Synthesis of polysubstituted furans based on a stepwise sonogashira coupling of (Z)-3-iodoalk-2-en-1-ols with terminal propargylic alcohols and subsequent Au(I)- or Pd(II)-catalyzed cyclization?aromatization via elimination of H2O

Article abstract of DOI:10.1021/jo100146p

Recently, we have developed highly regio- and stereoselective carbometalation of 2-alkynols and 2,3-allenols. The organometallacyclic intermediates may be trapped with I₂ to afford 3-iodoalk-2-en-1-ols. These 3-iodoalk-2-en-1-ols may readily undergo the Sonogashira coupling with terminal propargyl alcohols to form 4-alkyn-2-ene-1,6-diols. Subsequent cycloisomerization in DMA or CH₂Cl₂ with Au(PPh ₃)Cl and AgOTf as the catalyst would afford polysubstituted 2-(1-alkenyl)furans; with PdCl₂ as the catalyst and the reaction in DMA in the presence of allylic bromides, the same substrates afforded polysubstituted 2-(1,4-alkadienyl)furans. In both types of catalyzed cyclization reactions, the elimination of H₂O promoted the aromatization to form the furan ring. Different alkyl or aryl groups could be introduced into different positions of furans due to the substituent-loading capability of 3-iodoalkenols and diversity of the terminal propargyl alcohols and allylic bromides.

Full text of DOI:10.1021/jo100146p

pubs.acs.org/joc
Synthesis of Polysubstituted Furans Based on a Stepwise Sonogashira
Coupling of (Z)-3-Iodoalk-2-en-1-ols with Terminal Propargylic Alcohols
and Subsequent Au(I)- or Pd(II)-Catalyzed Cyclization-Aromatization
via Elimination of H2O
Xiaobing Zhang, Zhan Lu, Chunling Fu, and Shengming Ma*
Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University,
Hangzhou 310027, Zhejiang, People’s Republic of China
masm@sioc.ac.cn
Received January 27, 2010
Recently, we have developed highly regio- and stereoselective carbometalation of 2-alkynols and 2,3-allenols.
The organometallacyclic intermediates may be trapped with I2 to afford 3-iodoalk-2-en-1-ols. These
3-iodoalk-2-en-1-ols may readily undergo the Sonogashira coupling with terminal propargyl alcohols to
form 4-alkyn-2-ene-1,6-diols. Subsequent cycloisomerization in DMA or CH2Cl2 with Au(PPh3)Cl and
AgOTf as the catalyst would afford polysubstituted 2-(1-alkenyl)furans; with PdCl2 as the catalyst and the
reaction in DMA in the presence of allylic bromides, the same substrates afforded polysubstituted 2-(1,4-
alkadienyl)furans. In both types of catalyzed cyclization reactions, the elimination of H2Opromotedthearo-
matization to form the furan ring. Different alkyl or aryl groups could be introduced into different positions
of furans due to the substituent-loading capability of 3-iodoalkenols and diversity of the terminal propargyl
alcohols and allylic bromides.
Introduction
As we know, transition-metal-catalyzed cyclization for
furan synthesis have been mostly realized under mild reac-
tion conditions:1c-f Alkynyl,5 allenyl,5b,6 or cyclopropyl5j,7
ketone derivatives and functionalized oxiranes8 have been
used as starting materials for such a purpose. Recently,
cycloisomerization of 3-yn-2-en-1-ols has been established
as an efficient approach for the assembly of the furan rings.
It has been reported that t-BuOK-,9a-c Ru-,9d-f Pd-,9d,g,j
Au-,5b,9h and IBX-catalyzed9i or promoted cyclization of
The synthesis of furans has been attracting exten-
sive interest1 because they are widely used as synthetic
building blocks,2 existing in numerous natural products3
and endowed with significant pharmacological potential.4
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DOI: 10.1021/jo100146p Published on Web 03/21/2010
r
J. Org. Chem. 2010, 75, 2589–2598 2589
2010 American Chemical Society

Zhang et al.
JOCArticle
SCHEME 1
3-alkyn-2-enols afforded 2-alkylfurans. However, there
are several disadvantages of the reactions; for example, a
strong base9a-c and high temperature are required,9d-g and
only an alkyl group (R4CH2-) could be introduced at the
2-position of furans5b,9 except in a case reported by Marshall9c
(Scheme 1). Herein, we wish to disclose a synthesis of poly-
substituted furans by a Sonogashira coupling of (Z)-3-iodoalk-
2-en-1-ols with terminal propargylic alcohols and sub-
sequent Au(I)- or Pd(II)-catalyzed cyclization in which
the hydroxyl group in the propargylic alcohols were
applied to realize the aromatization via elimination of
water10 under very mild conditions.
Results and Discussion
Sonogashira coupling of (Z)-3-iodoalk-2-en-1-ols and
terminal alkynes was developed as one of the most general
procedures for the synthesis of enynols.9a,11 Highly regio-
and stereoselective carbometalation of 2-alkynols12 and
2,3-allenols13 followed by quenching with I2 have been
developed to afford 3-iodoalk-2-en-1-ols. We initiated
our study by taking 4-iodo-3-(n-pentyl)-4-phenyl-3(Z)-
buten-2-ol 1a as the starting material. First, we conducted
the Sonogashira coupling reaction of 1a with 2-methyl-
3-butyn-2-ol 2a under the modified conditions developed
in our laboratory.14 The reaction afforded the crude pro-
duct, i.e., 2-methyl-6-pentyl-5-phenyl-3-yn-5(Z)-octen-2,7-diol
3aa. This crude product was purified by a flash chromato-
graphy on silica gel and further treated with 4 equiv of allyl
bromide 4a in the presence of 4-5 mol % of PdCl2 in DMA
at room temperature. It is interesting to observe that the reac-
tion afforded the cyclization-coupling-elimination product,
2-methyl-5-(2-methylhexa-2,5-dien-3-yl)-3-pentyl-4-phenylfuran
6aaa, as the major product together with the cycloisomeriza-
tion-elimination product, 2-methyl-5-(2-methylprop-1-enyl)-
3-pentyl-4-phenylfuran 5aa, in 64% and 0.5% yields, respectively
(entry 1, Table 1). The formation of 5-(2-hydroxy-2-methyl-
propyl)-2-methyl-3-pentyl-4-phenylfuran 7aa was not observed.
The reaction at 60 °C afforded a higher yield of 6aaa (81%)
(entry 2, Table 1), while the reaction at 80 °C afforded the
product 6aaa in a lower yield and selectivity (entry 4, Table 1).
Solvent had a remarkable influence on the reaction. DMF
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2590 J. Org. Chem. Vol. 75, No. 8, 2010

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TABLE 1. Effect of Temperature, Solvent, and Catalyst on the Selective Formation of 5aa or 6aaaa
NMR yieldb (%)
entry
cat. (4-5 mol %)
solvent
temp (°C)
time (h)
5aa
0.5
6aaa
64
87 (81)
0
55
71
0
1c
2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Pd(OAc)2
Pd(PhCN)2Cl2
Au(PPh3)Clf
Au(PPh3)Clf
Au(PPh3)Cl
AgOTf
DMA
DMA
DMA
DMA
DMF
DMSO
CH3CN
DMA
DMA
DMA
CH2Cl2
CH2Cl2
CH2Cl2
40
60
60
80
60
60
60
60
60
rt
14
4
4
6
4
4
4
4
4
2
2
2
2
0.7
3
1.4d
14
4c
5
2
0
11
15
15
83 (77)
81 (80)
6
7
8
0
43
33
0
0
0
9e
10
11
1g,h
13g,i
rt
rt
rt
0
8
0
aThe first step of the reaction was conducted by using 0.25 mmol of 1a, 2-3 mol % each of CuI and Pd(PPh3)2Cl2, and 2 equiv of 2-methyl-3-butyn-
2-ol in 1 mL each of DMSO and Et3N; the second step of the reaction was conducted by using the product of the first step 3aa and 1 mmol of allyl bromide
in the presence of corresponding catalyst in 2 mL of solvent. bThe numbers in the parentheses are the isolated yields. cThe reaction time of first step was 12 h.
dThe reaction was conducted in the absence of allyl bromide, and 65% of 3aa was recovered as determined by NMR analysis of the crude reaction
product. eRecovery of 3aa was 18%. f2 mol % of Au(PPh3)Cl was used together with 2-3 mol % of AgOTf; allyl bromide was not added. g2 mol % of
catalyst was used; allyl bromide was not added. hRecovery of 3aa was 74%. iRecovery of 3aa was 78%.
TABLE 2. Synthesis of 5 in DMA under the Reaction Conditions
for Entry 9 in Table 1 with Different Loadings of the Au(PPh3)Cl
and AgOTfa
offered a similar result in this reaction (entry 5, Table 1);
however, neither 5aa nor 6aaa was formed in DMSO (entry 6,
Table 1). The reaction in CH3CN afforded 5aa in 11% yield
exclusively (entry 7, Table 1). Pd(OAc)2 and Pd(PhCN)2Cl2
showed poor catalytic activities (entries 8 and 9, Table 1). With
the employment of Au(PPh3)Cl/AgOTf in DMA, 5aa was
afforded as a single product in 83% NMR yield (entry 10,
Table 1).
We then started to study the scope of the reaction. For the
synthesis of polysubstituted 2-(1-alkenyl)furans 5, with R3 as
a Ph group, the reaction afforded 5aa and 5da smoothly
(entries 1 and 4, Table 2). When R3 was H or n-hexyl, 10
mol % of catalyst is required (entries 3, 6, and 8, Table 2).
Fortunately, when the reaction was run in CH2Cl2, only
2 mol % of Au(PPh3)Cl/AgOTf was required (entry 10,
Table 1). The typical results shown in Table 3 indicated that
the reaction is quite general for the synthesis of polysubsti-
tuted 2-(1-alkenyl)furans 5 and 2-(1,4-alkadienyl)furans 6:
R1 may be hydrogen, alkyl, or aryl groups; R2 may be alkyl
or aryl groups; R3 may be hydrogen, alkyl, or aryl groups;
R4 may be alkyl or aryl groups. We also attempted to
conduct the reactions of 1.0302 g (2.99 mmol) and 1.0323 g
(3.01 mmol) of 4-iodo-3-(n-pentyl)-4-phenyl-3(Z)-buten-2-ol
1a under method A or B to provide 2-methyl-5-(2-methylprop-
1-enyl)-3-pentyl-4-phenylfuran 5aa in 81% yield (0.6882 g) and
2-methyl-5-(2-methylhexa-2,5-dien-3-yl)-3-pentyl-4-phenylfuran
6aaa in 72% yield (0.6948 g), respectively (entry 12, Table 3).
1
Auþ/Agþ
(mol %)
yield of
5b (%)
entry
R1/R2/R3
time (h)
1
2
3
4
5
6
7
8
Me/n-Pen/Ph (1a)
p-Tol/n-Pen/H (1c)
p-Tol/n-Pen/H (1c)
Me/i-Pr/Ph (1d)
Me/n-Bu/n-Hex (1g)
Me/n-Bu/n-Hex (1g)
Me/n-Pen/H (1h)
Me/n-Pen/H (1h)
2/2
2/2
9/5
2/2
2/2
10/5
2/2
9/5
2
21
2
4
21
2
83 (77) (5aa)
20 (5ca)c
82 (78) (5ca)
61 (60) (5da)
53 (5ga)d
71 (58) (5ga)
23 (5ha)e
85 (69) (5ha)
22
2
aThe first step of the reaction was conducted by using 0.25 mmol of 1,
2-3 mol % each of CuI and Pd(PPh3)2Cl2, and 2 equiv of 2-methyl-3-
butyn-2-ol in 1 mL each of DMSO and Et3N; the second step of the
reaction was conducted by using the product of the first step 3 in the
presence of Au(PPh3)Cl and AgOTf in 2 mL of DMA. bThe yield of 5
was determined by 1H NMR analysis, and the numbers in parentheses
are the isolated yields. cRecovery of 3ca was 63%. dRecovery of 3ga was
13%. eRecovery of 3ha was 62%.
J. Org. Chem. Vol. 75, No. 8, 2010 2591

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JOCArticle
TABLE 3. Sonogashira Coupling of Various (Z)-3-Iodoalk-2-en-1-ols
with Terminal Propargylic Alcohols and Subsequent Au(I)- or Pd(II)-
Catalyzed Cyclization Reactionsa
We proposed the following mechanism for this transfor-
mation (Scheme 4):16 Auþ may coordinate with the triple
bound of 3 to afford coordination complex 8, and then
the hydroxyl group acted as a nucleophile to undergo oxy-
metalation forming intermediate 9. Hydrolysis afforded
dihydrofuran 10, which subsequently underwent an H2O-
elimination-induced aromatization to afford final product 5.
On the other hand, the exo-oxypalladation of 11 would form
vinylic palladium intermediate 12, which is inert toward
protonolysis. Carbometalation of allyl bromide with 12
would provide intermediate 13, which would undergo sub-
sequent debromopalladation to regenerate the catalyst Pd2þ
and release the cross-coupling product 14. Aromatization via
elimination of H2O would afford final product 6.
1/2
yield of
5 (%)
yield of
6 (%)
entry
R1/R2/R3/R4/ R4
Conclusion
1
2
3
4
5
6
7
8
9
Me/n-Pen/Ph (1a)/Me/Me (2a)
H/n-Bu/n-Hex (1b)/Me/Me (2a)
p-Tol/n-Pen/H (1c)/Me/Me (2a)
Me/i-Pr/Ph (1d)/Me/Me (2a)
Me/Ph/n-Hex (1e)/Me/Me (2a)
Me/Anb/Ph (1f)/Me/Me (2a)
Me/n-Bu/n-Hex (1g)/Me/Me (2a)
Me/n-Pen/H (1h)/Me/Me (2a)
Me/n-Pen/H (1h)/n-Pr/n-Pr (2b)
Me/n-Pen/H (1h)/(CH2)5 (2c)
Me/n-Pen/H (1h)/Ph/Ph (2d)
Me/n-Pen/Ph (1a)/Me/Me (2a)
80 (5aa)
72 (5ba)
87 (5ca)
78 (5da)
77 (5ea)
75 (5fa)
68 (5ga)
83 (5ha)
84 (5hb)
80 (5hc)
73 (5hd)
81 (5aa)e, f
81 (6aaa)
65 (6baa)
72 (6caa)
62 (6daa)
77 (6eaa)
64 (6faa)c
76 (6gaa)
68 (6haa)
61 (6hba)
71 (6hca)
55 (6hda)d
72 (6aaa)c, f
In summary, we have demonstrated a synthesis of poly-
substituted furans. 4-Alkyn-2-ene-1,6-diols derived from
the Sonogashira coupling of different (Z)-3-iodoalk-2-en-
1-ols with terminal propargyl alcohols undergo a cyclization-
eliminaton-aromatization reaction catalyzed by Au(PPh3)Cl/
AgOTf to provide polysubstituted 2-(1-alkenyl)furans or a
cyclization-coupling-eliminaton-aromatization reaction cat-
alyzed by Pd(II) to provide polysubstituted 2-(1,4-alkadienyl)-
furans in moderate to excellent yields. The reaction is quite
general, and different alkyl and aryl groups may be introduced
into the 3-, 4-, and 5-positions of the 2-(1-alkenyl)furans or
2-(1,4-alkadienyl)furans. The introduction of such substituents
with CdC bond(s) to the furans will provide further opportunity
for elaboration.9c Due to the easily availability and diversity of
the starting materials and the potential of the furans, this method
will be useful in organic synthesis, medicinal chemistry, and
material sciences. Further studies are being pursued in our
laboratory.
10
11
12
aThe first step of reaction was conducted by using 0.25 mmol of 1, 2-
3 mol % each of CuI and Pd(PPh3)2Cl2, 2 equiv of 2 in 1 mL each of
DMSO and Et3N. Method A: A mixture of 3 prepared from the first step
and 2-3 mol % each of Au(PPh3)Cl and AgOTf in 2 mL of CH2Cl2
stirred at 25 °C for 2 h. Method B: A mixture of 3 prepared from the first
step, 4 equiv of allyl bromide, and 4-5 mol % PdCl2 in 2 mL of DMA
stirred at 60 °C for 4 h. bAn is the abbreviation of p-MeOC6H4. The
c
reaction time of the first step was 4 h. dThe reaction time of the second
step was 5 h. e1 mol % each of Au(PPh3)Cl and AgOTf were used. fThe
reaction was conducted by using 3 mmol of 1.
Furthermore, 2-methylallyl bromide could also be used in
the reaction to afford 6aab in 63% yield (Scheme 2). The
structures of these products were further confirmed by the
X-ray diffraction analysis of 2-methyl-5-(2-methylprop-
1-enyl)-3-(p-methoxyphenyl)-4-phenylfuran 5fa (Figure S1,
Supporting Information).15
However, when secondary alcohol, i.e., 3-butyn-2-ol 2e,
was used, a 1:1 Z/E mixture of the expected product 5ae
was afforded with method A while a complicated mixture
was formed with method B (Scheme 3, eq 1). In addition,
with method A, the reaction of 1a with 2-propyn-1-ol 2f
afforded 2-methyl-3-pentyl-4-phenyl-5-vinylfuran 5af in
very low yield (21%); with method B, the reaction is not
clean: besides the cycloiosmerization-elimination product
5af, the CdC bond migrated product 7afa was formed in
11% yield instead of the normal product 6afa probably due
to the higher stability of the conjugated CdC double bonds.
The reaction at 40 °C did produce 6afa in 2% yield
(Scheme 3, eq 2).
Experimental Section
Materials. Et3N and DMSO were distilled from KOH
and CaH2, respectively. The commercially available chemicals
including Au(PPh3)Cl and AgOTf were used without additional
treatment.
Starting materials 1a,12e 1b,13 1c,12c 1d,12e 1e,13 1f,12e 1g,13 and
1h12c were prepared according to the published procedures.
1. Experimental Details for the Results Presented in Table 2. (1)
2-Methyl-5-(2-methylpropen-1-yl)-3-pentyl-4-phenylfuran (5aa).
Typical procedure: To a dry Schlenk tube were added CuI
(1.0 mg, 0.005 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.4 mg, 0.005
mmol, 2 mol %), 1a (86.0 mg, 0.25 mmol), Et3N (1 mL), 2a
(41.7 mg, 0.50 mmol, 2.0 equiv), and DMSO (1 mL). The
resulting mixture was then heated at 40-45 °C. After complete
conversion of the starting material as monitored by TLC, the
reaction mixture was quenched with an aqueous solution of
saturated NH4Cl (5 mL) and extracted with Et2O (3 ꢀ 15 mL).
The combined organic layer was washed sequentially with 5%
HCl, satd NaHCO3 (aq), and brine and then dried over anhy-
drous Na2SO4. Filtration, evaporation, and chromatography
on silica gel (eluent: petroleum ether/ethyl acetate = 2/1)
afforded the product 3aa in a round-bottom flask. To this flask
were added DMA (2 mL), Au(PPh3)Cl (2.6 mg, 0.005 mmol,
2 mol %), and AgOTf (1.4 mg, 0.005 mmol, 2 mol %). The
resulting mixture was stirred at room temperature until com-
plete conversion of 3aa as monitored by TLC. The reaction
(15) Crystal data for 5fa: C22H22O2, MW = 318.40, monoclinic, space
group P2(1)/n, final R indices [I > 2σ(I)], R1 = 0.0436, wR2 = 0.1154, R
˚
indices (all data) R1 = 0.0502, wR2 = 0.1241, a = 9.8004(4) A, b = 19.8870
o
˚
˚
(9) A, c = 10.0615(4) A, R = 90°, β = 113.9110(10) , γ = 90°, V =
1792.69(13) A , T = 296(2) K, Z = 4, reflections collected/unique: 20432/
3
˚
3146 (Rint = 0.0227), number of observations [>2σ(I)] 2720, parameters 217.
Supplementary crystallographic data have been deposited at the Cambridge
Crystallographic Data Centre, CCDC 756341.
(16) Jiang, X.; Ma, X.; Zheng, Z.; Ma, S. Chem.;Eur. J. 2008, 14, 8572.
2592 J. Org. Chem. Vol. 75, No. 8, 2010

Zhang et al.
JOCArticle
SCHEME 2
SCHEME 3
SCHEME 4
combined organic layer was sequentially washed with 5% HCl,
satd NaHCO3 (aq), and brine and then dried over anhydrous
Na2SO4. After filtration and evaporation, the NMR yield
(83%) was determined by using 1,3,5-trimethylbenzene as the
internal standard (14 μL, 0.1 mmol). Chromatography on silica
gel (eluent: petroleum ether) afforded the product 5aa (54.5 mg,
77%): liquid; 1H NMR (300 MHz, CDCl3) δ 7.41-7.34 (m,
2 H), 7.31-7.22 (m, 3 H), 5.85 (d, J = 1.2 Hz, 1 H), 2.34-2.27
(m, 5 H), 2.05 (s, 3 H), 1.80 (s, 3 H), 1.32-1.08 (m, 6 H), 0.78 (t,
J = 6.6 Hz, 3 H); 13C NMR (CDCl3, 75 MHz) δ 147.4, 145.9,
134.4, 133.4, 129.8, 128.2, 126.4, 124.2, 119.7, 112.4, 31.4, 29.8,
27.3, 23.3, 22.3, 20.2, 14.0, 12.0; IR (neat, cm-1) 3028, 2957,
2927, 2858, 1655, 1604, 1547, 1491, 1445, 1376, 1272, 1191, 1055,
1005; MS (m/z) 283 (Mþ þ 1, 23.2), 282 (Mþ, 100); HRMS calcd
for C20H26O 282.1984, found 282.1984.
(2) 2-(p-Methylphenyl)-5-(2-methylpropen-1-yl)-3-pentylfuran
(5ca). The reaction of the first step using CuI (1.1 mg, 0.006 mmol,
2 mol %), Pd(PPh3)2Cl2 (3.4 mg, 0.005 mmol, 2 mol %), 1c (87.0
mg, 0.25 mmol)/Et3N (1 mL), and 2a (42.3 mg, 0.50 mmol,
2 equiv)/DMSO (1 mL) afforded 3ca. The reaction of the second
step using 3ca (from the first step)/DMA (2 mL), Au(PPh3)Cl
(11.5 mg, 0.023 mmol, 9 mol %), and AgOTf (3.4 mg, 0.013
mmol, 5 mol %) afforded 5ca (55.4 mg, 78%) (according to 1H
NMR analysis of the crude reaction mixture before separation,
product 5ca was formed in 82% NMR yield): liquid; 1H NMR
(300 MHz, CDCl3) δ 7.50 (d, J = 7.5 Hz, 2 H), 7.19 (d, J = 7.8
Hz, 2 H), 6.13 (s, 1 H), 6.05 (s, 1 H), 2.62 (t, J = 7.8 Hz, 2 H), 2.35
(s, 3 H), 2.06 (s, 3 H), 1.91 (s, 3 H), 1.70-1.56 (m, 2 H),
mixture was then quenched with an aqueous solution of satu-
rated NH4Cl (5 mL) and extracted with Et2O (3 ꢀ 15 mL). The
J. Org. Chem. Vol. 75, No. 8, 2010 2593

Zhang et al.
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1.44-1.29 (m, 4 H), 0.89 (t, J = 6.6 Hz, 3 H); 13C NMR (CDCl3,
75 MHz) δ 151.6, 146.5, 136.1, 134.6, 129.21, 129.17, 125.2,
122.7, 114.3, 111.5, 31.8, 29.7, 27.1, 25.9, 22.6, 21.2, 20.2, 14.1;
IR (neat, cm-1) 3025, 2957, 2926, 2859, 1658, 1614, 1593, 1530,
1501, 1455, 1376, 1341, 1296, 1186, 1108, 1058, 1006; MS (m/z)
283 (Mþ þ 1, 21.6), 282 (Mþ, 100); HRMS calcd for C20H26O
282.1984, found 282.1983.
(3) 3-Isopropyl-2-methyl-5-(2-methylpropen-1-yl)-4-phenylfuran
(5da). The reaction of the first step using CuI (1.0 mg, 0.005 mmol,
2 mol %), Pd(PPh3)2Cl2 (3.7 mg, 0.005 mmol, 2 mol %), 1d (79.2
mg, 0.25 mmol)/Et3N (1 mL), and 2a (41.1 mg, 0.49 mmol,
2 equiv)/DMSO (1 mL) afforded 3da. The reaction of the second
step using 3da (from the first step)/DMA (2 mL), Au(PPh3)Cl
(2.6 mg, 0.005 mmol, 2 mol %), and AgOTf (1.6 mg, 0.005 mmol,
2 mol %) afforded 5da (37.9 mg, 60%) (according to 1H NMR
analysis of the crude reaction mixture before separation, product
5da was formed in 61% NMR yield): liquid; 1H NMR (300 MHz,
CDCl3) δ 7.42-7.34 (m, 2 H), 7.33-7.26 (m, 1 H), 7.26-7.20 (m,
2 H), 5.73(s, 1 H), 2.73 (septet, J = 7.1Hz, 1 H), 2.37 (s, 3 H), 2.05
(s, 3 H), 1.77 (s, 3 H), 1.13 (d, J = 7.2Hz, 6 H);13C NMR(CDCl3,
75 MHz) δ 147.2, 144.8, 134.5, 133.1, 130.5, 128.0, 126.6, 125.3,
124.4, 112.3, 27.3, 24.1, 22.7, 20.1, 13.4; IR (neat, cm-1) 3021,
2962, 2925, 1658, 1603, 1545, 1444, 1375, 1363, 1273, 1186, 1076,
1027, 1005; MS (m/z) 255 (Mþþ1, 20.1), 254 (Mþ, 100); HRMS
calcd for C18H22O 254.1671, found 254.1671.
(4) 3-Butyl-4-hexyl-2-methyl-5-(2-methylpropen-1-yl)furan (5ga).
The reaction of the first step using CuI (1.1 mg, 0.006 mmol,
2 mol %), Pd(PPh3)2Cl2 (3.6 mg, 0.005 mmol, 2 mol %), 1g (85.4 mg,
0.25 mmol)/Et3N (1 mL), and 2a (44.7 mg, 0.53 mmol, 2 equiv)/
DMSO (1 mL) afforded 3ga. The reaction of the second step using
3ga (from the first step)/DMA (2 mL), Au(PPh3)Cl (12.5 mg, 0.025
mmol, 10 mol %), and AgOTf (3.1 mg, 0.012 mmol, 5 mol %)
afforded 5ga (40.1 mg, 58%) (according to 1H NMR analysis of the
crude reaction mixture before separation, product 5ga was formed
in NMR 71% yield): liquid; 1H NMR (300 MHz, CDCl3) δ 5.88 (s,
1 H), 2.33-2.22 (m, 4 H), 2.20 (s, 3 H), 2.04 (s, 3 H), 1.87 (s, 3 H),
1.48-1.24 (m, 12 H), 0.95-0.84 (m, 6 H); 13C NMR (CDCl3,
75 MHz) δ 146.6, 145.4, 131.4, 122.4, 119.8, 112.1, 32.9, 31.7, 31.0,
29.3, 27.3, 23.7, 23.2, 22.7, 22.6, 20.0, 14.1, 14.0, 11.9; IR (neat,
cm-1) 2955, 2926, 2857, 2732, 1622, 1547, 1457, 1376, 1296, 1251,
1198, 1154, 1107, 1064, 1035; MS (m/z) 277 (Mþ þ 1, 21.6), 276
(Mþ, 100); HRMS calcd for C19H32O 276.2453, found 276.2451.
(5) 2-Methyl-5-(2-methylpropen-1-yl)-3-pentylfuran (5ha). The
reaction of the first step using CuI (1.2 mg, 0.006 mmol, 2 mol %),
Pd(PPh3)2Cl2 (3.6 mg, 0.005 mmol, 2 mol %), 1h (68.3 mg, 0.25
mmol)/Et3N (1 mL), and 2a (44.0 mg, 0.52 mmol, 2 equiv)/
DMSO (1 mL) afforded 5ha. The reaction of the second step
using 3ha (from the first step)/DMA (2 mL), Au(PPh3)Cl (11.4
mg, 0.023 mmol, 9 mol %), and AgOTf (3.0 mg, 0.012 mmol,
5 mol %) afforded 5ha (36.4 mg, 69%) (according to 1H NMR
analysis of the crude reaction mixture before separation, product
5ha was formed in 85% NMR yield): liquid; 1H NMR (300 MHz,
CDCl3) δ 5.97 (s, 2 H), 2.28 (t, J = 7.5, 2 H), 2.20 (s, 3 H), 1.96
(s, 3 H), 1.87 (s, 3 H), 1.55-1.44 (m, 2 H), 1.39-1.21 (m, 4 H),
0.89 (t, J = 6.9 Hz, 3 H); 13C NMR (CDCl3, 75 MHz) δ 150.8,
145.2, 133.1, 120.6, 114.5, 109.4, 31.4, 30.1, 26.9, 24.8, 22.5, 20.0,
14.1, 11.5; IR (neat, cm-1) 2958, 2926, 2857, 1662, 1624, 1542,
1450, 1376, 1340, 1295, 1241, 1200, 1158, 1060; MS (m/z) 207
(Mþ þ 1, 12.4), 206 (Mþ, 79.0), 150 ((M - C4H8)þ, 100); HRMS
calcd for C14H22O 206.1671, found 206.1672.
reaction mixture was quenched with an aqueous solution of
saturated NH4Cl (5 mL) and extracted with Et2O (3 ꢀ 15 mL).
The combined organic layer was washed sequentially with 5%
HCl, satd NaHCO3 (aq), and brine and then dried over anhy-
drous Na2SO4. Filtration, evaporation, and chromatography
on silica gel (eluent: petroleum ether/ethyl acetate = 2/1) affor-
ded the product 3aa in a round-bottom flask. Then the catalyst
was prepared by sequential addition of 1 mL of CH2Cl2, Au-
(PPh3)Cl (2.5 mg, 0.005 mmol, 2 mol %), and AgOTf (1.6 mg,
0.006 mmol, 2 mol %) followed by stirring at rt for 5 min. This
resulting solution was then added to a solution of the above
prepared 3aa in CH2Cl2 (1 mL). The resulting mixture
was stirred at room temperature until complete conversion of
the 3aa as monitored by TLC. The reaction mixture was then
quenched with water and extracted with Et2O (3 ꢀ 15 mL). The
combined organic layer was washed with brine and then dried
over anhydrous Na2SO4. After filtration and evaporation, the
NMR yield (81%) was determined by using 1,3,5-trimethylben-
zene as the internal standard (14 μL, 0.1 mmol). Chromato-
graphy on silica gel (eluent: petroleum ether) afforded the
product 5aa (56.2 mg, 80%). The data of the compound are
the same as listed above.
(2) 2-Methyl-5-(2-methylpropen-1-yl)-3-pentyl-4-phenylfuran
(5aa). Following method A, the reaction of the first step using
CuI (11.0 mg, 0.058 mmol, 2 mol %), Pd(PPh3)2Cl2 (42.7 mg,
0.061 mmol, 2 mol %), 1a (1030.2 mg, 3.0 mmol)/Et3N (12 mL),
and 2a (504.4 mg, 6.0 mmol, 2 equiv)/DMSO (12 mL) afforded
3aa. The reaction of the second step using 3aa (from the first
step)/CH2Cl2 (12 mL) and Au(PPh3)Cl (14.7 mg, 0.03 mmol,
1 mol %)/AgOTf (8.0 mg, 0.03 mmol, 1 mol %)/CH2Cl2 (12 mL)
afforded 5aa (688.2 mg, 81%). The data of the compound are
the same as those listed above.
(3) 4-Butyl-3-hexyl-2-(2-methylpropen-1-yl)furan (5ba). Follow-
ing method A, the reaction of the first step using CuI (1.1 mg, 0.005
mmol, 2 mol %), Pd(PPh3)2Cl2 (3.7 mg, 0.005 mmol, 2 mol %), 1b
(80.0 mg, 0.25 mmol)/Et3N (1 mL), and 2a (43.3 mg, 0.52 mmol, 2
equiv)/DMSO (1 mL) afforded 3ba. The reaction of the second
step using 3ba (from the first step)/CH2Cl2 (1mL) andAu(PPh3)Cl
(2.4 mg, 0.005 mmol, 2 mol %)/AgOTf (1.9 mg, 0.007 mmol, 3
mol %)/CH2Cl2 (1 mL) afforded 5ba (46.5 mg, 72%): liquid; 1H
NMR (300 MHz, CDCl3) δ 7.08 (s, 1 H), 5.91 (s, 1 H), 2.36-2.28
(m, 4 H), 2.04 (s, 3 H), 1.88 (s, 3 H), 1.59-1.24 (m, 12 H),
0.98-0.84 (m, 6 H); 13C NMR (CDCl3, 75 MHz) δ 149.3, 136.6,
133.2, 126.0, 121.5, 112.2, 31.7, 31.6, 30.6, 29.2, 27.3, 23.5, 23.4,
22.7, 22.6, 20.0, 14.1, 13.9; IR (neat, cm-1) 2957, 2927, 2858, 2732,
1662, 1534, 1465, 1376, 1344, 1284, 1233, 1202, 1136, 1099, 1059,
1020; MS (m/z) 263 (Mþ þ 1, 14.3), 262 (Mþ, 65.5), 205 (100);
HRMS calcd for C18H30O 262.2297, found 262.2296.
(4) 2-(p-Methylphenyl)-5-(2-methylpropen-1-yl)-4-pentylfuran
(5ca). Following method A, the reaction of the first step using
CuI (1.0 mg, 0.005 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.6 mg, 0.005
mmol, 2 mol %), 1c (85.2 mg, 0.25 mmol)/Et3N (1 mL), and 2a
(45.1 mg, 0.54 mmol, 2 equiv)/DMSO (1 mL) afforded 3ca. The
reaction of the second step using 3ca (from the first step)/
CH2Cl2 (1 mL) and Au(PPh3)Cl (2.4 mg, 0.005 mmol, 2 mol %)/
AgOTf (1.4 mg, 0.005 mmol, 2 mol %)/CH2Cl2 (1 mL) afforded
5ca (61.1 mg, 87%). The data of the compound are the same as
those listed above.
(5) 3-Isopropyl-2-methyl-5-(2-methylpropen-1-yl)-4-phenylfuran
(5da). Following method A, the reaction of the first step using
CuI (1.1 mg, 0.005 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.3 mg, 0.005
mmol, 2 mol %), 1d (79.1 mg, 0.25 mmol)/Et3N (1 mL), and 2a
(41.4 mg, 0.49 mmol, 2 equiv)/DMSO (1 mL) afforded 3da. The
reaction of the second step using 3da (from the first step)/CH2Cl2
(1 mL) and Au(PPh3)Cl (2.5 mg, 0.005 mmol, 2 mol %)/AgOTf
(1.4 mg, 0.005 mmol, 2 mol %)/CH2Cl2 (1 mL) afforded 5da
(49.5 mg, 78%). The data of the compound are the same as those
listed above.
2. Experimental Details for Method A (Table 3). (1) 2-Methyl-
5-(2-methylpropen-1-yl)-3-pentyl-4-phenylfuran (5aa). Typical
procedure for method A: To a dry Schlenk tube were added
CuI (1.0 mg, 0.005 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.7 mg, 0.005
mmol, 2 mol %), 1a (85.5 mg, 0.25 mmol), Et3N (1 mL), 2a
(44.2 mg, 0.53 mmol, 2.1 equiv), and DMSO (1 mL). The
resulting mixture was then heated at 40-45 °C. After complete
conversion of the starting material as monitored by TLC, the
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(6) 4-Hexyl-2-methyl-5-(2-methylpropen-1-yl)-3-phenylfuran
(5ea). Following method A, the reaction of the first step using
CuI (1.4 mg, 0.006 mmol, 3 mol %), Pd(PPh3)2Cl2 (3.8 mg, 0.005
mmol, 2 mol %), 1e (88.5 mg, 0.25 mmol)/Et3N (1 mL), and 2a
(44.0 mg, 0.52 mmol, 2 equiv)/DMSO (1 mL) afforded 3ea. The
reaction of the second step using 3ea (from the first step)/
CH2Cl2 (1 mL) and Au(PPh3)Cl (2.5 mg, 0.005 mmol, 2 mol %)/
AgOTf (1.7 mg, 0.007 mmol, 3 mol %)/CH2Cl2 (1 mL) afforded
5ea (56.3 mg, 77%): liquid; 1H NMR (300 MHz, CDCl3) δ
7.42-7.34 (m, 2 H), 7.32-7.21 (m, 3 H), 5.96 (s, 1 H), 2.36 (t, J =
7.5 Hz, 2 H), 2.26 (s, 3 H), 2.09 (s, 3 H), 1.91 (s, 3 H), 1.33-1.08
(m, 8 H), 0.81 (t, J = 6.6 Hz, 3 H); 13C NMR (CDCl3, 75 MHz) δ
147.1, 146.3, 134.3, 132.7, 129.4, 128.2, 126.4, 122.8, 121.8,
111.9, 31.4, 30.4, 29.0, 27.4, 23.5, 22.5, 20.1, 14.0, 12.4; IR
(neat, cm-1) 2926, 2857, 1621, 1599, 1549, 1495, 1444, 1376,
1309, 1250, 1202, 1109, 1069, 1011; MS (m/z) 297 (Mþ þ 1, 22.7),
296 (Mþ, 100); HRMS calcd for C21H28O 296.2140, found
296.2141.
(7) 2-Methyl-3-(methoxylpheyl)-5-(2-methylpropen-1-yl)-4-
phenylfuran (5fa). Following method A, the reaction of the first
step using CuI (1.3 mg, 0.006 mmol, 3 mol %), Pd(PPh3)2Cl2
(3.7 mg, 0.005 mmol, 2 mol %), 1f (95.1 mg, 0.25 mmol)/Et3N
(1 mL), and 2a (43.3 mg, 0.52 mmol, 2 equiv)/DMSO (1 mL)
afforded 3fa. The reaction of the second step using 3fa (from the
first step)/CH2Cl2 (1 mL) and Au(PPh3)Cl (2.4 mg, 0.005 mmol,
2 mol %)/AgOTf (1.5 mg, 0.006 mmol, 2 mol %)/CH2Cl2 (1 mL)
afforded 5fa (59.4 mg, 75%) (petroleum ether/ethyl acetate =
100/1): solid; mp 111.4-111.8 °C (hexane/ethyl acetate); 1H
NMR (300 MHz, CDCl3) δ 7.30-7.16 (m, 3 H), 7.13-7.06 (m,
2 H), 7.01-6.94 (m, 2 H), 6.83-6.76 (m, 2 H), 5.99 (s, 1 H), 3.78 (s,
3 H), 2.37 (s, 3 H), 2.09 (s, 3 H), 1.85 (s, 3 H); 13C NMR (CDCl3,
75 MHz) δ 158.0, 147.8, 146.6, 134.9, 133.5, 130.7, 130.1, 127.9,
126.2, 125.6, 123.0, 121.4, 113.5, 112.4, 55.1, 27.3, 20.3, 12.6; IR
(KBr, cm-1) 3035, 2914, 2835, 1655, 1602, 1573, 1549, 1511, 1443,
1376, 1321, 1288, 1246, 1176, 1106, 1041, 1021; MS (m/z) 319
(Mþ þ 1, 24.2), 318 (Mþ, 100). Anal. Calcd for C22H22O2: C,
82.99; H, 6.96. Found: C, 82.82; H, 6.91.
(8) 3-Butyl-4-hexyl-2-methyl-5-(2-methylpropen-1-yl)furan (5ga).
Following method A, the reaction of the first step using CuI
(1.3 mg, 0.006 mmol, 3 mol %), Pd(PPh3)2Cl2 (3.6 mg, 0.005 mmol,
2 mol %), 1g (84.2 mg, 0.25 mmol)/Et3N (1 mL), and 2a (43.0 mg,
0.51 mmol, 2 equiv)/DMSO (1 mL) afforded 3ga. The reaction
of the second step using 3ga (from the first step)/CH2Cl2 (1 mL)
and Au(PPh3)Cl (2.6 mg, 0.005 mmol, 2 mol %)/AgOTf (1.8 mg,
0.006 mmol, 3 mol %)/CH2Cl2 (1 mL) afforded 5ga (46.9 mg,
68%). The data of the compound are the same as those listed above.
(9) 2-Methyl-5-(2-methylpropen-1-yl)-3-pentylfuran (5ha).
Following method A, the reaction of the first step using CuI
(1.2 mg, 0.006 mmol, 3 mol %), Pd(PPh3)2Cl2 (3.5 mg, 0.005
mmol, 2 mol %), 1h (67.1 mg, 0.25 mmol)/Et3N (1 mL), and 2a
(42.2 mg, 0.50 mmol, 2 equiv)/DMSO (1 mL) afforded 3ha. The
reaction of the second step using 3ha (from the first step)/
CH2Cl2 (1 mL) and Au(PPh3)Cl (2.6 mg, 0.005 mmol, 2 mol %)/
AgOTf (1.6 mg, 0.006 mmol, 2 mol %)/CH2Cl2 (1 mL) afforded
5ha (42.6 mg, 83%). The data of the compound are the same as
those listed above.
(10) 2-Methyl-3-pentyl-5-(2-propyl-1-penten-1-yl)furan (5hb).
Following method A, the reaction of the first step using CuI (1.1
mg, 0.006 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.5 mg, 0.005 mmol,
2 mol %), 1h (66.1 mg, 0.25 mmol)/Et3N (1 mL), and 2b (71.7
mg, 0.51 mmol, 2 equiv)/DMSO (1 mL) afforded 3hb. The
reaction of the second step using 3hb (from the first step)/
CH2Cl2 (1 mL) and Au(PPh3)Cl (2.3 mg, 0.005 mmol, 2 mol %)/
AgOTf (1.6 mg, 0.006 mmol, 2 mol %)/CH2Cl2 (1 mL) afforded
5hb (54.6 mg, 84%): liquid; 1H NMR (300 MHz, CDCl3) δ 5.96
(s, 1 H), 5.94 (s, 1 H), 2.36-2.24 (m, 4 H), 2.20 (s, 3 H), 2.09 (t,
J = 7.2 Hz, 2 H), 1.57-1.41 (m, 6 H), 1.38-1.22 (m, 4 H),
1.01-0.84 (m, 9 H); 13C NMR (CDCl3, 75 MHz) δ 150.6, 145.2,
141.4, 120.6, 113.9, 109.3, 40.3, 34.1, 31.5, 30.1, 24.7, 22.5, 21.36,
21.34, 14.4, 14.1, 13.9, 11.5; IR (neat, cm-1) 2958, 2929, 2871,
1651, 1623, 1540, 1465, 1378, 1338, 1296, 1211, 1102; MS (m/z)
263 (Mþþ1, 14.3), 262 (Mþ, 76.3), 233 (M-C2H5)þ, 100);
HRMS calcd for C18H30O 262.2297, found 262.2296.
(11) 5-Cyclohexylidenemethyl-2-methyl-3-pentylfuran (5hc).
Following method A, the reaction of the first step using CuI
(1.0 mg, 0.005 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.4 mg, 0.005
mmol, 2 mol %), 1h (66.5 mg, 0.25 mmol)/Et3N (1 mL), and 2c
(58.2 mg, 0.47 mmol, 2 equiv)/DMSO (1 mL) afforded 3hc. The
reaction of the second step using 3hc (from the first step)/
CH2Cl2 (1 mL) and Au(PPh3)Cl (2.5 mg, 0.005 mmol, 2 mol %)/
AgOTf (1.3 mg, 0.005 mmol, 2 mol %)/CH2Cl2 (1 mL) afforded
5hc (48.8 mg, 80%): liquid; 1H NMR (300 MHz, CDCl3) δ 5.97
(s, 1 H), 5.87 (s, 1 H), 2.61-2.54 (m, 2 H), 2.27 (t, J = 7.5 Hz,
2 H), 2.22-2.16 (m, 5 H), 1.64-1.54 (m, 6 H), 1.54-1.42
(m, 2 H), 1.38-1.22 (m, 4 H), 0.88 (t, J = 6.9 Hz, 3 H); 13C
NMR (CDCl3, 75 MHz) δ 150.4, 145.3, 141.4, 120.5, 111.2,
109.9, 37.6, 31.4, 30.1, 30.0, 28.6, 27.5, 26.5, 24.7, 22.5, 14.1,
11.5; IR (neat, cm-1) 2927, 2854, 1659, 1624, 1543, 1447,
1378, 1342, 1296, 1233, 1213, 1002; MS (m/z) 247 (Mþ þ 1,
18.9), 246 (Mþ, 100); HRMS calcd for C17H26O 246.1984, found
246.1986.
(12) 5-(2,2-Diphenylvinyl)-2-methyl-3-pentylfuran (5hd). Follow-
ing method A, the reaction of the first step using CuI (1.3 mg,
0.006 mmol, 3 mol %), Pd(PPh3)2Cl2 (3.8 mg, 0.005 mmol,
2 mol %), 1h (67.3 mg, 0.25 mmol)/Et3N (1 mL), and 2d (101.1
mg, 0.49 mmol, 2 equiv)/DMSO (1 mL) afforded 3hd. The reaction
of the second step using 3hd (from the first step)/CH2Cl2 (1 mL)
and Au(PPh3)Cl (2.4 mg, 0.005 mmol, 2 mol %)/AgOTf (1.7 mg,
0.007 mmol, 3 mol %)/CH2Cl2 (1 mL) afforded 5hd (60.6 mg,
73%): liquid; 1H NMR (300 MHz, CDCl3) δ 7.47-7.35 (m, 3 H),
7.34-7.18 (m, 7 H), 6.89 (s, 1 H), 5.23 (s, 1 H), 2.16-2.09 (m, 5 H),
1.37-1.10 (m, 6 H), 0.86 (t, J = 6.9 Hz, 3 H); 13C NMR (CDCl3,
75 MHz) δ 150.2, 146.6, 141.9, 140.5, 137.9, 129.7, 128.8, 128.2,
127.4, 127.0, 126.6, 121.5, 116.3, 111.5, 31.2, 29.8, 24.5, 22.4, 14.1,
11.5; IR (neat, cm-1) 3057, 2956, 2927, 2856, 1593, 1531, 1491,
1444, 1375, 1277, 1186, 1145, 1073, 1031, 1001; MS (m/z) 331
(Mþ þ 1, 26.2), 330 (Mþ, 100); HRMS calcd for C24H26O
330.1984, found 330.1974.
(13) (E)-2-Methyl-3-pentyl-4-phenyl-5-propenylfuran (E-5ae) and
(Z)-2-methyl-3-pentyl-4-phenyl-5-propenylfuran (Z-5ae). Following
method A, the reaction of the first step using CuI (1.3 mg, 0.006
mmol, 3 mol %), Pd(PPh3)2Cl2 (3.8 mg, 0.005 mmol, 2 mol %), 1a
(83.0 mg, 0.24 mmol)/Et3N (1 mL), and 2e (37.3 mg, 0.53 mmol, 2
equiv)/DMSO (1 mL) afforded 3ae. The reaction of the second step
using 3ae (from the first step)/CH2Cl2 (1 mL) and Au(PPh3)Cl (2.5
mg, 0.005 mmol, 2 mol %)/AgOTf (1.6 mg, 0.007 mmol, 2 mol %)/
CH2Cl2 (1 mL) afforded E-5ae (11.9 mg, 18%, purity: 95%) and
Z-5ae (11.2 mg, 17%). According to 1H NMR analysis of the crude
reaction mixture before separation, product E-5ae was formed in
24% yield together with 25% of the Z-5ae. E-5ae: liquid; 1H NMR
(300 MHz, CDCl3) δ 7.41-7.34 (m, 2 H), 7.32-7.22 (m, 3 H), 6.00
(dq, J = 11.7 and 1.7 Hz, 1 H), 5.53-5.40 (m, 1 H), 2.35-2.26 (m,
5 H), 2.06 (dd, J= 7.5 and 1.7 Hz, 3 H), 1.33-1.10 (m, 6 H), 0.78 (t,
J= 6.8 Hz, 3 H); 13CNMR(CDCl3,75MHz) δ147.6, 146.7, 134.1,
129.7, 128.2, 126.6, 125.9, 123.5, 119.8, 116.5, 31.4, 29.8, 23.2, 22.3,
15.3, 13.9, 12.0; IR (neat, cm-1) 3030, 2956, 2929, 2858, 1673, 1604,
1491, 1445, 1296, 1005; MS (m/z) 268 (Mþ, 34.61), 43 (100); HRMS
calcd for C19H24O (Mþ) 268.1827, found 268.1828. Z-5ae: liquid;
1H NMR (300 MHz, CDCl3) δ 7.43-7.35 (m, 2 H), 7.33-7.23 (m,
3 H), 6.16-6.10 (m, 2 H), 2.34-2.26 (m, 5 H), 1.82-1.78 (m, 3 H),
1.31-1.08 (m, 6 H), 0.78 (t, J= 6.8 Hz, 3 H); 13CNMR(CDCl3, 75
MHz) δ 146.6, 146.3, 133.9, 129.6, 128.2, 126.6, 123.4, 123.0, 120.2,
118.6, 31.4, 29.7, 23.3, 22.3, 18.4, 14.0, 11.8; IR (neat, cm-1) 3032,
2956, 2929, 2858, 1673, 1604, 1493, 1445, 1377, 1283, 1008; MS
(m/z) 268 (Mþ, 68.34), 43 (100); HRMS calcd for C19H24O (Mþ)
268.1827, found 268.1829.
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Zhang et al.
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(14) 2-Methyl-3-pentyl-4-phenyl-5-vinylfuran (5af). Following
method A, the reaction of the first step using CuI (1.2 mg, 0.006
mmol, 3 mol %), Pd(PPh3)2Cl2 (3.7 mg, 0.005 mmol, 2 mol %),
1a (85.9 mg, 0.25 mmol)/Et3N (1 mL), and 2f (29.5 mg, 0.53
mmol, 2 equiv)/DMSO (1 mL) afforded 3af. The reaction of the
second step using 3af (from the first step)/CH2Cl2 (1 mL),
Au(PPh3)Cl (2.6 mg, 0.005 mmol, 2 mol %)/AgOTf (1.4 mg,
0.005 mmol, 2 mol %)/CH2Cl2 (1 mL) afforded 5af (10.9 mg,
17%): liquid; 1H NMR (300 MHz, CDCl3) δ 7.43-7.35 (m,
2 H), 7.34-7.23 (m, 3 H), 6.41 (dd, J = 17.6 and 11.3 Hz, 1 H),
5.60 (dd, J = 17.4 and 1.8 Hz, 1 H), 5.02 (dd, J = 11.3 and 1.7
Hz, 1 H), 2.35-2.28 (m, 5 H), 1.32-1.08 (m, 6 H), 0.78 (t, J =
6.8 Hz, 3 H); 13C NMR (CDCl3, 75 MHz) δ 147.3, 146.6, 133.5,
129.6, 128.3, 126.9, 125.8, 123.9, 120.5, 110.2, 31.4, 29.7, 23.2,
22.3, 14.0, 11.9; IR (neat, cm-1) 2955, 2929, 2859, 1672, 1605,
1545, 1493, 1445, 1377, 1289, 1266, 1156, 1037; MS (m/z) 254
(Mþ, 26.4), 43 (100); HRMS calcd for C18H22O (Mþ) 254.1671,
found 256.1679.
2 mol %), 1b (80.1 mg, 0.25 mmol)/Et3N (1 mL), and 2a (42.5 mg,
0.51 mmol, 2 equiv)/DMSO (1 mL) afforded 3ba. The reaction of
the second step using 3ba (from the first step)/DMA (1 mL), 4a
(121.7 mg, 1.0 mmol, 4.0 equiv)/DMA (1 mL), and PdCl2 (1.7 mg,
1
0.01 mmol, 4 mol %) afforded 6baa (48.7 mg, 65%): liquid; H
NMR (300 MHz, CDCl3) δ 7.07 (s, 1 H), 5.80-5.65 (m, 1 H),
5.03-4.88 (m, 2 H), 3.04 (d, J = 6.3Hz, 2 H), 2.35 (td, J = 7.8and
1.2 Hz, 2 H), 2.25-2.17 (m, 2 H), 1.81 (s, 3 H), 1.63 (s, 3 H),
1.60-1.48 (m, 2 H), 1.46-1.34 (m, 4 H), 1.30-1.22 (m, 6 H), 0.94
(t, J = 7.2 Hz, 3 H), 0.88 (t, J = 6.8 Hz, 3 H); 13C NMR (CDCl3,
75 MHz) δ 150.7, 136.8, 136.1, 135.2, 125.7, 123.1, 120.5, 114.5,
36.8, 31.7, 31.3, 29.6, 29.5, 24.2, 23.9, 22.72, 22.69, 22.6, 22.0, 14.1,
14.0; IR (neat, cm-1) 3076, 2956, 2927, 2858, 1637, 1549, 1458,
1378, 1278, 1261, 1218, 1137, 1100, 1038; MS (m/z) 303 (Mþ þ 1,
19.8), 302 (Mþ, 83.1), 259 (100); HRMS calcd for C21H34O
302.2610, found 302.2609.
(4) 5-(2-Methylhexa-2,5-dien-3-yl)-2-(p-methylphenyl)-3-pentyl-
furan (6caa). Following method B, the reaction of the first step
using CuI (1.5 mg, 0.008 mmol, 3 mol %), Pd(PPh3)2Cl2 (3.6 mg,
0.005 mmol, 2 mol %), 1c (86.0 mg, 0.25 mmol)/Et3N (1 mL), and
2a (42.1 mg, 0.50 mmol, 2 equiv)/DMSO (1 mL) afforded 3ca. The
reaction of the second step using 3ca (from the first step)/DMA
(1 mL), 4a (124.1 mg, 1.0 mmol, 4.1 equiv)/DMA (1 mL), and
PdCl2 (2.0 mg, 0.011 mmol, 5 mol %) afforded 6caa (57.8 mg,
72%): liquid; 1H NMR (300 MHz, CDCl3) δ 7.50 (d, J = 8.1 Hz,
2 H), 7.19 (d, J = 7.8 Hz, 2 H), 6.18 (s, 1 H), 5.93-5.77 (m, 1 H),
5.12-4.93 (m, 2 H), 3.20 (d, J = 5.7 Hz, 2 H), 2.63 (t, J = 7.7 Hz,
2 H), 2.35 (s, 3 H), 2.07 (s, 3 H), 1.87 (s, 3 H), 1.70-1.56 (m, 2 H),
1.44-1.26 (m, 4 H), 1.00-0.90 (m, 3 H); 13C NMR (CDCl3,
75 MHz) δ 153.0, 146.3, 136.3, 136.0, 131.8, 129.3, 129.1, 125.1,
122.3, 122.0, 114.6, 112.0, 35.5, 31.8, 29.6, 26.0, 23.1, 22.5, 21.9,
21.2, 14.1; IR (neat, cm-1) 2955, 2927, 2859, 1637, 1524, 1501,
1454, 1377, 1184, 1109, 1037; MS (m/z) 323 (Mþ þ 1, 24.2), 322
(Mþ, 100); HRMS calcd for C23H30O 322.2297, found 322.2299.
(5) 3-Isopropyl-2-methyl-5-(2-methylhexa-2,5-dien-3-yl)-4-
phenylfuran (6daa). Following method B, the reaction of the first
step using CuI (1.0 mg, 0.005 mmol, 2 mol %), Pd(PPh3)2-
Cl2 (3.5 mg, 0.005 mmol, 2 mol %), 1d (78.6 mg, 0.25 mmol)/
Et3N (1 mL), and 2a (42.3 mg, 0.50 mmol, 2 equiv)/DMSO
(1 mL) afforded 3da. The reaction of the second step using 3da
(from the first step)/DMA (1 mL), 4a (123.1 mg, 1.0 mmol,
4.1 equiv)/DMA (1 mL), and PdCl2 (1.9 mg, 0.011 mmol,
4 mol %) afforded 6daa (45.5 mg, 62%): liquid; 1H NMR
(300 MHz, CDCl3) δ 7.35-7.27 (m, 2 H), 7.26-7.21 (m, 1 H),
7.20-7.14 (m, 2 H), 5.80-5.65 (m, 1 H), 5.00-4.85 (m, 2 H), 2.96
(d, J = 6.6 Hz, 2 H), 2.76 (septet, J = 7.1 Hz, 1 H), 2.33 (s, 3 H),
1.66 (s, 3 H), 1.37 (s, 3 H), 1.15 (d, J = 6.9 Hz, 6 H); 13C NMR
(CDCl3, 75 MHz) δ 148.0, 144.6, 136.2, 135.2, 134.6, 129.9, 127.9,
126.2, 124.6, 123.9, 122.4, 114.6, 36.6, 24.0, 22.8, 22.7, 20.2, 13.4; IR
(neat, cm-1) 3077, 3029, 2961, 2927, 2872, 1637, 1604, 1561, 1491,
1444, 1363, 1255, 1214, 1185, 1163, 1127, 1109, 1073, 1037, 1021;
MS (m/z) 295 (Mþ þ 1, 21.6), 294 (Mþ, 100); HRMS calcd for
C21H26O 294.1984, found 294.1983.
(6) 4-Hexyl-2-methyl-5-(2-methylhexa-2,5-dien-3-yl)-3-phenyl-
furan (6eaa). Following method B, the reaction of the first step
using CuI (1.3 mg, 0.007 mmol, 3 mol %), Pd(PPh3)2Cl2 (3.5 mg,
0.005 mmol, 2 mol %), 1e (90.1 mg, 0.25 mmol)/Et3N (1 mL), and
2a (43.4 mg, 0.52 mmol, 2 equiv)/DMSO (1 mL) afforded 3ea.
The reaction of the second step using 3ea (from the first step)/
DMA (1 mL), 4a (126.1 mg, 1.0 mmol, 4.2 equiv)/DMA (1 mL),
and PdCl2 (1.7 mg, 0.01 mmol, 4 mol %) afforded 6eaa (65.1 mg,
77%) (petroleum ether/ethyl acetate = 200 mL/6 drops): liquid;
1H NMR (300 MHz, CDCl3) δ 7.41-7.33 (m, 2 H), 7.30-7.22
(m, 3 H), 5.86-5.70 (m, 1 H), 5.07-4.90 (m, 2 H), 3.11 (d, J = 6.3
Hz, 2 H), 2.30-2.22 (m, 5 H), 1.83 (s, 3 H), 1.73 (s, 3 H),
1.18-1.00 (m, 8 H), 0.78 (t, J = 6.9 Hz, 3 H); 13C NMR
(CDCl3, 75 MHz) δ 148.5, 146.2, 136.1, 135.1, 134.8, 129.2,
128.2, 126.2, 122.9, 122.0, 120.8, 114.5, 36.8, 31.4, 29.2, 28.9,
3. Experimental Details for Method B (Table 3). (1) 2-Methyl-
5-(2-methylhexa-2,5-dien-3-yl)-3-pentyl-4-phenylfuran (6aaa).
Typical procedure for method B: To a dry Schlenk tube were
added CuI (1.5 mg, 0.008 mmol, 3 mol %), Pd(PPh3)2Cl2
(3.8 mg, 0.005 mmol, 2 mol %), 1a (88.0 mg, 0.26 mmol),
Et3N (1 mL), 2a (44.8 mg, 0.53 mmol, 2.1 equiv), and DMSO
(1 mL). The resulting mixture was then heated at 40-45 °C.
After complete conversion of the starting material as monitored
by TLC, the reaction mixture was quenched with an aqueous
solution of saturated NH4Cl (5 mL) and extracted with Et2O
(3 ꢀ 15 mL). The combined organic layer was washed sequen-
tially with 5% HCl, satd NaHCO3 (aq), and brine and then dried
over anhydrous Na2SO4. Filtration, evaporation, and chroma-
tography on silica gel (eluent: petroleum ether/ethyl acetate =
2/1) afforded the product 3aa in a round-bottom flask. Then
DMA (1 mL), 4a (122.0 mmg, 1.0 mmol, 4.0 equiv), DMA
(1 mL), and PdCl2 (2.3 mg, 0.013 mmol, 5 mol %) were added
into this flask. The resulting mixture was then heated at 60 °C
until complete conversion of 3aa as monitored by TLC. The
reaction mixture was then quenched with an aqueous solution of
saturated NH4Cl (5 mL) and extracted with Et2O (3 ꢀ 15 mL).
The combined organic layer was washed sequentially with 5%
HCl, satd NaHCO3 (aq), and brine and dried over anhydrous
Na2SO4. After filtration and evaporation, the NMR yield (87%)
was determined by using 1,3,5-trimethylbenzene as the internal
standard (14 μL, 0.1 mmol). Chromatography on silica gel
(eluent: petroleum ether) afforded the product 6aaa (67.0 mg,
81%): liquid; 1H NMR (300 MHz, CDCl3) δ 7.34-7.26 (m,
2 H), 7.25-7.17 (m, 3 H), 5.82-5.67 (m, 1 H), 5.02-4.88 (m,
2 H), 3.00 (d, J = 6.6 Hz, 2 H), 2.33 (t, J = 7.7 Hz, 2 H), 2.25 (s,
3 H), 1.69 (s, 3 H), 1.37 (s, 3 H), 1.35-1.10 (m, 6 H), 0.79 (t, J =
6.8 Hz, 3 H); 13C NMR (CDCl3, 75 MHz) δ 148.4, 145.8, 136.2,
135.2, 134.5, 129.0, 128.1, 126.1, 123.8, 122.5, 119.1, 114.7, 36.6,
31.5, 29.9, 23.5, 22.7, 22.3, 20.2, 14.0, 11.9; IR (neat, cm-1) 3077,
3031, 2956, 2928, 2858, 1637, 1605, 1566, 1492, 1445, 1378, 1255,
1225, 1175, 1128, 1044, 1026; MS (m/z) 323 (Mþ þ 1, 24.7), 322
(Mþ, 100); HRMS calcd for C23H30O 322.2291, found 322.2302.
(2) 2-Methyl-5-(2-methylhexa-2,5-dien-3-yl)-3-pentyl-4-phenyl-
furan (6aaa). Following method B, the reaction of the first step
using CuI (11.5 mg, 0.061 mmol, 2 mol %), Pd(PPh3)2Cl2 (42.0
mg, 0.060 mmol, 2 mol %), 1a (1035.3 mg, 3.0 mmol)/Et3N (12
mL), and 2a (501.3 mg, 6.0 mmol, 2 equiv)/DMSO (12 mL)
afforded 3aa. The reaction of the second step using 3aa (from the
first step)/DMA (12 mL), 4a (1447.2 mg, 12.0 mmol, 4.0 equiv)/
DMA(12 mL), and PdCl2 (21.4 mg, 0.12 mmol, 5 mol %)
afforded 6aaa (694.8 mg, 72%). The data of the compound are
the same as those listed above.
(3) 4-Butyl-3-hexyl-2-(2-methylhexa-2,5-dien-3-yl)furan (6baa).
Following method B, the reaction of the first step using CuI (1.0
mg, 0.005 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.7 mg, 0.005 mmol,
2596 J. Org. Chem. Vol. 75, No. 8, 2010

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JOCArticle
24.4, 22.8, 22.4, 20.1, 14.0, 12.3; IR (neat, cm-1) 3078, 3057, 3031,
2954, 2925, 2857, 1637, 1602, 1574, 1495, 1443, 1377, 1246, 1112,
1070, 1018; MS (m/z) 337 (Mþ þ 1, 22.8), 336 (Mþ, 71.8), 293
(100); HRMS calcd for C24H32O 336.2448, found 336.2443.
(s, 1 H), 5.87-5.76 (m, 1 H), 5.03 (dq, J = 16.8 and 1.7 Hz, 1 H),
4.95 (dq, J = 10.0 and 1.6 Hz, 1 H), 3.12 (d, J = 5.6 Hz, 2 H),
2.33-2.25 (m, 4 H), 2.21 (s, 3 H), 2.14-2.09 (m, 2 H), 1.56-1.42
(m, 6 H), 1.39-1.26 (m, 4 H), 0.96 (t, J =7.2Hz, 6 H), 0.91 (t, J =
7.0 Hz, 3 H); 13C NMR (CDCl3, 100 MHz) δ 152.1, 145.0, 140.1,
137.1, 122.4, 120.0, 114.4, 109.6, 35.9, 35.25, 35.19, 31.5, 30.1,
24.8, 22.5, 22.4, 22.0, 14.5, 14.4, 14.1, 11.5; IR (neat, cm-1) 3077,
2958, 2928, 2870, 1637, 1466, 1377, 1210, 1132, 1078; MS (m/z)
303 (Mþ þ 1, 21.3), 302 (Mþ, 92.9), 273 (100); HRMS calcd for
C21H34O 302.2604, found 302.2604.
(11) 5-(1-Cyclohexylidenebut-3-en-1-yl)-2-methyl-3-pentyl-
furan (6hca). Following method B, the reaction of the first step
using CuI (1.5 mg, 0.008 mmol, 3 mol %), Pd(PPh3)2Cl2
(3.7 mg, 0.005 mmol, 2 mol %), 1h (66.8 mg, 0.25 mmol)/Et3N
(1 mL), and 2c (61.3 mg, 0.49 mmol, 2 equiv)/DMSO (1 mL)
afforded 3hc. The reaction of the second step using 3hc (from the
first step)/DMA (1 mL), 4a (122.1 mg, 1.0 mmol, 4.0 equiv)/
DMA (1 mL), and PdCl2 (1.9 mg, 0.01 mmol, 4 mol %) afforded
6hca (50.8 mg, 71%): liquid; 1H NMR (300 MHz, CDCl3) δ 5.94
(s, 1 H), 5.87-5.72 (m, 1 H), 5.01 (dq, J = 16.8 and 1.8 Hz, 1 H),
4.93 (dq, J = 10.2 and 1.7 Hz, 1 H), 3.11 (d, J = 6.0 Hz, 2 H),
2.50-2.41 (m, 2 H), 2.32-2.20 (m, 4 H), 2.19 (s, 3 H), 1.62-1.43
(m, 8 H), 1.38-1.22 (m, 4 H), 0.89 (t, J = 6.9 Hz, 3 H); 13C NMR
(CDCl3, 75 MHz) δ 151.9, 145.0, 140.1, 136.8, 119.9, 119.4, 114.3,
110.0, 35.3, 32.2, 31.5, 31.3, 30.1, 28.3, 28.2, 26.8, 24.8, 22.5, 14.1,
11.6; IR (neat, cm-1) 2926, 2854, 1637, 1552, 1448, 1377, 1216;
MS (m/z) 287 (Mþ þ 1, 21.4), 286 (Mþ, 100); HRMS calcd for
C20H30O 286.2291, found 286.2294.
(7)
2-Methyl-3-(methoxylpheyl)-5-(2-methylhexa-2,5-dien-
3-yl)-4-phenylfuran (6faa). Following method B, the reaction
of the first step using CuI (1.1 mg, 0.006 mmol, 2 mol %),
Pd(PPh3)2Cl2 (3.7 mg, 0.005 mmol, 2 mol %), 1f (95.8 mg, 0.25
mmol)/Et3N (1 mL), and 2a (41.7 mg, 0.50 mmol, 2 equiv)/
DMSO (1 mL) afforded 3fa. The reaction of the second step
using 3fa (from the first step)/DMA (1 mL), 4a (121.7 mg, 1.0
mmol, 4.0 equiv)/DMA (1 mL), and PdCl2 (1.7 mg, 0.01 mmol,
4 mol %) afforded 6faa (57.7 mg, 64%) (petroleum ether/ethyl
acetate = 100/1): liquid; 1H NMR (300 MHz, CDCl3) δ 7.21-
7.10 (m, 3 H), 7.04-6.97 (m, 4 H), 6.84-6.78 (m, 2 H), 5.88-5.74
(m, 1 H), 5.06-4.93 (m, 2 H), 3.79 (s, 3 H), 3.05 (d, J = 6.6 Hz,
2 H), 2.33 (s, 3 H), 1.74 (s, 3 H), 1.40 (s, 3 H); 13C NMR (CDCl3,
75 MHz) δ 157.9, 149.1, 146.6, 136.1, 135.4, 134.1, 130.8, 129.3,
127.8, 125.90, 125.87, 122.7, 122.3, 114.9, 113.4, 55.1, 36.6, 22.7,
20.3, 12.5; IR (neat, cm-1) 3034, 2919, 2854, 1636, 1603, 1574,
1511, 1444, 1374, 1329, 1287, 1245, 1175, 1107, 1072, 1042, 1021,
1006; MS (m/z) 359 (Mþ þ 1, 27.4), 358 (Mþ, 100); HRMS calcd
for C25H26O2 358.1933, found 358.1925.
(8) 3-Butyl-4-hexyl-2-methyl-5-(2-methylhexa-2,5-dien-3-yl)-
furan (6gaa). Following method B, the reaction of the first step
using CuI (1.1 mg, 0.005 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.6 mg,
0.005 mmol, 2 mol %), 1g (84.3 mg, 0.25 mmol)/Et3N (1 mL),
and 2a (42.1 mg, 0.50 mmol, 2 equiv)/DMSO (1 mL) afforded
3ga. The reaction of the second step using 3ga (from the first
step)/DMA (1 mL), 4a (123.2 mg, 1.1 mmol, 4.2 equiv)/DMA
(1 mL), and PdCl2 (2.3 mg, 0.01 mmol, 5 mol %) afforded 6faa
(12) 5-(1,1-Diphenylpenta-1,4-dien-2-yl)-2-methyl-3-pentyl-
furan (6hda). Following method B, the reaction of the first step
using CuI (1.1 mg, 0.006 mmol, 2 mol %), Pd(PPh3)2Cl2 (3.7
mg, 0.005 mmol, 2 mol %), 1h (66.3 mg, 0.25 mmol)/Et3N
(1 mL), and 2d (103.6 mg, 0.50 mmol, 2 equiv)/DMSO (1 mL)
afforded 3hb. The reaction of the second step using 3hb (from
the first step)/DMA (1 mL), 4a (122.1 mg, 1.0 mmol, 4.0 equiv)/
DMA (1 mL), and PdCl2 (1.8 mg, 0.01 mmol, 4 mol %)
1
(60.1 mg, 76%): liquid; H NMR (300 MHz, CDCl3) δ 5.80-
5.65 (m, 1 H), 5.03-4.87 (m, 2 H), 3.04 (d, J = 6.6 Hz, 2 H), 2.28
(t, J = 7.7 Hz, 2 H), 2.20-2.12 (m, 5 H), 1.80 (s, 3 H), 1.65 (s,
3 H), 1.49-1.20 (m, 12 H), 0.96-0.84 (m, 6 H); 13C NMR
(CDCl3, 75 MHz) δ 147.7, 145.2, 136.3, 134.4, 123.4, 121.2,
119.3, 114.3, 36.9, 32.7, 31.7, 29.8, 29.6, 24.5, 23.7, 22.8, 22.6,
20.0, 14.1, 14.0, 11.8; IR (neat, cm-1) 2956, 2928, 2858, 2729,
1637, 1575, 1456, 1378, 1246, 1211, 1115; MS (m/z) 317 (Mþþ1,
19.9), 316 (Mþ, 85.7), 273 (100); HRMS calcd for C22H36O
316.2761, found 316.2767.
1
afforded 6hda (50.3 mg, 55%): liquid; H NMR (300 MHz,
CDCl3) δ 7.33-7.16 (m, 8 H), 7.13-7.08 (m, 2 H), 6.00-5.84
(m, 1 H), 5.52 (s, 1 H), 5.08-4.97 (m, 2 H), 3.23 (d, J = 6.0 Hz,
2 H), 2.14 (t, J = 7.2 Hz, 2 H), 2.02 (s, 3 H), 1.38-1.08 (m, 6 H),
0.86 (t, J = 7.1 Hz, 3 H); 13C NMR (CDCl3, 75 MHz) δ 151.0,
145.7, 144.0, 142.9, 138.7, 137.3, 129.6, 129.4, 127.94, 127.91,
126.9, 126.7, 126.4, 120.7, 115.3, 112.6, 36.4, 31.2, 29.8, 24.5, 22.5,
14.1, 11.4; IR (neat, cm-1) 3077, 3057, 3019, 2956, 2927, 2856,
1637, 1598, 1530, 1490, 1442, 1377, 1270, 1204, 1139, 1074, 1030;
MS (m/z) 371 (Mþ þ 1, 22.2), 370 (Mþ, 75.5), 329 ((Mþ - C3H5),
100); HRMS calcd for C27H30O: 370.2291, found 370.2283.
(13) 5-(2,2-Dimethylhexa-2,5-dien-3-yl)-2-methyl-3-pentyl-4-
phenylfuran (6aab). Following method B, the reaction of the
first step using CuI (1.0 mg, 0.005 mmol, 2 mol %), Pd(PPh3)2-
Cl2 (3.6 mg, 0.005 mmol, 2 mol %), 1a (86.5 mg, 0.25 mmol)/
Et3N (1 mL), and 2a (42.0 mg, 0.50 mmol, 2 equiv)/DMSO
(1 mL) afforded 3aa. The reaction of the second step using 3aa
(from the first step)/DMA (1 mL), 4b (132.0 mg, 1.0 mmol, 3.9
equiv)/DMA (1 mL), and PdCl2 (1.7 mg, 0.01 mmol, 4 mol %)
afforded 6aab (53.3 mg, 63%): liquid; 1H NMR (400 MHz,
CDCl3) δ 7.35-7.26 (m, 2 H), 7.25-7.16 (m, 3 H), 4.66 (s, 1 H),
4.60 (s, 1 H), 2.89 (s, 2 H), 2.31 (t, J = 7.5 Hz, 2 H), 2.25 (s, 3 H),
1.70 (s, 3 H), 1.62 (s, 3 H), 1.45 (s, 3 H), 1.38-1.08 (m, 6 H), 0.78
(t, J = 6.8 Hz, 3 H); 13C NMR (CDCl3, 100z) δ 148.6, 145.5,
143.8, 135.3, 135.1, 129.1, 128.0, 126.1, 123.6, 122.8, 119.2,
110.8, 40.0, 31.4, 29.8, 23.5, 22.8, 22.6, 22.3, 20.6, 14.0, 11.9;
IR (neat, cm-1) 3075, 3030, 2956, 2928, 2858, 1651, 1606, 1564,
1491, 1445, 1373, 1253, 1225, 1170, 1089, 1070, 1051, 1028; MS
(m/z) 337 (Mþ þ 1, 26.1), 336 (Mþ, 100); HRMS calcd for
C24H32O 336.2453, found 336.2456.
(9) 2-Methyl-5-(2-methylhexa-2,5-dien-3-yl)-3-pentylfuran (6haa).
Following method B, the reaction of the first step using CuI (1.4 mg,
0.007 mmol, 3 mol %), Pd(PPh3)2Cl2 (4.0 mg, 0.006 mmol,
2 mol %), 1h (67.7 mg, 0.25 mmol)/Et3N (1 mL), and 2a (45.3 mg,
0.54 mmol, 2 equiv)/DMSO (1 mL) afforded 3ha. The reaction of
the second step using 3ha (from the first step)/DMA (1 mL), 4a
(127.4 mg, 1.1 mmol, 4.2 equiv)/DMA (1 mL), and PdCl2 (2.4 mg,
1
0.014 mmol, 5 mol %) afforded 6haa (42.5 mg, 68%): liquid; H
NMR (300 MHz, CDCl3) δ 5.98 (s, 1 H), 5.88-5.73 (m, 1 H),
5.06-4.90 (m, 2 H), 3.13 (d, J = 6.0 Hz, 2 H), 2.28 (t, J = 7.7 Hz,
2 H), 2.19 (s, 3 H), 1.96 (s, 3 H), 1.82 (s, 3 H), 1.56-1.40 (m, 2 H),
1.39-1.20 (m, 4 H), 0.89 (t, J = 6.9 Hz, 3 H); 13C NMR (CDCl3,
75 MHz) δ 152.1, 144.9, 136.4, 130.7, 122.3, 120.1, 114.3, 110.1,
35.5, 31.5, 30.1, 24.8, 22.9, 22.5, 21.6, 14.1, 11.5; IR (neat, cm-1
)
2957, 2927, 2857, 1637, 1456, 1377, 1215, 1128, 1034; MS (m/z) 247
(Mþ þ 1, 19.1), 246 (Mþ, 100); HRMS calcd for C17H26O 246.1978,
found 246.1981.
(10) 2-Methyl-3-pentyl-5-(5-propylocta-1,4-dien-4-yl)furan
(6hba). Following method B, the reaction of the first step
using CuI (1.4 mg, 0.007 mmol, 3 mol %), Pd(PPh3)2Cl2
(3.6 mg, 0.005 mmol, 2 mol %), 1h (68.2 mg, 0.25 mmol)/Et3N
(1 mL), and 2b (71.2 mg, 0.51 mmol, 2 equiv)/DMSO (1 mL)
afforded 3hb. The reaction of the second step using 3hb (from
the first step)/DMA (1 mL), 4a (126.4 mg, 1.0 mmol,
4.2 equiv)/DMA (1 mL), and PdCl2 (2.1 mg, 0.012 mmol,
5 mol %) afforded 6hba (47.2 mg, 61%) (chromatography
twice on silica gel): liquid; 1H NMR (400 MHz, CDCl3) δ 5.99
(14) (E)-(2-Methyl-5-(penta-2,4-dien-2-yl)-3-pentyl-4-phenyl-
furan (7afa). Following method B, the reaction of the first step
J. Org. Chem. Vol. 75, No. 8, 2010 2597

Zhang et al.
JOCArticle
using CuI (1.2 mg, 0.006 mmol, 3 mol %), Pd(PPh3)2Cl2
(3.4 mg, 0.005 mmol, 2 mol %), 1a (83.7 mg, 0.24 mmol)/
Et3N (1 mL), and 2f (28.8 mg, 0.51 mmol, 2 equiv)/DMSO
(1 mL) afforded 3af. The reaction of the second step using 3af
(from the first step)/DMA (1 mL), 4a (121.7 mg, 1.0 mmol, 4.0
equiv)/DMA (1 mL), and PdCl2 (2.2 mg, 0.01 mmol, 5 mol %)
afforded 5af (12.8 mg, 21%) and 7afa (6.2 mg, 9%). According
to 1H NMR analysis of the crude reaction mixture before
separation, product 7afa was formed in 11% yield together with
23% of the 5af. 7afa: liquid; 1H NMR (300 MHz, CDCl3)
δ 7.39-7.29 (m, 3 H), 7.25-7.20 (m, 2 H), 6.69-6.55 (m,
1 H), 6.48-6.40 (m, 1 H), 5.18-5.02 (m, 2 H), 2.28 (s, 3 H),
2.16 (t, J = 7.4 Hz, 2 H), 1.71 (d, J = 1.2 Hz, 3 H), 1.26-1.06 (m,
6 H), 0.77 (t, J = 6.8 Hz, 3 H); 13C NMR (CDCl3, 100 MHz) δ
148.1, 146.1, 135.1, 132.9, 130.1, 128.0, 127.3, 126.9, 125.3,
125.0, 122.0, 116.7, 31.3, 29.8, 23.2, 22.2, 14.4, 13.9, 11.9; IR
(neat, cm-1) 2956, 2928, 2858, 1655, 1606, 1489, 1444, 1378,
1249, 1071; MS (m/z) 294 (Mþ, 100); HRMS calcd for C21H26O
294.1984, found 294.1981.
Acknowledgment. We greatly acknowledge financial sup-
port from the NSF of China (20732005) and the Major State
Basic Research Development Program (2006CB806105).
S.M. is a Qiu Shi Adjunct Professor at Zhejiang University.
We thank Mr. Deng Youqian in this group for reproducing the
results presented in entries 1 and 7 in Table 3 and Scheme 2.
Supporting Information Available: 1H and 13C NMR spec-
tra of all compounds and an ORTEP drawing of 5fa. This
material is available free of charge via the Internet at http://
pubs.acs.org.
2598 J. Org. Chem. Vol. 75, No. 8, 2010