1025, 820, 765,
J = 13.6 Hz, 1H), 1.15 (s,3H). 13C NMR (100 MHz, CDCl3): δ 749, 694 cm-1. HRMS (ESI) m/z calculated for C22H21ClONa
148.1, 146.2, 143.5, 141.7, 136.4, 134.6, 134.5, 129.9, 128.8, [M+Na]+ 359.1179, found 359.1184.
128.5, 128.1, 127.4, 127.3, 127.0, 126.4, 115.0, 66.9, 60.1,
3a-Methyl-6-phenyl-5-(thiophen-2-yl)-5-vinyl-3,3a,4,5-
53.1, 52.2, 46.7, 24.4, 21.6. IR (KBr): 3057, 2924, 2854, 1634, tetrahydro-1H-cyclopenta[c]furan (3e′). Yellow oil (42.6 mg,
1493, 1345, 1264, 1159, 1093, 749, 662 cm-1. HRMS (ESI) m/z 69 % yield). 1H NMR (400 MHz, CDCl3): δ 7.22 (d J = 5.0 Hz, 1H),
6 | J. Name., 2012, 00, 1-3
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COMMUNICATION
Tanakaa and Y. Fukuyama, Tetrahedron, 2001, 57, 4691; (c) J.
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7.16-7.12 (m, 3H), 6.97-6.93 (m, 1H), 6.89 (s, 1H), 6.81-6.76 (m,
2H), 6.49 (dd, J = 17.1, 10.7 Hz, 1H), 5.25 (d, J = 10.5 Hz, 1H),
5.19 (d, J = 17.3 Hz, 1H), 4.66 (d, J = 13.5 Hz, 1H), 4.51 (d, J =
13.6 Hz, 1H), 3.82 (d, J = 7.0 Hz, 1H), 3.49 (d, J = 7.0 Hz, 1H),
2.57-2.34 (m, 2H), 1.37 (s, 3H).13C NMR (100 MHz, CDCl3): δ
153.7, 151.9, 142.5, 135.0, 134.0, 128.4, 127.9, 126.9, 126.8,
124.4, 124.3, 115.4, 79.0, 66.1, 64.8, 54.3, 53.4, 23.4. IR (KBr):
3054, 2959, 2851, 1634, 1442, 1372, 1263, 1023, 920, 763,
749, 693 cm-1. HRMS (ESI) m/z calculated for C20H20OSNa
[M+Na]+ 331.1133, found 331.1146.
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3a-Methyl-5,6-diphenyl-5-(prop-1-en-1-yl)-3,3a,4,5-
tetrahydro-1H-cyclopenta[c]furan (3f′). The product was
obtained as an inseparable mixture of E/Z isomers. The NMR
data were referenced to the major product. Yellow oil (41.8
1
mg, 66% yield). E/Z isomer 5:1. H NMR (400 MHz, CDCl3): δ
7.41-7.35 (m, 2H), 7.28 (t, J = 7.6 Hz, 2H), 7.24-7.16 (m, 1H),
7.11-7.01 (m, 3H), 6.81-6.72 (m, 2H), 6.12 (dd, J = 15.6, 1.4 Hz,
1H), 5.64-5.51 (m, 1H), 4.74-4.57 (m, 2H), 3.80 (d, J = 7.4 Hz,
1H), 3.54-3.44 (m, 1H), 2.35-2.24 (m, 2H), 1.76 (d, J = 6.4 Hz,
3H), 1.36 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 151.9, 149.2,
135.0, 134.8, 134.4, 128.6, 128.4, 127.9, 127.0, 126.6, 126.1,
125.3, 78.7, 67.7, 65.1, 54.9, 52.4, 23.6, 18.3. IR (KBr): 3055,
2959, 2852, 1597, 1494, 1443, 1371, 1265, 1027, 979, 767, 738,
700 cm-1. HRMS (ESI) m/z calculated for C23H24ONa [M+Na]+
339.1725, found 339.1737.
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Acknowledgements
This work was supported by the NSFC (61605158), the Science
and Technology Department of Shaanxi Province
(2016JQ2028), and the Education Department of Shaanxi
Province (12JS113).
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Palladium(0)-catalyzed [2+2+1] cyclization of 1,6-enynes with vinyl bromides: a
highly diastereoselective synthesis of terahydro-1H-cyclopenta[c]furans bearing two
quaternary carbon centers†
Yunxia Diao, Zhijun Zuo, Hui Wang, Jingjing Liu* and Xinjun Luan*
A highly efficient method for the diastereoselective synthesis of terahydro-1H-cyclopenta[c]furans was
developed by palladium-catalyzed [2+2+1] cyclization of 1,6-enynes with vinyl bromides.