FeCl3-catalyzed propargylation-cycloisomerization tandem reaction: A facile one-pot synthesis of substituted furans

Article abstract of DOI:10.1055/s-0028-1087344

An efficient FeCl₃-catalyzed tandem propargylation- cycloisomerization reaction of propargylic alcohols or acetates with 1,3-dicarbonyl compounds, leading to the synthesis of substituted furans, has been developed. Georg Thieme Verlag Stuttgart

Full text of DOI:10.1055/s-0028-1087344

3046
LETTER
FeCl3-Catalyzed Propargylation–Cycloisomerization Tandem Reaction:
A Facile One-Pot Synthesis of Substituted Furans
F
acile One-Pot Synthesi
e
s
of Substit
n
uted Furans -hua Ji, Ying-ming Pan, Su-yan Zhao, Zhuang-ping Zhan*
Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, Fujian, P. R. of China
Fax +86(592)2180318; E-mail: zpzhan@xmu.edu.cn
Received 1 July 2008
O
FeCl3 (5 mol%)
toluene, reflux
Abstract: An efficient FeCl3-catalyzed tandem propargylation–
cycloisomerization reaction of propargylic alcohols or acetates with
1,3-dicarbonyl compounds, leading to the synthesis of substituted
furans, has been developed.
R1
X
O
O
R4
R3
R1
R3
R4
+
R2
R2
O
HX
3
1 X = OH
2 X = OAc
5
Key words: furans, iron(III) chloride, propargylic acetates, propar-
gylic alcohols, tandem reaction
O
O
propargylation
FeCl3
Nucleophilic substitution and cyclization are two major
reactions in organic chemistry.1,2 More powerful and use-
ful transformations are possible when these two classes of
reactions are combined in a one-pot procedure. Propargyl-
ic substitution followed by cycloisomerization recently
developed in our group is a good example of such trans-
formation.3
cycloisomerization
FeCl3 + HX
R3
R4
R1
R2
HX
4
Scheme 1 Synthesis of furans from propargylic alcohols or acetates
and 1,3-dicarbonyl compounds
To extend the scope of the FeCl3-catalyzed propargylic
substitution reaction,3a,c we sought to explore the coupling
of propargylic alcohols or acetates with 1,3-dicarbonyl
compounds and subsequent cycloisomerization for the
synthesis of tetrasubstituted furans. Recently, the efficient
propargylation–cycloisomerization sequential reactions
of propargylic alcohols with ketones or 1,3-dicarbonyl
compounds in the presence of [Cp*RuCl(m2-SMe)2-
RuCp*Cl]–PtCl2,4 CF3CO2H–Ru(II)5 or TsOH–K2CO3,6
which lead to the synthesis of substituted furans, have
been reported. However, these methods are only applica-
ble to a relatively narrow range of substrates, and two dif-
ferent catalysts are needed. More recently, Tan7 described
an efficient method to synthesize tetrasubstituted furans
via In-catalyzed propargylation–cyclization process, but
the reaction was performed under N2 atmosphere and re-
quired a rather long time for completion. Herein, we de-
scribe an efficient FeCl3-catalyzed propargylation–
cycloisomerization tandem reaction (Scheme 1).8 FeCl3
acts as a bifunctional catalyst and effectively catalyzes
two reaction processes in a single reaction vessel under
the same conditions. A range of secondary propargylic al-
cohols or acetates could be employed and a number of
functionalities, such as chloro, bromo, ester, and methoxy,
are tolerated under the reaction conditions.
ene, r.t.), produced the coupling product 4a (R1 = Ph; R2 =
TMS; R3 = Me; R4 = OEt) in low yield, and no cyclo-
isomerization product 5aa (R1 = Ph; R2 = H; R3 = Me; R4 =
OEt) was obtained. Gratifyingly, the tandem propargylic
substitution–cycloisomerization proceeded well at reflux
temperature for 0.8 hour, affording a 35% isolated yield of
5aa and a 47% isolated yield of 4a which could be com-
pletely converted into 5aa in 82% total yield by extending
the reaction time from 0.8 to 2 hours.
With these conditions in hand, we examined the propargy-
lation–cycloisomerization tandem reaction of a range of
propargylic alcohols with various 1,3-dicarbonyl com-
pounds (Table 1). The secondary propargylic alcohols 1a
and 1b participated well in the tandem reaction, producing
the propargylation–cycloisomerization products in high to
excellent yields with complete regioselectivity (Table 1,
entries 1–5 and 7–11). The reaction proceeded smoothly
under mild conditions and air was tolerated. These were in
contrast to the ruthenium-catalyzed processes4,5 where the
reactions had to be performed under a N2 atmosphere.
However, the trimethylsilyl group was not tolerated under
the acidic condition and got removed during workup. Pro-
pargylic alcohol 1c possessing an electron-donating group
at the aryl ring reacted smoothly with 1,3-dicarbonyl com-
pounds to afford the furans 5ca and 5cc in high yields
(Table 1, entries 12 and 13). Moreover, substrates 1d and
1e possessing electron-withdrawing group (bromo and es-
ter functionalities) at the aryl ring were also successfully
employed in the tandem reaction to give the furans 5da–
5ec in moderate yields (Table 1, entries 14–17). Obvious-
ly, electron-rich propargylic alcohols provided propargy-
Reaction of propargylic alcohol 1a (1: X = OH; R1 = Ph;
R2 = TMS) with ethyl acetoacetate (3a; R3 = Me; R4 =
OEt) under the reaction conditions (5 mol% FeCl3, tolu-
SYNLETT 2008, No. 19, pp 3046–3052
x
x
.x
x
.2
0
0
8
Advanced online publication: 12.11.2008
DOI: 10.1055/s-0028-1087344; Art ID: W10508ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Facile One-Pot Synthesis of Substituted Furans
3047
lation–cycloisomerization products in higher yields than ters 3a and 3b also gave the propargylation–cycloisomer-
electron-poor propargylic alcohols. It should also be noted ization products in moderate to good yields except for
that functional groups such as bromo, ester, and methoxy entries 18 and 19 (Table 1, entries 1, 2, 7, 8, 12, 14 and
in the propargylic alcohols, were readily carried through 16). However, by using diethyl malonate (3f), no furan
the propargylation–cycloisomerization tandem reaction, formation was observed (Table 1, entry 6). In all cases,
allowing for the subsequent elaboration of the products the results showed that the reactivity of various 1,3-dicar-
(Table 1, entries 12–17). Unfortunately, attempted propar- bonyl compounds followed the general trend 3d >3c >3a,
gylation–cycloisomerization of terminal propargylic alco- 3b >3f. Nevertheless, compared with b-keto esters 3a and
hol 1f and internal propargylic alcohol 1g did not lead to 3b, 1,3-cyclohexanedione (3e) reacted more sluggishly to
the expected furans, but to a g-alkynyl ketone intermedi- give the propargylation–cycloisomerization products in
ate (Table 1, entries 18 and 19). The results suggested that lower yields (Table 1, entries 5 and 11), possibly due to
the presence of trimethylsilyl group was vital to the FeCl3- the steric bulkiness of 3e. Unfortunately, the reaction of
catalyzed cyclization of g-alkynyl ketones.9 Among the propargylic alcohol 1a with 1,3-cyclopentadione afforded
1,3-dicarbonyl compounds that were examined, b-di- a complex mixture.
ketones 3d and 3c gave the most desirable results
(Table 1, entries 3, 4, 9, 10, 13, 15 and 17), and b-keto es-
Table 1 Synthesis of Furans from Propargylic Alcohols 1a–1g and 1,3-Dicarbonyl Compounds 3a
O
FeCl3 (5 mol%)
R1
O
O
HO
R1
R4
R3
toluene, reflux
R2
R3
R4
+
R2
O
H2O
1a–1g
3a–f
5aa–ga
Entry
1
Propargylic alcohol
1,3-Dicarbonyl compound
Product
Time (h) Isolated yield (%)
O
Ph
1a: R1 = Ph; R2 = TMS
3a: R3 = Me; R4 = OEt
2
82
81
86
90
72
EtO
O
5aa
O
Ph
3b: R3 = Me; R4 = Oi-Pr
2
i-PrO
2
3
4
O
5ab
O
Ph
3c: R3 = R4 = Me
0.7
0.7
3
O
5ac
O
Ph
3d: R3 = R4 = Ph
Ph
Ph
O
5ad
O
Ph
5
6
3e: R3 = R4 = (CH2)3
O
5ae
3f: R3 = OEt; R4 = OEt
–
24
0b
b
O
7
1b: R1 = 1-naphthyl; R2 = TMS
3a: R3 = Me; R4 = OEt
2
84
EtO
O
5ba
Synlett 2008, No. 19, 3046–3052 © Thieme Stuttgart · New York

3048
W.-h. Ji et al.
LETTER
Table 1 Synthesis of Furans from Propargylic Alcohols 1a–1g and 1,3-Dicarbonyl Compounds 3a (continued)
O
FeCl3 (5 mol%)
R1
O
O
HO
R1
R4
R3
toluene, reflux
R2
R3
R4
+
R2
O
H2O
1a–1g
3a–f
5aa–ga
Entry
8
Propargylic alcohol
1,3-Dicarbonyl compound
Product
Time (h) Isolated yield (%)
O
3b: R3 = Me; R4 = Oi-Pr
2
82
87
92
73
i-PrO
O
5bb
O
9
10
11
3c: R3 = R4 = Me
3d: R3 = R4 = Ph
3e: R3 = R4 = (CH2)3
0.7
0.7
3
O
5bc
O
Ph
Ph
O
5bd
O
O
O
5be
OMe
12
13
14
15
16
1c: R1 = PMP; R2 = TMS
3a: R3 = Me; R4 = OEt
1.5
0.5
4
84
88
62
67
47
EtO
O
5ca
OMe
O
3c: R3 = R4 = Me
O
5cc
Br
O
1d: R1 = 4-BrC6H4; R2 = TMS
3a: R3 = Me; R4 = OEt
EtO
O
5da
Br
O
3c: R3 = R4 = Me
3
O
5dc
COOMe
O
1e: R1 = 4-MeO2CC6H4; R2 = TMS 3a: R3 = Me; R4 = OEt
4.5
EtO
O
5ea
Synlett 2008, No. 19, 3046–3052 © Thieme Stuttgart · New York

LETTER
Facile One-Pot Synthesis of Substituted Furans
3049
Table 1 Synthesis of Furans from Propargylic Alcohols 1a–1g and 1,3-Dicarbonyl Compounds 3a (continued)
O
FeCl3 (5 mol%)
R1
O
O
HO
R1
R4
R3
toluene, reflux
R2
R3
R4
+
R2
O
H2O
1a–1g
3a–f
5aa–ga
Entry
17
Propargylic alcohol
1,3-Dicarbonyl compound
Product
Time (h) Isolated yield (%)
COOMe
O
3c: R3 = R4 = Me
3.5
55
O
5ec
O
Ph
Ph
1f: R1 = Ph; R2 = H
3a: R3 = Me; R4 = OEt
3a: R3 = Me; R4 = OEt
24
0c
EtO
18
19
O
O
5aa
O
1g: R1 = Ph; R2 = n-Bu
24
0c
EtO
5ga
a Conditions: propargylic alcohols 1 (0.5 mmol), 1,3-dicarbonyl compounds 3 (2.0 mmol), FeCl3 (0.025 mmol), toluene (2.0 mL), reflux.
b A complex mixture was obtained.
c The propargylic alcohols were completely consumed and g-alkynyl ketones 4f and 4g were obtained in 75 and 81% yield, respectively.
O
O
O
O
OEt
OEt
4f
4g
We propose the sequence outlined in Scheme 2 as the trimethylsilyl group at R2 would exhibit unique reactivity.
likely mechanism for the propargylation–cycloisomeriza- In addition, the proposed mechanism is also in accordance
tion tandem reaction. Firstly, the ionization of propargylic with the observation that the reactivity of 1,3-dicarbonyl
alcohol 1 would lead to a propargylic cation 7 and the sub- compounds follows the trend 3d >3c >3a, 3b >3f.11
sequent nucleophilic attack of the enol 6 would give a g-
As shown in Table 1, some cases gave the desired furans
in somewhat low yields, or even could not afford cycliza-
tion products. We reasoned that one equivalent of water
produced in the propargylic substitution would suppress
the cycloisomerization reaction. Accordingly, we began
searching for an appropriate leaving group, which we
thought would readily allow for the propargylation–
cycloisomerization tandem reaction. We were pleased to
alkynyl ketone 4. Coordination of iron(III) to the alkyne
would form the p-alkyne iron complex 9 and would en-
hance the electrophilicity of alkyne. Subsequent 5-exo-dig
nucleophilic attack of the hydroxyl group on b-carbon of
Fe(III)–alkyne complex 9 would generate the alkenyl-iron
derivative 10. Protonolysis of 10 would afford a dihydro-
furan 11, which would then undergo isomerization and
desilylation to give furan 5.
find that replacement of the propargylic alcohols with the
In the proposed mechanism, the formation of propargylic corresponding propargylic acetates gave the substituted
cation 7 and the intramolecular nucleophilic addition of furans in desired yields, and acetic acid produced in the
the p-alkyne iron complex 9 are the two critical steps, and propargylic substitution has no effect on the catalyst activ-
the g-effect and b-effect of the silicon atom play important ity of FeCl3. To assess the synthetic utility of propargylic
roles here.10 The g-effect of silicon atom stabilizes posi- acetates versus propargylic alcohols, comparative experi-
tive charges in the g-carbon of propargylic cation 7 and fa- ments were performed. Obviously, significantly increased
vors the propargylic substitution. On the other hand, the b- yields of the desired products were obtained for all cases
effect of silicon atom polarizes the acetylenic bond of when propargylic acetates were used as substrates, com-
complex 9, and leads to a decrease in the electronic densi- pared to propargylic alcohols. The typical results are de-
ties on b-carbon, so b-carbon undergoes readily intramo- picted in Table 2. For example, treatment of propargylic
lecular nucleophilic attack with the hydroxyl group. Thus, acetate 2e with ethyl acetoacetate (3a) greatly increased
it is anticipated that the propargylic alcohols possessing the yield of the tetrasubstituted furan 5ea from 47% to
Synlett 2008, No. 19, 3046–3052 © Thieme Stuttgart · New York

3050
W.-h. Ji et al.
LETTER
OH
O
O
O
R3
R4
R3
R4
6
3
O
O
OH
R1
O
OH
R3
R4
R3
R4
FeCl3
OH–
R1
γ
TMS
γ
α
β
R1
R1
β
α
H+
TMS
TMS
TMS
4
8
1
7
O
R3
O
R1
R1
O
R4
R3
OH
R4
R3
H
[Fe]2+
TMS
FeCl3
R4
TMS
O
γ
α
β
O
H
TMS
[Fe]3+
R1
[Fe]3+
9
11
10
O
R1
H+
R4
R3
[TMS]+
O
5
Scheme 2 Proposed mechanism for the propargylation–cycloisomerization tandem reaction
63% whilst reducing the reaction time from 4.5 to 3 hours To verify the effects of water and acetic acid on the cyclo-
(Table 2, entry 3). Most notably, terminal propargylic ac- isomerization reaction, the FeCl3-catalyzed cycloisomer-
etate 2f and internal propargylic acetates 2g–2i possessing izations of g-alkynyl ketones 4f and 4g were studied as
a n-Bu group at R2 were successfully employed in the pro- model reactions. The results are summarized in Table 3.
pargylation–cycloisomerization tandem reaction to give g-Alkynyl ketones 4f and 4g underwent the intramolecu-
the desired furans, albeit in somewhat low yields (Table 2, lar cycloisomerization in the presence of 5 mol% FeCl3 to
entries 5–10).
give the corresponding furans in 45% and 42% yields, re-
Table 2 Synthesis of Furans from Propargylic Acetates 2d–2i and 1,3-Dicarbonyl Compounds 3a
O
FeCl3 (5 mol%)
R1
R4
R3
O
O
AcO
R1
toluene, reflux
R2
+
R3
R4
R2
O
AcOH
2
3
5
Entry
2
3
5
Time (h)
3 (4)b
Isolated yield (%)
73 (62)c
77 (67)c
63 (47)c
70 (55)c
33 (0)c
1
2
2d: R1 = 4-BrC6H4; R2 = TMS
3a: R3 = Me; R4 = OEt
3c: R3 = R4 = Me
5da
5dc
5ea
5ec
5aa
5ac
5ga
5gc
5hc
5ic
2.5 (3)b
3 (4.5)b
3 (3.5)b
4 (24)b
3
2e: R1 = 4-MeO2CC6H4; R2 = TMS
2f: R1 = Ph; R2 = H
3a: R3 = Me; R4 = OEt
3c: R3 = R4 = Me
4
5
3a: R3 = Me; R4 = OEt
3c: R3 = R4 = Me
6
3 (24)d
45 (0)e
7
2g: R1 = Ph; R2 = n-Bu
3a: R3 = Me; R4 = OEt
3c: R3 = R4 = Me
4.5 (24)b
3.5 (24)d
3 (24)d
36 (0)c
8
48 (0)e
9
2h: R1 = 2-MeOC6H4; R2 = n-Bu
2i: R1 = 4-ClC6H4; R2 = n-Bu
3c: R3 = R4 = Me
54 (0)e
10
3c: R3 = R4 = Me
3.5 (24)d
37 (0)e
a Conditions: propargylic acetates 2 (0.5 mmol), 1,3-dicarbonyl compounds 3 (2.0 mmol), FeCl3 (0.025 mmol), toluene (2.0 mL), reflux.
b Values in parentheses are the reaction times when the corresponding propargylic alcohols are used as substrates. See Table 1.
c Values in parentheses are the yields when the corresponding propargylic alcohols are used as substrates. See Table 1.
d Values in parentheses are the reaction times when the corresponding propargylic alcohols are used as substrates.
e Values in parentheses are the yields when the corresponding propargylic alcohols are used as substrates.
Synlett 2008, No. 19, 3046–3052 © Thieme Stuttgart · New York

LETTER
Facile One-Pot Synthesis of Substituted Furans
3051
Table 3 FeCl3-Catalyzed Cycloisomerization of 4f and 4ga
O
O
O
Ph
OEt
R2
EtO
cat.
R2
toluene, reflux
O
4f R2 = H
4g R2 = n-Bu
5aa R2 = H
5ga R2 = n-Bu
Entry
4
Catalyst
Time (h)
Isolated yield (%)
1
2
3
4
5
6
7
8
4f: R2 = H
FeCl3 (5 mol%)
3
2.5
24
24
3.5
3
45
FeCl3 (5 mol%)–AcOH (1 equiv)
FeCl3 (5 mol%)–H2O (1 equiv)
AcOH (1 equiv)
44
n.r.b
n.r.b
42
4g: R2 = n-Bu
FeCl3 (5 mol%)
FeCl3 (5 mol%)–AcOH (1 equiv)
FeCl3 (5 mol%)–H2O (1 equiv)
AcOH (1 equiv)
40
24
24
n.r.b
n.r.b
a The cycloisomerization reactions of 4f and 4g (0.5 mmol) were carried out in the presence of catalyst in toluene (2.0 mL) at reflux.
b n.r. = no reaction.
spectively (Table 3, entries 1 and 5). Addition of one Acknowledgment
equivalent of acetic acid accelerated the intramolecular
The research was financially supported by the National Natural Sci-
ence Foundation of China (Nos. 20772098 and 30572250), and the
Program for New Century Excellent Talents in Fujian Province
University.
cycloisomerization while retaining the moderate yields
(Table 3, entries 2 and 6). In contrast, in the presence of
one equivalent of H2O, no formation of the desired furans
was observed (Table 3, entries 3 and 7). The results sug-
gested that water completely inhibited the FeCl3-cata-
lyzed intramolecular cycloisomerization of the g-alkynyl
ketones 4f and 4g, whereas acetic acid had essentially no
effect. The propargylation of 1,3-dicarbonyl compounds
with propargylic acetates provided one equivalent of
AcOH, while the reaction with propargylic alcohols pro-
vided one equivalent of H2O. Therefore, it is anticipated
that the propargylic acetates have higher reactivity than
propargylic alcohols in the propargylation–cycloisomer-
ization tandem reaction catalyzed by FeCl3.
References and Notes
(1) Rossi, R. A.; Pierini, A. B.; Peñéñory, A. B. Chem. Rev.
2003, 103, 71; and references cited therein.
(2) Winnik, M. A. Chem. Rev. 1981, 81, 491; and references
cited therein.
(3) (a) Zhan, Z.-P.; Cai, X.-B.; Wang, S.-P.; Yu, J.-L.; Liu,
H.-J.; Cui, Y.-Y. J. Org. Chem. 2007, 72, 9838. (b) Zhan,
Z.-P.; Wang, S.-P.; Cai, X.-B.; Liu, H.-J.; Yu, J.-L.; Cui,
Y.-Y. Adv. Synth. Catal. 2007, 349, 2097. (c) Zhan, Z.-P.;
Yu, J.-L.; Liu, H.-J.; Cui, Y.-Y.; Yang, R.-F.; Yang, W.-Z.;
Li, J.-P. J. Org. Chem. 2006, 71, 8298. (d) Zhan, Z.-P.;
Yang, W.-Z.; Yang, R.-F.; Yu, J.-L.; Liu, H.-J. Chem.
Commun. 2006, 3352.
(4) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Milton, M. D.;
Hidai, M.; Uemura, S. Angew. Chem. Int. Ed. 2003, 42,
2681.
(5) Cadierno, V.; Gimeno, J.; Nebra, N. Adv. Synth. Catal. 2007,
349, 382.
In summary, we have developed an efficient method for
the synthesis of the substituted furans using FeCl3 as cat-
alyst. Iron(III) chloride operating as a bifunctional cata-
lyst, catalyzes two mechanistically distinct processes in a
single pot under the same reaction conditions; namely,
propargylation followed by cycloisomerization. This fac-
ile methodology allows rapid access to a variety of tetra-
substituted furans. In comparison with the ruthenium
complex, FeCl3 as the catalyst offers several relevant ad-
vantages including being inexpensive and commercially
available and allowing mild reaction conditions. Further
development of this methodology is currently underway
in our laboratory.
(6) Sanz, R.; Miguel, D.; Martínez, A.; Álvarez-Gutiérrez, J. M.;
Rodríguez, F. Org. Lett. 2007, 9, 727.
(7) Feng, X.-B.; Tan, Z.; Chen, D.; Shen, Y.-M.; Guo, C.-C.;
Xiang, J.-N.; Zhu, C.-L. Tetrahedron Lett. 2008, 49, 4110.
(8) General Procedure for Synthesis of Tetrasubstituted
Furans: To a 5-mL flask, propargylic alcohols 1 or
propargylic acetates 2 (0.5 mmol), 1,3-dicarbonyl
compounds 3 (2.0 mmol), toluene (2.0 mL), and FeCl3
(0.025 mmol, 4 mg) were successively added. The reaction
mixture was stirred at reflux, and monitored periodically by
TLC. Upon completion, toluene was removed under reduced
pressure by an aspirator, and then the residue was purified by
silica gel column chromatography (EtOAc–hexane) to
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Synlett 2008, No. 19, 3046–3052 © Thieme Stuttgart · New York

3052
W.-h. Ji et al.
LETTER
HRMS: m/z calcd for C17H19O5H+: 303.1236; found:
afford the corresponding tetrasubstituted furans 5.
Data of selected compounds: 5ab: yellow solid; mp 50–
51 °C. 1H NMR (400 MHz, CDCl3): d = 1.08 (d, 6 H, J = 6.0
Hz), 2.18 (s, 3 H), 2.56 (s, 3 H), 5.01 (sept, 1 H, J = 6.4 Hz),
7.22–7.25 (m, 2 H), 7.27–7.30 (m, 1 H), 7.32–7.37 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 11.7, 14.0, 21.7, 67.2,
113.9, 122.5, 126.7, 127.6, 130.1, 133.4, 146.9, 157.2,
163.9. IR (film): 1704 cm–1. MS (ESI): m/z (%) = 281 (100)
[M + Na+]. Anal. Calcd for C16H18O3: C, 74.39; H, 7.02.
Found: C, 74.24; H, 7.19. 5ad: white solid; mp 117–118 °C.
1H NMR (400 MHz, CDCl3): d = 2.46 (s, 3 H), 7.12–7.28 (m,
10 H), 7.35–7.39 (m, 1 H), 7.55–7.58 (m, 2 H), 7.80–7.82
(m, 2 H). 13C NMR (100 MHz, CDCl3): d = 12.3, 121.7,
123.5, 126.2, 126.9, 128.1, 128.2, 128.3, 128.4, 129.0,
129.7, 129.8, 132.2, 133.2, 137.4, 148.1, 150.8, 193.8. IR
(film): 1669 cm–1. MS (ESI): m/z (%) = 361 (100) [M + Na+].
Anal. Calcd for C24H18O2: C, 85.18; H, 5.36. Found: C,
85.31; H, 5.14. 5ae: yellow oil. 1H NMR (400 MHz, CDCl3):
d = 2.12–2.19 (m, 2 H), 2.30 (s, 3 H), 2.46–2.49 (m, 2 H),
2.87 (t, 2 H, J = 6.4 Hz), 7.26–7.31 (m, 1 H), 7.34–7.39 (m,
4 H). 13C NMR (100 MHz, CDCl3): d = 12.2, 22.7, 23.9,
38.9, 119.4, 119.9, 127.3, 128.1, 130.0, 131.9, 148.9, 165.9,
194.3. IR (film): 1675 cm–1. MS (ESI): m/z (%) = 227 (36)
[M + H+], 249 (100) [M + Na+]. Anal. Calcd for C15H14O2:
C, 79.62; H, 6.24. Found: C, 79.79; H, 6.09. 5bb: pale
yellow oil. 1H NMR (400 MHz, CDCl3): d = 0.39 (d, 3 H,
J = 6.4 Hz), 0.68 (d, 3 H, J = 6.4 Hz), 2.11 (s, 3 H), 2.65 (s,
3 H), 4.68 (sept, 1 H, J = 6.4 Hz), 7.28–7.48 (m, 4 H), 7.64
(d, 1 H, J = 8.4 Hz), 7.81 (d, 1 H, J = 8.4 Hz), 7.84 (d, 1 H,
J = 8.0 Hz). 13C NMR (100 MHz, CDCl3): d = 11.7, 13.7,
20.7, 21.3, 66.6, 115.3, 119.1, 125.1, 125.5, 125.6, 126.2,
127.4, 127.9, 131.9, 133.3, 133.4, 147.6, 157.6, 163.7. IR
(film): 1704 cm–1. HRMS: m/z calcd for C20H20O3:
303.1227. 5ec: yellow solid; mp 100–101 °C. 1H NMR (400
MHz, CDCl3): d = 1.97 (s, 3 H), 2.18 (s, 3 H), 2.54 (s, 3 H),
3.94 (s, 3 H), 7.33 (d, 2 H, J = 8.4 Hz), 8.08 (d, 2 H, J = 8.4
Hz). 13C NMR (100 MHz, CDCl3): d = 11.6, 14.2, 30.7, 52.2,
120.1, 122.8, 129.0, 129.6, 129.8, 138.7, 147.3, 156.4,
166.8, 195.4. IR (film): 1725, 1671 cm–1. MS (ESI): m/z (%)
= 273 (18) [M + H+], 295 (100) [M + Na+]. Anal. Calcd for
C16H16O4: C, 70.57; H, 5.92. Found: C, 70.85; H, 5.81. 5ga:
yellow oil. 1H NMR (400 MHz, CDCl3): d = 0.84 (t, 3 H,
J = 6.8 Hz), 1.07 (t, 3 H, J = 7.2 Hz), 1.20–1.27 (m, 4 H),
1.54–1.62 (m, 2 H), 2.49 (t, 2 H, J = 7.6 Hz), 2.58 (s, 3 H),
4.09 (q, 2 H, J = 7.2 Hz), 7.22–7.24 (m, 2 H), 7.27–7.30 (m,
1 H), 7.31–7.36 (m, 2 H). 13C NMR (100 MHz, CDCl3): d =
13.8, 13.9, 14.1, 22.3, 25.8, 28.2, 31.2, 59.7, 113.5, 121.2,
126.7, 127.5, 130.0, 133.4, 151.3, 157.4, 164.4. IR (film):
1712 cm–1. MS (ESI): m/z (%) = 323 (100) [M + Na+]. Anal.
Calcd for C19H24O3: C, 75.97; H, 8.05. Found: C, 75.80; H,
8.23. 5hc: yellow oil. 1H NMR (400 MHz, CDCl3): d = 0.84
(t, 3 H,
J = 6.8 Hz), 1.18–1.28 (m, 4 H), 1.53–1.61 (m, 2 H), 1.90 (s,
3 H), 2.43 (t, 2 H, J = 8.0 Hz), 2.54 (s, 3 H), 3.75 (s, 3 H),
6.93 (d, 1 H, J = 8.4 Hz), 6.90–7.02 (m, 1 H), 7.16 (dd, 1 H,
J = 7.6, 1.6 Hz), 7.32–7.36 (m, 1 H). 13C NMR (100 MHz,
CDCl3): d = 13.9, 14.3, 22.3, 25.9, 28.1, 29.3, 31.2, 55.2,
110.6, 116.6, 120.6, 122.7, 123.2, 129.2, 131.4, 151.1,
155.8, 157.3, 196.2. IR (film): 1673 cm–1. HRMS: m/z [M +
H+] calcd for C19H25O3: 301.1806; found: 301.1798. 5ic:
yellow oil. 1H NMR (400 MHz, CDCl3): d = 0.77 (t, 3 H,
J = 7.2 Hz), 1.09–1.22 (m, 4 H), 1.44–1.52 (m, 2 H), 1.88 (s,
3 H), 2.36 (t, 2 H, J = 7.6 Hz), 2.46 (s, 3 H), 7.09 (d, 2 H,
J = 8.4 Hz), 7.29 (d, 2 H, J = 8.4 Hz). 13C NMR (100 MHz,
CDCl3): d = 13.9, 14.4, 22.2, 25.7, 28.1, 30.8, 31.1, 119.5,
122.7, 128.6, 131.2, 132.3, 133.3, 151.3, 156.5, 195.5. IR
(film): 1675 cm–1. MS (ESI): m/z (%) = 305 (24) [M + H+],
327 (100) [M + Na+]. Anal. Calcd for C18H21ClO2: C, 70.93;
H, 6.94. Found: C, 70.81; H, 7.09.
308.1412; found: 308.1413. 5bd: pale yellow oil. 1H NMR
(400 MHz, CDCl3): d = 2.27 (s, 3 H), 7.03 (dd, app. t, 2 H,
J = 7.6, 7.6 Hz), 7.17–7.32 (m, 6 H), 7.39–7.41 (m, 2 H),
7.62–7.67 (m, 5 H), 7.73–7.75 (m, 1 H), 7.84–7.86 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 12.5, 121.5, 123.2, 125.1,
125.7, 125.76, 126.1, 126.5, 127.8, 127.9, 128.2, 128.3,
128.4, 128.5, 129.4, 129.7, 129.9, 132.2, 132.7, 133.5,
137.4, 149.2, 151.9, 193.3. IR (film): 1658 cm–1. MS (ESI):
m/z (%) = 389 (100) [M + H+]. Anal. Calcd for C28H20O2: C,
86.57; H, 5.19. Found: C, 86.39; H, 5.34. 5da: white solid;
mp 96–97 °C. 1H NMR (400 MHz, CDCl3): d = 1.15 (t, 3 H,
J = 7.2 Hz), 2.19 (s, 3 H), 2.57 (s, 3 H), 4.15 (q, 2 H, J = 7.2
(9) Gabriele has also reported that 4-ethyl-2-methylfuran could
be obtained directly by treatment of (Z)-2-ethyl-5-trimethyl-
silylpent-2-en-4-yn-1-ol with TBAF without added solvent
followed by transfer distillation; however, PdI2 as the
catalyst is needed in the absence of trimethylsilyl group
(Scheme 3). See: Gabriele, B.; Salerno, G.; Lauria, E. J. Org.
Chem. 1999, 64, 7687.
Hz), 7.14 (d, 2 H, J = 8.4 Hz), 7.49 (d, 2 H, J = 8.4 Hz). 13
C
Et
Et
1) TBAF
NMR (100 MHz, CDCl3): d = 11.7, 14.0, 14.1, 59.9, 113.2,
120.4, 120.9, 130.8, 131.7, 132.3, 147.2, 157.7, 164.1. IR
(film): 1701 cm–1. MS (ESI): m/z (%) = 345 (100), 347 (90)
[M + Na+]. Anal. Calcd for C15H15BrO3: C, 55.75; H, 4.68.
Found: C, 55.51; H, 4.82. 5dc: yellow oil. 1H NMR (400
MHz, CDCl3): d = 2.00 (s, 3 H), 2.17 (s, 3 H), 2.55 (s, 3 H),
7.14 (d, 2 H, J = 8.8 Hz), 7.55 (d, 2 H, J = 8.4 Hz). 13C NMR
(100 MHz, CDCl3): d = 11.6, 14.3, 30.8, 119.8, 121.5, 122.8,
131.5, 131.6, 132.7, 147.2, 156.4, 195.5. IR (film): 1623 cm–
1. MS (ESI): m/z (%) = 315 (100), 317 (86) [M + Na+]. Anal.
Calcd for C14H13BrO2: C, 57.36; H, 4.47. Found: C, 57.47;
H, 4.29. 5ea: yellow oil. 1H NMR (400 MHz, CDCl3): d =
1.09 (t, 3 H, J = 7.2 Hz), 2.20 (s, 3 H), 2.58 (s, 3 H), 3.93 (s,
3 H), 4.12 (q, 2 H, J = 7.2 Hz), 7.33 (d, 2 H, J = 8.4 Hz), 8.03
(d, 2 H, J = 8.4 Hz). 13C NMR (100 MHz, CDCl3): d = 11.8,
13.9, 14.1, 52.1, 59.9, 113.3, 120.6, 128.4, 128.9, 130.0,
138.4, 147.5, 157.9, 164.1, 167.1. IR (film): 1723 cm–1.
2) transfer distillation
OH
O
TMS
Scheme 3
(10) For synthetic applications of the g-effect and b-effect of
silicon, see: (a) Sakurai, H.; Imai, T.; Hosomi, A.
Tetrahedron Lett. 1977, 18, 4045. (b) Hatanaka, Y.;
Kuwajima, I. Tetrahedron Lett. 1986, 27, 719. (c) Antras,
F.; Ahmar, M.; Cazes, B. Tetrahedron Lett. 2001, 42, 8157.
(11) The percentages of the enol content of 1,3-dicarbonyl
compounds in CCl4 follow the order: dibenzoylmethane (3d;
96%) > acetylacetone (3c; 80%) > ethyl acetoacetate (3a;
7.5%) > diethyl malonate (3f; 0.007%). See: Burdett, J. L.;
Rogers, M. T. J. Am. Chem. Soc. 1964, 86, 2105.
Synlett 2008, No. 19, 3046–3052 © Thieme Stuttgart · New York