PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols: An efficient synthesis of 4-(1′,3′-dien-2′-yl)- 2,5-dihydrofuran derivatives

Article abstract of DOI:10.1021/jo702332m

(Chemical Equation Presented) A PdCl₂/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols was observed to provide an efficient route to 4-(1′,3′-dien-2′-yl)-2,5-dihydrofuran derivatives. By using the easily available optical

Full text of DOI:10.1021/jo702332m

PdCl2/NaI-Catalyzed Homodimeric Coupling-Cyclization Reaction of
2,3-Allenols: An Efficient Synthesis of
4-(1′,3′-Dien-2′-yl)-2,5-dihydrofuran Derivatives
Youqian Deng,† Yihua Yu,‡ and Shengming Ma*,†,§
Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang UniVersity,
Hangzhou 310027, Zhejiang, People’s Republic of China, Shanghai Key Laboratory of Functional
Magnetic Resonance Imaging, Department of Physics, East China Normal UniVersity, Shanghai 200062,
People’s Republic of China, and State Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, People’s Republic of
China
masm@mail.sioc.ac.cn
ReceiVed October 29, 2007
A PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols was observed to provide
an efficient route to 4-(1′,3′-dien-2′-yl)-2,5-dihydrofuran derivatives. By using the easily available optically
active starting materials, 2,5-dihydrofurans with high enantiopurity may be prepared. A Pd(II)-catalyzed
mechanism was also discussed.
Introduction
allenes were cyclized.7 Recently, Hashmi et al. reported the
AuCl3-catalyzed reaction of 2,3-allenols, which afforded bis-
(2,5-dihydrofuran)s as a byproduct in low yield.8 On the other
The transition metal-catalyzed cyclizative dimerization reac-
tion of two functionalized allenes is attractive for synthetic
organic chemists due to the issues of chirality transfer, diversity,
and substituent-loading capability of allenes.1,2 The first pal-
ladium-catalyzed homodimerization reaction of 1,2-allenyl
ketones has been reported by Hashmi et al., which led to the
formation of monocyclic 3-(3′-oxo-1′-alkenyl)-substituted furan
derivatives.3,4 The reaction of 1,2-allenyl ketones would also
afford 2-(3′-oxo-1′-alkenyl)-substituted furan derivatives when
AuCl3 was used as the catalyst.5 The palladium-catalyzed
macrocyclization reaction of 1,ω-bis(1,2-allenylketone)s was
also reported.6 We have reported the homodimerization reaction
of 2,3-allenoic acids affording bibutenolides, in which both
(2) For reviews and accounts, see: (a) Yamamoto, Y.; Radhakrishnan,
U. Chem. Soc. ReV. 1999, 28, 199. (b) Larock, R. C. J. Organomet. Chem.
1999, 576, 111. (c) Grigg, R.; Sridharan, V. J. Organomet. Chem. 1999,
576, 65. (d) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem.
ReV. 2000, 100, 3067. (e) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000,
39, 3590. (f) Reissig, H.-U.; Hormuth, S.; Schade, W.; Okala Amombo,
M.; Watanabe, T.; Pulz, R.; Hausherr, A.; Zimmer, R. J. Heterocycl. Chem.
2000, 37, 597. (g) Ma, S.; Li, L. Synlett 2001, 1206. (h) Reissig, H.-U.;
Schade, W.; Okala Amombo, M.; Pulz, R.; Hausherr, A. Pure Appl. Chem.
2002, 74, 175. (i) Ma, S. Carbopalladation of Allenes. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-
Interscience: New York, 2002; p 1491. (j) Ma, S. Acc. Chem. Res. 2003,
36, 701. (k) Ma, S. Chem. ReV. 2005, 105, 2829. (l) Ma, S. Pd-Catalyzed
two- or three-component cyclization of functionalized allenes. In Topics in
Organometallic Chemistry; Tsuji, J., Ed.; Springer-Verlag: Heidelberg,
Germany, 2005; pp 183-210.
(3) (a) Hashmi, A. S. K. Angew. Chem., Int. Ed. Engl. 1995, 34, 1581.
(b) Hashmi, A. S. K.; Ruppert, T. L.; Kno¨fel, T.; Bats, J. W. J. Org. Chem.
1997, 62, 7295.
(4) For a most recent report from Alcaide’s group, see: Alcaide, B.;
Almendros, P.; Mart´ınez del Campo, T. Eur. J. Org. Chem. 2007, 2844.
(5) Hashmi, A. S. K.; Schwarz, L.; Choi, J.-H.; Frost, T. M. Angew.
Chem., Int. Ed. 2000, 39, 2285.
* Address correspondence to this author. Phone: 86-21-549-25147. Fax: 86-
21-641-67510.
† Zhejiang University.
‡ East China Normal University.
§ Chinese Academy of Sciences.
(1) (a) Patai, S. The Chemistry of Ketenes, Allenes, and Related
Compounds; John Wiley & Sons: New York, 1980; Part 1. (b) Schuster,
H. F.; Coppola, G. M. Allenes in Organic Synthesis; John Wiley & Sons:
New York, 1984. (c) Landor, S. R. The Chemistry of Allenes; Academic
Press: New York, 1982; Vols. 1-3. (d) Krause, N.; Hashmi, A. S. K.,
Eds. Modern Allene Chemistry; Wiley-VCH: Weinheim, Germany, 2004;
Vols. 1 and 2.
(6) Hashmi, A. S. K.; Schwarz, L.; Bolte, M. Eur. J. Org. Chem. 2004,
1923.
(7) (a) Ma, S.; Yu, Z. Org. Lett. 2003, 5, 1507. (b) Ma, S.; Yu, Z.; Gu,
Z. Chem. Eur. J. 2005, 11, 2351.
10.1021/jo702332m CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/19/2007
J. Org. Chem. 2008, 73, 585-589
585

Deng et al.
TABLE 1. Pd(ΙΙ)-Catalyzed Homodimeric Coupling-Cyclization
Reaction of 2,3-Allenol (1a)
hand, 2,5-dihydrofurans, an important class of heterocyclic
compounds, are useful intermediates for organic synthesis9 and
common structural units in many natural products.10 These
compounds are usually prepared via cyclization of 2,3-
allenols,11-16 a RCM reaction,17 Ag(I)-catalyzed rearrangement-
cyclization of 4-hydroxypropargyl esters,18 dehydration of cis-
2-alken-1,4-diols,19 palladium-catalyzed reaction of cyclic alkynyl
carbonates with electron-deficient alkenes,20 Prins reaction of
terminal alkene and formaldehyde,21 reaction of oxazirconacy-
clopentenes with propynoates,22 reaction of 1,4-dilithio-1,3-
dienes with aldehydes,23 tungsten-promoted intramolecular
annulation of propargyl bromides with ketones and aldehydes,24
and Au(I)-catalyzed rearrangement of butynediol monoben-
zoates.25 In this paper, we wish to report an efficient synthesis
of 4-(1′,3′-dien-2′-yl)-2,5-dihydrofuran derivatives via the PdCl2/
additive
(equiv)
time
(h)
yield of 2aa
entry
solvent
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
THF
none
24
12
12
5
5
5
21
5
5
0.5
3
1.5
17
17
17
trace
22b,d
25b
42
NaCl (0.5)
LiCl (0.5)
NaI (0.1)
NaI (0.3)
NaI (0.5)
NaI (0.5)
NaI (1.0)
KI (0.5)
I2 (0.25)
I2 (0.05)
CH3I (10)
NaI (0.5)
NaI (0.5)
NaI (0.5)
80
86
75b,c,e
81
(8) Hashmi, A. S. K.; Carmen Blanco, M.; Fischer, D.; Bats, J. W. Eur.
J. Org. Chem. 2006, 1387.
85
66
42
86
(9) (a) Marshall, J. A.; Pinney, K. G. J. Org. Chem. 1993, 58, 7180. (b)
Marshall, J. A.; Yu, B. J. Org. Chem. 1994, 59, 324. (c) Yamada, O.;
Ogasawara, K. Synlett 1995, 427. (d) Kim, S.; Kim, K. H. J. Chem. Soc.,
Perkin Trans. 1 1997, 1095. (e) Paolucci, C.; Musiani, L.; Venturelli, F.;
Fava, A. Synthesis 1997, 1415. (f) Shieh, S.-J.; Fan, J.-S.; Chandrasekharam,
M.; Liao, F.-L.; Wang, S.-L.; Liu, R.-S. Organometallics 1997, 16, 3987.
(g) Doyle, M. P.; Forbes, D. C.; Protopopova, M. N.; Stanley, S. A.;
Vasbinder, M. M.; Xavier, K. R. J. Org. Chem. 1997, 62, 7210. (h) Crotti,
P.; Bussolo, V. D.; Favero, L.; Pineschi, M. Tetrahedron 1997, 53, 1417.
(i) Bauer, T. Tetrahedron 1997, 53, 4763.
(10) (a) Kupchan, S. M.; Davies, V. H.; Fujita, T.; Cox, M. R.; Restivo,
R. J.; Bryan, R. F. J. Org. Chem. 1973, 38, 1853. (b) Semple, J. E.; Wang,
P. C.; Lysenko, Z.; Joullie, M. M. J. Am. Chem. Soc. 1980, 102, 7505.
(11) For a related recent review, see ref 1d.
(12) For the electrophilic cyclization of 2,3-allenols, see: (a) Beaulieu,
P. L.; Morisset, V. M.; Garratt, D. G. Tetrahedron Lett. 1980, 21, 129. (b)
Smadja, W. Chem. ReV. 1983, 83, 263. (c) Bridges, A. J.; Thomas, R. D.
J. Chem. Soc., Chem. Commun. 1984, 694. (d) Whitby, R.; Kocienski, P.
Tetrahedron Lett. 1987, 28, 3619. (e) Marshall, J. A.; Wang, X. J. Org.
Chem. 1990, 55, 2995. (f) Marshall, J. A.; Wang, X. J. Org. Chem. 1991,
56, 4913.
(13) For the base-mediated cyclization of 2,3-allenols, see: (a) Hoff,
S.; Brandsma, L.; Arens, J. F. Recl. TraV. Chim, Pays-Bas 1969, 88, 609.
(b) Brasholz, M.; Ressig, H.-U. Angew. Chem., Int. Ed. 2007, 46, 1634. (c)
Katritzky, A. R.; Verin, S. V. J. Heterocycl. Chem. 1995, 32, 323. (d)
Magnus, P.; Albaugh-Robertson, P. J. Chem. Soc., Chem. Commun. 1984,
805.
60b,f
47b,g
44b,h
acetone
CH3CN
a Isolated yield. b Determined by 1H NMR analysis using 1,3,5-trimeth-
ylbenzene as the internal standard. c 2 mol % PdCl2 was used. d 10% of 1a
was recovered. e 16% of 1a was recovered. f 11% of 1a was recovered.
g 40% of 1a was recovered. h 33% of 1a was recovered.
NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-
allenols, in which one molecule of the 2,3-allenol was cyclized
while the other formed the 1,3-diene unit and helped to
regenerate the catalytically active Pd(II) species.26
Results and Discussion
PdCl2/NaI-Catalyzed Homodimeric Coupling-Cyclization
Reaction of 2,3-Allenols. The homodimeric coupling-cycliza-
tion reaction of 2,3-allenol (1a) was chosen to establish the
protocol. Some representative results are listed in Table 1. From
Table 1, it was observed that under the catalysis of PdCl2, the
reaction of 1a afforded a trace amount of 3-(1-cyclohexyliden-
emethylvinyl)-1-oxaspiro[4.5]dec-3-ene (2a) (Table 1, entry 1).
When NaCl or LiCl was applied as the additive, the reaction
afforded 2a in 22% and 25% yields, respectively (Table 1,
entries 2 and 3). Surprisingly, when NaI7b was applied as the
additive, the reaction afforded 2a in higher yields (Table 1,
entries 4-8). Addition of KI7b (Table 1, entry 9), I27b(Table 1,
entries 10 and 11), or CH3I7a (Table 1, entry 12) is also effective
for this reaction. Among the solvents tested, DMA is the best.
In THF, acetone, and CH3CN, the yields were lower and some
of 1a was recovered (Table 1, entries 13-15). In conclusion,
the best results were obtained when the reaction was conducted
using 5 mol % PdCl2 and 0.5 equiv of NaI in DMA leading to
a 86% yield of product 2a (Table 1, entry 6).
(14) For the metal-catalyzed cycloisomerization reaction, see: Ag+: (a)
Olsson, L. I.; Claesson, A. Synthesis 1979, 743. (b) Nikam, S. S.; Chu, K.
H.; Wang, K. K. J. Org. Chem. 1986, 51, 745. (c) Marshall, J. A.; Sehon,
C. A. J. Org. Chem. 1995, 60, 5966.(d) Marshall, J. A.; Yu, R. H.; Perkins,
J. F. J. Org. Chem. 1995, 60, 5550. Hg2+: (a) Gelin, R.; Gelin, S.; Albrand,
M. Bull. Soc. Chim. Fr. 1972, 1946. (b) Walkup, R. D.; Park, G. Tetrahedron
Lett. 1987, 28, 1023. Au3+: Hoffmann-Ro¨der, A.; Krause, N. Org. Lett.
2001, 3, 2537.
(15) For the Pd-catalyzed cyclization reaction of 2,3-allenols in the
presence of allylic halides, see: (a) Ma, S.; Gao, W. Tetrahedron Lett. 2000,
41, 8933. (b) Ma, S.; Gao, W. J. Org. Chem. 2002, 67, 6104.
(16) For the Pd-Cu-catalyzed, domino cyclization of 2,3-allenols with
acrylate, alkynes, and boronic acids, see: Alcaide, B.; Almendros, P.;
Rodr´ıguez-Acebes, R. Chem. Eur. J. 2005, 11, 5708.
(17) Carda, M.; Castillo, E.; Rodr´ıguez, S.; Uriel, S.; Marco, J. A. Synlett
1999, 1639.
(18) (a) Shigemasa, Y.; Yasui, M.; Ohrai, S.; Sasaki, M.; Sashiwa, H.;
Saimoto, H. J. Org. Chem. 1991, 56, 910. (b) Saimoto, H.; Yasui, M.; Ohrai,
S.; Oikawa, H.; Yokoyama, K.; Shigemasa, Y. Bull. Chem. Soc. Jpn. 1999,
72, 279.
(19) Sato, F.; Kanbara, H.; Tanaka, Y. Tetrahedron Lett. 1984, 25, 5063.
(20) Darcel, C.; Bruneau, C.; Albert, M.; Dixneuf, P. H. Chem. Commun.
1996, 919.
(21) Talipov, R. F.; Starikov, A. S.; Gorina, I. A.; Akmanova, N. A.;
Safarov, M. G. Zh. Org. Khim. 1993, 29, 1024.
(22) Xi, C.; Kotora, M.; Takahashi, T. Tetrahedron Lett. 1999, 40, 2375.
(23) Chen, J.; Song, Q.; Li, P.; Guan, H.; Jin, X.; Xi, Z. Org. Lett. 2002,
4, 2269.
Some typical results are summarized in Tables 2 and 3.
Various substituted 2,3-allenols that bear alkyl or aryl groups
were successfully used to afford 4-(1′,3′-dien-2′-yl)-2,5-dihy-
drofuran derivatives in moderate to good yields. Furthermore,
it is important to note that a high stereoselectivity for the
(24) Shieh, S.-J.; Tang, T.-C.; Lee, J.-S.; Lee, G.-H.; Peng, S.-M.; Liu,
R.-S. J. Org. Chem. 1996, 61, 3245.
(25) Buzas, A.; Istrate, F.; Gagosz, F. Org. Lett. 2006, 8, 1957.
(26) This reaction was first observed in this group during the study of
the PdCl2-catalyzed cyclization of propadienyl cyclohexanol in the presence
of allylic bromide, see ref 15b.
586 J. Org. Chem., Vol. 73, No. 2, 2008

Synthesis of 4-(1′,3′-Dien-2′-yl)-2,5-dihydrofuran DeriVatiVes
SCHEME 1. Homodimeric Coupling-Cyclization Reaction of Optically Active 2,3-Allenols (1g)
TABLE 2. Homodimeric Coupling-Cyclization Reaction of
2,3-Allenols
SCHEME 2. PdX2-Catalyzed Homodimeric Self-Coupling
Cyclization Reaction of 2,3-Allenol (1a)
time isolated yield
entry
R1
R2
R2
(h)
of 2 (%)
1
2
3
4
5
6
H
H
H
H
(CH2)5 (1a)
CH3
C2H5
n-C4H9
H
5
5
4
10
12
12
86 (2a)
66 (2b)
85 (2c)
92 (2d)
84 (2e)
87 (2f)
CH3 (1b)
C2H5 (1c)
n-C4H9 (1d)
H (1e)
To clarify the mechanism of this reaction, three control
experiments were conducted (Scheme 2). It should be noted
that when 5 mol % PdBr2 or PdI2 was used, the reaction
proceeded even in the absence of NaI affording 2a in 65% or
90% yields, respectively, indicating the possible in situ formation
of PdI2 under the current reaction conditions.
On the basis of these experimental findings, it was proposed
that the interaction of 1g with PdI2, which might be produced
in situ from PdCl2 and NaI, would form 2,5-dihydrofuranyl
palladium intermediate M1 via cyclic oxypalladation. Then
regioselective carbopalladation of a second molecule of 1g with
M1 would highly regioselectively form the π-allylic palladium
intermediate M2. Subsequent trans-â-hydroxide elimination28-31
would afford 2g and IPd+[OH-]. Finally, IPd+[OH-] was
converted to the catalytically active species PdI2 by its reaction
with HI generated in the first step (Scheme 3). It should be
noted when R1 * H, R2 * H, and R3 ) H, the intermediate
M3 was more favored for its thermodynamic stability over M4.
M3 would afford E-isomers highly stereoselectively through a
trans-â-hydroxide elimination (Scheme 4).
n-C4H9
n-C7H15
H
H (1f)
TABLE 3. Stereoselective Homodimeric Coupling-Cyclization
Reaction of 2,3-Allenols
time
(h)
yield of 2a
E/Z ratio
of 2b
entry
R1
R2
(%)
1
2
3
4
5
n-C4H9
n-C4H9
Ph
CO2CH3
allyl
CH3 (1g)
C2H5 (1h)
n-C4H9 (1i)
C2H5 (1j)
CH3 (1k)
13
14
11
17
1.5
83 (2g)
86 (2h)
75 (2i)
58 (2j)
61(2k)
g95:5
g96:4
>99:1c
95:5c
>99:1
a Isolated yield. b E/Z was determined by 1H NMR analysis. c Z/E ratio.
(28) Ma, S.; Gu, Z. J. Am. Chem. Soc. 2005, 127, 6182.
(29) (a) Harrington, P. J.; Hegedus, L. S.; McDaniel, K. F. J. Am. Chem.
Soc. 1987, 109, 4335. (b) Francis, J. W.; Henry, P. M. Organometallics
1991, 10, 3498. (c) Saito, S.; Hara, T.; Takahashi, N.; Hirai, M.; Moriwake,
T. Synlett 1992, 237. (d) Ma, S.; Lu, X. J. Organomet. Chem. 1993, 447,
305.
(30) (a) Kimura, M.; Horino, Y.; Mukai, R.; Tanaka, S.; Tamaru, Y. J.
Am. Chem. Soc. 2001, 123, 10401. (b) Ozawa, F.; Okamoto, H.; Kawagishi,
S.; Yamamoto, S.; Minami, T.; Yoshifuji, M. J. Am. Chem. Soc. 2002, 124,
10968. (c) Manabe, K.; Kobayashi, S. Org. Lett. 2003, 5, 3241. (d) Kabalka,
G. W.; Dong, G.; Venkataiah, B. Org. Lett. 2003, 5, 893. (e) Yoshida, M.;
Gotou, T.; Ihara, M. Chem. Commun. 2004, 1124.
(31) For the stereoselectivity of â-heteroatom elimination, see: (a) Frost,
C. G.; Howarth, J.; Williams, J. M. J. Tetrahedron: Asymmetry 1992, 3,
1089. (b) Daves, G. D., Jr. Acc. Chem. Res. 1990, 23, 201. (c) Zhu, G.; Lu,
X. Organometallics 1995, 14, 4899. (d) Zhang, Z.; Lu, X.; Xu, Z.; Zhang,
Q.; Han, X. Organometallics 2001, 20, 3724. (e) Alcaide, B.; Almendros,
P.; Mart´ınez del Campo, T. Angew. Chem., Int. Ed. 2006, 45, 4501.
formation of the CdC bond carrying R1 and R2 groups was
observed affording the products (E)-2 when secondary 2,3-
allenols were applied (Table 3). The stereochemistry of these
products was determined by the NOESY study of (E)-2h.
In addition, by using the optically active 2,3-allenols R-(+)-
1g (97% ee) and S-(-)-1g (98% ee),27 the reaction occurred
smoothly to give the product R-2g in 86% yield and 97% ee
and S-2g in 88% yield and 99% ee, respectively (Scheme 1).
These results indicated that no racemization was observed under
the standard reaction conditions.
(27) Xu, D.; Li, Z.; Ma, S. Chem. Eur. J. 2002, 8, 5012.
J. Org. Chem, Vol. 73, No. 2, 2008 587

Deng et al.
SCHEME 3. Possible Mechanism of the Homodimeric
Coupling-Cyclization Reaction of 1g
SCHEME 4. A Rationale for the Stereoselectivity Observed
FIGURE 1. ORTEP structure of 4aa.
added 1a (136.8 mg, 0.99 mmol) and DMA (2 mL). After being
stirred at 80 °C for 5 h the reaction was complete as monitored by
TLC and the resulting mixture was cooled to room temperature
and quenched by 10 mL of water. The mixture was extracted with
Et2O (3 × 25 mL). The combined organic layer was washed with
a saturated aqueous solution of Na2S2O3 and brine. The product
solution was dried over anhydrous Na2SO4. Evaporation and column
chromatography on silica gel (petroleum ether/diethyl ether ) 20:
1) afforded 2a (109.3 mg, 86%): liquid; 1H NMR (400 MHz,
CDCl3) δ 5.78 (s, 1H), 5.74 (s, 1H), 4.89 (s, 1H), 4.86 (s, 1H),
4.73 (d, J ) 2.0 Hz, 2H), 2.20 (t, J ) 5.6 Hz, 2H), 2.16 (t, J ) 5.6
Hz, 2H), 1.72-1.28 (m, 16H).
SCHEME 5. The Diels-Alder Reaction of 2a with 3
Synthesis of Polycyclic Compound 4aa. To maleamide 3 (519.3
mg, 3.0 mmol) were added 2a (387.8 mg, 1.5 mmol) and toluene
(15 mL). The mixture was refluxed at 130 °C for 5 h. After the
reaction was complete as monitored by TLC, it was cooled to room
temperature, evaporated, and analyzed by 300 MHz 1H NMR
spectroscopic analysis with CH2Br2 (105 µL, 1.5 mmol) as the
internal standard, which showed that the diastereomeric ratio of
4aa/4ab is 91/9. Column chromatography on silica gel (petroleum
ether/ethyl acetate ) 8:1) afforded 54.1 mg (8%) of 4ab and 524.0
mg (81%) of 4aa. 4ab: oil; 1H NMR (300 MHz, CDCl3) δ 7.52-
7.43 (m, 2H), 7.43-7.34 (m, 1H), 7.30 (d, J ) 7.5 Hz, 2H), 5.55
(s, 1H), 4.26 (dd, J1 ) 27.9 Hz, J2 ) 13.8 Hz, 2H), 3.08-2.95 (m,
2H), 2.80-2.69 (m, 1H), 2.50-2.40 (m, 1H), 2.25-1.90 (m, 6H),
1.80-1.40 (m, 15H); 13C NMR (75 MHz, CDCl3) δ 178.00, 177.95,
143.5, 137.3, 131.7, 129.1, 128.5, 126.3, 124.8, 119.7, 83.7, 66.4,
48.9, 40.6, 40.3, 37.0, 36.4, 30.7, 30.1, 29.1, 28.5, 27.7, 26.4, 25.6,
Furthermore, the Diels-Alder reaction of 2a with maleamide
3 afforded diastereoisomeric polycyclic compounds 4aa and 4ab
in 81% and 8% yields, respectively (Scheme 5). The structure
of the major product 4aa was further established by the X-ray
diffraction study (Figure 1).
In conclusion, we have developed a homodimeric coupling-
cyclization reaction of 2,3-allenols using PdCl2/NaI as the
catalyst, which provides an efficient route to 4-(1′,3′-dien-2′-
yl)-2,5-dihydrofuran derivatives. By using the optically active
2,3-allenols, no racemization was observed under the standard
reaction conditions, affording optically active products in good
yields. On the basis of control experiment, it was found that
the addition of NaI is very important for this transformation.
Due to the easy availability of the starting allenols and usefulness
of 2,5-dihydrofuran, this method will be useful in organic
synthesis. Further studies on the scope, mechanism, and
synthetic applications of this reaction are being carried out in
our laboratory.
22.8, 21.7; MS (m/z) 431 (M+, 3.21), 333 (100); IR (neat, cm-1
)
2929, 2853, 1779, 1716, 1599, 1500, 1447, 1380, 1178; HRMS
calcd for C28H33NO3 (M+) 431.2460, found 431.2450. 4aa: solid,
1
mp 178-179 °C (ethyl acetate); H NMR (300 MHz, CDCl3) δ
7.46-7.27 (m, 3H), 7.13 (d, J ) 8.1 Hz, 2H), 5.44 (s, 1H), 4.21
(s, 2H), 3.54-3.44 (m, 1H), 3.27 (t, J ) 8.1 Hz, 1H), 2.78 (d, J )
14.7 Hz, 1H), 2.55-2.38 (m, 2H), 2.40-2.30 (m, 1H), 2.20-2.00
(m, 4H), 2.08-1.30 (m, 15H); 13C NMR (75 MHz, CDCl3) δ 178.4,
175.5, 143.7, 139.7, 131.9, 128.8, 128.3, 126.4, 125.1, 119.7, 82.9,
66.1, 49.9, 41.7, 41.1, 36.8, 36.1, 32.1, 31.7, 30.5, 28.3, 27.5, 26.3,
25.6, 23.0; MS (m/z) 431 (M+, 7.89), 333 (100); IR (neat, cm-1
)
2928, 2853, 1775, 1713, 1598, 1500, 1446, 1382. Elemental analysis
calcd for C28H33NO3: C, 77.93; H, 7.71; N, 3.25. Found: C, 77.74;
H, 7.81; N, 2.99. Crystal data for 4aa: C28H33NO3, MW ) 431.55,
monoclinic, space group P2(1)/c, final R indices [I > 2σ(I)], R1 )
0.0688, wR2 ) 0.1807, a ) 16.051(6) Å, b ) 13.024(5) Å, c )
11.211(4) Å, R ) 90°, â ) 97.815(8)o, γ ) 90°, V ) 2322.0(15)
Å,3 crystal size 0.490 × 0.362 × 0.178 mm3, T ) 293(2) K, Z )
4, reflections collected/unique 13674/5282 (Rint ) 0.0967), 5282
Experimental Section
Synthesisof3-(1-Cyclohexylidenemethylvinyl)-1-oxaspiro[4.5]-
dec-3-ene (2a): Typical Procedure. To a mixture of PdCl2 (8.8
mg, 5 mol %, 0.050 mmol) and NaI (75.1 mg, 0.50 mmol) were
588 J. Org. Chem., Vol. 73, No. 2, 2008

Synthesis of 4-(1′,3′-Dien-2′-yl)-2,5-dihydrofuran DeriVatiVes
data, 1 restraint, 302 parameters. Supplementary crystallographic
dada have been deposited at the Cambridge Crystallographic Data
Center as CCDC 651148.
Guangke He in this group for reproducing the results presented
in entries 1 and 4 of Table 2 and entries 1 and 4 of Table 3.
Supporting Information Available: Experimental procedures,
copies of 1H and 13C NMR spectra of all compounds, and the CIF
file of compound 4aa. This material is available free of charge via
the Internet at http://pubs.acs.org.
Acknowledgment. Financial support from the National
Natural Science Foundation of China (20332060), Major State
Basic Research and Development Program (2006CB806105),
and Cheung Kong Scholar Program is greatly appreciated. This
work was conducted at Zhejiang University. We thank Mr.
JO702332M
J. Org. Chem, Vol. 73, No. 2, 2008 589