Palladium-catalyzed synthesis of 1,3,4-alkatrien-2-yldihydrofurans from 2,3-allenylacetylacetates and propargylic carbonates and their application to synthesize polysubstituted dihydrofurylcyclopentenones

Article abstract of DOI:10.1016/j.tet.2010.02.030

An efficient route to 1,3,4-alkatrien-2-yldihydrofurans via a highly chemo- and regioselective palladium(0)-catalyzed coupling-cyclization reaction of 2-(2′,3′-allenyl)acetylacetates with propargylic carbonates was reported. The reaction proceeded smoothly under neutral conditions, affording the O-attacked five-membered products with a 1,3,4-trienyl substituent exclusively in good to excellent yields. The products can be efficiently applied to the synthesis of polysubstituted 2-(dihydrofuryl)cyclopentenone derivatives via a catalytic Pauson-Khand reaction under ambient conditions.

Full text of DOI:10.1016/j.tet.2010.02.030

Tetrahedron 66 (2010) 2869–2874
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed synthesis of 1,3,4-alkatrien-2-yldihydrofurans from
2,3-allenylacetylacetates and propargylic carbonates and their application
to synthesize polysubstituted dihydrofurylcyclopentenones
,b,
Wei Shu a, Shengming Ma a
*
a State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, PR China
b Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal University, 3663 North Zhongshan Road,
Shanghai 200062, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 January 2010
Received in revised form 2 February 2010
Accepted 5 February 2010
Available online 10 February 2010
An efficient route to 1,3,4-alkatrien-2-yldihydrofurans via
a highly chemo- and regioselective
palladium(0)-catalyzed coupling–cyclization reaction of 2-(20,30-allenyl)acetylacetates with propargylic
carbonates was reported. The reaction proceeded smoothly under neutral conditions, affording the
O-attacked five-membered products with a 1,3,4-trienyl substituent exclusively in good to excellent
yields. The products can be efficiently applied to the synthesis of polysubstituted 2-(dihydrofur-
yl)cyclopentenone derivatives via a catalytic Pauson–Khand reaction under ambient conditions.
Ó 2010 Published by Elsevier Ltd.
Keywords:
Allene
Cyclization
Dihydrofuran
Pauson–Khand reaction
Palladium
1. Introduction
2. Results and discussion
Recently, much attention has been paid to the chemistry of
allenes, demonstrating their potential in organic synthesis.1,2 Thus,
synthesis of allenes has started to become and will continue to be
a hot research topic in organic synthesis.3,4 For the synthesis of
allenes, the palladium-catalyzed reaction of propargylic alcohol
derivatives should be one of the most straight forward pro-
cedures.5,6 On the other hand, dihydrofurans are also widely existed
in biologically active compounds,7,8 thus, many new methods have
been developed for the efficient synthesis of dihydrofurans.9,10 To
the best of our knowledge, the synthesis of molecules with such
two important structural cores has not been nicely explored.11 As
a part of our research program toward the synthesis12 and the
transition-metal-catalyzed coupling cyclization of functionalized
allenes,1f,k we wish to report an efficient construction of 1,3,4-
alkatrien-2-yldihydrofuran derivatives from palladium-catalyzed
coupling cyclization of 2,3-allenylacetylacetates and propargylic
carbonates with exclusive chemo- and regioselectivity.
On the basis of our previous work on the palladium-catalyzed
reaction of (2,3-allenyl)malonates with propargylic carbonates
forming 1,3,4-alkatrien-2-ylcyclopropane derivatives exclusively,13
we envisioned that Pd(0)-catalyzed cyclization of propargylic
carbonates with (2,3-allenyl)acetylacetates may form 1,3,4-alkatrien-
2-yl 4,5-dihydrofurans, 2,5-dihydroxepines, cyclopropanes, or cyclo-
pentenes via the intramolecular attack of the enolate intermediate
(Scheme 1).
We started our investigation with the reaction employing 1a
and 2a catalyzed by 5 mol % Pd(PPh3)4 and 10 mol % TBAI in CH3CN
at 80 ꢀC. To our delight, 1,3,4-alkatrien-2-yldihydrofuran 3aa was
obtained in 87% yield as the only product through highly chemo-
and regioselective O-attacked at the
p-allylic species (entry 1,
Table 1). The formation of O-attacked seven-membered product
4aa and the C-attacked products 5aa and 6aa were not observed.
Further investigation on the solvent effect revealed that the
reaction proceeded smoothly to afford the desired product 3aa
within a short period of time in all the tested aprotic solvents
(entries 1, 2 and 4–8, Table 1) except DCE (entry 3, Table 1): THF
gave the best result, affording the product 3aa in 95% isolated yield
(entry 4, Table 1). The reaction only gave complicated results in
protic solvents such as MeOH or HOAc (entries 9 and 10, Table 1).
* Corresponding author. Tel./fax: þ86 21 6260 9305.
E-mail address: masm@mail.sioc.ac.cn (S. Ma).
0040-4020/$ – see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tet.2010.02.030

2870
W. Shu, S. Ma / Tetrahedron 66 (2010) 2869–2874
R5
R5
R4
R3
not very effective for this transformation. Thus, we defined the
R2
O-attack a
O-attack b
O
reaction of 1 equiv of 1 and 1 equiv of 2 catalyzed by 5 mol %
Pd(PPh3)4 and 10 mol % TBAI in refluxing THF as the standard
conditions.
With the optimized conditions in hand, we examined the scope
of the substrates. To our delight, various different substituted 2,3-
allenylacetylacetates and terminal or non-terminal propargylic
carbonates worked well under the standard conditions, affording
CO2R1
R5
R5
R4
R3
R5
R5
R5
OCO2Me
R5
R4
R4
O
a
CO2R1
b
R3
R2
Pd(0)
+
R3
Pd+
R5
R5
R4
-O
R2
the five-membered products
(Table 2).
3 in good to excellent yields
CO2R1
R2
CO2R1
R3
C-attack a
C-attack b
O
O
R2
R1O2C
Table 2
R5
R5
R4
Palladium(0)-catalyzed coupling–cyclization reaction of 1 with 2a
O
R2
CO2R1
R3
Scheme 1.
Entry
1
2
Time (min) Isolated
yield
Table 1
Solvent effect on the reaction of ethyl 2-acetyl-4,5-hexadienoate 1a and propargylic
R1 R2
R3
R4
R5
carbonate 2aa
of 3 (%)
1
2
3
4
5
6
7
8
Et Me H (1a) Ph
Me (2a)
Me (2b)
–C5H10– (2c) 43
Et (2d) 65
–C5H10– (2c) 40
100
43
95 (3aa)
82 (3ab)
75 (3ac)
96 (3ad)
79 (3bc)
74 (3ae)
85 (3af)
89 (3ag)
92 (3bf)
65 (3bb)
80 (3cd)
75 (3cc)
83 (3dd)
Et Me H (1a)
Et Me H (1a)
Et Me H (1a)
Me i-Pr H (1b)
H
H
H
H
Et Me H (1a) CO2Me
Et Me H (1a) n-Bu
Et Me H (1a) CH2OTBDMS Me (2g)
Me (2e)
Me (2f)
50
54
70
60
28
50
9
Me i-Pr H (1b) n-Bu
Me (2f)
Me (2b)
Et (2d)
–C5H10– (2c) 75
Et (2d) 43
10
11
12
13
Me i-Pr H (1b)
Me i-Pr Bn (1c)
Me i-Pr Bn (1c)
Me Me H (1d)
H
H
H
H
Entry
Solvent
Time (h)
Isolated yield
of 3aa (%)
a
The reaction was carried out using 0.2 mmol of 1, 0.2 mmol of 2, 5 mol %
1
2
3
4
5
6
7
8
9
10
CH3CN
Toluene
DCE
THF
DMSO
DMF
CH3NO2
Dioxane
MeOH
HOAc
0.6
1
1.5
1.5
1
1
1
1.5
1.5
1.5
87
Pd(PPh3)4, and 10 mol % of TBAI in 2 mL of THF.
65
38b
95
66
66
68
The
g position of the propargylic carbonates does not have an
obvious influence against this reaction (entries 6 and 7, Table 2). It is
noteworthy that TBDMSOCH2 (TBDMS¼tert-butyldimethylsilyl) is
alsocompatibleinthiscoupling–cyclizationprocess (entry8, Table 2).
Besides thenormal2,3-allenylacetylacetates, a substituent R3 canalso
be introduced onto the allene moiety to afford the same type of
product with a quaternary carbon center in good yields (entries 11
and 12, Table 2). It should be noted that the formation of all-carbon
quaternary centers is not easy since the process requires the crea-
tion of a new C–C bond at a sterically hindered carbon center.14 The
structure of 3 was confirmed by the X-ray study of 3bb (Fig. 1).15
A plausible rationale for this reaction is shown in Scheme 3. Ox-
idative addition of propargylic carbonate 2 with Pd(0) would afford
allenylpalladium intermediate M1, which underwent intermolecular
84
Complicatedc
Complicatedc
a
The reaction was carried out with 0.2 mmol of 1a, 0.2 mmol of 2a, 5 mol %
Pd(PPh3)4, and 10 mol % TBAI in 2 mL ofindicated solvent. TBAI¼tetrabutylammonium
iodide.
b
The yield was determined by 1H NMR analysis using dibromomethane as the
internal standard, and 45% of the starting material remained.
c
The starting materials were completely consumed.
Next, we tested the effect of tetrabutylammonium halides by
using THF as the solvent. As shown in Scheme 2, the reaction is also
operative in the absence of a tetrabutylammonium halide, affording
3aa in a relatively lower yield (76%) after 2.5 h. TBAB and TBAC are
carbopalladation with the allene moiety of 1 to generate
ladium intermediate M2. In the presence of TBAI, the
p-allylpal-
p-allylpalla-
Ph
CO2Et
dium intermediate would prefer syn configuration, i.e., syn-M2.16 The
acetylacetate moiety in M2 would be deprotonated by the methoxy
anion generated in situ in the oxidative addition step to yield the
intermediate M3, which would isomerize to the enolate intermediate
M4. M4 underwent regioselective intramolecular allylation to afford
the final product 3 and regenerate the catalytically active species
Pd(0).
5 mol % Pd(PPh3)4
additive
O
+
Ph
OCO2Me
1 equiv 2a
THF, reflux
CO2Et
O
1 equiv 1a
3aa
a
time (h)
yield of 3aa
PTC
10 mol % TBAI
1.5
2
95%
71%
10 mol % TBABb
When the 1,3,4-alkatrien-2-yldihydrofurans 3 were exposed
to the catalytic Pauson–Khand reaction conditions catalyzed by
[RhCl(CO)2]2 under 1 atm of carbon monoxide,13,17 various poly-
substituted dihydrofurylcyclopententone derivatives were
obtained in good yields (Table 3), which are structural motifs
extensively existing in natural products and bioactive
molecules.18
10 mol % TBACb
2
66%
76%
none
2.5
a The reaction was carried out in 0.2 mmol scale.
b TBAB = tetrabutylammonium bromide. TBAC = tetrabutylammonium chloride.
Scheme 2. Effect of tetrabutylammonium halide on the reaction of 1a with 2a.

W. Shu, S. Ma / Tetrahedron 66 (2010) 2869–2874
2871
3. Conclusion
We have demonstrated an efficient and direct route for the
preparation of functionalized vinyl allene with a dihyrofuryl sub-
stituent. This reaction proceeded smoothly under neutral condi-
tions with an exclusive selectivity. The dihydrofurylvinyl allenes
can be successfully applied to the preparation of polysubstituted
dihydrofurylcyclopentenones under ambient conditions. Further
study in this area and synthetic application of the products
including the cyclization between dihydrofuran ring and the allene
moiety is ongoing in our laboratory.
4. Experimental section
4.1. General remarks
NMR spectra were taken with a Varian Mercury-300 spec-
trometer (300 MHz for 1H NMR, 75.4 MHz for 13C NMR) or Varian
Mercury-400 spectrometer (400 MHz for 1H NMR, 100.5 MHz for
13C NMR) in CDCl3. Chemical shifts were recorded in parts per
million (ppm) relative to internal standard CDCl3 and coupling
constants were reported in hertz (Hz). The high-resolution mass
spectra were recorded with a Finnigan MAT 8430 spectrometer.
Other mass spectra were obtained on a Shimadzu GCMS-2010 or
Shimadzu LCMS-2010 spectrometer. IR studies were carried out on
a Perkin–Elmer 983 spectrometer. X-ray intensity data were mea-
sured at 173 K on a Bruker SMART APEX CCD-based X-ray diffrac-
tometer system equipped with a fine-focus Mo-target X-ray tube
Figure 1. ORTEP representation of 3bb.
(l¼0.71073 Å) operated at 1500 W. The detector was placed at
a distance of 6.042 cm from the crystal. The frames were integrated
with the SAINT software package (Bruker, Billerica, MA) by using
a narrow-frame integration algorithm. All reactions were carried
out in an oven dried Schlenk tube under argon atmosphere. All
solvents were distilled from the indicated drying reagents right
before use: toluene and THF (Na, benzophenone), DCE, MeCN,
MeNO2, DMSO, dioxane, DMF (CaH2). Purification by column
chromatography was performed using Huanghai (Shandong, China)
silica gel (10–40 m).
4.2. Synthesis of 1,3,4-alkatrien-2-yldihydrofurans 3
4.2.1. 3-(Ethoxycarbonyl)-2-methyl-5-(5-methyl-3-phenyl-1,3,4-
hexatrien-2-yl)-4,5-dihydrofuran (3aa). To a flame-dried Schlenk
tube were added TBAI (7 mg, 0.019 mmol), Pd(PPh3)4 (12 mg,
0.010 mmol), 1a (35 mg, 0.19 mmol), 2a (45 mg, 0.21 mmol), and
2 mL of THF sequentially under argon. The resulting mixture was
stirred under reflux. When the reaction was completed in 100 min,
the solvent was evaporated under vacuum, and the residue was
purified by chromatography on silica gel (eluent: petroleum ether/
ethyl acetate¼15:1 (precooled in the refrigerator at ꢁ20 ꢀC)) to
afford 59 mg (95%) of 3aa as a viscous oil: 1H NMR (300 MHz,
Scheme 3. Plausible mechanism for the palladium-catalyzed reaction of 1 with 2.
Table 3
The Pauson–Khand reaction of 1,3,4-alkatrien-2-yldihydrofurans 3a
CDCl3)
d 7.38–7.20 (m, 5H), 5.29–5.20 (m, 2H), 4.97 (s, 1H), 4.17 (q,
J¼7.2 Hz, 2H), 3.18–3.08 (m,1H), 2.85–2.76 (m,1H), 2.25 (s, 3H),1.79
(s, 6H), 1.28 (t, J¼7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d 202.8,
167.6, 166.2, 144.5, 137.3, 129.0, 128.1, 126.9, 111.9, 104.7, 101.7, 98.4,
82.2, 59.4, 36.6, 20.3, 14.4, 14.1; MS (EI) m/z (%) 324 (Mþ, 5.77), 43
(100); IR (neat) 1947, 1701, 1651, 1598, 1491, 1445, 1383, 1340, 1324,
1257, 1224, 1171, 1142, 1125, 1083 cmꢁ1; HRMS calcd for C21H24O3
(Mþ): 324.1725. Found: 324.1711.
Entry
R1
R2
R3
R4
R5 (3)
Yield of 7b (%)
1
Me
Me
Me
Et
Et
Et
i-Pr
i-Pr
i-Pr
Me
Me
Me
Me
H
H
H
H
H
n-Bu
Ph
H
Me (3bb)
Et (3cd)
–C5H10– (3cc)
Et (3ad)
Me (3af)
Me (3aa)
Et (3dd)
90 (7a)
89 (7b)
96 (7c)
84 (7d)
71 (7e)
81 (7f)
88 (7g)
2
Bn
Bn
H
H
H
3c
4
5d
6d
7
4.2.2. 3-(Ethoxycarbonyl)-2-methyl-5-(5-methyl-1,3,4-hexatrien-2-
yl)-4,5-dihydrofuran (3ab). The reaction of Pd(PPh3)4 (12 mg,
0.010 mmol), TBAI (7 mg, 0.019 mmol), 1a (33 mg, 0.18 mmol), and
2b (28 mg, 0.20 mmol) in 2 mL of THF afforded 37 mg (82%) of 3ab
as an oil (eluent: petroleum ether/ethyl acetate¼20:1): 1H NMR
Me
H
a
The reaction was carried out with 0.1–0.2 mmol of 3 in 2 mL of dichloroethane.
Isolated yield.
The reaction finished within 1 h.
b
c
d
The reaction was complete within 48 h.
(300 MHz, CDCl3)
d
5.73–5.68 (m, 1H), 5.08 (dd, J¼10.8, 8.7 Hz, 1H),

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W. Shu, S. Ma / Tetrahedron 66 (2010) 2869–2874
5.02 (s, 1H), 4.99 (s, 1H), 4.15 (q, J¼7.2 Hz, 2H), 3.08–2.98 (m, 1H),
2.74–2.64 (m, 1H), 2.22 (t, J¼1.5 Hz, 3H), 1.71 (d, J¼3.0 Hz, 3H), 1.68
(d, J¼3.0 Hz, 3H), 1.26 (t, J¼7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
36.0, 19.44, 19.41, 14.4, 14.0; MS (EI) m/z (%) 306 (Mþ, 11.14), 43
(100); IR (neat) 1948, 1758, 1723, 1703, 1651, 1436, 1384, 1320, 1283,
1261, 1224, 1171, 1143, 1085 cmꢁ1; HRMS calcd for C17H22O5 (Mþ):
306.1467. Found: 306.1463.
d
202.9, 167.6, 166.2, 143.5, 111.2, 101.9, 98.3, 90.7, 81.9, 59.4, 36.2,
20.2, 20.1, 14.4, 14.0; MS (EI) m/z (%) 248 (Mþ, 2.40), 43 (100); IR
(neat) 1954, 1701, 1651, 1447, 1385, 1375, 1341, 1325, 1260, 1224,
1171, 1142, 1126, 1084, 1017 cmꢁ1; HRMS calcd for C15H20O3 (Mþ):
248.1412. Found: 248.1402.
4.2.7. 5-(3-Butyl-5-methyl-1,3,4-hexatrien-2-yl)-3-(ethox-
ycarbonyl)-2-methyl-4,5-dihydrofuran (3af). The reaction of
Pd(PPh3)4 (13 mg, 0.011 mmol), TBAI (7 mg, 0.019 mmol), 1a
(36 mg, 0.20 mmol), and 2f (42 mg, 0.21 mmol) in 2 mL of THF
afforded 51 mg (85%) of 3af as an oil (petroleum ether/ethyl
4.2.3. 3-(Ethoxycarbonyl)-2-methyl-5-(5,5-pentamethylene-1,3,4-
pentatrien-2-yl)-4,5-dihydrofuran (3ac). The reaction of Pd(PPh3)4
(12 mg, 0.010 mmol), TBAI (7 mg, 0.019 mmol), 1a (33 mg,
0.18 mmol), and 2c (34 mg, 0.19 mmol) in 2 mL of THF afforded
39 mg (75%) of 3ac as an oil (eluent: petroleum ether/ethyl
acetate¼20:1): 1H NMR (300 MHz, CDCl3)
5.12 (dd, J¼10.8, 8.1 Hz,
d
1H), 5.06 (s, 1H), 5.02 (s, 1H), 4.15 (q, J¼7.2 Hz, 2H), 3.08–2.98 (m,
1H), 2.60 (dd, J¼14.4, 8.1 Hz, 1H), 2.23 (s, 3H), 2.15 (t, J¼7.2 Hz, 2H),
1.71 (s, 3H), 1.68 (s, 3H), 1.50–1.26 (m, 4H), 1.26 (t, J¼7.2 Hz, 3H),
acetate¼10:1): 1H NMR (300 MHz, CDCl3)
d
5.73 (s, 1H), 5.09 (dd,
0.90 (t, J¼7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d 201.6, 167.6,
J¼11.1, 8.7 Hz, 1H), 5.01 (s, 1H), 4.98 (s, 1H), 4.15 (q, J¼7.2 Hz, 2H),
3.11–3.01 (m, 1H), 2.72–2.63 (m, 1H), 2.26–2.21 (m, 3H), 2.17–2.08
(m, 4H), 1.72–1.45 (m, 6H), 1.25 (t, J¼7.2 Hz, 3H); 13C NMR
166.2, 145.3, 107.3, 101.7, 100.9, 98.1, 82.3, 59.3, 37.1, 29.7, 29.2, 22.4,
20.3, 20.2, 14.4, 14.1, 14.0; MS (EI) m/z (%) 304 (Mþ, 3.89), 43 (100);
IR (neat) 1948, 1703, 1651, 1620, 1446, 1384, 1324, 1254, 1223, 1170,
1142, 1125, 1084 cmꢁ1; HRMS calcd for C19H28O3 (Mþ): 304.2038.
Found: 304.2042.
(75.4 MHz, CDCl3)
d 199.5, 167.6, 166.2, 143.7, 110.5, 105.3, 101.9,
90.7, 81.6, 59.3, 36.3, 31.1, 31.0, 27.0, 25.8, 14.4, 14.0; MS (EI) m/z (%)
288 (Mþ, 1.74), 43 (100); IR (neat) 1949,1702, 1651,1624, 1446,1381,
1340, 1324, 1253, 1222, 1170, 1141, 1126, 1084 cmꢁ1; HRMS calcd for
C18H24O3 (Mþ): 288.1725. Found: 288.1733.
4.2.8. 3-(Ethoxycarbonyl)-2-methyl-5-(5-methyl-3-(tert-butyl-dime-
thylsilyloxy)-methyl-1,3,4-hexatrien-2-yl)-4,5-dihydrofuran
(3ag). The reaction of Pd(PPh3)4 (12 mg, 0.010 mmol), TBAI
(8 mg, 0.022 mmol), 1a (35 mg, 0.19 mmol), and 2g (56 mg,
0.20 mmol) in 2 mL of THF afforded 67 mg (89%) of 3ag as an oil
(petroleum ether/ethyl acetate¼20:1): 1H NMR (400 MHz, CDCl3)
4.2.4. 3-(Ethoxycarbonyl)-5-(5-ethyl-1,3,4-heptatrien-2-yl)-2-
methyl-4,5-dihydrofuran (3ad). The reaction of Pd(PPh3)4 (13 mg,
0.011 mmol), TBAI (9 mg, 0.024 mmol), 1a (31 mg, 0.17 mmol),
and 2d (31 mg, 0.18 mmol) in 2 mL of THF at 80 ꢀC afforded 45 mg
(96%) of 3ad as an oil (petroleum ether/ethyl acetate¼20:1): 1H
d
5.12 (s, 1H), 5.11–5.05 (m, 2H), 4.35 (d, J¼12.0 Hz, 1H), 4.31
(d, J¼12.0 Hz, 1H), 4.15 (qd, J¼7.2, 1.2 Hz, 2H), 3.06–2.97 (m, 1H),
2.68–2.60 (m, 1H), 2.22 (t, J¼1.2 Hz, 3H), 1.73 (s, 3H), 1.70 (s, 3H),
1.25 (t, J¼7.2 Hz, 3H), 0.88 (s, 9H), 0.05 (s, 6H); 13C NMR
NMR (300 MHz, CDCl3)
d
5.96–5.90 (m, 1H), 5.08 (dd, J¼11.1,
8.7 Hz, 1H), 5.02–4.98 (m, 2H), 4.15 (q, J¼6.9 Hz, 2H), 3.09–2.98
(m, 1H), 2.74–2.64 (m, 1H), 2.22 (t, J¼1.2 Hz, 3H), 2.14–1.91
(m, 4H), 1.26 (t, J¼6.9 Hz, 3H), 1.03 (t, J¼7.2 Hz, 3H), 1.00
(75.4 MHz, CDCl3)
d 201.5, 167.6, 166.2, 143.0, 108.6, 101.8, 101.6,
99.1, 82.4, 62.5, 59.3, 36.7, 25.7, 20.2, 20.1, 18.1, 14.4, 14.0, ꢁ5.3;
MS (EI) m/z (%) 392 (Mþ, 3.17), 75 (100); IR (neat) 1952, 1703,
1651, 1622, 1471, 1463, 1446, 1384, 1341, 1325, 1255, 1224, 1170,
(t, J¼7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d 201.4, 167.6, 166.2,
143.9, 111.2, 110.2, 101.8, 94.8, 81.4, 59.4, 36.6, 25.7, 25.6, 14.4,
14.0, 12.2, 12.1; MS (EI) m/z (%) 276 (Mþ, 1.55), 43 (100); IR (neat)
1945, 1703, 1652, 1625, 1458, 1382, 1341, 1324, 1250, 1223, 1171,
1142, 1126, 1084 cmꢁ1; HRMS calcd for C17H24O3 (Mþ): 276.1725.
Found: 276.1721.
1139, 1084, 1006 cmꢁ1
;
HRMS calcd for C22H36O4Si (Mþ):
392.2383. Found: 392.2388.
4.2.9. 5-(3-Butyl-5-methyl-1,3,4-hexatrien-2-yl)-2-isopropyl-3-
(methoxycarbonyl)-4,5-dihydrofuran (3bf). The reaction of
Pd(PPh3)4 (12 mg, 0.010 mmol), TBAI (7 mg, 0.019 mmol), 1b
(38 mg, 0.19 mmol), and 2f (40 mg, 0.20 mmol) in 2 mL of THF
afforded 57 mg (92%) of 3bf as an oil (petroleum ether/ethyl
4.2.5. 2-Isopropyl-3-(methoxycarbonyl)-5-(5,5-pentamethylene-
1,3,4-pentatrien-2-yl)-4,5-dihydrofuran (3bc). The reaction of
Pd(PPh3)4 (13 mg, 0.011 mmol), TBAI (9 mg, 0.024 mmol), 1b
(41 mg, 0.21 mmol), and 2c (43 mg, 0.24 mmol) in 2 mL of THF
afforded 50 mg (79%) of 3bc as an oil (petroleum ether/ethyl
acetate¼20:1): 1H NMR (400 MHz, CDCl3)
d
5.12 (dd, J¼11.6,
7.6 Hz, 1H), 5.05 (s, 1H), 5.00 (s, 1H), 3.74–3.63 (m, 4H), 3.05
(dd, J¼14.4, 11.6 Hz, 1H), 2.53 (dd, J¼14.4, 7.6 Hz, 1H), 2.20–
2.08 (m, 2H), 1.74 (s, 3H), 1.71 (s, 3H), 1.46–1.25 (m, 4H), 1.20
(d, J¼6.8 Hz, 3H), 1.15 (d, J¼6.8 Hz, 3H), 0.90 (t, J¼7.2 Hz, 3H);
acetate¼20:1): 1H NMR (300 MHz, CDCl3)
d 5.74–5.72 (m, 1H), 5.09
(dd, J¼11.1, 7.8 Hz, 1H), 4.99 (s, 1H), 4.95 (s, 1H), 3.69–3.60 (m, 4H),
3.08 (dd, J¼14.7, 11.4 Hz, 1H), 2.61 (dd, J¼14.7, 7.8 Hz, 1H), 2.22–2.07
(m, 4H), 1.72–1.43 (m, 6H), 1.18 (d, J¼6.6 Hz, 3H), 1.15 (d, J¼7.2 Hz,
13C NMR (75.4 MHz, CDCl3)
d 201.7, 175.6, 166.5, 145.8, 105.9,
3H); 13C NMR (75.4 MHz, CDCl3)
d
199.6, 175.6, 166.4, 144.2, 109.1,
101.3, 98.9, 98.2, 81.1, 50.6, 37.5, 29.8, 29.1, 26.8, 22.4, 20.4,
20.3, 19.7, 14.0; MS (EI) m/z (%) 318 (Mþ, 8.28), 43 (100); IR
(neat) 1947, 1707, 1642, 1468, 1436, 1361, 1348, 1300, 1257,
1230, 1189, 1118, 1067, 1050 cmꢁ1; HRMS calcd for C20H30O3
(Mþ): 318.2195. Found: 318.2202.
105.6, 99.1, 91.1, 80.4, 50.7, 36.7, 31.3, 31.1, 27.20, 27.16, 26.8, 25.9,
19.7, 19.6; MS (EI) m/z (%) 302 (Mþ, 2.15), 43 (100); IR (neat) 1949,
1758, 1705, 1642, 1469, 1437, 1387, 1349, 1231, 1189, 1118, 1068,
1048 cmꢁ1; HRMS calcd for C19H26O3 (Mþ): 302.1882. Found:
302.1876.
4.2.10. 2-Isopropyl-3-(methoxycarbonyl)-5-(5-methyl-1,3,4-
hexatrien-2-yl)-4,5-dihydrofuran (3bb). The reaction of Pd(PPh3)4
(12 mg, 0.010 mmol), TBAI (7 mg, 0.019 mmol), 1b (37 mg,
0.19 mmol), and 2b (27 mg, 0.19 mmol) in 2 mL of THF afforded
32 mg (65%) of 3bb as an oil (petroleum ether/ethyl acetate¼20:1):
4.2.6. 3-(Ethoxycarbonyl)-2-methyl-5-(3-(methoxycarbonyl)-5-
methyl-1,3,4-hexatrien-2-yl)-4,5-dihydrofuran (3ae). The reaction
of Pd(PPh3)4 (12 mg, 0.010 mmol), TBAI (8 mg, 0.022 mmol), 1a
(36 mg, 0.20 mmol), and 2e (40 mg, 0.20 mmol) in 2 mL of THF
afforded 45 mg (74%) of 3ae as an oil (petroleum ether/ethyl
1H NMR (400 MHz, CDCl3)
d
5.75–5.69 (m, 1H), 5.06 (dd, J¼10.8,
acetate¼10:1): 1H NMR (300 MHz, CDCl3)
d
5.66 (s, 1H), 5.33 (s, 1H),
8.4 Hz, 1H), 5.01 (s, 1H), 4.96 (s, 1H), 3.73–3.61 (m, 4H), 3.04 (dd,
J¼14.0, 10.8 Hz, 1H), 2.61 (dd, J¼14.0, 8.4 Hz, 1H), 1.74 (d, J¼2.8 Hz,
3H), 1.71 (d, J¼2.4 Hz, 3H), 1.18 (d, J¼6.8 Hz, 3H), 1.15 (d, J¼7.2 Hz,
5.11 (dd, J¼10.8, 8.7 Hz, 1H), 4.13 (q, J¼6.9 Hz, 2H), 3.72 (s, 3H),
3.05–2.95 (m, 1H), 2.71–2.62 (m, 1H), 2.20 (s, 3H), 1.80 (s, 3H), 1.78
(s, 3H), 1.24 (t, J¼6.9 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d
208.1,
3H); 13C NMR (100.5 MHz, CDCl3)
d 203.0, 175.7, 166.4, 144.1,
167.5, 166.5, 166.0, 139.6, 114.1, 101.7, 101.2, 97.5, 82.2, 59.4, 52.1,
109.5, 99.1, 98.6, 91.3, 80.6, 50.7, 36.6, 26.8, 20.3, 20.2, 19.7, 19.6; MS

W. Shu, S. Ma / Tetrahedron 66 (2010) 2869–2874
2873
(EI) m/z (%) 262 (Mþ, 19.53), 43 (100); IR (neat) 1951, 1705, 1641,
1469, 1436, 1349, 1300, 1230, 1189, 1118, 1068, 1050 cmꢁ1; HRMS
calcd for C16H22O3 (Mþ): 262.1569. Found: 262.1572.
2.24 (s, 3H), 1.95 (s, 3H),1.12 (d, J¼6.8 Hz, 6H); 13C NMR (100.5 MHz,
CDCl3) d 203.9, 175.4, 166.0, 145.2, 138.5, 133.1, 127.9, 99.1, 80.1, 50.8,
41.7, 34.3, 26.8, 23.6, 20.2, 19.6, 19.5; MS (EI) m/z (%) 290 (Mþ,
38.58), 187 (100); IR (neat) 1718, 1634, 1469, 1436, 1349, 1299, 1232,
1190, 1168, 1118, 1064, 1041 cmꢁ1; HRMS calcd for C17H22O4 (Mþ):
290.1518. Found: 290.1507.
4.2.11. 5-Benzyl-2-isopropyl-5-(5-ethyl-1,3,4-heptatrien-2-yl)-3-
(methoxycarbonyl)-4,5-dihydrofuran
(3cd). The
reaction
of
Pd(PPh3)4 (12 mg, 0.010 mmol), TBAI (7 mg, 0.019 mmol), 1c
(59 mg, 0.21 mmol), and 2d (35 mg, 0.21 mmol) in 2 mL of THF
afforded 59 mg (80%) of 3cd as an oil (petroleum ether/ethyl
4.3.2. 4-(5-Benzyl-2-isopropyl-3-(methoxycarbonyl)-4,5-dihy-
drofuran-5-yl)-2-(1-ethylpropylidene)cyclopent-3-enone (7b). The
reaction of [RhCl(CO)2]2 (1 mg, 0.0026 mmol) and 3cd (46 mg,
0.12 mmol) in 2 mL of DCE under carbon monoxide atmosphere
afforded 44 mg (89%) of 7b as an oil: 1H NMR (400 MHz, CDCl3)
acetate¼20:1): 1H NMR (400 MHz, CDCl3)
d 7.19–7.08 (m, 5H), 5.84–
5.81 (m, 1H), 4.87 (s, 2H), 3.59–3.48 (m, 4H), 3.03 (d, J¼14.0 Hz, 1H),
2.98 (d, J¼14.0 Hz, 1H), 2.93 (d, J¼14.8 Hz, 1H), 2.73 (d, J¼14.8 Hz,
1H), 2.18–1.95 (m, 4H), 1.09 (d, J¼6.8 Hz, 3H), 1.06–0.99 (m, 9H); 13C
d
7.21–7.08 (m, 5H), 6.46–6.44 (m, 1H), 3.57 (s, 3H), 3.52 (heptet,
NMR (100.5 MHz, CDCl3)
d
201.8, 173.7, 166.3, 145.9, 136.3, 130.7,
J¼6.8 Hz, 1H), 3.04 (d, J¼14.0 Hz, 1H), 2.98 (d, J¼14.0 Hz, 1H),
2.90–2.84 (m, 3H), 2.78 (d, J¼14.8 Hz, 1H), 2.62 (q, J¼7.2 Hz, 2H),
2.19–2.08 (m, 2H), 1.08 (d, J¼6.8 Hz, 3H), 1.07 (d, J¼6.8 Hz, 3H), 0.96
127.6, 126.4, 112.0, 109.9, 99.1, 94.2, 89.8, 50.6, 44.6, 40.3, 26.8,
25.63, 25.60, 19.9, 19.7, 12.3, 12.0; MS (EI) m/z (%) 380 (Mþ, 5.80), 43
(100); IR (neat) 1944, 1706, 1643, 1612, 1496, 1468, 1455, 1435, 1351,
1280, 1242, 1188, 1125, 1103, 1067, 1046 cmꢁ1; HRMS calcd for
C25H32O3 (Mþ): 380.2351. Found: 380.2340.
(t, J¼7.6 Hz, 6H); 13C NMR (100.5 MHz, CDCl3)
d 203.8, 174.3, 166.0,
156.3, 142.4, 135.3, 132.1, 130.6, 128.0, 126.8, 126.4, 98.9, 88.4, 50.7,
44.5, 42.8, 38.7, 27.8, 26.8, 24.1, 19.8, 19.6, 12.84, 12.76; MS (EI) m/z
(%) 408 (Mþ, 1.70), 317 (100); IR (neat) 1715, 1640, 1496, 1455, 1436,
1396, 1360, 1285, 1242, 1189, 1119, 1065, 1016 cmꢁ1; HRMS calcd for
C26H32O4 (Mþ): 408.2301. Found: 408.2300.
4.2.12. 5-Benzyl-2-isopropyl-3-(methoxycarbonyl)-5-(5,5-pentam-
ethylene-1,3,4-pentatrien-2-yl)-4,5-dihydrofuran (3cc). The reaction
of Pd(PPh3)4 (12 mg, 0.010 mmol), TBAI (7 mg, 0.019 mmol), 1c
(61 mg, 0.21 mmol), and 2c (37 mg, 0.20 mmol) in 2 mL of THF
afforded 60 mg (75%) of 3cc as an oil (petroleum ether/ethyl
4.3.3. 4-(5-Benzyl-2-isopropyl-3-(methoxycarbonyl)-4,5-dihy-
drofuran-5-yl)-2-(1-cyclohexylidene)cyclopent-3-enone
(7c). The
acetate¼20:1): 1H NMR (400 MHz, CDCl3)
d
7.27–7.18 (m, 5H), 5.75
reaction of [RhCl(CO)2]2 (1 mg, 0.0026 mmol) and 3cc (36 mg,
0.092 mmol) in 2 mL of DCE under carbon monoxide atmosphere
afforded 37 mg (96%) of 7c as an oil: 1H NMR (400 MHz, CDCl3)
(s, 1H), 4.92 (s, 1H), 4.88 (s, 1H), 3.68–3.57 (m, 4H), 3.14 (d,
J¼13.6 Hz, 1H), 3.06 (d, J¼13.6 Hz, 1H), 3.00 (d, J¼14.8 Hz, 1H), 2.86
(d, J¼14.8 Hz, 1H), 2.37–2.18 (m, 4H), 1.75–1.51 (m, 6H), 1.20 (d,
J¼6.8 Hz, 3H), 1.13 (d, J¼7.2 Hz, 3H); 13C NMR (100.5 MHz, CDCl3)
d
7.22–7.08 (m, 5H), 6.53–6.51 (m, 1H), 3.57 (s, 3H), 3.51 (heptet,
J¼6.8 Hz, 1H), 3.05 (d, J¼14.0 Hz, 1H), 2.97 (d, J¼14.0 Hz, 1H),
2.92–2.80 (m, 5H), 2.78 (d, J¼14.4 Hz, 1H), 2.23–2.19 (m, 2H),
1.62–1.51 (m, 6H), 1.07 (t, J¼6.6 Hz, 6H); 13C NMR (100.5 MHz,
d
200.1, 173.6, 166.4, 145.6, 136.5, 130.5, 127.5, 126.3, 112.5, 104.4,
99.1, 91.2, 89.8, 50.7, 44.7, 40.9, 31.1, 31.0, 26.9, 26.8, 26.6, 25.9, 19.9,
19.7; MS (EI) m/z (%) 392 (Mþ, 11.58), 43 (100); IR (neat) 1949, 1705,
1643, 1612, 1496, 1468, 1435, 1385, 1351, 1279, 1241, 1188, 1124,1101,
1067, 1046 cmꢁ1; HRMS calcd for C26H32O3 (Mþ): 392.2351. Found:
392.2368.
CDCl3)
d 204.8, 174.3, 166.0, 153.0, 141.7, 135.4, 130.6, 130.4, 128.0,
126.8, 126.2, 98.9, 88.3, 50.7, 44.5, 43.2, 38.7, 33.1, 28.6, 28.3, 28.1,
26.8, 26.2, 19.8, 19.7; MS (EI) m/z (%) 420 (Mþ, 2.12), 329 (100); IR
(neat) 1714, 1639, 1496, 1468, 1437, 1387, 1352, 1286, 1243, 1188,
1121, 1065, 1016 cmꢁ1; HRMS calcd for C27H32O4 (Mþ): 420.2301.
Found: 420.2310.
4.2.13. 5-(5-Ethyl-1,3,4-heptatrien-2-yl)-2-methyl-3-(methox-
ycarbonyl)-4,5-dihydrofuran (3dd). The reaction of Pd(PPh3)4
(12 mg, 0.010 mmol), TBAI (7 mg, 0.019 mmol), 1d (37 mg,
0.22 mmol), and 2d (38 mg, 0.22 mmol) in 2 mL of THF afforded
48 mg (83%) of 3dd as an oil (petroleum ether/ethyl acetate¼20:1):
4.3.4. 4-(3-(Ethoxycarbonyl)-2-methyl-4,5-dihydrofuran-5-yl)-2-
(1-ethylpropylidene)cyclopent-3-enone (7d). The reaction of
[RhCl(CO)2]2 (1 mg, 0.0026 mmol) and 3ad (28 mg, 0.10 mmol)
in 2 mL of DCE under carbon monoxide atmosphere afforded
1H NMR (300 MHz, CDCl3)
d
5.95–5.90 (m, 1H), 5.08 (dd, J¼10.2,
8.4 Hz, 1H), 4.99 (s, 2H), 3.68 (s, 3H), 3.03 (dd, J¼14.1, 10.2 Hz, 1H),
2.67 (dd, J¼14.1, 8.4 Hz, 1H), 2.22 (s, 3H), 2.17–1.89 (m, 4H), 1.06–
26 mg (84%) of 7d as an oil: 1H NMR (400 MHz, CDCl3)
d 6.68
(s, 1H), 5.27 (t, J¼6.9 Hz, 1H), 4.16 (q, J¼7.2 Hz, 2H), 3.11–3.03
(m, 1H), 2.95 (d, J¼17.1 Hz, 1H), 2.89 (d, J¼17.1 Hz, 1H), 2.82–2.74
(m, 1H), 2.70 (q, J¼7.6 Hz, 2H), 2.26 (q, J¼7.2 Hz, 2H), 2.21 (s, 3H),
1.27 (t, J¼7.2 Hz, 3H), 1.08 (t, J¼7.6 Hz, 3H), 1.03 (t, J¼7.2 Hz, 3H);
0.95 (m, 6H); 13C NMR (75.4 MHz, CDCl3)
d 201.4,168.0,166.5,143.8,
111.2,110.1,101.5, 94.8, 81.4, 50.8, 36.5, 25.7, 25.5,14.0,12.2,12.1; MS
(EI) m/z (%) 262 (Mþ, 18.12), 43 (100); IR (neat) 1944, 1708, 1651,
1625, 1437, 1384, 1360, 1329, 1250, 1223, 1189, 1140, 1089 cmꢁ1
HRMS calcd for C16H22O3 (Mþ): 262.1569. Found: 262.1560.
;
13C NMR (100.5 MHz, CDCl3)
d 203.8, 167.4, 165.9, 157.0, 138.6,
132.0, 128.0, 101.8, 80.5, 59.6, 42.0, 34.2, 27.9, 24.1, 14.4, 14.0,
12.9, 12.8; MS (EI) m/z (%) 305 (Mþþ1, 12.15), 304 (Mþ, 51.56), 43
(100); IR (neat) 1716, 1650, 1619, 1461, 1383, 1319, 1256, 1222,
1167, 1126, 1082 cmꢁ1; HRMS calcd for C18H24O4 (Mþ): 304.1675.
Found: 304.1677.
4.3. The Pauson–Khand reaction of 3
4.3.1. 4-(2-Isopropyl-3-(methoxycarbonyl)-4,5-dihydrofuran-5-yl)-
2-(isopropylidene)cyclopent-3-enone (7a). To a flame-dried Schlenk
tube containing [RhCl(CO)2]2 (1 mg, 0.0026 mmol) were added 3bb
(26 mg, 0.099 mmol) and 2 mL of DCE sequentially under the
atmosphere of CO. The resulting mixture was stirred at room
temperature with CO (1 atm) being introduced via the installation
of a CO balloon. When the reaction was completed as monitored by
TLC in 3 h, the solvent was evaporated under vacuum and the
residue was purified by flash chromatography on silica gel (eluent:
petroleum ether/ethyl acetate¼10:1) to afford 26 mg (90%) of 7a as
4.3.5. 3-Butyl-4-(3-(ethoxycarbonyl)-2-methyl-4,5-dihydrofuran-5-
yl)-2-(isopropylidene)cyclopent-3-enone (7e). The reaction of
[RhCl(CO)2]2 (1 mg, 0.0026 mmol) and 3af (44 mg, 0.14 mmol) in
2 mL of DCE under carbon monoxide atmosphere afforded 34 mg
(71%) of 7e as an oil: 1H NMR (400 MHz, CDCl3)
d
5.63 (dd, J¼10.8,
8.4 Hz, 1H), 4.15 (q, J¼7.2 Hz, 2H), 3.10–3.02 (m, 1H), 2.83 (s, 2H),
2.71–2.64 (m, 1H), 2.49 (t, J¼7.2 Hz, 2H), 2.28 (s, 3H), 2.17
(t, J¼1.6 Hz, 3H), 2.08 (s, 3H), 1.53–1.29 (m, 4H), 1.26 (t, J¼7.2 Hz,
an oil: 1H NMR (400 MHz, CDCl3)
d
6.68–6.66 (m, 1H), 5.27 (dd,
3H), 0.92 (t, J¼7.2 Hz, 3H); 13C NMR (100.5 MHz, CDCl3)
d 205.0,
J¼10.8, 7.6 Hz,1H), 3.69 (s, 3H), 3.64 (heptet, J¼6.8 Hz,1H), 3.08 (dd,
167.6, 165.8, 145.7, 142.2, 134.0, 133.4, 101.9, 77.4, 59.5, 39.9, 34.9,
J¼14.4, 10.8 Hz, 1H), 2.91–2.89 (m, 2H), 2.74 (dd, J¼14.4, 7.6 Hz, 1H),
31.9, 27.4, 23.5, 22.6, 14.4, 13.92, 13.85; MS (EI) m/z (%) 333 (Mþþ1,

2874
W. Shu, S. Ma / Tetrahedron 66 (2010) 2869–2874
12.58), 332 (Mþ, 46.43), 43 (100); IR (neat) 1704, 1649, 1604, 1463,
1382, 1322, 1256, 1221, 1143, 1125, 1082 cmꢁ1; HRMS calcd for
C20H28O4 (Mþ): 332.1988. Found: 332.1975.
3. For a review on the synthesis of allenes, see: Brummond, K. M.; DeForrest, J. E.
Synthesis 2007, 795.
4. For most recent reports on the synthesis of allenes, see: (a) Lee, K.; Lee, P. H.
Org. Lett. 2008, 10, 2441; (b) Campbell, M. J.; Pohlhaus, P. D.; Min, G.; Ohmatsu,
K.; Johnson, J. S. J. Am. Chem. Soc. 2008, 130, 9180; (c) Miura, T.; Shimada, M.; Ku,
S. Y.; Tamai, T.; Murakami, M. Angew. Chem., Int. Ed. 2007, 46, 7101; (d) Pu, X.;
Ready, J. M. J. Am. Chem. Soc. 2008, 130, 10874.
5. For reviews, see: (a) Tsuji, J. Angew. Chem., Int. Ed. Engl. 1995, 34, 2589; (b) Tsuji,
J.; Mandai, T. In Metal-catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P.
J., Eds.; Wiley-VCH: NY, 1998; p 455.
6. For examples on palladium catalyzed propargylic alcohol derivatives to syn-
thesize allenes, see: (a) Monteiro, N.; Arnold, A.; Balme, G. Synlett 1998, 1111;
(b) Cacchi, S.; Fabrizi, G.; Moro, L. Tetrahedron Lett. 1998, 39, 5101; (c) Ishikura,
M.; Matsuzaki, Y.; Katagiri, N. Tetrahedron 1998, 54, 13929; (d) Mandai, T.;
Ogawa, M.; Yamaoki, H.; Nakata, T.; Murayama, H.; Kawada, M.; Tsuji, J. Tetra-
hedron Lett. 1991, 32, 3397; (e) Marshall, J. A.; Wolf, M. A.; Wallace, E. M. J. Org.
Chem. 1997, 62, 367; (f) Bartley, G. S.; Wallace, E. M. J. Org. Chem. 1996, 61, 5729;
(g) Marshall, J. A.; Wallace, E. M. J. Org. Chem. 1995, 60, 796; (h) Marshall, J. A.;
Van Devender, E. A. J. Org. Chem. 2001, 66, 8037; (i) Tsuji, J.; Sugiura, T.; Minami,
I. Tetrahedron Lett. 1986, 27, 731; (j) Mandai, T.; Tsujiguchi, Y.; Matsuoka, S.;
Tsuji, J.; Saito, S. Tetrahedron Lett. 1994, 35, 5697; (k) Li, Y.; Zou, H.; Gong, J.;
Xiang, J.; Luo, T.; Quan, J.; Wang, G.; Yang, Z. Org. Lett. 2007, 9, 4057; (l) Imada,
Y.; Alper, A. J. Org. Chem. 1996, 61, 6766.
4.3.6. 4-(3-(Ethoxycarbonyl)-2-methyl-4,5-dihydrofuran-5-yl)-2-
(isopropylidene)-3-phenylcyclopent-3-enone (7f). The reaction of
[RhCl(CO)2]2 (1 mg, 0.0026 mmol) and 3aa (32 mg, 0.10 mmol) in
2 mL of DCE under carbon monoxide atmosphere afforded 28 mg
(81%) of 7f as an oil: 1H NMR (400 MHz, CDCl3)
d 7.41–7.28 (m, 3H),
7.26–7.03 (m, 2H), 5.14 (dd, J¼10.4, 8.4 Hz, 1H), 4.14 (q, J¼7.0 Hz, 2H),
3.02 (s, 2H), 2.97–2.89 (m,1H), 2.78–2.71 (m,1H), 2.26 (s, 3H), 2.14 (s,
3H), 1.36 (s, 3H), 1.25 (t, J¼7.0 Hz, 3H); 13C NMR (100.5 MHz, CDCl3)
d
204.0, 167.6, 165.8, 148.1, 143.3, 136.8, 135.4, 133.8, 128.5, 127.6,
101.8, 77.9, 59.5, 40.0, 34.9, 24.1, 22.6, 14.4, 13.9; MS (EI) m/z (%) 353
(Mþþ1, 13.97), 352 (Mþ, 60.25), 263 (100); IR (neat) 1717, 1698,1649,
1608, 1494, 1443, 1382, 1321, 1257, 1218, 1170, 1122, 1082 cmꢁ1
HRMS calcd for C22H24O4 (Mþ): 352.1675. Found: 352.1690.
;
7. (a) Sasaki, T.; Yamakoshi, J.; Saito, M.; Kasai, K.; Matsudo, T. Biosci. Biotechnol.
Biochem. 1998, 62, 1865; (b) Ottinger, H.; Soldo, T.; Hofmann, T. J. Agric. Food
Chem. 2001, 49, 5383; (c) Vaittinen, S.-L.; Komulainen, H.; Kosma, V.-M.;
Julkunene, A.; Maeki-Paakkanen, J. Food Chem. Toxicol. 1995, 33, 1027; (d) Moh,
J. H.; Kim, J. K.; Jeong, Y. S.; Kim, J. Y.; Choi, Y. H.; Koh, H.-J. J. Med. Chem. 2004,
47, 792; (e) Vleet, T. R. V.; Klein, P. J.; Coulombe, R. A. J. Toxicol. Environ. Health
2002, 65, 853.
4.3.7. 2-(1-Ethylpropylidene)-4-(2-methyl-3-(methoxycarbonyl)-
4,5-dihydrofuran-5-yl)-cyclopent-3-enone (7g). The reaction of
[RhCl(CO)2]2 (2 mg, 0.0051 mmol) and 3dd (45 mg, 0.17 mmol) in
2 mL of DCE under carbon monoxide atmosphere afforded 44 mg
(88%) of 7g as an oil: 1H NMR (300 MHz, CDCl3)
d 6.66 (s, 1H), 5.26
8. (a) Gottlieb, O. R. New Natural Products and Plant Drugs with Pharmacological,
Biological, or Therapeutical Activity; Springer: Berlin/Heidelberg, Germany, 1987;
p 227; (b) Ward, R. S. Tetrahedron 1990, 46, 5029; (c) Fraga, B. M. Nat. Prod. Rep.
1992, 9, 217; (d) Merrit, A. T.; Ley, S. V. Nat. Prod. Rep. 1992, 9, 243; (e) Moody, C.
J.; Davies, M. Stud. Nat. Prod. Chem. 1992, 10, 201; (f) Koert, U. Synthesis 1995,
115; (g) Benassi, R. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.,
Rees, C. W., Scrivan, E. F. V., Bird, C. W., Eds.; Elsevier: Oxford, UK, 1996; Vol. 2,
p 259; (h) Koch, S. S. C.; Chamberlin, A. R. Stud. Nat. Prod. Chem. 1995, 16, 687; (i)
Ward, R. S. Nat. Prod. Rep. 1999, 16, 75.
(t, J¼9.6 Hz, 1H), 3.68 (s, 3H), 3.10–2.97 (m, 1H), 2.90 (s, 2H), 2.82–
2.63 (m, 3H), 2.24 (q, J¼7.5 Hz, 2H), 2.19 (s, 3H), 1.06 (t, J¼7.5 Hz,
3H), 1.01 (t, J¼7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d 203.7, 167.7,
166.2,157.0,138.4,131.9,128.1,101.5, 80.6, 50.8, 41.9, 34.0, 27.8, 24.0,
13.9, 12.81, 12.79; MS (EI) m/z (%) 291 (Mþþ1, 11.20), 290 (Mþ,
72.90), 43 (100); IR (neat) 1713, 1649, 1618, 1438, 1384, 1360, 1327,
1258, 1223, 1189, 1166, 1132, 1087 cmꢁ1; HRMS calcd for C17H22O4
(Mþ): 290.1518. Found: 290.1509.
9. For some reviews, see: (a) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239;
´
(b) Alvarez-Corral, M.; Mun˜oz-Dorado, M.; Rodrı´guez-Garcı´a, I. Chem. Rev. 2008,
108, 3174; (c) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395; (d) Arcadi, A.
Chem. Rev. 2008, 108, 3266.
Acknowledgements
10. For some recent reports on the synthesis of dihydrofurans, see: (a) Funayama,
A.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2005, 127, 15354; (b) Istrate, F.;
Gagosz, F. Org. Lett. 2006, 8, 1957; (c) Liu, Y.; Song, F.; Song, Z.; Liu, M.; Yan, B.
Org. Lett. 2005, 7, 5409; (d) Ma, S.; Zheng, Z.; Jiang, X. Org. Lett. 2007, 9, 529;
(e) Yamamoto, H.; Sasaki, I.; Imagawa, H.; Nishizawa, M. Org. Lett. 2007, 9,
1399; (f) Shen, R.; Huang, X. Org. Lett. 2008, 10, 3283; (g) Bambuch, V.; Pohl,
R.; Hocek, M. Eur. J. Org. Chem. 2008, 2783; (h) Jiang, X.; Ma, X.; Zheng, Z.; Ma,
S. Chem.dEur. J. 2008, 14, 8572; (i) Deng, Y.; Li, J.; Ma, S. Chem.dEur. J. 2008,
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11. (a) Landor, S. R.; Rogers, V.; Sood, H. R. Tetrahedron 1977, 33, 73; (b) Ho¨germeier,
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12. (a) Ma, S.; Zhang, A. J. Org. Chem. 1998, 63, 9601; (b) Ma, S.; Zhang, A.; Yu, Y.;
Xia, W. J. Org. Chem. 2000, 65, 2287; (c) Ma, S.; He, Q. Angew. Chem., Int. Ed.
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Financial support from National Natural Science Foundation of
China (20732005), State Basic and Research Development Program
(Grant No. 2006CB806105), and Chinese Academy of Sciences is
greatly appreciated. We also thank Mr. Bo Chen in this group for
reproducing the results presented in entries 2, 6, and 12 of Table 2
and entry 1 of Table 3.
Supplementary data
1H/13C NMR spectra of all new compounds. Supplementary data
associated with this article can be found in the online version, at
doi:10.1016/j.tet.2010.02.030.
13. Shu, W.; Jia, G.; Ma, S. Org. Lett. 2009, 11, 117.
14. For selected recent reviews, see: (a) Quaternary Stereocenters: Challenges and
Solutions for Organic Synthesis; Christoffers, J., Baro, A., Eds.; Wiley-VCH:
Weinheim, Germany, 2005; (b) Trost, B. M.; Jiang, C. H. Synthesis 2006, 369.
15. Crystal data for 3bb: C16H22O3, MW¼262.34, monoclinic; space group C2/c,
References and notes
final R indices [I>2
s
(I)], R1¼0.0358, wR2¼0.0978; R indices (all data): R1¼0.
1. (a) Landor, S. R. In The Chemistry of the Allenes; Academic: London, 1982; Vol. 1;
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0445, wR2¼0.0892; a¼12.2634(4) Å, b¼13.3406(6) Å, c¼19.574 Å,
a
¼90(10)ꢀ,
b
¼101.18ꢀ,
g
¼90ꢀ, V¼3141.59(17) Å3, T¼173(2) K, wavelength: 0.71073 Å, Z¼8,
reflections collected/unique: 17,893/2775 (Rint¼0.0233); number of observa-
tions [>2s(I)] 2363, Parameters: 180. Supplementary crystallographic data
have been deposited at the Cambridge Crystallographic Data Center. CCDC
756489.
16. Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1999, 121, 4545.
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