Catalytic regioselectivity control in ring-opening cycloisomerization of methylene- or alkylidenecyclopropyl ketones

Article abstract of DOI:10.1021/ja0494860

2-Methylene- or alkylidenecyclopropanyl ketones were easily prepared by the regioselective cyclopropanation of allenes or the reaction of methylene-/alkylidenecyclopropanyllithium with N,N-dimethyl carboxylic acid amides. Due to the presence of the exo-cy

Full text of DOI:10.1021/ja0494860

Published on Web 07/16/2004
Catalytic Regioselectivity Control in Ring-Opening
Cycloisomerization of Methylene- or Alkylidenecyclopropyl
Ketones
Shengming Ma,* Lianghua Lu, and Junliang Zhang
Contribution from the State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, P. R. China
Received January 29, 2004; E-mail: masm@mail.sioc.ac.cn
Abstract: 2-Methylene- or alkylidenecyclopropanyl ketones were easily prepared by the regioselective
cyclopropanation of allenes or the reaction of methylene-/alkylidenecyclopropanyllithium with N,N-dimethyl
carboxylic acid amides. Due to the presence of the exo-cyclic CdC bond and the strained cyclopropane,
their highly selective ring-opening cycloisomerization using PdCl2(CH3CN)2, NaI (or PdCl2(CH3CN)2 + NaI),
and Pd(PPh3)4 as catalysts provided five different products, i.e., 4H-pyrans, 2,3,4-trisubstituted furans (or
4,5-disubstituted-3-alkylidene-2,3-dihydrofurans), and 2,3,4,5-tetrasubtituted furans (or 2,4,5-trisubstituted-
3-alkylidene-2,3-dihydrofurans) in good yields, respectively, depending on the nature of the catalyst and
reaction conditions. The less-substituted CdC bonds in these products can be highly selectively
hydrogenated or hydroborated to afford new heterocyclic products stereoselectively. These three types of
different reactions may proceed through a highly regioselective cleavage of a carbon-carbon single bond
in the cyclopropane ring triggered by regioselective halometalation of the CdC bond and â-decarbopal-
ladation, halogen anion attack on the nonsubstituted carbon atom of the cyclopropane ring, or the direct
oxidative addition of the distal carbon-carbon single bond of the cyclopropane ring with Pd(0). In some
cases substituent effects were successfully applied to synthesize 2H-pyrans 8 and 3-alkylidene-2,3-
dihydrofurans 5, which also provided some mechanistic information.
hydrometalation8,9 or carbometalation10,11 of the CdC bond,
Introduction
have been observed in the transition-metal-catalyzed reactions
of MCPs (Scheme 1).
Although the chloropalladation reaction of the CdC bond in
MCPs with stoichiometric PdCl2(PhCN)2 has been studied,12
no catalytic reaction involving halometalation has been reported.
During the course of our systematic study of functionalized
Selective synthesis of different products from the same
materials by just choosing different catalysts is an interesting
research topic for chemists.1 Recently, much attention has been
paid to methylenecyclopropanes (MCPs)2-5 due to the presence
of an exo-cyclic carbon-carbon double bond and a strained
three-membered carbocycle. For the transition metal-mediated
reactions, various reaction pathways, including oxidative addi-
tion of the distal or proximal C-C bond6,7 and regioselective
(6) (a) Noyori, R,; Odagi, T.; Tayaka, H. J. Am. Chem. Soc. 1970, 92, 5780.
(b) Noyori, R.; Kumagai, Y.; Umeda, I.; Tayaka, H. J. Am. Chem. Soc.
1972, 94, 4018. (c) Binger, P.; Schuchardt, U. Angew. Chem., Int. Ed. Engl.
1977, 16, 249.
(1) (a) Keinan, E.; Bosch, E. J. Org. Chem. 1986, 51, 4006. (b) Radinov, R.;
Hutchings, S. D. Tetrahedron Lett. 1999, 40, 8955. (c) Luna, A. P.; Bonin,
M.; Micouin, L.; Husson, H. J. Am. Chem. Soc. 2002, 124, 12098. (d)
Doyle, M. P.; Yan, M.; Hu, W.; Gronenberg, L. S. J. Am. Chem. Soc.
2003, 125, 4692. (e) Ma, S.; Zhang, J. J. Am. Chem. Soc. 2003, 125, 12386.
(2) Lazzara, M. G.; Harrison, J. J.; Rule, M.; Hilinski, E. F.; Berson, J. A. J.
Am. Chem. Soc. 1982, 104, 2233.
(3) (a) Hassall, C. H.; Reyle, K.; Feng, P. Nature 1954, 173, 356. (b) Hassall,
C. H.; Reyle, K. Biochem. J. 1955, 60, 344. (c) Carbon, J. A.; Martin, W.
B.; Swett, L. R. J. Am. Chem. Soc. 1958, 80, 1002. (d) Lenn, N. D.; Shih,
Y.; Stankovuch, M. T.; Liu, H. J. Am. Chem. Soc. 1989, 111, 3065.
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(b) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1986, 25, 1. (c) Yamago, S.;
Nakamura, E. J. Am. Chem. Soc. 1989, 111, 7285. (d) Brandi, A.; Goti, A.
Chem. ReV. 1998, 98, 589.
(7) Suginome, M.; Matsuda, T.; Ito, Y. J. Am. Chem. Soc. 2000, 122, 11015.
(8) (a) Lautens, M.; Meyer, C.; Lorenz, A. J. Am. Chem. Soc. 1996, 118, 10676.
(b) Bessmertnykh, A. G.; Blinov, K. A.; Grishin, Y. K.; Donskaya, N. A.;
Tveritinova, E. V.; Yur’eva, N. M.; Beletskaya, I. P. J. Org. Chem. 1997,
62, 6069.
(9) (a) Tsukada, N.; Shibuya, A.; Nakamura, I.; Yamamoto, Y. J. Am. Chem.
Soc. 1997, 119, 8123. (b) Nakamura, I.; Itagaki, H.; Yamamoto, Y. J. Org.
Chem. 1998, 63, 6458. (c) Camacho, D. H.; Nakamura, I.; Saito, S.;
Yamamoto, Y. Angew. Chem., Int. Ed. 1999, 38, 3365. (d) Nakamura, I.;
Saito, S.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 2661. (e) Camacho,
D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2001, 66,
270.
(10) (a) Fournet, G.; Balme, G.; Barieux, J. J.; Gore´, J. Tetraherdron 1988, 44,
5809, 5821. (b) Bra¨se, S.; de Meijere, A. Angew. Chem., Int. Ed. Engl.
1995, 34, 2545.
(5) For reviews, see: (a) Binger, P.; Bu¨ch, H. M. Top. Curr. Chem. 1987,
135, 77. (b) Ohta, T.; Takaya, H. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Paquette, L. A., Eds.; Pergamon: Oxford, 1991;
Vol. 5, p 1185. (c) “Carbocyclic Three-Membered Ring Compounds”:
Methods of Organic Chemistry (Houben-Weyl), 4th ed.; de Meijere, A.,
Ed.; Thieme Stuttgart: New York, 1996; Vol. E17, 2217. (d) Lautens, M.;
Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49. (e) Brandi, A.; Cicchi, S.;
Cordero, F. M.; Goti, A. Chem. ReV. 2003, 103, 1213. (f) Nakamura, I.;
Yammamoto, Y. AdV. Synth. Catal. 2002, 344, 111-129.
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1993, 34, 153. (b) Ang, K. H.; Braese, S.; Steinig, A. G.; Meyer, F. E.;
Llebaria, A.; Voigt, K.; de Meijere, A. Tetrahedron 1996, 52, 11503.
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Clemens, P. R.; Hughes, R. P.; Margerum, L. D. J. Am. Chem. Soc. 1981,
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references therein.
9
10.1021/ja0494860 CCC: $27.50 © 2004 American Chemical Society
J. AM. CHEM. SOC. 2004, 126, 9645-9660
9645

A R T I C L E S
Ma et al.
Scheme 1. Transition Metal-Catalyzed Reactions of MCPs
Scheme 2. Three Different Paths for the Catalytic
Cycloisomerization of Alkylidenecyclopropyl Ketones 1
the CdC bond of 1 in cases of mixtures were tentatively
assigned based on the influence of the carbonyl group to the
chemical shift of olefinic protons.18
The alkylidenecyclopropyl ketone 1m and methylenecyclo-
propyl ketones 1n-y were synthesized according to the method
developed by Thomas, E. W. et al. except that the corresponding
N,N-dimethyl amide was used instead of the lithium carboxylate
(Scheme 4).19
Ring-Opening Cycloisomerization under the Catalysis of
PdCl2(CH3CN)2. Formation of 4H-Pyrans: We examined the
cycloisomerization of methylenecyclopropyl ketone 1a in the
presence of a catalytic amount of PdCl2(CH3CN)2.20 The
reaction was completed within 15 min at rt in acetone to afford
4H-pyran 2a, which is air-sensitive (entry 1, Table 1).
This transformation is general for the alkylidenecyclopropyl
ketones 1a-h and 1m under the catalysis of 5 mol %
PdCl2(CH3CN)2 in acetone at rt (Table 1). In some cases,
benzene is a better solvent. For example, the reaction of 1c in
CH2Cl2 afforded 2c in 80% yield, while the same reaction in
acetone afforded 2c in 69% yield (entries 3 and 4, Table 1).
The reaction of 1d, which contains the TBS-protected hydroxyl
group, gave 2d in 85% yield in benzene (entry 5, Table 1). The
presence of electron-withdrawing group R2 is not necessary,
since the reaction of 1m also occurred well to afford 2m in
70% yield (entry 10, Table 1). It should be noted that the 2H-
pyran 8-type products (see the equation in Table 1) were not
formed in these cases.
allenes,13 we were interested in the chemistry of its analogues,
i.e., alkylidenecyclopropyl ketone 1. In principle, due to the
presence of the carbonyl group, the strained carbon-carbon
single bonds a and b are further activated. In this paper, we
wish to report the highly selective ring-opening cycloisomer-
ization of methylene- or alkylidenecyclopropyl ketones under
different reaction conditions leading to three types of different
products 2, 3 (or 4), and 5 (or 6), respectively (Scheme 2).
Results and Discussion
Synthesis of Starting Materials: The starting alkylidenecy-
clopropyl ketones 1a-k were easily prepared by the Rh2(OAc)4-
catalyzed cyclopropanation14 of the corresponding 1,2-allenes15
with the R-diazo ketones 7a-e16 (Scheme 3). For 1f, 1g, and
1l, only one isomer was observed. The stereochemistry of 1l
was determined by the X-ray diffraction study (Figure 1).17 The
corresponding ratios of Z/E isomers of other starting materials
With the hydroboration-oxidation reaction of 2, a series of
cyclic alcohols 9 can be prepared highly stereoselectively
(Scheme 5). The stereochemistry of 9 was established by the
X-ray diffraction study of 9g (Figure 2).21 The hydroboration
of the cyclic tetrasubstituted CdC bond was not observed.
1
(17) X-ray data for compound 1l: C12H11O3SCl, MW ) 270.72, monoclinic,
space group P2(1)/n, Mo KR, final R indices [I > 2σ(I)], R1 ) 0.0494,
wR2 ) 0.0755, a ) 11.3404(19) Å, b ) 10.0567(17) Å, c ) 12.770(2) Å,
R ) 90°, â ) 115.267(3)°, γ ) 90°, V ) 1317.0(4) Å3, T ) 293(2) K, Z
) 4, reflections collected/unique: 7763/3016 (Rint ) 0.1005), parameters
199. CCDC 228763 contains the supplementary crystallographic data.
(18) Tables of Spectral Data for Structure Determination of Organic Compounds;
Prestch, E., Clerc, T., Seibl, J., Simon, W. (Translator: Biemann, K.);
Springer-Verlag: Berlin, 1983; p. H-215.
were determined by H NMR spectra. The configurations of
(13) For some of the most recent results from this group, see: (a) Ma, S.; Wu,
S. Chem. Commun. 2001, 441. (b) Ma, S.; Zhao, S. J. Am. Chem. Soc.
2001, 123, 5578. (c) Ma, S.; Shi, Z. Chem. Commun. 2002, 540. (d) Ma,
S.; Gao, W. Synlett 2002, 65. (e) Ma, S.; Yin, S.; Li, L.; Tao, F. Org. Lett.
2002, 4, 505. (f) Ma, S.; Jiao, N.; Zhao, S.; Hou, H. J. Org. Chem. 2002,
67, 2837. (g) Ma, S.; Duan, D.; Wang, Y. J. Comb. Chem. 2002, 4, 239.
(h) Ma, S.; Yu, Z. Angew. Chem., Int. Ed. 2002, 41, 1775.
(14) Cheng, C.; Shimo, T.; Somekawa, K.; Baba, M. Tetrahedron 1998, 10,
2031.
(15) Taherirastgar, F.; Brandsma, L. Synth. Commun. 1997, 27, 4035.
(16) Regitz, M.; Hocher, J. Org. Synth. Coll. Vol. V 1973, 179.
(19) 1m-y were prepared according to the following reference with slight
modification; i.e., the corresponding N,N-dimethyl amide was used instead
of the lithium carboxylate: Thomas, E. W.; Szmuszkovicz, J. R. J. Org.
Chem. 1990, 55, 6054.
(20) Ma, S.; Zhang, J. Angew. Chem., Int. Ed. 2003, 42, 184.
9
9646 J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004

Methylene- or Alkylidenecyclopropyl Ketones
A R T I C L E S
Scheme 3. Synthesis of Starting Materials 1a-l
Scheme 4. Synthesis of Starting Materials 1m-y
Figure 1. ORTEP representation of E-1l.
A one-pot reaction of 1a-c with 5 mol % PdCl2(CH3CN)2
in CH2Cl2 followed by highly selective Pd/C-catalyzed hydro-
genation afforded dihydropyran derivatives 10a-c (Scheme 6),
indicating the high regioselectivity of this hydrogenation step.
the cationic bicyclic Pd intermediate 12A, which would
subsequently lead to 13A and 13 via rearrangement.22 If R4 )
H, the regiospecific â-R4 elimination of 13 and hydropalladation
with a reversed regioselectivity of 14 would afford 17.23 After
these steps, 4H-pyrans 2 would be formed via â-dechloropal-
ladation. If R4 * H, â-Ha elimination of the proton atom at the
4-position and hydropalladation of 15 with a reversed regiose-
lectivity and â-dechloropalladation would form 8.
Furthermore, it is interesting to observe that in the presence
of PdCl2(CH3CN)2 the cycloisomerization of 1j afforded 2H-
pyran 8j in 96% yield (eq 1).
To probe the real nature of this PdCl2(MeCN)2-catalyzed
isomerization of 1, we designed the deuterium-labeling experi-
ment to study the possible mechanism we proposed. With
deuterated compound 18, 19 (76% D incorporation) with the
(21) X-ray data for compound 9g: C16H22O4S, MW ) 310.40, monoclinic, space
group P2(1)/c, Mo KR, final R indices [I > 2σ(I)], R1 ) 0.0553, wR2 )
0.1280, a ) 17.931(4) Å, b ) 8.4053(16) Å, c ) 10.938(2) Å, R ) 90°,
â ) 94.494(3)°, γ ) 90°, V ) 1643.5(5) Å3, T ) 293(2) K, Z ) 4,
reflections collected/unique: 9438/3824 (Rint ) 0.0457), no observation [I
> 2σ(I)] 3824, parameters 257. CCDC 190370 contains the supplementary
crystallographic data.
(22) We thank the referees for the suggestion of this possibility.
(23) (a) Bender, D. D.; Stakem, F. G.; Heck, R. F. J. Org. Chem. 1982, 47,
1278. (b) Larock, R. C.; Lu, Y.; Bain, A. C. J. Org. Chem. 1991, 56, 4589.
(c) Ma, S.; Yu, Z. Angew. Chem., Int. Ed. 2003, 42, 1955.
Based on these results, a plausible mechanism was proposed
for the transformation (Scheme 7). Regioselective chloropalla-
dation of 1 with PdCl2 affords intermediate 11, which would
undergo â-decarbopalladation forming palladium enolate 12.
Endo-mode insertion of the CdC bond into the oxygen-
palladium bond in 12 would generate 13. An alternative pathway
leading to intermediate 13 would be the oxypalladation to form
9
J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004 9647

A R T I C L E S
Ma et al.
Table 1. Regioselective Cycloisomerization of Ketones 1 under
the Catalysis of Pd(II) Leading to 4H-Pyrans 2a
1
time
(min)
yield of
2 (%)
1
2
3
entry
R
R
R
1
2
3
C7H15
C4H9
Bn
CO2Et
CO2Et
CO2Et
1c
CO2Et
COCH3
SO2Ph
SO2Ph
CO2Et
H
Me (1a)
Me (1b)
Me (1c)
15
15
15
10
10
40
40
15
30
15
80 (2a)
75 (2b)
69 (2c)
80 (2c)
85 (2d)
60 (2e)
56 (2f)
91 (2g)
96 (2h)
70 (2m)
4b
5c
6
TBSO(CH2)3
C7H15
C7H15
C4H9
C7H15
Me (1d)
Me (1e)
Me (1f)
Me (1g)
Ph (1h)
Ph (1m)
7c
8
9c
10c
Figure 2. ORTEP representation of 9g.
C8H17
Scheme 6. PdCl2(MeCN)2-Catalyzed Cycloisomerization of 1a-c
and the Subsequent Selective Hydrogenation
a Unless otherwise specified, all reactions were carried out by using 1
(0.5 mmol) in the presence of 5 mol % [PdCl2(CH3CN)2] in 2 mL of acetone
at rt. b The solvent used was CH2Cl2. c The solvent used was benzene.
Scheme 5. PdCl2(MeCN)2-Catalyzed Cycloisomerization of 1 and
the Subsequent Selective Hydroboration
sodium iodide afforded 2-phenyl-4-methylfuran 4n in 80% yield.
LiBr or Bu4NBr also showed a similar effect, albeit yields of
4n were lower, while LiCl showed no effect (Scheme 8).
deuterium at the 3-position was isolated in 76% yield (eq 2).
Figure 3. ORTEP representation of 20l.
The cycloisomerization of methylene- and alkylidenecyclo-
propyl ketones 1 under the catalysis of PdCl2(CH3CN)2 and
sodium iodide afforded the corresponding 2,3,4-trisubstituted
furans 3 in good to excellent yields (Table 2). The scope of the
reaction is very broad: it is obvious that R1 can be alkyl, benzyl,
or H; R2 can be CO2Et, SO2Ph, or H; R3 group can be alkyl or
aromatic groups with an electron-withdrawing or electron-
donating group, indicating many functional groups could be
tolerated.
To some extent, this result confirmed the process from 13 to
17 via â-R4 (R4 ) D, R1 ) C7H15) elimination and deuterio-
palladation of 14 with a reversed regioselectivity. Another
evidence for the mechanism was offered by the reaction of 1l
(eq 3). The structure of the corresponding product 20l was
confirmed by the direct X-ray diffraction study (Figure 3).24
Cycloisomerization under the Catalysis of NaI in the
Presence or Absence of PdCl2(CH3CN)2. Formation of
4-Alkylidene-2,5-Dihydrofurans and 2,3,4-Trisubstituted
Furans. During the course of screening of the reaction condi-
tions for the isomerization reaction of 1n, it is surprising and
interesting to observe that the isomerization of 1n in refluxing
acetone in the presence of PdCl2(CH3CN)2 and 2.0 equiv of
(24) X-ray data for compound 20l: C12H21ClO3S, MW ) 270.72, triclinic, space
group P-1, Mo KR, final R indices [I > 2σ(I)], R1 ) 0.0422, wR2 )
0.1114, a ) 7.6277(7) Å, b ) 9.1238(9) Å, c ) 9.5937(9) Å, R ) 82.377-
(2)°, â ) 68.451(2)°, γ ) 75.268(2)°, V ) 600.01(10) Å3, T ) 293(2) K,
Z ) 2, reflections collected/unique: 3607/2625 (Rint ) 0.0260), no
observation [I > 2σ(I)] 3607, parameters 191. CCDC 224467 contains the
supplementary crystallographic data.
9
9648 J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004

Methylene- or Alkylidenecyclopropyl Ketones
A R T I C L E S
Scheme 7. Mechanism of PdCl2(MeCN)2-Catalyzed Cycloisomerization of 1
Scheme 8. PdCl2(MeCN)2-Catalyzed Cycloisomerization of 1n in
the Presence of Different Additives
cases 3 M HCl was added to induce the aromatization of 3
(entries 3, 5-7, Table 4)
The isomerization reaction of tetrasubstituted alkene 1k in
the presence of NaI occurred smoothly to afford the 3-cyclo-
hexylidene-2,3-dihydrofuran 3k in 58% yield. Here the isomer-
ization of the exo-cyclic CdC bond did not occur due to
presence of the cyclohexyl group even with prolonged reaction
time (eq 4).
Furthermore, it is interesting to note that the reaction of 1e
gave 4-octylidene-4,5-dihydrofuran Z-3e (determined by the
NOE study) in 55% yield together with the 2,3,4-trisubstituted
furans 4e (15%) within 1 h while the yield of 4e reached up to
80% after 20.5 h, indicating that the reaction proceeded through
the intermediacy of 3e (Scheme 9). Further investigation
indicated that both NaI (76%) and PdCl2(CH3CN)2 (74%) can
catalyze the transformation of Z-3e to 4e.
However, when 1a was treated with 5 mol % of NaI alone,
the nonisomerized 3-alkylidene-2,3-dihydrofuran 3a was formed
in 79% yield, indicating that the ring-opening cycloisomerization
can also be induced by a catalytic amount of NaI. Some of the
typical results are summarized in Table 3.
The structures of 3 were established by the X-ray diffraction
study of 3g (Figure 4).25
With more NaI and prolonged reaction time, although the
reaction may not be as clean as that in the presence of a Pd(II)
catalyst, the isomerized 1,2,3-trisubstituted furans were formed
slowly. Some of these results are given in Table 4. In some
A rationale for this transformation was proposed as shown
in Scheme 10. As compared to what is shown in Scheme 7, X-
may act as a nucleophile to attack the CdC bond with an
opposite regioselectivity followed by ring-opening to afford
enolate-type intermediate 22, which would undergo the intramo-
lecular substitution reaction between the in situ formed allylic
halide moiety and the enolate moiety to form 3.26 A CdC
isomerization process would lead to 2,3,4-trisubstituted furans
4.8c An alternative mechanism is that the direct attack of X-
on the nonsubstituted carbon atom of the cyclopropane ring
generates 2-alkylidenehomoallylic halide intermediate 23,27
which can then undergo a 5-exo-tet cyclization,28 just as shown
in path B.
(26) (a) Negishi, E.; Coperet, S. M.; Ma, S.; Mita, T.; Sugihara, T.; Tour, J. M.
J. Am. Chem. Soc. 1996, 118, 5919. (b) Negishi, E.; Coperet, S. M.; Ma,
S.; Mita, T.; Sugihara, T.; Tour, J. M. J. Am. Chem. Soc. 1996, 118, 5904.
(c) Gagnier, S. V.; Larock, R. C. J. Am. Chem. Soc. 2003, 125, 4804.
(27) (a) Miller, R. D.; Mckean, D. R. J. Org. Chem. 1981, 46, 2412. (b) Dieter,
R. K.; Pounds, S. J. Org. Chem. 1982, 47, 3174. (c) Lautens, M.; Han, W.
J. Am. Chem. Soc. 2002, 124, 6312. (d) Alper, P. B.; Meyers, C.; Lerchner,
A.; Siegel, D. R.; Carreira, E. M. Angew. Chem., Int. Ed. 1999, 38, 3186.
For an account of nucleophilic ring-opening of cyclopropanes, see:
Danishefsky, S. Acc. Chem. Res. 1979, 12, 66. We thank the referees for
the suggestion of this possibility.
(25) X-ray data for compound 3g: C16H20O3S, MW ) 292.38, triclinic, space
group P-1, Mo KR, final R indices [I > 2σ(I)], R1 ) 0.0510, wR2 )
0.1042, a ) 7.9721(9) Å, b ) 9.2400(11) Å, c ) 11.3859(13) Å, R )
109.621(2)°, â ) 94.117(2)°, γ ) 101.647(2)°, V ) 764.84(15) Å3, T )
293(2) K, Z ) 2, reflections collected/unique: 4763/3441 (Rint ) 0.0368),
no observation [I > 2σ(I)] 3441, parameters 239. CCDC 224466 contains
the supplementary crystallographic data.
(28) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
9
J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004 9649

A R T I C L E S
Ma et al.
Table 2. Cycloisomerization of Ketones 1 under the Catalysis of Pd(II) Leading to Furans 3a
1
NaI
(equiv)
time
(h)
yield of
4 (%)
1
2
3
entry
R
R
R
1
2
C7H15
C4H9
Bn
TBSO(CH2)3
C7H15
CO2Et
CO2Et
CO2Et
CO2Et
SO2Ph
1f
Me (1a)
Me (1b)
Me (1c)
Me (1d)
Me (1f)
2
10
74 (4a)
2
14
13.5
26
24
6c
74 (4b)
78 (4c)
82 (4d)
3
2
4
2
5
2
84 (4f + 3f)d
89 (4f)
6b
7
0.2
2
C4H9
SO2Ph
1g
Me (1g)
Ph (1h)
24
8.5c
24
8c
6
6
12
12
10
5
6
5
76 (4g + 3g)e
72 (4g)
8b
9
0.7
2
C7H15
CO2Et
1h
88 (4h + 3h)f
82 (4h)
10b
11
12
13
14
15
16
17
18
19
20
21
1
H
H
H
H
H
H
H
H
H
H
H
H
p-MeC6H4 (1o)
p-MeOC6H4 (1p)
p-FC6H4 (1q)
p-ClC6H4 (1r)
p-BrC6H4 (1s)
p-IC6H4 (1t)
1-naphthyl (1u)
2-furyl (1v)
PhC2H4 (1w)
2
73 (4o)
H
2
88 (4p)
H
2
84 (4q)
H
2
69 (4r)
H
2
76 (4s)
H
2
72 (4t)
H
2
83 (4u)
H
2
70 (4v)
H
2
12
11
14
77 (4w)
72 (4x)
H
p-MeOC6H4C2H4 (1x)
BnOC3H6 (1y)
2
H
2
66 (4y)
a Unless otherwise specified, the reaction was carried out using 1 (0.25-1.5 mmol) in the presence of 5 mol % PdCl2(CH3CN)2 and sodium iodide in 2
mL of acetone under reflux. b 3 mL of 3 M HCl was added to the in situ formed product for aromatization. c The time referred to the Pd-catalyzed reaction
only. d A mixture of 4f and 3f (4f:3f ) 1:9.6) was formed. e A mixture of 4g and 3g (4g:3g ) 3.2:1) was formed. f A mixture of 4h and 3h (4h:3h ) 1:5.5)
was formed.
Scheme 9. PdCl2(MeCN)2-Catalyzed Cycloisomerization of 1e in the Presence of NaI
Table 3. Cycloisomerization of Ketones 1 under the Catalysis of
Sodium Iodide Leading to 3-Alkyliene-2,3-dihydrofurans 3a
1
time
(h)
yield of
3 (%) (Z/E)
1
2
3
entry
R
R
R
1
2
3
4
5
6
C7H15
C4H9
Bn
C7H15
C4H9
C7H15
CO2Et
CO2Et
CO2Et
COCH3
SO2Ph
CO2Et
Me (1a)
Me (1b)
Me (1c)
Me (1e)
Me (1g)
Ph (1h)
11
3
2.5
1.5
2.5
2.5
79 (3a) (2.3:1)
46 (3b) (3:1)
80 (3c) (1.5:1)
79 (3e) (1.9:1)
78 (E-3g)b
79 (3h) (3.3:1)
Figure 4. ORTEP representation of 3g.
a Unless otherwise specified, the reaction was carried out using 1 (0.25-
0.5 mmol) in the presence of 5 mol % sodium iodide in 2 mL of acetone
under reflux. b Only one isomer was observed. The structure of E-3g was
confirmed by the X-ray diffraction study (Figure 4).
the chemisty of 1 with a Pd(II) catalyst, we wish to explore the
chemistry of 1 under a Pd(0) catalyst. The reaction of alkyli-
denecyclopropyl ketone 1a in the presence of a catalytic amount
of different Pd(0) catalyst in MeCN was examined, and the
results were listed in Table 5. Under the catalysis of Pd2(dba)2‚
CHCl3 together with a ligand and the treatment of the in situ
Cycloisomerization under the Catalysis of Pd(PPh3)4.
Formation of 2,4,5-Trisubstituted 3-Alkylidene-2,3-dihydro-
furans and 2,3,4,5-Tetrasubstituted Furans. After studying
9
9650 J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004

Methylene- or Alkylidenecyclopropyl Ketones
A R T I C L E S
Table 4. Cycloisomerization of Ketones 1 under the Catalysis of
Sodium Iodide Leading to Furans 4a
If the reaction mixture was submitted directly to chromatog-
raphy on silica gel without the treatment of 3 M HCl, the
unisomerized 4-methylene-substituted furans 5 may be isolated
(Table 8). In some cases, the reaction was carried out in the
presence of Et3N to avoid the transformation of 5 to 6 (entries
1 and 4, Table 8). With cyclohexylidene-substituted cyclopropyl
ketones 1j-k, the isomerization of the exo CdC bond is not
possible; thus, 5j-k were formed in high yields respectively
(Scheme 11).
1
NaI
(equiv) (h)
time
yield of
4 (%)
1
2
3
entry
R
R
R
1
2
C7H15
C4H9
CO2Et Me (1a)
CO2Et Me (1b)
CO2Et Me (1c)
1.0
1.0
24 75 (4a)
12 92 (4b)
2.5 79 (4c)
16 80 (4d)
1.5 94 (4f)
2.5 52 (4g)
1.5 68 (4h)
42 90 (4n)
96 57 (4o)
Based on the isolation of 5-type product, a mechanism was
proposed (Scheme 12). The regiospecific oxidative addition of
the distal C-C bond of 1 would afford palladacyclobutane
intermadiate 24, which may be transformed into enolate-type
allylic palladium intermediate 25.6c,29 Reductive elimination or
intramolecular allylic substitution of 25 at the more substituted
terminal30 would lead to 5, which can be aromatized to give
tetrasubstituted furans 6.
In conclusion, we have observed three different types of
reactions for ring-opening cycloisomerization of methylene- or
alkylidenecyclopropyl ketones. With the application of different
reaction conditions and catalysts, a highly selective formation
of 4H-pyrans, 3-alkylidene-2,3-dihydrofurans (or 2,4- or 2,3,4-
trisubstituted furans), and 2,3,4,5-tetrasubstituted furans (or
3-alkylidene-2,4,5-trisubstituted- 2,3-dihydrofurans) can be real-
ized. Due to the easy availability of the starting materials and
synthetic potential of these products, this methodology will show
its utility in organic synthesis. Further studies in this area are
being pursued in our laboratory.
3b Bn
0.05
1.0
0.05
0.05
0.10
0.2
4
TBSO(CH2)3 CO2Et Me (1d)
5b C7H15
SO2Ph Me (1f)
SO2Ph Me (1g)
CO2Et Ph (1h)
6b C4H9
7b C7H15
8
9
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph (1n)
p-MeC6H4 (1o)
p-MeOC6H4 (1p)
p-FC6H4 (1q)
p-ClC6H4 (1r)
p-BrC6H4 (1s)
p-IC6H4 (1t)
1-naphthyl (1u)
2-furyl (1v)
p-MeOC6H4C2H4 (1x) 1.0
BnOC3H6 (1y) 0.2
0.2
10
11
12
13
14
15
16
17
18
0.2 144 61 (4p)
0.2
0.2
0.2
0.2
0.2
0.2
37 76 (4q)
24 71 (4r)
48 81 (4s)
24 73 (4t)
48 98 (4u)
30 78 (4v)
96 67 (4x)
96 24 (4y)
a The reaction was carried out using 1 (0.25-0.5 mmol) in the presence
of sodium iodide in 2 mL of acetone under reflux. b After the starting
material was completely consumed, 3 mL of 3 M HCl was added to the
solution and the mixture was stirred under rt as monitored by TLC.
Scheme 10. Mechanism for the Conversion of
Alkylidenecyclopropyl Ketones 1 to 2,3,4-Trisubstituted Furans
Experimental Section
Starting Materials. Alkyl-1,2-dienes used in this study were
prepared from the reaction of alkyl Grignard reagents with propargyl
bromide as reported.15
Diazo compounds 7a-e were prepared from p-toluenesulfonyl azide
with corresponding acyl substrates.16
General Procedure for the Synthesis of Alkylidenecyclopropyl
Ketones: (A) 1-(Ethoxycarbonyl)-2-(octylidene)cyclopropyl Methyl
Ketone (1a): A solution of 2-diazo-3-oxobutyric acid ethyl ester 7a
(1.97 g, 13 mmol) in 15 mL of CH2Cl2 was added with a syringe to a
solution of deca-1,2-diene (13.51 g, 97 mmol) and Rh2(OAc)4 (20 mg,
0.9 mmol) in 5 mL of CH2Cl2 under reflux. After the addition was
over, the mixture was stirred for 2 h under reflux. After 7.64 g (55
mmol) of deca-1,2-diene was recovered by distillation, the residue was
purified by column chromatography on silica gel (hexane/ether ) 10:
1) to afford 1.80 g (52%) of 1a: liquid; mixture of Z/E isomers, ratio
) 2.5:1; 1H NMR (300 MHz, CDCl3) δ [5.87-5. 97 (m, 0.71 H), 5.80-
5.86 (m, 0.29 H)], 4.10-4.30 (m, 2 H), [2.33 (s, 0.87 H), 2.31 (s, 2.13
H)], 2.10-2.28 (m, 4 H), 1.36-1.50 (m, 2 H), 1.20-1.36 (m, 11 H),
0.82-0.90 (m, 3 H); MS m/z 266 (M+, 3.32), 181 (100); IR (neat)
1723, 1708, 1295, 1091 cm-1. Anal. Calcd for C16H26O3: C, 72.14; H,
9.84. Found: C, 71.96; H, 10.01.
formed product with 3 M HCl, the reaction afforded a mixture
of 2,3,4-trisubstituted furan 4a and 2,3,4,5-tetrasubstituted furan
6a with different ratios (entries 1-4, Table 5). It is quite
surprising that with Pd(PPh3)4 as the catalyst tetrasubstituted
furan 6a was formed highly selectively in MeCN (entry 7, Table
5)! With PPh3 as the catalyst, the reaction can also occur;
however, instead of 4a and 6a, a mixture of 4a and 3a with a
ratio of 1:29 was formed. The reaction can also proceed in the
absence of any catalyst at 80 °C to afford a mixture of 4a and
3a in a 2.5:1 ratio (entry 6, Table 5). The solvent effect on the
Pd(PPh3)4-catalyzed isomerization of 1 was shown in Table 6
with the best solvent being MeCN. Some of the typical examples
under the catalysis of Pd(PPh3)4 in MeCN are summarized in
Table 7.
1-(Ethoxycarbonyl)-2-(1′-deutrooctylidene)cyclopropyl Methyl
Ketone (18): The reaction of 2-diazo-3-oxobutyric acid ethyl ester 7a
(2.35 g, 15 mmol) with 3-deutro-1,2-heptadiene (5.32 g, 39 mmol) and
Rh2(OAc)4 (33 mg, 0.075 mmol) afforded 1.66 g (41%) of 18 as an
E/Z mixture (Z/E ) 1.7:1). 1H NMR (300 MHz, CDCl3) δ 4.10-4.30
(m, 2 H), [2.33 (s, 1.06 H), 2.31 (s, 1.94 H)], 2.10-2.25 (m, 4 H),
(29) Binger, P. Angew. Chem., Int. Ed. Engl. 1972, 11, 433.
(30) (a) Tsuji, J.; Watanabe, H.; Minami, I.; Shimizu, I. J. Am. Chem. Soc. 1985,
107, 21969. (b) Minami, I.; Yuhara, M.; Tsuji, J. Tetrahedron Lett. 1987,
8, 629. (c) Minami, I.; Yuhara, M.; Watanabe, H.; Tsuji, J. J. Organomet.
Chem. 1987, 334, 225. (d) Kadota, J.; Komori, S.; Fukumoto, Y.; Murai,
S. J. Org. Chem. 1999, 64, 7523. (e) Kadota, J.; Chatani, N.; Murai, S.
Tetrahedron 2000, 56, 2231.
9
J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004 9651

A R T I C L E S
Ma et al.
Table 5. Effects of Catalyst on the Pd(0)-Catalyzed Cycloisomerization of 1aa
temp
(°C)
time
(h)
yield (%)
(6a:4a)
entry
catalyst
1
2
3
4
5
6
7
Pd2(dba)3‚CHCl3/PCy3
Pd2(dba)3‚CHCl3/P(R-furanyl)3
Pd2(dba)3/(t-Bu)3P
Pd2(dba)3‚CHCl3/PPh3
PPh3(20 mmol %)
80
80
80
80
80
80
80
13.5
13.5
12
27.5
42
50 (1:2.5)
47 (2.5:1)
39 (1:5.6)
74 (9:1)
47 (4a:3a ) 1:29)
22 (4a:3a ) 2.5:1)
84 (50:1)
48
12
Pd(PPh3)4
a Unless otherwise specified, all reactions were conducted by using 1a (0.25-0.5 mmol) with 5 mmol % catalyst in 3 mL of CH3CN.
Table 6. Effects of Solvent on Cycloisomorization of 1aa
temp
(°C)
time
(h)
yield (%)
(6a:4a)
entry
solvent
catalyst
1b
2
3
4
5
6
7
THF
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
80
reflux
80
80
80
14
6
72 (6.7:1)
61 (12:1)
complicated
68 (40:1)
79 (18:1)
37 (3.5:1)
84 (50:1)
acetone
CHCl3
dioxane
toluene
DMF
10
13
12.5
8.5
12
80
80
CH3CN
a Unless otherwise specified, all reactions were carried out by using 1a (0.25-0.5 mmol) with 5 mmol % Pd(PPh3)4 in 3 mL of solvent. b 10 mol %
Pd(PPh3)4 was used.
Table 7. Cycloisomerization of Ketones 1 under the Catalysis of
Pd(0) Leading to Furans 6a
Table 8. Cycloisomerization of Ketones 1 under the Catalysis of
Pd(0) Leading to 5 with an exo-Cyclic Carbon-Carbon Double
Bonda
1
time
(h)
yield of
6 (%)
1
time
(h)
yield of
5 (%)
1
2
3
entry
R
R
R
1
2
3
entry
R
R
R
1
2
C7H15
C4H9
CO2Et
CO2Et
CO2Et
COCH3
SO2Ph
CO2Et
Me (1a)
Me (1b)
Me (1d)
Me (1e)
Me (1f)
Ph (1h)
12
12
22
13
29
48
84 (6a)
78 (6b)
62 (6d′)
75 (6e)
74 (6f)
77 (6h)
1b
2
C7H15
TBSO(CH2)3
C7H15
CO2Et
CO2Et
SO2Ph
CO2Et
Me (1a)
Me (1d)
Me (1f)
Ph (1h)
14.5
12
13
90 (5a)
90 (5d)
86 (5f)
70 (5h)
3b,c
4
TBSO(CH2)3
C7H15
3
4b,c
C7H15
34
5
C7H15
C7H15
6b
a Unless otherwise specified, the reaction was carried out using 1 (0.25-
0.5 mmol) in the presence of 5 mol % Pd(PPh3)4 in 4 mL of CH3CN under
80 °C. b 0.2-0.5 mL Et3N was added to avoid the isomerization from 5 to
6. c 10 mol % Pd(PPh3)4 was used.
a Unless otherwise specified, the reaction was carried out using 1 (0.25-
0.5 mmol) in the presence of 5 mol % Pd(PPh3)4 in 4 mL of CH3CN under
80 °C. After the starting material was completely consumed, the solvent
was evaporated. Then 3 mL of THF and 3 mL of 3 M HCl were added to
the residue, and the mixture was stirred under rt as monitored by TLC.b 10
mol % Pd(PPh3)4 was used. c The TBS group was removed due to the
presence of HCl; thus, the product was 6d′.
MHz, CDCl3) δ [5.87-5.95 (m, 0. 68 H), 5.80-5.87 (m, 0.32 H)],
4.13-4.30 (m, 2 H), [2.34 (s, 0.96 H), 2.32 (s, 2.04 H)], 2.10-2.30
(m, 4 H), 1.37-1.50 (m, 2 H),1.20-1.37 (m, 5 H), 0.87 (t, J ) 7.2
Hz, 3 H); MS m/z 225 (M+ + 1, 69.06), 181 (100); IR (neat) 1708,
1296, 1091 cm-1. Anal. Calcd for C13H20O3: C, 69.61; H, 8.99.
Found: C, 69.54; H, 9.34.
1.36-1.50 (m, 2 H), 1.20-1.36 (m, 11 H), 0.82-0.94 (m, 3 H); MS
m/z 267 (M+, 0.87), 43 (100); IR (neat) 1721, 1708, 1294, 1101 cm-1
.
HRMS calcd for C16H25DO3: 267.19447. Found: 267.19612.
(C) 1-(Ethoxycarbonyl)-2-(2′-phenylethylidene)cyclopropyl Meth-
yl Ketone (1c): The reaction of 2-diazo-3-oxobutyric acid ethyl ester
7a (3.97 g, 25 mmol) with buta-2,3-dienylbenzene (13.22 g, 102 mmol)
and Rh2(OAc)4 (22 mg + 22 mg + 14 mg, 0.13 mmol) afforded 3.58
(B) 1-(Ethoxycarbonyl)-2-(pentylidene)cyclopropyl Methyl Ke-
tone (1b): The reaction of 2-diazo-3-oxobutyric acid ethyl ester 7a
(3.15 g, 20 mmol) with hepta-1,2-diene (13.53 g, 141 mmol) and Rh2-
(OAc)4 (20 mg + 18 mg + 10 mg, 0.11 mmol) afforded 1.91 g (43%)
1
1
of 1b: liquid; mixture of Z/E isomers, ratio ) 2.1:1; H NMR (300
g (56%) of 1c: liquid; mixture of Z/E isomers, ratio ) 1:1; H NMR
9
9652 J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004

Methylene- or Alkylidenecyclopropyl Ketones
A R T I C L E S
Scheme 11. Pd(PPh3)4-Catalyzed Cyclization of 1j-k
H), 2.60-2.70 (m, 1 H), 2.25-2.35 (m, 3 H), 2.06 (s, 3 H), 1.43-
1.55 (m, 2 H), 1.30-1.43 (m, 2 H), 0.91 (t, J ) 7.2 Hz, 3 H); 13C
NMR (75.4 MHz, CDCl3) δ 196.8, 139.3, 133.6, 129.1, 128.7, 125.1,
118.4, 53.6, 31.0, 30.4, 26.4, 22.2, 17.5, 13.8; MS m/z 292 (M+, 1.8),
43 (100); IR (neat) 1705, 1585, 1319, 1158 cm-1. Anal. Calcd for
C16H20O3S: C, 65.72; H, 6.89. Found: C, 65.53; H, 6.88.
(H) 1-(Ethoxycarbonyl)-2-(octylidene)cyclopropyl Phenyl Ketone
(1h): The reaction of 2-diazo-3-oxo-3-phenylpropionic acid ethyl ester
7e (3.27 g, 15 mmol) with deca-1,2-diene (17.89 g, 130 mmol) and
Rh2(OAc)4 (22 mg, 0.05 mmol) afforded 1.94 g (40%) of 1h with 13.16
g (95 mmol) of deca-1,2-diene recovered. 1h: liquid; mixture of Z/E
Scheme 12. Mechanism for Pd(PPh3)4-Catalyzed Cyclization of 1
1
isomers; H NMR (300 MHz, CDCl3) δ 7.90-8.00 (m, 2 H), 7.40-
7.60 (m, 3 H), 5.95-6.07 (m, 1 H), 3.97-4.18 (m, 2 H), 2.07-2.43
(m, 4 H), 1.37-1.55 (m, 2 H), 1.15-1.37 (m, 8 H), 1.01 (t, J ) 7.5
Hz, 3 H), 0.87 (t, J ) 6.3 Hz, 3 H); MS m/z 328 (M+, 7.73), 43 (100);
IR (neat) 1732, 1685, 1599, 1259, 1121 cm-1. Anal. Calcd for
C21H28O3: C, 76.79; H, 8.59. Found: C, 76.81; H, 8.59.
(I) 1-(Ethoxycarbonyl)-2,2-(cyclohexylidene)cyclopropyl Methyl
Ketone (1j): The reaction of 2-diazo-3-oxobutyric acid ethyl ester 7a
(3.11 g, 20 mmol) with vinylidenecyclohexane (9.51 g, 88 mmol) and
Rh2(OAc)4 (28 mg + 20 mg, 0.11 mmol) afforded 2.71 g (57%) of 1j:
liquid; 1H NMR (300 MHz, CDCl3) δ 4.19 (q, J ) 7.2 Hz, 2 H), 2.25
(s, 3 H), 2.17-2.40 (m, 4 H), 2.10-2.17 (m, 2 H), 1.40-1.70 (m, 6
H), 1.25 (t, J ) 7.2 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 201.1,
169.1, 131.0, 114.9, 60.9, 39.9, 33.0, 32.8, 27.6, 27.2, 27.0, 25.9, 17.6,
13.8; MS m/z 236 (M+, 2.37), 43 (100); IR (neat) 1733, 1705, 1293,
1104 cm-1. HRMS calcd for C14H20O3: 236.14125. Found: 236.14358.
(J) 1-Acetyl-2-(cyclohexylidene)cyclopropyl Methyl Ketone (1k):
The reaction of 3-diazopenta-2,4-dione 7b (2.52 g, 20 mmol) with
vinylidenecyclohexane (6.20 g, 57 mmol) and Rh2(OAc)4 (9 mg + 12
(300 MHz, CDCl3) δ 7.10-7.40 (m, 5 H), [6.05-6.15 (m, 0.5 H),
5.95-6.05 (m, 0.5 H)], 4.20 (m, 2 H), 3.50-3.65 (m, 2 H), [2.34 (s,
1.5 H), 2.33 (s, 1.5 H)], 2.05-2.30 (m, 2 H), 1.18-1.40 (m, 3 H); MS
m/z 258 (M+, 3.66), 91(100); IR (neat) 1720, 1708, 1603, 1296, 1091
cm-1. HRMS cacld for C16H18O3: 258.12560. Found: 258.12630.
(D) 1-(Ethoxycarbonyl)-2-((4′-tert-butyldimethylsilyloxyl)butyl-
idene)cyclopropyl Methyl Ketone (1d): The reaction of 2-diazo-3-
oxobutyric acid ethyl ester 7a (1.32 g, 8.5 mmol) with 6-(tert-
butyldimethylsilyloxyl)hexa-1,2-diene (5.30 g, 25 mmol) and Rh2(OAc)4
(20 mg + 20 mg, 0.09 mmol) afforded 1.17 g (41%) of 1d: liquid;
mixture of Z/E isomers, ratio ) 3.4:1; 1H NMR (300 MHz, CDCl3) δ
[5.90-6.00 (m, 0.78 H), 5.80-5.90 (m, 0.22 H)], 4.10-4.30 (m, 2
H), 3.60 (t, J ) 6.3 Hz, 2 H), [2.33 and 2.31 (s, 3 H)], 2.10-2.42 (m,
4 H), 1.52-1.82 (m, 2 H), 1.25 (t, J ) 7.5 Hz, 3 H), [0.87 and 0.84 (s,
9 H)], 0.03 (s, 6 H); MS m/z 341 (M+ + 1, 0.90), 325 (M+ - CH3,
0.82), 43 (100); IR (neat) 1723, 1709, 1295, 1257, 1093 cm-1. HRMS
calcd for C17H29O4Si [M+ - CH3]: 325.18351. Found 325.18780.
(E) 1-Acetyl-2-(octylidene)cyclopropyl Methyl Ketone (1e): The
reaction of 3-diazopenta-2,4-dione 7b (2.78 g, 18 mmol) with deca-
1,2-diene (14.16 g, 103 mmol) and Rh2(OAc)4 (22 mg + 22 mg, 0.1
mmol) afforded 1.20 g (28%) of 1e: liquid; mixture of Z/E isomers,
ratio ) 2.5:1; 1H NMR (300 MHz, CDCl3) δ [5.90-5.97 (m, 0.71 H),
5.80-5.90 (m, 0.29 H)], 2.10-2.27 (m, 4 H), [2.16 (s, 1.74 H), 2.13
(s, 4.26 H)], 1.36-1.50 (m, 2 H), 1.19-1.36 (m, 8 H), 0.80-0.90 (m,
3 H). MS m/z 236 (M+, 1.78), 43 (100); IR (neat) 1709, 1695, 1654
cm-1. HRMS calcd for C15H24O2: 236.17764. Found: 236.18220.
(F) 1-(Benzenesulfonyl)-2-(octylidene)cyclopropyl Methyl Ketone
(E-1f): The reaction of 1-(benzenesulfonyl)-1-diazopropan-2-one 7c
(4.49 g, 20 mmol) with deca-1,2-diene (27.29 g, 200 mmol) and Rh2-
(OAc)4 (22 mg, 0.05 mmol) afforded 2.56 g (38%) of E-1f as an oil,
and only one isomer was formed. 1H NMR (300 MHz, CDCl3) δ 7.95-
8.00 (m, 2 H), 7.48-7.66 (m, 3 H), 6.05-6.15 (m, 1 H), 2.60-2.70
(m, 1 H), 2.25-2.35 (m, 3 H), 2.06 (s, 3 H), 1.40-1.60 (m, 2 H),
1.19-1.40 (m, 8 H), 0.87 (t, J ) 6.6 Hz, 3 H); 13C NMR (75.4 MHz,
CDCl3) δ 196.8, 139.2, 133.6, 129.1, 128.6, 125.1, 118.3, 53.5, 31.6,
31.3, 29.0, 28.9, 28.2, 26.2, 22.5, 17.5, 14.0; MS m/z 334 (M+, 4.45),
43 (100); IR (neat) 1706, 1586, 1320, 1157 cm-1. HRMS calcd for
C19H26O3S: 334.16026. Found: 334.16405. The stereochemistry of this
1
mg, 0.05 mmol) afforded 0.92 g (22%) of 1k: liquid; H NMR (300
MHz, CDCl3) δ 2.18-2.25 (m, 2 H), 2.10-2.18 (m, 2 H), 2.05-2.10
(m, 8 H), 1.40-1.60 (m, 6 H); 13C NMR (75.4 MHz, CDCl3) δ 202.7,
131.2, 115.4, 48.0, 33.3, 33.0, 27.2, 27.1, 26.9, 25.8, 16.8; MS m/z
206 (M+, 4.07), 43 (100); IR (neat) 1691, 1358, 1282 cm-1. HRMS
calcd for C13H18O2: 206.13068. Found: 206.13239.
(K) 1-(Benzenesulfonyl)-2-(chloromethylene)cyclopropyl Methyl
Ketone (E-1l): The reaction of 2-diazo-3-oxobutyric acid ester 7c (3.36
g, 15 mmol) with 1-chloropropa-1,2-diene (9.11 g, 122 mmol) and Rh2-
(OAc)4 (50 mg + 30 mg + 18 mg, 0.22 mmol) afforded 0.41 g (10%)
1
of E-1l: solid, mp 71-72 °C (petroleum ether/ether); H NMR (300
MHz, CDCl3) δ 7.90-7.97 (m, 2 H), 7.50-7.70 (m, 3 H), 6.70 (t, J )
3.0 Hz, 1 H), 2.71 (dd, J ) 10.8 Hz, 3.0 Hz, 1 H), 2.40 (dd, J ) 10.8,
3.0 Hz, 1 H), 2.19 (s, 3 H); 13C NMR (75.4 MHz, C6D6) δ 195.0,
138.2, 134.2, 129.1, 129.0, 120.8, 114.9, 56.1, 27.0, 18.0; MS m/z 273
(M+ + 1 (37Cl), 1.38), 271 (M+ + 1 (35Cl), 4.17), 43 (100); IR (neat)
1762, 1712, 1321, 1157 cm-1. Anal. Calcd for C12H11O3SCl: C, 53.24;
H, 4.10. Found: C, 53.17; H, 4.03.
General Procedure for the Synthesis of Methylenecyclopropyl
Ketones:19 To an oven-dried three-necked round-bottom flask charged
with a solution of methylenecyclopropyllithium (1 equiv) (prepared
from the reaction of 1.2 equiv of methylenecyclopropane with 1 equiv
of n-BuLi) was added a solution of N,N-dimethyl amide (1.2 equiv) in
THF dropwise at -78 °C under Ar. After being stirred for 2 h, the
mixture was poured into water, extracted with ether, and dried over
MgSO4. After evaporation of the solvent, the residue was purified by
column chromatography on silica gel (petroleum ether/Et2O ) 100:1)
to afford the corresponding product.
(A) Methylenecyclopropyl Phenyl Ketone (1n):31 The reaction of
N,N-dimethylbenzamide (6.6 g, 44 mmol) with methylenecyclopropyl-
lithium (35 mmol) afforded 4.93 g (89%) of 1n: liquid; 1H NMR (300
MHz, CDCl3) δ 8.00-8.08 (m, 2 H), 7.40-7.63 (m, 3 H), 5.48-5.52
(m, 1 H), 5.40-5.45 (m, 1 H), 3.20-3.30 (m, 1 H), 2.10-2.19 (m, 1
H), 1.70-1.80 (m, 1 H); 13C NMR (75.4 MHz, CDCl3) δ 196.6, 137.4,
1
product was determined by the H-1H NOESY spectra (400 MHz).
(G) 1-(Benzenesulfonyl)-2-(pentylidene)cyclopropyl Methyl Ke-
tone (E-1g): The reaction of 1-(benzenesulfonyl)-1-diazopropan-2-one
7c (2.26 g, 10 mmol) with hepta-1,2-diene (12.05 g, 125 mmol) and
Rh2(OAc)4 (24 mg + 16 mg, 0.09 mmol) afforded 0.75 g (26%) of
E-1g as an oil, and only one isomer was formed. 1H NMR (300 MHz,
CDCl3) δ 7.94-8.00 (m, 2 H), 7.48-7.66 (m, 3 H), 6.05-6.15 (m, 1
(31) Thomas, E. W.; Szmuszkovicz, J. R. J. Org. Chem. 1990, 55, 6054.
9
J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004 9653

A R T I C L E S
Ma et al.
1
132.9, 132.7, 128.5, 128.2, 103.2, 22.9, 11.7; MS m/z 158 (M+, 63.99),
(77%) of 1u: liquid; H NMR (300 MHz, CDCl3) δ 8.51 (d, J ) 8.4
Hz, 1 H), 7.92 (d, J ) 7.2 Hz, 2 H), 7.82 (d, J ) 8.1 Hz, 1 H), 7.40-
7.60 (m, 3 H), 5.50-5.55 (m, 2 H), 3.10-3.20 (m, 1 H), 2.10-2.22
(m, 1 H), 1.77 (t, J ) 8.1 Hz, 1 H); 13C NMR (75.4 MHz, CDCl3) δ
200.7, 136.3, 133.7, 133.1, 132.3, 129.9, 128.3, 127.9, 127.7, 126.4,
125.6, 124.4, 103.4, 26.7, 12.7; MS m/z 208 (M+, 56.09), 127 (100);
IR (neat) 1669, 1509 cm-1. Anal. Calcd for C15H12O: C, 86.51; H,
5.81. Found: C, 86.29; H, 5.85.
157 (100); IR (neat) 1674, 1597, 1580 cm-1
.
(B) Methylenecyclopropyl 4-Methylphenyl Ketone (1o): The
reaction of 25 mL of methylenecyclopropyllithium (0.78 M, 20 mmol)
with N,N-dimethyl-4-methylbenzamide (4.5 g, 28 mmol) afforded 3.0
g (89%) of 1o: liquid; 1H NMR (300 MHz, CDCl3) δ 7.87 (d, J ) 8.1
Hz, 2 H), 7.22 (d, J ) 8.1 Hz, 2 H), 5.40-5.45 (m, 1 H), 5.32-5.38
(m, 1 H), 3.14-3.26 (m, 1 H), 2.35 (s, 3 H), 2.00-2.12 (m, 1 H),
1.60-1.75 (m, 1 H); 13C NMR (75.4 MHz, CDCl3) δ 196.2, 143.7,
134.9, 132.8, 129.2, 128.4, 103.2, 22.7, 21.5, 11.6; MS m/z 172 (M+,
88.39), 119 (100); IR (neat) 1671, 1609 cm-1. Anal. Calcd for
C12H12O: C, 83.69; H, 7.02. Found: C, 83.64; H, 6.82.
(I) Methylenecyclopropyl 2-Furyl Ketone (1v): The reaction of
25 mL of methylenecyclopropyllithium (0.78 M, 20 mmol) with N,N-
dimethyl 2-furoyl amide (3.48 g, 25 mmol) afforded 2.27 g (79%) of
1v: liquid; 1H NMR (300 MHz, CDCl3) δ 7.53-7.57 (m, 1 H), 7.15-
7.20 (m, 1 H), 6.40-6.55 (m, 1 H), 5.40-5.45 (m, 1 H), 5.30-5.40
(m, 1 H), 3.06-3.15 (m, 1 H), 1.95-2.04 (m, 1 H), 1.62-1.72 (m, 1
H);13C NMR (75.4 MHz, CDCl3) δ 185.6, 152.6, 146.3, 132.3, 117.0,
112.0, 103.4, 22.2, 12.1; MS m/z 148 (M+, 58.89), 95 (100); IR (neat)
1666, 1569 cm-1. Anal. Calcd for C9H8O2: C, 72.96; H, 5.44. Found:
C, 72.86; H, 5.50.
(J) Methylenecyclopropyl Phenylethyl Ketone (1w): The reaction
of 25 mL of methylenecyclopropyllithium (0.78 M, 20 mmol) with
N,N-dimethyl phenylpropionamide (3.540 g, 20 mmol) afforded 2.07
g (57%) of 1w: liquid; 1H NMR (300 MHz, CDCl3) δ 7.10-7.40 (m,
5 H), 5.45-5.55 (m, 1 H), 5.30-5.45 (m, 1 H), 2.80-3.03 (m, 2 H),
2.65-2.80 (m, 2 H), 2.47-2.60 (m, 1 H), 1.75-1.90 (m, 1 H), 1.55-
1.70 (m, 1 H); 13C NMR (75.4 MHz, CDCl3) δ 206.7, 140.8, 131.4,
128.3, 128.2, 125.9, 104.1, 42.1, 29.8, 26.6, 12.1; MS m/z 186 (M+,
11.31), 91(100); IR (neat) 1699, 1604 cm-1. Anal. Calcd for C13H14O:
C, 83.83; H, 7.58. Found: C, 83.71; H, 7.46.
(K) Methylenecyclopropyl 4-Methoxylphenylethyl Ketone (1x):
The reaction of 25 mL of methylenecyclopropyllithium (0.78 M, 20
mmol) with N,N-dimethyl 4-methoxylphenylpropionamide (4.14 g, 20
mmol) afforded 1.94 g (46%) of 1x: liquid; 1H NMR (300 MHz,
CDCl3) δ 7.09 (d, J ) 8.4 Hz, 2 H), 6.82 (d, J ) 8.7 Hz, 2 H), 5.45-
5.50 (m, 1 H), 5.35-5.40 (m, 1 H), 3.77 (s, 3 H), 2.80-2.90 (m, 2 H),
2.63-2.73 (m, 2 H), 2.47-2.57 (m, 1 H), 1.75-1.85 (m, 1 H), 1.58-
1.70 (m, 1 H); 13C NMR (75.4 MHz, CDCl3) δ 206.9, 157.8, 132.9,
131.5, 129.1, 113.7, 104.1, 55.1, 42.4, 29.0, 26.7, 12.1; MS m/z 216
(M+, 14.31), 121(100); IR (neat) 1699, 1612, 1247 cm-1. Anal. Calcd
for C14H16O2: C, 77.75, H, 7.46. Found: C, 77.64, H, 7.36.
(L) Methylenecyclopropyl 3-Benzoxypropyl Ketone (1y): The
reaction of methylenecyclopropyllithium (19.2 mL, 0.78 M, 15 mmol)
with N,N-dimethyl 3-benzoxypropionamide (4.42 g, 20 mmol) afforded
3.00 g (87%) of 1y: liquid; 1H NMR (300 MHz, CDCl3) δ 7.10-7.38
(m, 5 H), 5.40-5.45 (m, 1 H), 5.28-5.34 (m, 1 H), 4.41 (s, 2 H), 3.41
(t, J ) 6.1 Hz, 2 H), 2.40-2.52 (m, 3 H), 1.70-1.90 (m, 3 H), 1.50-
1.64 (m, 1 H); 13C NMR (75.4 MHz, CDCl3) δ 207.4, 138.3, 131.7,
128.3, 127.5, 127.5, 103.9, 72.7, 69.1, 37.5, 26.5, 23.8, 12.2; MS m/z
199 (0.96), 91(100); IR (neat) 1700, 1104 cm-1. Anal. Calcd for
C15H18O2: C, 78.23; H, 7.88. Found: C, 77.76; H, 7.80.
(M) 2-(Nonylidene)cyclopropyl Phenyl Ketone (1m). The reaction
of nonanylidenecyclopropyllithium (prepared from 3.65 g, 22 mmol
with BuLi (20 mL, 1.6 M, 32 mmol)) with N,N-dimethyl benzamide
(3.725 g, 25 mmol) afforded 2.91 g (54%) of 1m: liquid, mixture of
Z/E isomers, ratio ) 1.8:1; 1H NMR (300 MHz, CDCl3) δ 7.90-8.10
(m, 2 H), 7.40-7.65 (m, 3 H), 5.77-5.90 (m, 1 H), [3.26-3.33 (m,
0.36 H), 3.20-3.26 (m, 0.64)], 2.17-2.27 (m, 1 H), 2.00-2.17 (m, 2
H), 1.65-1.82 (m, 1 H), 1.40-1.50 (m, 2 H), 1.03-1.40 (m, 10 H),
0.80-1.00 (m, 3 H); MS m/z 270 (M+, 2.55), 171(100); IR (neat) 1677,
1214 cm-1. Anal. Calcd for C19H26O: C, 84.39; H, 9.69. Found: C,
84.53; H, 9.29.
(C) Methylenecyclopropyl 4-Methoxylphenyl Ketone (1p): The
reaction of methylenecyclopropyllithium (30 mmol) with N,N-dimethyl-
4-methoxylbenzamide (5.4 g, 30 mmol) afforded 4.9 g (87%) of 1p:
1
solid, mp 33-34 °C (hexanes/ether); H NMR (300 MHz, CDCl3) δ
8.02 (m, 2 H), 6.96 (m, 2 H), 5.46-5.52 (m, 1 H), 5.38-5.45 (m, 1
H), 3.88 (s, 3 H), 3.16-3.28 (m, 1 H), 2.05-2.18 (m, 1 H), 1.60-
1.80 (m, 1 H); 13C NMR (75.4 MHz, CDCl3) δ 195.1, 163.3, 132.8,
130.4, 130.3, 113.6, 103.1, 55.3, 22.3, 11.5; MS m/z 188 (M+, 61.44),
135 (100); IR (neat) 1666, 1603, 1344, 1221 cm-1. Anal. Calcd for
C12H12O2: C, 76.57; H, 6.43. Found: C, 76.58; H, 6.54.
(D) Methylenecyclopropyl 4-Fluorophenyl Ketone (1q): The
reaction of methylenecyclopropyllithium with N,N-dimethyl 4-fluo-
robenzamide (5.0 g, 30 mmol) afforded 3.1 g (88%) of 1q: liquid; 1H
NMR (300 MHz, CDCl3) δ 7.95-8.05 (m, 2 H), 7.05-7.15 (m, 2 H),
5.42-5.50 (m, 1 H), 5.35-5.40 (m, 1 H), 3.15-3.24 (m, 1 H), 2.05-
2.15 (m, 1 H), 1.65-1.78 (m, 1 H); 13C NMR (75.4 MHz, CDCl3) δ
3
2
194.9, 167.2, 163.9, 133.8 (d, JF-C ) 3.2 Hz), 132.5, 130.8 (d, JF-C
) 9.5 Hz), 115.5 (d, JF-C ) 21.9 Hz), 103.3, 22.7, 11.7; 19F NMR
1
(282 MHz, CDCl3) δ -105.8; MS m/z 176 (M+, 63.85), 123 (100); IR
(neat) 1675, 1602, 1340 cm-1. Anal. Calcd for C11H9FO: C, 74.99; H,
5.15. Found: C, 75.18; H, 5.35.
(E) Methylenecyclopropyl 4-Chlorophenyl Ketone (1r): The
reaction of 40 mL of methylenecyclopropyllithium (0.70 M, 28 mmol)
with N,N-dimethyl 4-chlorobenzamide (7.3 g, 40 mmol) afforded 5.1
g (95%) of 1r: liquid; 1H NMR (300 MHz, CDCl3) δ 7.97 (d, J ) 8.4
Hz, 2 H), 7.47 (d, J ) 8.4 Hz, 2 H), 5.49-5.53 (m, 1 H), 5.40-5.44
(m, 1 H), 3.16-3.28 (m, 1 H), 2.10-2.20 (m, 1 H), 1.70-1.83 (m, 1
H); 13C NMR (75.4 MHz, CDCl3) δ 195.5, 139.4, 135.7, 132.5, 129.7,
128.8, 103.5, 22.8, 12.0; MS m/z 194 (M+ (37Cl), 9.65), 192 (M+ (35Cl),
30.80), 139 (100); IR (neat) 1675, 1590 cm-1. Anal. Calcd for C11H9-
ClO: C, 68.58; H, 4.71. Found: C, 68.56; H, 4.92.
(F) Methylenecyclopropyl 4-Bromophenyl Ketone (1s): The
reaction of 25 mL of methylenecyclopropyllithium (0.78 M, 20 mmol)
with N,N-dimethyl 4-bromobenzamide (5.70 g, 25 mmol) afforded 3.31
g (70%) of 1s: liquid; 1H NMR (300 MHz, CDCl3) δ 7.88 (d, J ) 8.4
Hz, 2 H), 7.62 (d, J ) 8.4 Hz, 2 H), 5.48-5.53 (m, 1 H), 5.40-5.45
(m, 1 H), 3.18-3.26 (m, 1 H), 2.08-2.20 (m, 1 H), 1.70-1.82 (m, 1
H); 13C NMR (75.4 MHz, CDCl3) δ 195.7, 136.1, 132.5, 131.8, 129.8,
128.1, 103.6, 22.8, 12.0; MS m/z 238 (M+ (81Br), 59.76), 236 (M+
(79Br), 60.10), 129 (100); IR (neat) 1675, 1586 cm-1. Anal. Calcd for
C11H9BrO: C, 55.72; H, 3.83. Found: C, 55.79; H, 4.02.
(G) Methylenecyclopropyl 4-Iodophenyl Ketone (1t): The reaction
of 30 mL of methylenecyclopropyllithium (0.70 M, 21 mmol) with
N,N-dimethyl 4-iodobenzamide (8.25 g, 30 mmol) afforded 4.49 g
1
(73%) of 1t: liquid; H NMR (300 MHz, CDCl3) δ 7.83 (d, J ) 8.7
Hz, 2 H), 7.71 (d, J ) 8.7 Hz, 2 H), 5.45-5.52 (m, 1 H), 5.38-5.42
(m, 1 H), 3.15-3.25 (m, 1 H), 2.08-2.18 (m, 1 H), 1.70-1.80 (m, 1
H); 13C NMR (75.4 MHz, CDCl3) δ 196.0, 137.85, 136.7, 132.5, 129.7,
103.6, 101.0, 22.8, 12.1; MS m/z 284 (M+, 100); IR (neat) 1671, 1581
cm-1. Anal. Calcd for C11H9IO: C, 46.51; H, 3.19. Found: C, 46.32;
H, 3.16.
(H) Methylenecyclopropyl 1-Naphthyl Ketone (1u): The reaction
of 25 mL of methylenecyclopropyllithium (0.78 M, 20 mmol) with
N,N-dimethyl 1-naphthoyl amide (4.98 g, 40 mmol) afforded 3.1 g
Typical Procedure for PdCl2(CH3CN)2-Catalyzed Cycloisomer-
ization (Procedure A). (A) 2-Methyl-3-(ethoxycarbonyl)-6-(n-hep-
tyl)-4H-pyran (2a): PdCl2(MeCN)2 (6 mg, 5 mol %) was added to a
solution of 1a (133 mg, 0.50 mmol) in 2 mL of acetone under the
atmosphere of argon. The mixture was then stirred at rt for 15 min.
Evaporation and chromatography on silica gel (petroleum ether/ether
9
9654 J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004

Methylene- or Alkylidenecyclopropyl Ketones
A R T I C L E S
100:1) under Ar afforded 106 mg (80%) of pure 2a as an air-sensitive
liquid. H NMR (300 MHz, CDCl3) δ 4.75 (t, J ) 3.6 Hz, 1 H), 4.10
Hydroboration-Oxidation Reaction of 2b. Synthesis of trans-
2-Butyl-3-hydroxy-5-(ethyloxycarbonyl)-6-methyl-3,4-dihydro-2H-
pyran (9b): Following procedure A, the reaction of 1b (224 mg, 1.0
mmol) and PdCl2(CH3CN)2 (13 mg, 0.05 mmol) in 3 mL of CH2Cl2
afforded the crude product 2b. Following procedure B, the reaction of
2b, BH3‚Et2O (0.80 mmol/mL) (1 mL, 0.80 mmol), THF (5 mL), NaOH
(3 M) (0.5 mL, 1.5 mmol), and H2O2 (30%) (0.5 mL) afforded 136 mg
1
(q, J ) 6.9 Hz, 2 H), 2.80-2.85 (m, 2 H), 2.17 (t, J ) 1.2 Hz, 3 H),
2.02 (t, J ) 7.2 Hz, 2 H), 1.37-1.50 (m, 2 H), 1.20-1.35 (m, 8 H),
1.22 (t, J ) 6.9 Hz, 3 H), 0.87 (t, J ) 6.6 Hz, 3 H); 13C NMR (75.4
Hz, CDCl3): δ 168.2, 161.0, 150.2, 100.3, 97.3, 59.8, 32.6, 31.8, 29.0,
28.9, 26.4, 22.6, 21.9, 19.1, 14.3, 14.1; MS m/z 266 (M+, 7.89), 43
(100); IR (neat) 1720, 1637, 1265, 1164 cm-1. HRMS calcd for
C16H26O3: 266.18819. Found 266.1857.
1
(59%) of 9b as solid, mp 65-66 °C (ether/hexanes). H NMR (300
MHz, CDCl3) δ 4.15 (q, J ) 7.2 Hz, 2 H), 3.70-3.88 (m, 2 H), 2.55-
2.65 (m, 1 H), 2.20-2.38 (m, 1 H), 2.25 (s, 3 H), 1.77-1.84 (bs, 1 H),
1.43-1.70 (m, 3 H), 1.20-1.43 (m, 3 H), 1.27 (t, J ) 7.2 Hz, 3 H),
0.91 (t, J ) 7.2 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 168.2, 163.5,
98.2, 79.6, 65.7, 59.8, 30.9, 28.9, 27.4, 22.6, 20.0, 14.4, 14.0; MS m/z
242 (M+, 10.71), 43 (100); IR (KBr) 3466, 1690, 1619, 1236, 1067
cm-1. Anal. Calcd for C13H22O3: C, 64.44; H, 9.15. Found: C, 64.38;
H, 9.15.
2-Methyl-3-(ethoxycarbonyl)-5-deutero-6-(n-heptyl)-4H-pyran (19):
Following procedure A, the reaction of 18 (120 mg, 0.45 mmol) and
PdCl2(MeCN)2 (5 mg, 0.02 mmol) in 2 mL of acetone afforded 91 mg
1
(76%) of 19: liquid; H NMR (300 MHz, d6-acetone) δ 4.77 (t, J )
3.6 Hz, 0.20 H), 4.13 (q, J ) 7.2 Hz, 2 H), 2.80-2.90 (m, 2 H), 2.17-
2.23 (m, 3 H), 2.04 (td, J ) 7.2, 1.2 Hz, 2 H), 1.40-1.53 (m, 2 H),
1.20-1.40 (m, 8 H), 1.24 (t, J ) 7.2 Hz, 3 H), 0.83-0.93 (m, 3 H);
13C NMR (75.4 Hz, d6-acetone) δ 168.0, 161.1, 151.0, 101.2 (t, J )
5.6 Hz), 98.2, 60.4, 33.1, 32.5, 29.8, 29.6, 27.1, 23.3, 22.6, 19.1, 14.6,
14.4; MS m/z 267 (M+, 0.88), 43 (100); IR (neat) 1721, 1638, 1265,
1165 cm-1. HRMS calcd for C16H25DO3: 267.19447. Found 267.19418.
Hydroboration-Oxidation Reaction of 2a (Procedure B). Syn-
thesis of trans-2-Heptyl-3-hydroxy-5-(ethyloxycarbonyl)-6-methyl-
3,4-dihydro-2H-pyran (9a): A mixture of 1a (266 mg, 1.0 mmol) and
PdCl2(CH3CN)2 (13 mg, 0.05 mmol) in 3 mL of CH2Cl2 was stirred
for 5 min at rt to afford the crude product 1a (procedure A). After
removal of the sovlent, 5 mL of dry THF was added to the reaction
tube, which was followed by the addition of 0.1 mL of 10 M BH3‚
SMe2 at 0 °C. After the mixture was stirred for 1 h at rt, 0.5 mL of 3
N NaOH and 0.5 mL of 30% H2O2 were added at 0 °C and the mixture
was stirred overnight at rt. After the usual workup, the residue was
purified via column chromatography on silica gel to afford 166 mg
Hydrogenation Reaction of 2b. Synthesis of 2-Butyl-5-(ethyloxy-
carbonyl)-6-methyl-3,4-dihydro-2H-pyran (10b): Following proce-
dure A, the reaction of 1b (224 mg, 1.0 mmol) and PdCl2(CH3CN)2
(13 mg, 0.05 mmol) in 2 mL of CH2Cl2 afforded the crude product 2b.
Then following procedure C, the reaction of 2b, 50 mg of 10% of Pd-C
in 10 mL of methanol under 10 atm of H2 at 50 °C afforded 112 mg
(50%) of 10b as a liquid. 1H NMR (300 MHz, CDCl3) δ 4.13 (q, J )
7.2 Hz, 2 H), 3.72-3.85 (m, 1 H), 2.30-2.44 (m, 1 H), 2.10-2.28
(m, 1 H), 2.20 (s, 3 H), 1.78-1.90 (m, 1 H), 1.56-1.73 (m, 1 H),
1.20-1.56 (m, 6 H), 1.25 (t, J ) 7.2 Hz, 3 H), 0.90 (t, J ) 7.2 Hz, 3
H); 13C NMR (75.4 MHz, CDCl3) δ 168.8, 164.8, 100.8, 76.5, 59.4,
34.5, 27.3, 26.6, 22.6, 21.4, 20.4, 14.4, 14.0; MS m/z 226 (M+, 17.02),
97 (100); IR (neat) 1707, 1623, 1272, 1087 cm-1. HRMS calcd for
C13H22O3: 226.15690. Found: 226.15489.
(C) 2-Methyl-3-(ethoxycarbonyl)-6-benzyl-4H-pyran (2c): Fol-
lowing procedure A, the reaction of 1c (150 mg, 0.58 mmol) and PdCl2-
(MeCN)2 (5 mg, 0.02 mmol) in 2 mL of CH2Cl2 afforded 120 mg (80%)
1
(59%) of 9a (procedure B): solid; mp 41-42 °C (Et2O/hexanes); H
NMR (300 MHz, CDCl3) δ 4.15 (q, J ) 7.2 Hz, 2 H), 3.73-3.85 (m,
2 H), 2.45-2.63 (m, 1 H), 2.27-2.38 (m, 1 H), 2.28 (s, 3 H), 1.65-
1.80 (bs, 1 H), 1.45-1.65 (m, 4 H), 1.20-1.45 (m, 8 H), 1.28 (t, J )
7.1 Hz, 3 H), 0.88 (t, J ) 7.0 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3)
δ 168.2, 163.5, 98.2, 79.6, 65.7, 59.8, 31.8, 31.2, 29.4, 29.2, 28.9, 25.2,
22.6, 20.0, 14.4, 14.1; MS m/z 284 (M+, 6.62), 43 (100); IR (KBr)
3480, 1682, 1610, 1229, 1095 cm-1. Anal. Calcd for C16H28O3: C,
67.57; H, 9.92. Found: C, 67.59; H, 9.91.
1
of 2c: liquid; H NMR (300 MHz, CDCl3) δ 7.12-7.30 (m, 5 H),
4.60-4.68 (m, 1 H), 4.08 (q, J ) 7.2 Hz, 2 H), 3.26 (s, 2 H), 2.78-
2.82 (m, 2 H), 2.12 (t, J ) 0.9 Hz, 3 H), 1.19 (t, J ) 7.2 Hz, 3 H); 13
C
NMR (75.4 MHz, CDCl3) δ 168.0, 160.9, 149.2, 137.2, 128.9, 128.3,
126.5, 100.4, 99.3, 59.9, 39.1, 22.0, 19.1, 14.3; MS m/z 258 (M+, 4.27),
229 (100); IR (neat) 1720, 1638 cm-1. HRMS calcd for C16H18O3:
258.12559. Found: 258.13650.
Hydrogenation Reaction of 2a (Procedure C). Synthesis of
2-Heptyl-5-(ethoxycarbonyl)-6-methyl-3,4-dihydro-2H-pyran (10a):
Following procedure A, the reaction of 1a (170 mg, 0.64 mmol) and
PdCl2(CH3CN)2 (8 mg, 0.3 mmol) in 2.5 mL of CH2Cl2 afforded the
crude product 2a. Then 50 mg of 10% of Pd-C and 10 mL of methanol
were added. The mixture was stirred for 17 h at 50 °C under 10 atm
of H2. After the usual workup, the reaction afforded 104 mg (60%) of
Hydroboration-Oxidation Reaction of 2c. Synthesis of trans-2-
Benzyl-3-hydroxy-5-(ethyloxycarbonyl)-6-methyl-3,4-dihydro-2H-
pyran (9c): Following procedure A, the reaction of 1c (258 mg, 1.0
mmol) and PdCl2(CH3CN)2 (7.8 mg, 0.03 mmol) in 2 mL of CH2Cl2
afforded the crude product 2c. Following procedure B, the reaction of
2c, BH3‚SMe2 (10 M) (0.8 mL,0.80 mmol), NaOH (3 M) (0.5 mL, 1.5
mmol), and H2O2 (30%) (0.5 mL) in 5 mL of THF afforded 149 mg
1
1
10a (procedure C): liquid; H NMR (300 MHz, CDCl3) δ 4.13 (q, J
(54%) of 9c as solid, mp 70-71 °C (Et2O/hexanes). H NMR (300
) 7.2 Hz, 2 H), 3.72-3.82 (m, 1 H), 2.30-2.44 (m, 1 H), 2.10-2.28
(m, 1 H), 2.20 (s, 3 H), 1.80-1.90 (m, 1 H), 1.56-1.70 (m, 1 H),
1.37-1.56 (m, 3 H), 1.20-1.37 (m, 9 H), 1.25 (t, J ) 6.9 Hz, 3 H),
0.86 (t, J ) 6.6 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 168.8, 164.8,
100.8, 76.5, 59.5, 34.8, 31.8, 29.5, 29.2, 26.7, 25.2, 22.6, 21.4, 20.4,
14.4, 14.1; MS m/z 268 (M+, 24.80), 97 (100); IR (neat) 1708, 1623,
1271, 1086 cm-1. HRMS cacld for C16H28O3: 268.20385. Found:
268.19920.
MHz, CDCl3) δ 7.15-7.40 (m, 5 H), 4.15 (q, J ) 7.5 Hz, 2 H), 4.02-
4.10 (m, 1 H), 3.75 (q, J ) 5.7 Hz, 1 H), 2.80-3.00 (m, 2 H), 2.66
(ddd, J ) 16.5, 5.1 and 1.2 Hz, 1 H), 2.28-2.40 (m, 1 H), 2.23 (s, 3
H), 1.92 (bs, 1 H), 1.28 (t, J ) 7.5 Hz, 3 H); 13C NMR (75.4 MHz,
CDCl3) δ 168.1, 163.4, 136.99, 129.42, 128.4, 126.6, 98.5, 80.0, 64.9,
59.9, 37.4, 29.1, 19.9, 14.6; MS m/z 276 (M+, 3.54), 146 (100); IR
(KBr) 3464, 1684, 1623, 1230 cm-1. Anal. Calcd for C16H20O3: C,
69.55; H, 7.29. Found: C, 69.61; H, 7.32.
(B) 2-Methyl-3-(ethoxycarbonyl)-6-(n-butyl)-4H-pyran (2b): Fol-
lowing procedure A, the reaction of 1b (112 mg, 0.5 mmol) and PdCl2-
(MeCN)2 (5 mg, 0.02 mmol) in 2 mL of acetone afforded 84 mg (75%)
Hydrogenation Reaction of 2c. Synthesis of 2-Benzyl-5-(ethyl-
oxycarbonyl)-6-methyl-3,4-dihydro-2H-pyran (10c): Following pro-
cedure A, the reaction of 1c (100 mg, 0.38 mmol) and PdCl2(CH3-
CN)2 (13 mg, 0.05 mmol) in 2 mL of CH2Cl2 afforded the crude product
2c. Following procedure C, the reaction of 2c and 50 mg of 10% of
Pd-C in 10 mL of methanol under 10 atm of H2 at 50 °C afforded 54
1
of 2b: liquid; H NMR (300 MHz, CDCl3) δ 4.62-4.68 (m, 1 H),
4.14 (q, J ) 6.9 Hz, 2 H), 2.80-2.88 (m, 2 H), 2.20 (t, J ) 1.2 Hz, 3
H), 2.00 (t, J ) 6.9 Hz, 2 H), 1.20-1.48 (m, 4 H), 1.25 (t, J ) 6.9 Hz,
3 H), 0.88 (t, J ) 6.9 Hz, 3 H); 13C NMR (75.4 MHz, d6-acetone): δ
168.0, 161.1, 151.0, 101.2, 98.2, 60.3, 32.9, 29.3, 22.7, 22.6, 19.1, 14.6,
14.1; MS m/z 224 (M+, 3.96), 43 (100); IR (neat) 1720, 1637, 1268,
1072 cm-1. HRMS calcd for C13H20O3: 224.14124. Found: 224.13774.
1
mg (54%) of 10c: liquid; H NMR (300 MHz, CDCl3) δ 7.18-7.36
(m, 5 H), 4.14 (q, J ) 6.9 Hz, 2 H), 3.95-4.08 (m, 1 H), 3.02 (dd, J
) 13.2, 6.6 Hz, 1 H), 2.79 (dd, J ) 13.8, 6.6 Hz, 1 H), 2.36-2.44 (m,
1 H), 2.23 (s, 3 H), 2.10-2.25 (m, 1 H), 1.80-1.90 (m, 1 H), 1.40-
9
J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004 9655

A R T I C L E S
Ma et al.
1.58 (m, 1 H), 1.27 (t, J ) 7.2 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3)
δ 168.6, 164.5, 137.5, 129.5, 128.3, 126.5, 101.0, 77.0, 59.5, 41.1, 25.8,
21.2, 20.4, 14.4; MS m/z 260 (M+, 0.63), 130 (100); ESI-MS 283.2
(M + Na+); IR (neat) 1704, 1624, 1271, 1076 cm-1. HRMS calcd for
C16H20O3 Na: 283.13040. Found: 283.13047.
(D) 2-Methyl-3-(ethoxycarbonyl)-6-(3′-tert-butyldimethylsilyloxy-
propyl)-4H-pyran (2d): Following procedure A, the reaction of 1d
(130 mg, 0.38 mmol) and PdCl2(MeCN)2 (5 mg, 0.02 mmol) in 3 mL
of benzene afforded 110 mg (85%) of 2d: liquid; 1H NMR (300 MHz,
CDCl3) δ 4.68 (t, J ) 3.3 Hz, 1 H), 4.14 (q, J ) 7.2 Hz, 2 H), 3.61(t,
J ) 5.7 Hz, 2 H), 2.80-2.86 (m, 2 H), 2.20 (s, 3 H), 2.08 (t, J ) 7.2
Hz, 2 H), 1.60-1.70 (m, 2 H), 1.26 (t, J ) 7.2 Hz, 3 H), 0.88 (s, 9 H),
0.03 (s, 6 H); 13C NMR (75.4 MHz, CDCl3) δ 168.1, 160.9, 149.7,
100.3, 97.7, 62.1, 59.8, 29.5, 29.0, 25.9, 21.9, 19.1, 18.3, 14.3, -5.4;
MS m/z 340 (M+, 1.68), 75 (100); IR (neat) 1720, 1638 cm-1. HRMS
calcd for C18H32O4Si: 340.20699. Found: 340.20632.
Hydroboration-Oxidation Reaction of 2d. Synthesis of trans-
2-(3′-tert-Butyldimethylsilanyloxypropyl)-3-hydroxy-5-(ethyloxycar-
bonyl)-6-methyl-3,4-dihydro-2H-pyran (9d): Following procedure A,
the reaction of 1d (150 mg, 0.44 mmol) and PdCl2(CH3CN)2 (5 mg,
0.02 mmol) in 2 mL of CH2Cl2 afforded the crude product 2d. Then
following procedure B, the reaction of 2d, BH3‚SMe2 (10 M) (1 mL,
1 mmol), NaOH (3 M) (1 mL, 3 mmol), and H2O2 (30%) (1 mL) in 5
mL of THF afforded 58 mg (37%) of 9d: liquid; 1H NMR (300 MHz,
CDCl3) δ 4.14 (q, J ) 7.5 Hz, 2 H), 3.68-3.85 (m, 2 H), 3.64 (t, J )
5.1 Hz, 2 H), 2.55-2.65 (m, 1 H), 2.24-2.38 (m, 1 H), 2.23 (s, 3 H),
1.66-1.80 (m, 2 H), 1.60-1.66 (m, 1 H), 1.54-1.64 (m, 2 H), 1.27 (t,
J ) 7.2 Hz, 3 H), 0.88 (s, 9 H), 0.05 (s, 6 H); 13C NMR (75.4 MHz,
CDCl3) δ 168.2, 163.6, 98.5, 79.5, 65.7, 62.9, 59.8, 29.3, 28.0, 27.4,
25.9, 19.9, 18.3, 14.3, -5.3; ESI-MS 381.3 [M + Na+]; IR (neat) 3404,
1708, 1689, 1625, 1230, 1096 cm-1. HRMS for C18H34O5SiNa:
381.20677. Found: 381.20531.
107.69, 80.00, 65.37, 31.73, 31.03, 29.43, 29.33, 29.09, 25.03, 22.61,
18.90, 14.09; MS m/z 352 (M+, 4.52), 211 (100); IR (KBr) 3496, 1630,
1297 cm-1; Anal. Calcd for C19H28SO4: C, 64.74; H, 8.01. Found C,
64.71; H, 8.01.
(G) 2-Methyl-3-(benzenesulfonyl)-6-(n-butyl)-4H-pyran (2g): Fol-
lowing procedure A, the reaction of 1g (120 mg, 0.41 mmol) and
PdCl2(MeCN)2 (5 mg, 0.02 mmol) in 2 mL of acetone afforded 109
1
mg (91%) of 2g: liquid; H NMR (300 MHz, CDCl3) δ 7.80-7.90
(m, 2 H), 7.45-7.60 (m, 3 H), 4.60-4.66 (m, 1 H), 2.84-2.90 (m, 2
H), 2.29 (t, J ) 1.2 Hz, 3 H), 1.96 (t, J ) 6.9 Hz, 2 H), 1.20-1.42 (m,
4 H), 0.86 (t, J ) 7.2 Hz, 3 H); 13C NMR (75.4 MHz., CDCl3) δ 158.6,
150.3, 141.1, 132.9, 129.0, 126.9, 110.1, 96.4, 32.0, 28.3, 22.2, 22.0,
18.0, 13.7; MS m/z 292 (M+, 20.36), 150 (100); IR (neat) 1715, 1638,
1306, 1149 cm-1. HRMS calcd for C16H20O3S: 292.11332. Found:
292.11486.
Hydroboration-Oxidation Reaction of 2g. Synthesis of 2-Butyl-
3-hydroxy-5-(phenylsulfonyl)-6-methyl-3,4-dihydro-2H-pyran (9g):
Following procedure A, the reaction of 1g (292 mg, 1 mmol) and
PdCl2(CH3CN)2 (6.5 mg, 0.03 mmol) in 2 mL of CH2Cl2 afforded the
crude product 2g. Then following procedure B, the reaction of 2g, BH3‚
SMe2 (10 M) (0.8 mL, 0.80 mmol), NaOH (3 M) (0.5 mL, 1.5 mmol),
and H2O2 (30%) (0.5 mL) in 5 mL of THF afforded 198 mg (64%) of
9g: solid; mp 88-89 °C (CH2Cl2/hexanes); 1H NMR (300 MHz,
CDCl3) δ 7.80-7.90 (m, 2 H), 7.45-7.60 (m, 3 H), 3.70-3.85 (m, 2
H), 2.55-2.70 (m, 1 H), 2.25-2.40 (m, 1 H), 2.29 (s, 3 H), 1.70-
1.85 (bs, 1 H), 1.20-1.70 (m, 6 H), 0.88 (t, J ) 6.6 Hz, 3 H); 13C
NMR (75.4 MHz, CDCl3) δ 161.7, 142.1, 132.7, 129.1, 126.6, 107.6,
80.0, 65.3, 30.7, 29.4, 27.1, 22.4, 18.9, 13.9; MS m/z 310 (M+, 8.98),
43 (100); IR (KBr) 3499, 1628, 1296, 1157, 724 cm-1; Anal. Calcd
for C16H22O4S: C, 61.91; H, 7.14. Found C, 62.03; H, 6.85.
(H) 2-Phenyl-3-(ethoxycarbonyl)-6-heptyl-4H-pyran (2h): Fol-
lowing procedure A, the reaction of 1h (85 mg, 0.26 mol) and PdCl2-
(MeCN)2 (4 mg, 0.015 mmol) in 3 mL of benzene afforded 82 mg
(96%) of 2h: air-sensitive solid; 1H NMR (300 MHz, CDCl3) δ 7.30-
7.40 (m, 5H), 4.76 (t, J ) 3.4 Hz, 1 H), 3.95 (q, J ) 7.2 Hz, 2 H),
3.05 (d, J ) 3.4 Hz, 2 H), 2.07 (t, J ) 7.2 Hz, 2 H), 1.40-1.55 (m, 2
H), 1.17-1.40 (m, 8 H), 0.93 (t, J ) 7.2 Hz, 3 H), 0.88 (t, J ) 7.2 Hz,
3 H); 13C NMR (75.4 MHz, CDCl3) δ 168.1, 159.1, 151.1, 135.8, 129.0,
128.2, 127.7, 102.1, 96.9, 59.9, 32.6, 31.7, 29.0, 28.9, 26.4, 22.7, 22.6,
14.1, 13.6; MS m/z 328 (M+, 7.52), 299 (100); IR (neat) 1717, 1290,
1260 cm-1. HRMS calcd for C21H28O3: 328.20385. Found: 328.20476.
(I) 2-Methyl-3-(ethoxycarbonyl)-1-oxa-spiro[5,5]undeca-2,4-diene
(8j): Following procedure A, the reaction of 1j (128 mg, 0.54 mol)
and PdCl2(MeCN)2 (8 mg, 0.03 mmol) in 3 mL of benzene afforded
(E) 2-Methyl-3-acetyl-6-(n-heptyl)-4H-pyran (2e): Following
procedure A, the reaction of 1e (134 mg, 0.57 mmol) and PdCl2-
(MeCN)2 (10 mg, 0.04 mmol) in 2.5 mL of acetone afforded 80 mg
1
(60%) of 2e: liquid; H NMR (300 MHz, d6-acetone) δ 4.81 (t, J )
3.6 Hz, 1 H), 2.92-3.00 (m, 2 H), 2.14 (s, 3 H), 2.12 (t, J ) 1.2 Hz,
3 H), 2.04 (td, J ) 6.9 Hz, 1.2 Hz, 2 H), 1.40-1.52 (m, 2 H), 1.20-
1.40 (m, 8 H), 0.88 (t, J ) 6.9 Hz, 3 H); 13C NMR (75.4 MHz, d6-
acetone) δ 198.8, 159.6, 151.2, 109.4, 98.4, 33.3, 32.7, 29.9, 29.8, 29.7,
27.2, 23.6, 23.4, 19.8, 14.5; MS m/z 236 (M+, 46.60), 43(100); IR (neat)
1716, 1682, 1595 cm-1. HRMS calcd for C15H24O2: 236.17763.
Found: 237.17411.
(F) 2-Methyl-3-(benzenesulfonyl)-6-heptyl-4H-pyran (2f): Fol-
lowing procedure A, the reaction of 1f (158 mg, 0.47 mol) and PdCl2-
(MeCN)2 (7 mg, 0.027 mmol) in 4 mL of benzene afforded 89 mg
1
123 mg (96%) of 8j: liquid; H NMR (300 MHz, CDCl3) δ 6.32 (d,
J ) 9.9 Hz, 1 H), 5.16 (d, J ) 9.9 Hz, 1 H), 4.16 (q, J ) 6.9 Hz, 2 H),
2.28 (s, 3 H), 1.78-1.90 (m, 2 H), 1.30-1.77 (m, 8 H), 1.27 (t, J )
6.9 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 166.5, 165.9, 120.2,
120.2, 103.6, 78.9, 59.7, 35.8, 25.2, 21.1, 20.1, 14.3; MS m/z 236 (M+,
32.01), 193 (100); IR (neat) 1710, 1636, 1581, 1269, 1103 cm-1. HRMS
calcd for C14H20O3: 236.14125. Found: 236.14293.
(J) 2-Methyl-3-(benzenesulfonyl)-5-chloro-4H-pyran (20l): Fol-
lowing procedure A, the reaction of 1l (135 mg, 0.5 mmol) and PdCl2-
(MeCN)2 (13 mg, 0.05 mmol) in 2 mL of benzene afforded 103 mg
(76%) of 20l: solid; mp 103-105 °C (n-hexane/ether); 1H NMR (300
MHz, CDCl3) δ 7.83-7.90 (m, 2 H), 7.50-7.68 (m, 3 H), 6.45 (t, J )
1.5 Hz, 1 H), 3.14 (s, 3 H), 2.31 (bs, 2 H); 13C NMR (75.4 MHz,
CDCl3) δ 157.3, 140.4, 136.0, 133.5, 129.3, 127.1, 113.6, 110.3, 28.8,
17.4; MS m/z 272 (M+ (37Cl), 9.49), 270 (M+ (35Cl), 24.65), 128 (100);
IR (KBr) 1699, 1637, 1206, 1143 cm-1. HRMS calcd for C12H11O3-
SCl: 270.00837. Found: 270.00919. Anal. Calcd for C12H11O3SCl: C,
53.24; H, 4.10. Found: C, 53.36; H, 4.14.
1
(56%) of 2f: liquid; H NMR (300 MHz, CDCl3) δ 7.83-7.90 (m, 2
H), 7.50-7.65 (m, 3 H), 4.63 (t, J ) 3.6 Hz, 1 H), 2.85-2.95 (m, 2
H), 2.30 (s, 3 H), 1.96 (t, J ) 2.7 Hz, 2 H), 1.32-1.50 (m, 2 H),
1.18-1.32 (m, 8 H), 0.86 (t, J ) 6.9 Hz, 3 H); 13C NMR (75.4 MHz,
CDCl3) δ 158.7, 150.4, 141.2, 133.0, 129.0, 127.0, 110.1, 96.4, 32.3,
31.7, 29.0, 28.9, 26.2, 22.6, 22.2, 18.1, 14.1; MS m/z 334 (M+, 32.11),
192 (100); IR (neat) 1715, 1637, 1305, 1149, 725 cm-1. HRMS calcd
for C19H26O3S: 334.16026. Found: 334.16283.
Hydroboration-Oxidation Reaction of 2f. Synthesis of trans-2-
Heptyl-3-hydroxy-5-(phenylsulfonyl)-6-methyl-3,4-dihydro-2H-py-
ran (9f): Following procedure A, the reaction of 1f (334 mg, 1 mmol)
and PdCl2(CH3CN)2 (6.5 mg, 0.03 mmol) in 2 mL of CH2Cl2 afforded
the crude product 2f. Then following procedure B, the reaction of 2f,
BH3‚SMe2 (10 M) (0.6 mL,0.80 mmol), NaOH (3 M) (0.6 mL, 1.5
mmol), and H2O2 (30%) (0.6 mL) in 4 mL of THF afforded 194 mg
1
(55%) of 9f: solid; mp 92-93 °C (CH2Cl2/hexanes); H NMR (300
MHz, CDCl3) δ 7.75-8.00 (m, 2 H), 7.40-7.65 (m, 3 H), 3.70-3.85
(m, 2 H), 2.55-2.70 (m, 1 H), 2.25-2.40 (m, 1 H), 2.28 (s, 3 H), 1.93
(d, J ) 5.4 Hz, 1 H), 1.15-1.75 (m, 12 H), 0.87 (t, J ) 6.9 Hz, 3 H);
13C NMR (75.4 MHz, CDCl3) δ 161.59, 142.13, 132.72, 129.08, 126.66,
(K) 2-Phenyl-6-(n-octyl)-4H-pyran (2m): Following procedure A,
the reaction of 1m (135 mg, 0.05 mmol) and PdCl2(MeCN)2 (6.5 mg,
0.025 mmol) in 1 mL of benzene afforded 94 mg (70%) of 2m: liquid;
1H NMR (300 MHz, d6-acetone) δ 7.54-7.68 (m, 2 H), 7.24-7.40
9
9656 J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004

Methylene- or Alkylidenecyclopropyl Ketones
A R T I C L E S
(m, 3 H), 5.40-5.48 (m, 1 H), 4.60-4.68 (m, 1 H), 2.80-2.90 (m, 2
H), 2.15(t, J ) 7.2 Hz, 2 H), 1.50-1.68 (m, 2 H), 1.22-1.44 (m, 10
H), 0.87 (t, J ) 6.9 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 151.9,
149.1, 134.9, 128.1, 127.9, 124.2, 96.5, 94.7, 33.5, 31.8, 31.6, 29.1,
29.1, 26.7, 22.7, 21.4, 14.1; MS m/z 270 (M+, 3.03), 105 (100); IR
(neat): 1706, 1654, 754 cm-1. HRMS calcd for C19H26O: 270.19837.
Found: 270.19765.
Typical Procedure for NaI-Catalyzed Cycloisomerization (Pro-
cedure D). (A) 3-Octylidene-4-(ethoxycarbonyl)-5-methyl-2,3-dihy-
drofuran (3a): A solution of 1a (134 mg, 0.5 mmol) and NaI (4 mg,
0.027 mmol, 5 mol %) in 4 mL of acetone was refluxed for 11 h.
Evaporation and flash chromatography on silica gel afforded 106 mg
(79%) of 3a (procedure D): liquid; mixture of Z/E isomers, ratio )
2.3:1; 1H NMR (300 MHz, CDCl3) δ 5.75-5.84 (m, 1 H), [4.93-5.01
(m, 1.4 H); 4.87-4.93 (m, 0.6 H)], [4.23 (q, J ) 7.2 Hz, 0.6 H); 4.22
(q, J ) 7.2 Hz, 1.4 H)], [2.28 (s, 2.1 H); 2.19 (s, 0.9 H)], [2.10-2.22
(m, 0.6 H); 1.82-1.95 (m, 1.4 H)], 1.20-1.43 (m, 10 H), 1.34 (t, J )
7.2 Hz, 3 H), 0.87 (t, J ) 6.6 Hz, 3 H); MS m/z 266 (M+, 77.83), 168
(100); IR (neat) 1704, 1613, 1172, 1085 cm-1. HRMS calcd for
C16H26O3: 266.18819. Found: 266.18844.
(B) 3-Pentylidene-4-(ethoxycarbonyl)-5-methyl-2,3-dihydrofuran
(3b): Following procedure D, the reaction of 1b (112 mg, 0.5 mmol)
and NaI (4 mg, 0.027 mmol) in 2 mL of acetone afforded 51 mg (46%)
of 3b: liquid; mixture of Z/E isomers, ratio ) 3:1; 1H NMR (300 MHz,
CDCl3) δ 5.75-5.85 (m, 1 H), [4.94-5.10 (m, 1.5 H); 4.90-4.94 (m,
0.5 H)], 4.17-4.40 (m, 2 H), [2.29 (s, 2.3 H); 2.19 (s, 0.7 H)], [2.10-
2.20 (m, 0.5 H); 1.80-1.95 (m, 1.5 H)], 1.20-1.50 (m, 4 H), 1.33 (t,
J ) 7.2 Hz, 3 H), 0.90 (q, J ) 6.9 Hz, 3 H); MS m/z 224 (M+, 100);
IR (neat) 1713, 1608, 1255, 1099 cm-1. HRMS calcd for C13H20O3:
224.14124. Found: 224.14282.
(C) 3-((2′-Phenyl)ethylidene)-4-(ethoxycarbonyl)-5-methyl-2,3-
dihydrofuran (3c): Following procedure D, the reaction of 1c (123
mg, 0.5 mmol) and NaI (4 mg, 0.027 mmol) in 2 mL of acetone afforded
95 mg (80%) of 3c: liquid; mixture of Z/E isomers, ratio ) 1.5:1; 1H
NMR (300 MHz, CDCl3) δ 7.15-7.35 (m, 5 H), [6.05-6.15 (m, 0.6
H); 5.13-5.20 (m, 0.4 H)], [5.03-5.08 (m, 1.3 H); 4.96-5.01 (m, 0.7
H)], 4.25 (q, J ) 7.5 Hz, 2 H), [3.60-3.68 (m, 0.7 H); 3.30 (d, J )
7.8 Hz, 1.3 H)], [2.34 (s, 1.9 H); 2.27 (s, 1.1 H)], [1.33 (t, J ) 7.5 Hz,
1.8 H); 1.29 (t, J ) 7.5 Hz, 1.2 H)]; MS m/z 258 (M+, 72.01), 137
(100); IR (neat) 1700, 1606, 1299, 1100 cm-1; HRMS calcd for
C16H18O3: 258.12559. Found: 258.12661.
(75.4 MHz, CDCl3) δ 172.8, 142.2, 132.8, 132.0, 128.8, 126.4, 115.6,
114.0, 73.9, 31.1, 29.4, 22.1, 14.5, 13.9; MS m/z 292 (M+, 42.32), 108
(100.00); IR (KBr) 1598, 1303, 1150 cm-1. HRMS calcd for
C16H20O3S: 292.11332. Found: 292.11430. Anal. Calcd for C16H20-
O3S: C, 65.72; H, 6.89. Found: C, 65.70; H, 6.78.
(F) 3-Octylidene-4-(ethoxycarbonyl)-5-phenyl-2,3-dihydrofuran
(3h): Following procedure D, the reaction of 1h (164 mg, 0.5 mmol)
and NaI (10 mg, 0.06 mmol) in 2 mL of acetone afforded 135 mg
1
(79%) of 3h: liquid; mixture of Z/E isomers, ratio ) 3.3:1; H NMR
(300 MHz, CDCl3) δ 7.55-7.68 (m, 2 H), 7.30-7.47 (m, 3 H), 5.86-
5.97 (m, 1 H), [5.11-5.17 (m, 1.54 H); 5.06-5.11 (m, 0.46 H)], [4.24
(q, J ) 7.5 Hz, 0.46 H); 4.18 (q, J ) 7.5 Hz, 1.54 H)], [2.02-2.17 (m,
0.46 H); 1.92-2.02 (m, 1.54 H)], 1.20-1.53 (m, 10 H), 1.18 (t, J )
7.5 Hz, 3 H), 0.82-0.95 (m, 3 H); MS m/z 328 (M+, 34.66), 230 (100);
IR (neat) 1706, 1591, 1379, 1096 cm-1. HRMS calcd for C21H28O3:
328.20385. Found: 328.20240.
(7) 3-Cyclohexylidene-4-acetyl-5-methyl-2,3-dihydrofuran (3k):
Following procedure D, the reaction of 1k (106 mg, 0.5 mmol) and
NaI (5 mg, 0.033 mmol) in 2 mL of acetone afforded 62 mg (58%) of
3k: liquid; 1H NMR (300 MHz, CDCl3) δ 4.93 (s, 2H), 2.20 (s, 3 H),
2.01 (s, 3 H), 1.87-2.00 (m, 4 H), 1.40-1.55 (m, 6 H); 13C NMR
(75.4 MHz, CDCl3) δ 197.8, 168.7, 127.5, 125.0, 118.1, 74.7, 32.4,
32.2, 30.3, 27.3, 27.0, 26.0, 14.1; MS m/z 206 (M+, 42.61), 43 (100);
IR (neat) 1672, 1594 cm-1. HRMS calcd for C13H18O2: 206.13068.
Found: 206.13107.
Typical Procedure for PdCl2(CH3CN)2 and NaI-Catalyzed Cy-
cloisomerization (Procedure E). (A) 2-Methyl-3-(ethoxycarbonyl)-
4-(n-heptyl)furan (4a): A solution of 1a (356 mg, 1.3 mmol), NaI
(400 mg, 2.6 mmol), and PdCl2(CH3CN)2 (17 mg, 0.65 mmol) in 5
mL of acetone was refluxed for 10 h. Evaporation and flash chroma-
tography on silica gel afforded 265 mg (74%) of 4a (procedure E). A
solution of 1a (139 mg, 0.5 mmol) and sodium iodide (77 mg, 0.5
mmol) in 1 mL of acetone was stirred under reflux for 24 h. Evaporation
and chromatography on silica gel (petroleum ether/ether 100:1) afforded
104 mg (75%) of 4a (procedure D): liquid; 1H NMR (300 MHz, C6D6)
δ 6.85 (s, 1 H), 4.06 (q, J ) 7.2 Hz, 2 H), 2.65 (t, J ) 7.5 Hz, 2 H),
2.40 (s, 3 H), 1.50-1.63 (m, 2 H), 1.15-1.40 (m, 10 H), 1.01 (t, J )
7.2 Hz, 3 H), 0.87 (t, J ) 7. 2 Hz, 3 H); 13C NMR (75.4 MHz, C6D6)
δ 164.2, 160.1, 137.7, 126.9, 113.6, 59.7, 32.3, 30.2, 30.1, 30.0, 29.8,
25.3. 23.1, 14.41, 14.36, 14.34; MS m/z 266 (M+, 1.14), 168 (100); IR
(neat) 1716, 1607, 1559, 1301, 1099 cm-1. HRMS calcd for
C16H26O3: 266.18819. Found: 266.18641.
(D) 3-Octylidene-4-acetyl-5-methyl-2,3-dihydrofuran (3e): Fol-
lowing procedure D, the reaction of 1e (120 mg, 0.5 mmol) and NaI
(4 mg, 0.027 mmol) in 2 mL of acetone afforded 95 mg (79%) of
E-3e and Z-3e: mixture of Z/E isomers, ratio ) 1.9:1. E-3e: liquid;
1H NMR (300 MHz, C6D6) δ 4.70-4.80 (m, 1 H), 4.54 (dd, J ) 4.8
Hz, 2.1 Hz, 2 H), 2.00-2.18 (m, 2 H), 2.06 (s, 3 H), 1.82 (s, 3 H),
1.10-1.40 (m, 10 H), 0.89 (t, J ) 7.5 H, 3 H); 13C NMR (75.4 MHz,
C6D6) δ 194.55, 171.32, 135.77, 118.28, 115.02, 76.54, 32.25, 30.63,
30.54, 30.26, 29.68, 23.07, 14.69, 14.37; MS m/z 236 (M+, 14.79),
138 (100); IR (neat) 1669, 1410 cm-1. HRMS calcd for C15H24O2:
236.17763. Found: 236.17520. Z-3e: liquid, 1H NMR (300 MHz,
CDCl3) δ 5.62-5.72 (m, 1 H), 4.80-4.86 (m, 2 H), 2.24 (s, 3 H), 2.20
(s, 3 H), 1.76-1.84 (m, 2 H), 1.24-1.38 (m, 2 H), 1.10-1.24 (m, 8
H), 0.77 (t, J ) 7.0 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 194.09,
174.86, 135.30, 115.99, 115.79, 73.99, 31.71, 30.94, 30.02, 29.25, 29.24,
29.10, 22.54, 16.36, 13.98; MS m/z 236 (M+, 7.39), 43 (100); IR (neat)
1775, 1695, 1671, 1362 cm-1. HRMS calcd for C15H24O2: 236.17763.
Found: 236.18120.
(B) 2-Methyl-3-(ethoxycarbonyl)-4-n-pentylfuran (4b): Following
procedure E, the reaction of 1b (178 mg, 0.8 mmol), NaI (150 mg, 1
mmol), and PdCl2(CH3CN)2 (4 mg, 0.015 mmol) in 2.5 mL of acetone
afforded 132 mg (74%) of 4b. Following procedure D, the reaction of
1b (108 mg, 0.5 mmol) and NaI (76 mg, 0.5 mmol) in 4 mL acetone
1
afforded 99 mg (92%) of 4b: liquid; H NMR (300 MHz, CDCl3) δ
6.99 (s, 1 H), 4.26 (q, J ) 7.2 Hz, 2 H), 2.54 (t, J ) 7.5 Hz, 2 H), 2.51
(s, 3 H), 1.44-1.60 (m, 2 H), 1.22-1.38 (m, 4 H), 1.33 (t, J ) 7.2 Hz,
3 H), 0.87 (t, J ) 7.2 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 164.6,
160.1, 137.2, 126.2, 112.8, 59.7, 31.7, 29.2, 24.7, 22.5, 14.3, 14.2, 14.0;
MS m/z 224 (M+, 17.47), 168 (100); IR (neat) 1716, 1607, 1561, 1099
cm-1. HRMS calcd for C13H20O3: 224.14125. Found: 224.13990.
(C) 2-Methyl-3-(ethoxycarbonyl)-4-(2′-phenylethyl)furan (4c):
Following procedure E, the reaction of 1c (129 mg, 0.5 mmol), NaI
(150 mg, 1 mmol), and PdCl2(CH3CN)2 (7 mg, 0.027 mmol) in 2 mL
of acetone afforded 101 mg (78%) of 4c. A solution of 1c (130 mg,
0.5 mmol) and NaI (4 mg, 0.025 mmol) in 2 mL of acetone was stirred
under reflux for 2.5 h until the reaction was finished. Then 3 mL of 3
M HCl was added to the mixture. The reaction was monitored by TLC.
Usual workup, evaporation, and chromatography on silica gel afforded
103 mg (79%) of 4c (procedure F): liquid; 1H NMR (300 MHz, CDCl3)
δ 7.18-7.35 (m, 5 H), 7.01 (s, 1 H), 4.34 (q, J ) 7.2 Hz, 2 H), 2.85-
2.95 (m, 4 H), 2.57 (s, 3 H), 1.39 (t, J ) 7.2 Hz, 3 H); 13C NMR (75.4
MHz, CDCl3) δ 164.5, 160.22, 141.9, 137.6, 128.4, 128.2, 125.8, 125.3,
(E) 3(E)-Pentylidene-4-(benzenesulfonyl)-5-methyl-2,3-dihydro-
furan (E-3g): Following procedure D, the reaction of 1g (145 mg, 0.5
mmol) and NaI (4 mg, 0.027 mmol) in 2 mL of acetone afforded 113
1
mg (78%) of E-3g: solid; mp 54-56 °C (petroleum ether/ether). H
NMR (300 MHz, CDCl3) δ 7.85-7.92 (m, 2 H), 7.45-7.65 (m, 3 H),
5.47-5.58 (m, 1 H), 4.90-4.95 (m, 2 H), 2.39 (s, 3 H), 1.77-1.87
(m, 2 H), 1.10-1.36 (m, 4 H), 0.82 (t, J ) 7.2 Hz, 3 H); 13C NMR
9
J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004 9657

A R T I C L E S
Ma et al.
112.8, 59.9, 36.0, 26.6, 14.44, 14.36; MS m/z 258 (M+, 17.57), 139
(100); IR (neat) 1713, 1605, 1561, 1099 cm-1. HRMS calcd for
C16H18O3: 258.12560. Found: 258.12406.
31.9, 29.55, 29.54, 29.4, 29.3, 24.8, 22.7, 14.1, 14.0; MS m/z 328 (M+,
28.47), 230 (100); IR (KBr) 1716, 1594, 1406 cm-1. HRMS calcd for
C21H28O3: 328.20385. Found: 328.20578.
(I) 2-Methyl-3-acetyl-4-cyclohexylfuran (4k): Following procedure
E, the reaction of 1k (103 mg, 0.5 mmol), NaI (46 mg, 0.3 mmol), and
PdCl2(CH3CN)2 (10 mg, 0.039 mmol) in 4 mL of acetone afforded 76
mg (74%) of 4k. Following procedure F, the reaction of 1k (103 mg,
0.5 mmol) and NaI (75 mg, 0.5 mmol) in 1 mL of acetone afforded 51
mg (50%) of 4k: solid; mp 55-57 °C (petroleum ether/ether); 1H NMR
(300 MHz, CDCl3) δ 6.97 (s, 1 H), 2.75-2.90 (m, 1 H), 2.51 (s, 3 H),
2.41 (s, 3 H), 1.83-2.00 (m, 2 H), 1.62-1.80 (m, 3 H), 1.28-1.50
(m, 2 H), 1.03-1.25 (m, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 194.8,
158.3, 136.3, 132.2, 121.7, 34.3, 33.8, 30.8, 26.6, 26.2, 15.4; MS m/z
206 (M+, 56.1), 43 (100); IR (KBr) 1656, 1538, 1406 cm-1. Anal. Calcd
for C13H18O2: C, 75.69; H, 8.80. Found: C, 75.45; H, 8.79.
(4) 2-Methyl-3-(ethoxycarbonyl)-4-(4′-tert-butyldimethylsilyloxy-
butyl)furan (4d): Following procedure E, the reaction of 1d (148 mg,
0.4 mmol), NaI (150 mg, 1 mmol), and PdCl2(CH3CN)2 (5 mg, 0.019
mmol) in 2 mL of acetone afforded 121 mg (82%) of 4d. Following
procedure D, the reaction of 1d (83 mg, 0.24 mmol) and NaI (37 mg,
0.25 mmol) in 2 mL of acetone afforded 66 mg (80%) of 4d: liquid;
1H NMR (300 MHz, C6D6) δ 6.83 (s, 1 H), 4.06 (q, J ) 6.9 Hz, 2 H),
3.54 (t, J ) 6.0 Hz, 2 H), 2.66 (t, J ) 7.5 Hz, 2 H), 2.39 (s, 3 H),
1.50-1.70 (m, 4 H), 1.00 (t, J ) 7.2 Hz, 3 H), 0.95 (s, 9 H), 0.03 (s,
6 H); 13C NMR (75.4 MHz, C6D6) δ 164.2, 160.2, 137.8, 126.6, 113.6,
63.2, 59.7, 33.1, 26.4, 26.2, 25.0, 18.5, 14.4, 14.3, -5.2; MS m/z 325
(M+ - CH3, 2.52), 283 (100); IR (neat) 1716, 1606, 1256, 1101 cm-1
.
HRMS calcd for C17H29O4Si [M+ - CH3]: 325.18351. Found:
325.18268.
(J) 2-Phenyl-4-methylfuran (4n):32 Following procedure E, the
reaction of 1n (158 mg, 1.0 mmol), NaI (300 mg, 2 mmol), and
PdCl2(CH3CN)2 (13 mg, 0.05 mmol) in 2 mL of acetone afforded 127
mg (80%) of 4n. Following procedure D, a solution of methylenecy-
clopropyl phenyl ketone 1n (80 mg, 0.50 mol) and NaI (15 mg, 0.1
mmol, 0.2 equiv) in 2 mL of acetone afforded 72 mg (90%) of 4n:
liquid; 1H NMR (300 MHz, C6D6) δ 7.67 (d, J ) 7.8 Hz, 2 H), 7.10-
7.40 (m, 2 H), 7.00-7.06 (m, 1 H), 6.96 (s, 1 H), 6.27 (s, 1 H), 1.78
(s, 3 H); 13C NMR (75.4 MHz, C6D6) δ 154.3, 139.1, 131.6, 128.9,
127.3, 123.9, 122.0, 108.0, 9.7; MS m/z 158 (M+, 100.00); IR (neat)
(E) 2-Methyl-3-acyl-4-(n-octyl)furan (4e): Following procedure
E, the reaction of 1e (127 mg, 0.5 mmol), NaI (150 mg, 1 mmol), and
PdCl2(CH3CN)2 (5 mg, 0.019 mmol) in 2 mL of acetone afforded 102
1
mg (80%) of 4e: liquid; H NMR (300 MHz, CDCl3) δ 6.76 (t, J )
0.9 Hz, 1 H), 2.32 (td, J ) 6.9, 0.9 Hz, 2 H), 2.29 (s, 3 H), 2.17 (s, 3
H), 1.20-1.32 (m, 2 H), 0.92-1.16 (m, 10 H), 0.62 (t, J ) 6.6 Hz, 3
H); 13C NMR (75.4 MHz, CDCl3) δ 194.8, 158.8, 137.4, 125.9, 122.0,
31.8, 30.8, 29.5, 29.4, 29.3, 29.2, 25.2, 22.6, 15.4, 14.0; MS m/z 236
1597, 1538, 1484, 1445, 914, 763 cm-1
.
(M+, 17.71), 138 (M+ - C7H14, 100); IR (neat) 1670, 1587, 1549 cm-1
.
HRMS calcd for C15H24O2: 236.17763. Found: 236.17648.
(K) 2-(4′-Methylphenyl)-4-methylfuran (4o):33 Following proce-
dure E, the reaction of 1o (172 mg, 1 mmol), NaI (300 mg, 2 mmol),
and PdCl2(CH3CN)2 (13 mg, 0.05 mmol) in 2 mL of acetone afforded
125 mg (73%) of 4o. Following procedure D, the reaction of
methylenecyclopropyl ketone 1o (84 mg, 0.5 mmol) and NaI (15 mg,
0.1 mmol) in 2 mL of acetone afforded 48 mg (57%) of 4o: solid; mp
55-56 °C;34 1H NMR (300 MHz, C6D6) δ 7.62 (d, J ) 7.2 Hz, 2 H),
6.97 (d, J ) 7.2 Hz, 2 H), 6.96 (s, 1 H), 6.25 (s, 1 H), 2.06 (s, 3 H),
1.78 (s, 3 H); 13C NMR (75.4 MHz, C6D6) δ 154.57, 138.78, 136.97,
129.67, 129.04, 124.03, 121.99, 107.40, 21.17, 9.79; MS m/z 172 (M+,
(F) 2-Methyl-3-(benzenesulfonyl)-4-octylfuran (4f): Following
procedure E, the reaction of 1f (164 mg, 0.5 mmol), NaI (148 mg, 1.0
mmol), and PdCl2(CH3CN)2 (6.5 mg, 0.025 mmol) in 2 mL of acetone
afforded 138 mg (84%) of a mixture of 4f and 3f (4f:3f ) 1:9.6).
Following procedure F, the reaction of 1f (168 mg, 0.5 mmol) and
NaI (4 mg, 0.025 mmol) in 2 mL of acetone afforded 158 mg (94%)
of 4f: oil; 1H NMR (300 MHz, CDCl3) δ 7.85-7.92 (m, 2 H), 7.47-
7.62 (m, 3 H), 7.02 (s, 1 H), 2.63 (s, 3 H), 2.41 (t, J ) 7.5 Hz, 2 H),
1.32-1.48 (m, 2 H), 1.15-1.30 (m, 10 H), 0.87 (t, J ) 6.9 Hz, 3 H);
13C NMR (75.4 MHz, CDCl3) δ 158.2, 142.8, 137.9, 132.9, 129.0,
126.6, 124.7, 121.0, 31.8, 29.3, 29.3, 29.2, 28.6, 23.6, 22.6, 14.1, 13.7;
MS m/z 334 (M+, 14.43), 236 (100); IR (neat) 1594, 1552, 1320, 1163
cm-1. Anal. Calcd for C19H26O3S: C, 68.23; H, 7.84. Found: C, 68.20;
H, 8.04.
(G) 2-Methyl-3-(benzensulfonyl)-4-pentylfuran (4g): Following
procedure E, the reaction of 1g (143 mg, 0.5 mmol), NaI (150 mg, 1
mmol), and PdCl2(CH3CN)2 (6.5 mg, 0.025 mmol) in 2 mL of acetone
afforded 109 mg (76%) of a mixture of 4g and 3g (4g:3g ) 3.2:1).
Following procedure F, the reaction of 1g (146 mg, 0.5 mmol) and
NaI (4 mg, 0.025 mmol) in 2 mL of acetone afforded 76 mg (52%) of
4g: solid, mp 60-62 °C (petroleum ether/ether); 1H NMR (300 MHz,
CDCl3) δ 7.85-7.90 (m, 2 H), 7.45-7.62 (m, 3 H), 7.02 (s, 1 H), 2.64
(s, 3 H), 2.41 (t, J ) 7.5 Hz, 2 H), 1.35-1.50 (m, 2 H), 1.15-1.35 (m,
4 H), 0.85 (t, J ) 7.2 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 158.2,
142.8, 137.9, 133.0, 129.1, 126.6, 124.7, 121.0, 31.5, 28.3, 23.6, 22.4,
14.0, 13.7; MS m/z 292 (M+, 13.22), 236 (100); IR (KBr) 1599, 1558,
1321, 725 cm-1. Anal. Calcd for C16H20O3S: C, 65.72; H, 6.89.
Found: C, 65.53; H, 6.49.
100.00); IR (KBr) 1605, 1543, 1490, 914, 805 cm-1
.
(L) 2-(4′-Methoxylphenyl)-4-methylfuran (4p):35 Following pro-
cedure E, the reaction of 1p (188 mg, 1 mmol), NaI (300 mg, 2 mmol),
and PdCl2(CH3CN)2 (13 mg, 0.05 mmol) in 2 mL of acetone afforded
165 mg (88%) of 4p. Following procedure D, the reaction of 1p (54
mg, 0.3 mmol) and NaI (8 mg, 0.05 mmol) in 2 mL of acetone afforded
33 mg (61%) of 4p: solid; mp 80-81 °C.33 1H NMR (300 MHz, C6D6)
δ 7.56 (d, J ) 9.0 Hz, 2 H), 7.19 (s, 1 H), 6.90 (d, J ) 9.0 Hz, 2 H),
6.39 (s, 1 H), 3.81 (s, 3 H), 2.06 (s, 3 H); 13C NMR (75.4 MHz, CDCl3)
δ 158.7, 153.8, 138.0, 124.9, 124.1, 121.8, 113.9, 106.1, 55.1, 9.8;
MS m/z 188 (M+, 100.00); IR (KBr) 1620, 1497, 915, 834 cm-1
.
(M) 2-(4′-Fluorophenyl)-4-methylfuran (4q): Following procedure
E, the reaction of 1q (106 mg, 0.6 mmol), NaI (180 mg, 1.2 mmol),
and PdCl2(CH3CN)2 (7.8 mg, 0.03 mmol) in 1.2 mL of acetone afforded
89 mg (84%) of 4q. Following procedure D, the reaction of 1q (87
mg, 0.5 mmol) and NaI (15 mg, 0.1 mmol) in 2 mL of acetone afforded
66 mg (76%) of 4q: solid; mp 47-48 °C; 1H NMR (300 MHz, C6D6)
δ 7.38 (dd, J ) 8.7 Hz, 5.4 Hz, 2 H), 6.91 (t, J ) 0.9 Hz, 1 H), 6.76
(t, J ) 9.0 Hz, 2 H), 6.10 (s, 1 H), 1.77 (d, J ) 0.9 Hz, 3 H); 19F NMR
(282 MHz, C6D6) δ -114.9; 13C NMR (75.4 MHz, C6D6) δ 164.0,
160.8, 153.4, 139.1, 125.7 (d, J ) 7.2 Hz), 122.1, 115.8 (d, J ) 21.8
Hz), 107.7 (d, J ) 1.6 Hz), 9.7; MS m/z 176 (M+, 100); IR (KBr)
1602, 1544, 1493, 917, 838, 808 cm-1. Anal. Calcd for C11H9FO: C,
74.99; H, 5.15. Found: C, 74.68; H, 5.20.
(H) 2-Phenyl-3-(ethoxycarbonyl)-4-octylfuran (4h): Following
procedure E, the reaction of 1h (164 mg, 0.5 mmol), NaI (150 mg, 1
mmol), and PdCl2(CH3CN)2 (6.5 mg, 0.025 mmol) in 2 mL of acetone
afforded 144 mg (88%) of a mixture of 4h and 3h (4h:3h ) 1:5.5).
Following procedure F, the reaction of 1h (164 mg, 0.5 mmol) and
NaI (8 mg, 0.05 mmol) in 2 mL of acetone afforded 111 mg (68%) of
4h: liquid; 1H NMR (300 MHz, CDCl3) δ 7.73-7.80 (m, 2 H), 7.30-
7.45 (m, 3 H), 7.24 (s, 1 H), 4.29 (q, J ) 7.2 Hz, 2 H), 2.64 (t, J ) 7.2
Hz, 2 H), 1.55-1.65 (m, 2 H), 1.30 (t, J ) 7.2 Hz, 3 H), 1.20-1.45
(m, 10 H), 0.90 (t, J ) 6.9 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ
164.5, 157.6, 138.7, 130.4, 128.9, 128.3, 127.9, 127.5, 113.6, 60.3,
(N) 2-(4′-Chlorophenyl)-4-methylfuran (4r):34 Following procedure
E, the reaction of 1r (192.5 mg, 1 mmol), NaI (300 mg, 2 mmol), and
(32) Hagiwara, H.; Uda, H. J. Chem. Soc., Perkin Trans. 1 1984, 91.
(33) Srikrishna, A.; Pullaiah, K. C. Tetrahedron Lett. 1987, 28, 5203.
(34) Fabrycy, A.; Wichertz. Rocz. Chem. 1977, 249.
(35) Scharf, H.; Wolters, E. Chem. Ber. 1978, 111, 639.
9
9658 J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004

Methylene- or Alkylidenecyclopropyl Ketones
A R T I C L E S
PdCl2(CH3CN)2 (13 mg, 0.025 mmol) in 2 mL of acetone afforded
132 mg (69%) of 4r. Following procedure D, the reaction of 1r (98
mg, 0.5 mmol) and NaI (15 mg, 0.1 mmol) in 2 mL of acetone afforded
70 mg (71%) of 4r: solid; mp 86-87 °C;32 1H NMR (300 MHz, CDCl3)
δ 7.55 (d, J ) 9.0 Hz, 2 H), 7.32 (d, J ) 9.0 Hz, 2 H), 7.23 (q, J )
1.2 Hz, 1 H), 6.51 (s, 1 H), 2.07 (d, J ) 1.2 Hz, 3 H); 13C NMR (75.4
MHz, C6D6) δ 153.1, 139.4, 133.0, 129.9, 129.1, 125.2, 122.2, 108.5,
9.7; MS m/z 192 (M+, 100.00); IR (KBr) 1612, 1533, 1480, 916, 810
108.0, 34.4, 30.0, 9.8; MS m/z 186 (M+, 28.25), 95 (100); IR (neat)
1618, 1604, 1552, 1498 cm-1; Anal. Calcd for C13H14O: C, 83.83; H,
7.58. Found: C, 83.76; H, 7.34.
(T) 2-(4′-Methoxylphenylethyl)-4-methylfuran (4x): Following
procedure E, the reaction of 1x (226 mg, 1 mmol), NaI (300 mg, 2
mmol), and PdCl2(CH3CN)2 (11 mg, 0.025 mmol) in 2 mL of acetone
afforded 138 mg (72%) of 4x. Following procedure D, the reaction of
1x (110 mg, 0.5 mmol) and NaI (74 mg, 0.5 mmol) in 2 mL of acetone
cm-1
.
1
afforded 74 mg (67%) of 4x: liquid; H NMR (300 MHz, CDCl3) δ
7.13 (d, J ) 8.4 Hz, 2 H), 7.12 (s, 1 H), 6.87 (d, J ) 8.1 Hz, 2 H),
5.89 (s, 1 H), 3.82 (s, 3 H), 2.80-3.00 (m, 4 H), 2.02 (s, 3 H); 13C
NMR (75.4 MHz, CDCl3) δ 157.8, 155.4, 137.3, 133.3, 129.2, 120.4,
113.7, 107.9, 55.1, 33.4, 30.2, 9.8; MS m/z 216 (M+, 8.12), 121 (100);
IR (neat) 1613, 1513, 1247, 910 cm-1. HRMS calcd for C14H16O2:
216.11503. Found: 216.11254.
(U) 2-(3′-Benzoxypropyl)-4-methylfuran (4y): Following procedure
E, the reaction of 1y (345 mg, 1.5 mmol), NaI (400 mg, 2.7 mmol),
and PdCl2(CH3CN)2 (13 mg, 0.025 mmol) in 4 mL of acetone afforded
230 mg (66%) of 4y. Following procedure D, the reaction of 1y (110
mg, 0.5 mmol) and NaI (15 mg, 0.11 mmol) in 2 mL of acetone afforded
26 mg (24%) of 4y: liquid; 1H NMR (300 MHz, CDCl3) δ 7.25-7.50
(m, 5 H), 7.10 (s, 1 H), 5.89 (s, 1 H), 4.55 (s, 2 H), 3.55 (t, J ) 6.3
Hz, 2 H), 2.73 (t, J ) 7.2 Hz, 2 H), 2.02 (s, 3 H), 1.90-2.05 (m, 2 H);
13C NMR (75.4 MHz, CDCl3) δ 155.6, 138.4, 137.3, 128.3, 127.6,
127.5, 120.3, 107.7, 72.8, 69.3, 28.1, 24.7, 9.8; MS m/z 230 (M+, 21.75),
109 (100); IR (neat) 1619, 1553, 1454, 736 cm-1. Anal. Calcd for
C15H18O2: C, 78.23; H, 7.88. Found: C, 77.91; H, 7.68.
(O) 2-(4′-Bromophenyl)-4-methylfuran (4s): Following procedure
E, the reaction of 1s (237 mg, 1 mmol), NaI (300 mg, 2 mmol), and
PdCl2(CH3CN)2 (13 mg, 0.025 mmol) in 2 mL of acetone afforded
180 mg (76%) of 4s. Following procedure D, the reaction of 1s (59
mg, 0.25 mmol) and NaI (7 mg, 0.05 mmol) in 2 mL of acetone afforded
48 mg (81%) of 4s: solid; mp 95-96 °C; 1H NMR (300 MHz, CDCl3)
δ 7.49 (s, 4 H), 7.23 (t, J ) 1.3 Hz, 1 H), 6.53 (s, 1 H), 2.07 (d, J )
1.3 Hz, 3 H); 13C NMR (75.4 MHz, C6D6) δ 153.1, 139.4, 132.1, 130.3,
125.4, 122.2, 121.2, 108.6, 9.7; MS m/z 238 (M+ (81Br), 54.05), 236
(M+ (79Br), 59.54), 128 (100.00); IR (KBr) 1608, 1533, 1476, 915,
809 cm-1. Anal. Calcd for C11H9BrO: C, 55.72; H, 3.83. Found: C,
55.67; H, 3.99.
(P) 2-(4′-Iodophenyl)-4-methylfuran (4t): Following procedure E,
the reaction of 1t (294 mg, 1 mmol), NaI (300 mg, 2 mmol), and
PdCl2(CH3CN)2 (13 mg, 0.025 mmol) in 2 mL of acetone afforded
211 mg (69%) of 4t. Following procedure D, the reaction of 1t (139
mg, 0.5 mmol) and NaI (15 mg, 0.10 mmol) in 2 mL of acetone afforded
1
102 mg (73%) of 4t: solid; mp 116-117 °C; H NMR (300 MHz,
C6D6) δ 7.44 (d, J ) 8.4 Hz, 2 H), 7.13 (d, J ) 8.4 Hz, 2 H), 6.90 (t,
J ) 0.9 Hz, 1 H), 6.12 (s, 1 H), 1.76 (d, J ) 0.9 Hz, 3 H); 13C NMR
(75.4 MHz, C6D6) δ 153.2, 139.5, 138.0, 130.8, 125.5, 122.2, 108.7,
92.5, 9.7; MS m/z 284 (M+, 100.00); IR (KBr) 1529, 1398, 914, 807
cm-1. Anal. Calcd for C11H9IO: C, 46.51; H, 3.19. Found: C, 46.73;
H, 3.36.
(Q) 2-(1′-Naphthyl)-4-methylfuran (4u): Following procedure E,
the reaction of 1u (208 mg, 1 mmol), NaI (300 mg, 2 mmol), and
PdCl2(CH3CN)2 (13 mg, 0.025 mmol) in 2 mL of acetone afforded
173 mg (83%) of 4u. Following procedure D, the reaction of 1u (50
mg, 0.24 mmol) and NaI (8 mg, 0.05 mmol) in 2 mL of acetone afforded
49 mg (98%) of 4u: liquid; 1H NMR (300 MHz, C6D6) δ 8.60 (d, J )
8.7 Hz, 1 H), 7.75 (dd, J ) 7.2, 1.5 Hz, 1 H), 7.63 (d, J ) 9.0 Hz, 1
H), 7.56 (d, J ) 8.1 Hz, 1 H), 7.20-7.40 (m, 3 H), 7.09 (t, J ) 0.9
Hz, 1 H), 6.40 (s, 1 H), 1.83 (d, J ) 0.9 Hz, 3 H); 13C NMR (75.4
MHz, C6D6) δ 153.8, 139.5, 134.5, 130.9, 129.4, 128.9, 128.7, 126.7,
126.3, 126.1, 126.1, 125.6, 121.8, 112.4, 9.8; MS m/z 208 (M+, 100);
IR (neat) 1589, 1509, 1390, 798, 773 cm-1. HRMS calcd for C15H12O:
208.08882. Found: 208.09197.
Typical Procedure for Pd(0)-Catalyzed Cycloisomerization (Pro-
cedures G and H). (A) 2,4-Dimethyl-3-(ethoxycarbonyl)-5-heptyl-
furan (6a). Procedure G: A solution of 1a (66 mg, 0.25 mmol) and
Pd(PPh3)4 (16 mg, 5 mol %) in 4 mL of CH3CN was stirred at 80 °C
under Ar for 12 h. After the reaction was over, the solvent was
evaporated, and 3 mL of THF and 3 mL of 3 M HCl were added to
the residue. After complete aromatization as monitored by TLC, the
solution was extracted with ethyl ether, and the organic layer was dried
over MgSO4. Filtration, evaporation, and flash chromatography on silica
gel afforded 57 mg (84%) of 6a as a liquid. 1H NMR (300 MHz, CDCl3)
δ 4.26 (q, J ) 7.2 Hz, 2 H), 2.49 (t, J ) 6.6 Hz, 2 H), 2.49 (s, 3 H),
2.06 (s, 3 H), 1.47-1.62 (m, 2 H), 1.34 (t, J ) 7.2 Hz, 3 H), 1.20-
1.40 (m, 8 H), 0.87 (t, J ) 6.9 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3)
δ 165.1, 157.2, 149.9, 114.3, 113.6, 59.6, 31.8, 29.0, 28.5, 25.4, 22.6,
14.3, 14.2, 14.0, 9.8; MS m/z 266 (M+, 31.69), 181 (100); IR (neat)
1714, 1585, 1286, 1091 cm-1. HRMS calcd for C16H26O3: 266.18820.
Found: 266.18753.
(B) 2,4-Dimethyl-3-(ethoxycarbonyl)-5-butylfuran (6b): Following
procedure G, the reaction of 1b (114 mg, 0.50 mmol) and Pd(PPh3)4
(26 mg, 0.023 mmol) in 4 mL of CH3CN afforded 89 mg (78%) of 6b:
liquid; 1H NMR (300 MHz, CDCl3) δ 4.27 (q, J ) 7.2 Hz, 2 H), 2.50
(s, 3 H), 2.49 (t, J ) 7.5 Hz, 2 H), 2.06 (s, 3 H), 1.50-1.65 (m, 2 H),
1.34 (t, J ) 7.2 Hz, 3 H), 1.20-1.40 (m, 2 H), 0.91 (t, J ) 7.5 Hz, 3
H); 13C NMR (75.4 MHz, CDCl3) δ 165.1, 157.2, 149.9, 114.3, 113.6,
59.6, 30.6, 25.1, 22.1, 14.3, 14.2, 13.7, 9.8; MS m/z 224 (M+, 30.19),
181 (100); IR (neat) 1714, 1585, 1286, 1091 cm-1. HRMS calcd for
C13H20O3: 224.14124. Found: 224.14031.
(R) 2-(2′-Furyl)-4-methylfuran (4v):36 Following procedure E, the
reaction of 1v (148 mg, 1 mmol), NaI (300 mg, 2 mmol), and
PdCl2(CH3CN)2 (13 mg, 0.025 mmol) in 2 mL of acetone afforded
104 mg (70%) of 4v. Following procedure D, the reaction of 1v (74
mg, 0.5 mmol) and NaI (14 mg, 0.09 mmol) in 2 mL of acetone afforded
1
58 mg (78%) of 4v: liquid; H NMR (300 MHz, C6D6) δ 7.00-7.03
(m, 1 H), 6.83-6.90 (m, 1 H), 6.51 (d, J ) 3.3 Hz, 1 H), 6.39 (s, 1 H),
6.07 (dd, J ) 3.3 Hz, 1.8 Hz, 1 H), 1.70 (s, 3 H); 13C NMR (75.4
MHz, C6D6) δ 147.4, 147.1, 141.8, 138.8, 121.8, 111.6, 108.1, 105.2,
9.5; MS m/z 148 (M+, 71.77), 91 (100); IR (neat) 1581, 1451, 1005
cm-1. HRMS calcd for C9H8O2: 148.05243. Found: 148.05316.
(S) 2-Phenethyl-4-methylfuran (4w): Following procedure E, the
reaction of 1w (290 mg, 1.55 mmol), NaI (300 mg, 2 mmol), and
PdCl2(CH3CN)2 (11 mg, 0.025 mmol) in 5 mL of acetone afforded
(C) 2,4-Dimethyl-3-(ethoxycarbonyl)-5-(3-hydroxypropyl)furan
(6d′): Following procedure G, the reaction of 1d (100 mg, 0.30 mmol)
and Pd(PPh3)4 (33 mg, 0.029 mmol) in 4 mL of CH3CN afforded 41
mg (62%) of 6d′: liquid; 1H NMR (300 MHz, CDCl3) δ 4.25 (q, J )
7.2 Hz, 2 H), 3.62 (t, J ) 6.3 Hz, 2 H), 2.61 (t, J )7.2 Hz, 2 H), 2.47
(s, 3 H), 2.05 (s, 3 H), 1.77-2.00 (m, 3 H), 1.32 (t, J ) 7.2 Hz, 3 H);
13C NMR (75.4 MHz, CDCl3) δ 165.0, 157.6, 148.9, 114.9, 113.7, 61.9,
59.7, 31.2, 21.7, 14.3, 14.2, 9.8; MS m/z 261 (M+, 61.50), 181 (100);
IR (neat) 3406, 1712, 1584, 1287, 1094 cm-1. HRMS calcd for
C12H18O4: 226.12051. Found: 226.12370.
1
223 mg (77%) of 4w: liquid; H NMR (400 MHz, CDCl3) δ 7.16-
7.10 (m, 2 H), 7.08-7.00 (m, 3 H), 6.97 (d, J ) 1.1 Hz, 1 H), 5.74 (s,
1 H), 2.90-2.78 (m, 4 H), 1.87 (d, J ) 1.1 Hz, 3 H); 13C NMR (100
MHz, CDCl3): δ 155.4, 141.3, 137.4, 128.35, 128.33, 126.0, 120.4,
(D) 2,4-Dimethyl-3-acetyl-5-heptylfuran (6e): Following procedure
G, the reaction of 1e (114 mg, 0.48 mmol) and Pd(PPh3)4 (31 mg,
(36) Dana, G.; Scribe, P.; Girault, J. P. Tetrahedron Lett. 1970, 4137.
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J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004 9659

A R T I C L E S
Ma et al.
0.027 mmol) in 4 mL of CH3CN afforded 86 mg (75%) of 6e: liquid;
1H NMR (300 MHz, CDCl3) δ 2.48 (s, 3 H), 2.47 (t, J ) 7.8 Hz, 2 H),
2.37 (s, 3 H), 2.06 (s, 3 H), 1.45-1.60 (m, 2 H), 1.17-1.37 (m, 8 H),
0.85 (t, J ) 7.2 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 195.0, 156.3,
150.1, 122.8, 113.6, 31.7, 30.7, 29.0, 28.9, 28.4, 25.2, 22.6, 15.1, 14.0,
10.5; MS m/z 236 (M+, 40.24), 151 (100); IR (neat) 1670, 1563, 1285
cm-1. HRMS calcd for C15H24O2: 236.17764. Found: 236.18043.
(E) 2,4-Dimethyl-3-(benzenesulfonyl)-5-heptylfuran (6f): Follow-
ing procedure G, the reaction of 1f (171 mg, 0.50 mmol) and Pd(PPh3)4
(33 mg, 0.029 mmol) in 4 mL of CH3CN afforded 104 mg (74%) of
6f: liquid; 1H NMR (300 MHz, CDCl3) δ 7.85-7.90 (m, 2 H), 7.45-
7.60 (m, 3 H), 2.59 (s, 3 H), 2.42 (t, J ) 7.8 Hz, 2 H), 1.92 (s, 3 H),
1.43-1.57 (m, 2 H), 1.15-1.30 (m, 8 H), 0.84 (t, J ) 6.6 Hz, 3 H);
13C NMR (75.4 MHz, CDCl3) δ 155.4, 151.0, 142.8, 132.8, 129.0,
126.6, 121.3, 112.5, 31.6, 28.9, 28.8, 28.1, 25.4, 22.5, 14.0, 13.4, 8.7;
MS m/z 334 (M+, 18.55), 249 (100); IR (neat) 1630, 1568, 1319, 1159
cm-1. HRMS calcd for C19H26O3S: 334.16027. Found: 334.16121.
(F) 2-Phenyl-3-(ethoxycarbonyl)-4-methyl-5-heptylfuran (6h):
Following procedure G, the reaction of 1h (87 mg, 0.27 mmol) and
Pd(PPh3)4 (31 mg, 0.027 mmol) in 4 mL of CH3CN afforded 67 mg
(77%) of 6h: liquid; 1H NMR (300 MHz, CDCl3) δ 7.75-7.80 (m, 2
H), 7.30-7.45 (m, 3 H), 4.29 (q, J ) 7.2 Hz, 2 H), 2.62 (t, J ) 7.2
Hz, 2 H), 2.14 (s, 3 H), 1.57-1.73 (m, 2 H), 1.30 (t, J ) 7.2 Hz, 3 H),
1.20-1.45 (m, 8 H), 0.89 (t, J ) 6.6 Hz, 3 H); 13C NMR (75.4 MHz,
CDCl3) δ 164.8, 154.9, 151.7, 130.6, 128.5, 128.1, 127.8, 116.0, 114.5,
60.2, 31.8, 29.0, 29.0, 28.4, 25.7, 22.6, 14.08, 14.07, 10.0; MS m/z
(I) 2-Heptyl-3-methylene-4-(benzenesulfonyl)-5-methyl-2,3-dihy-
drofuran (5f): Following procedure H, the reaction of 1f (138 mg,
0.41 mmol) and Pd(PPh3)4 (29 mg, 0.025 mmol) in 2 mL of CH3CN
1
afforded 119 mg (86%) of 5f: liquid; H NMR (300 MHz, CDCl3) δ
7.85-7.90 (m, 2 H), 7.45-7.60 (m, 3 H), 5.20 (d, J ) 3.0 Hz, 1 H),
4.97-5.07 (m, 1 H), 4.55 (d, J ) 2.7 Hz, 1 H), 2.40 (s, 3 H), 1.45-
1.75 (m, 2 H), 1.15-1.35 (m, 10 H), 0.85 (t, J ) 7.2 Hz, 3 H); 13C
NMR (75.4 MHz, CDCl3) δ 173.5, 144.3, 142.4, 132.8, 128.9, 126.3,
114.0, 98.4, 86.9, 36.0, 31.6, 29.2, 29.0, 23.6, 22.6, 14.6, 14.0; MS
m/z 334 (M+, 28.86), 249 (100); IR (neat) 1637, 1597, 1317, 1157
cm-1. HRMS calcd for C19H26O3S: 334.16026. Found: 334.16173.
(J) 2-Heptyl-3-methylene-4-(ethoxycarbonyl)-5-phenyl-2,3-dihy-
drofuran (5h): Following procedure H, the reaction of 1h (163 mg,
0.5 mmol), Et3N (0.5 mL), and Pd(PPh3)4 (58 mg, 0.05 mmol) in 2
1
mL of CH3CN afforded 114 mg (70%) of 5h: liquid; H NMR (300
MHz, C6D6) δ 7.70-7.80 (m, 2 H), 7.03-7.10 (m, 3 H), 6.05 (d, J )
3.0 Hz, 1 H), 4.93-5.03 (m, 1 H), 4.77 (d, J ) 2.4 Hz, 1 H), 3.99 (q,
J ) 7.5 Hz, 2 H), 1.50-1.70 (m, 3 H), 1.15-1.55 (m, 9 H), 0.87 (t, J
) 6.6 Hz, 3 H), 0.84 (t, J ) 7.5 Hz, 3 H); 13C NMR (75.4 MHz, C6D6)
δ 170.8, 164.2, 149.0, 131.4, 130.6, 129.7, 127.8, 107.7, 100.5, 86.4,
59.8, 37.0, 32.0, 29.9, 29.6, 24.6, 23.0, 14.3, 14.0; MS m/z 328 (M+,
34.19), 243 (100); IR (neat) 1708, 1610, 1591, 1380, 1089 cm-1. HRMS
calcd for C21H28O3: 328.21172. Found: 328.20778.
(K) 2-Methyl-3-(ethoxycarbonyl)-4-methylene-1-oxa-spiro[4,5]-
dec-2-ene (5j): Following procedure H, the reaction of 1j (116 mg,
0.50 mol) and Pd(PPh3)4 (31 mg, 0.027 mmol) in 4 mL of CH3CN
328 (M+, 46.37), 243(100); IR (neat) 1716, 1557, 1290, 1108 cm-1
.
1
afforded 102 mg (88%) of 5j: liquid; H NMR (300 MHz, CDCl3) δ
Anal. Calcd for C21H28O3: C, 76.79; H, 8.59. Found: C, 76.66; H,
8.53.
5.35 (s, 1 H), 4.42 (s, 1 H), 4.21 (q, J ) 7.5 Hz, 2 H), 2.31 (s, 3 H),
1.57-1.80 (m, 7 H), 1.10-1.43 (m, 3 H), 1.30 (t, J ) 7.5 Hz, 3 H);
13C NMR (75.4 MHz, CDCl3) δ 174.0, 165.4, 152.2, 105.2, 97.3, 91.1,
59.4, 37.4, 24.8, 21.9, 15.8, 14.2; MS m/z 236 (M+, 38.50), 181
(100.00); IR (neat) 1701, 1663, 1608, 1230, 1079 cm-1. HRMS calcd
for C14H20O3: 236.14125. Found: 236.14468.
(G) 2-Heptyl-3-methylene-4-(ethoxycarbonyl)-5-methyl-2,3-di-
hydrofuran (5a). Procedure H: A solution of 1a (134 mg, 0.50 mmol),
0.5 mL of Et3N, and Pd(PPh3)4 (29 mg, 0.025 mmol) in 2 mL of CH3-
CN was stirred at 80 °C under Ar for 14.5 h. Evaporation and flash
chromatography on silica gel (petroleum ether/Et2O/Et3N ) 20:1:0.1)
(L) 2-Methyl-3-acetyl-4-methylene-1-oxa-spiro[4,5]dec-2-ene (5k):
Following procedure H, the reaction of 1k (106 mg, 0.51 mol) and
Pd(PPh3)4 (31 mg, 0.027 mmol) in 4 mL of CH3CN afforded 89 mg
1
afforded 120 mg (90%) of 5a: liquid; H NMR (300 MHz, C6D6) δ
5.93 (d, J ) 3.0 Hz, 1 H), 4.80-4.90 (m, 1 H), 4.66 (d, J ) 3.0 Hz,
1 H), 4.08 (q, J ) 7.2 Hz, 2 H), 2.21 (s, 3 H), 1.45-1.65 (m, 2 H),
1.10-1.40 (m, 10 H), 0.99 (t, J ) 7.2 Hz, 3 H), 0.96 (t, J ) 6.3 Hz,
3 H); 13C NMR (75.4 MHz, C6D6) δ 175.6, 164.6, 147.7, 107.2, 98.6,
87.0, 59.5, 36.8, 32.2, 29.8, 29.6, 24.6, 23.0, 15.6, 14.4, 14.3; MS m/z
1
(84%) of 5k: solid; mp 67-69 °C (petroleum ether/ether); H NMR
(300 MHz, CDCl3) δ 5.25 (s, 1 H), 4.45 (s, 1 H), 2.31 (s, 6 H), 1.57-
1.87 (m, 7 H), 1.18-1.40 (m, 3 H); 13C NMR (75.4 MHz, CDCl3) δ
194.5, 173.8, 152.8, 114.9, 97.7, 91.2, 37.4, 31.0, 24.8, 21.9, 16.8; MS
m/z 206 (M+, 56.66), 43(100); IR (KBr) 1636, 1571, 1229 cm-1. Anal.
Calcd for C13H18O2: C, 75.69; H, 8.80. Found: C, 75.67; H, 8.83.
266 (M+, 45.75), 181 (100); IR (neat) 1711, 1610, 1288, 1093 cm-1
HRMS calcd for C16H26O3: 266.18819. Found: 266.18944.
.
(H)
2-[(3′-tert-Butyldimethylsilyloxy)propyl]-3-methylene-4-
(ethoxycarbonyl)-5-methyl-2,3-dihydrofuran (5d): Following pro-
cedure H, the reaction of 1d (171 mg, 0.50 mmol) and Pd(PPh3)4 (29
mg, 0.025 mmol) in 3 mL of CH3CN afforded 154 mg (90%) of 5d:
liquid; 1H NMR (300 MHz, CDCl3) δ 5.41 (d, J ) 2.5 Hz, 1 H), 5.02-
5.10 (m, 1 H), 4.58 (d, J ) 2.5 Hz, 1 H), 4.23 (q, J ) 7.5 Hz, 2 H),
3.58-3.68 (m, 2 H), 2.30 (s, 3 H), 1.50-1.90 (m, 4 H), 1.32 (t, J )
7.5 Hz, 3 H), 0.88 (s, 9 H), 0.03 (s, 6 H); 13C NMR (75.4 MHz, CDCl3)
δ 175.8, 165.1, 146.9, 106.5, 98.1, 86.6, 62.6, 59.6, 32.7, 27.3, 25.9,
18.3, 15.6, 14.3, 1.0, -5.4; MS m/z 340 (M+, 2.51), 283 (100); IR
(neat) 1706, 1610, 1205, 1097 cm-1. HRMS calcd for C18H32O4Si:
340.20699. Found: 340.20949.
Acknowledgment. We are grateful to the Major State Basic
Research Development Program (Grant No. G2000077500), the
National Natural Science Foundation of China, and Shanghai
Municipal Committee of Science and Technology for financial
support.
Supporting Information Available: Copies of 1H/13C NMR
spectra of all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
JA0494860
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9660 J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004