Palladium acetate-catalyzed cyclization reaction of 2,3-allenoic acids in the presence of simple allenes: An efficient synthesis of 4-(1′-Bromoalk- 2′(Z)-en-2′-yl)furan-2(5H)-one derivatives and the synthetic application

Article abstract of DOI:10.1021/ja072790j

We have realized a cyclization reaction of 2,3-allenoic acids 1 in the presence of simple alkyl-or aryl-substituted allenes 3. In this reaction, the cyclic oxypalladation of 2,3-allenoic acid with Pd(II) would afford the furanonyl palladium intermediate 2

Full text of DOI:10.1021/ja072790j

Published on Web 08/11/2007
Palladium Acetate-Catalyzed Cyclization Reaction of
2,3-Allenoic Acids in the Presence of Simple Allenes:
An Efficient Synthesis of
4-(1′-Bromoalk-2′(Z)-en-2′-yl)furan-2(5H)-one Derivatives and
the Synthetic Application
Zhenhua Gu, Xinke Wang, Wei Shu, and Shengming Ma*
Contribution from the 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
Received April 30, 2007; E-mail: masm@mail.sioc.ac.cn
Abstract: We have realized a cyclization reaction of 2,3-allenoic acids 1 in the presence of simple alkyl-
or aryl-substituted allenes 3. In this reaction, the cyclic oxypalladation of 2,3-allenoic acid with Pd(II) would
afford the furanonyl palladium intermediate 2, which could be trapped by the simple allene to afford a
π-allylic intermediate anti-9. This intermediate anti-9 could be nucleophilically attacked by Br- to yield 4-(1′-
bromoalk-2′(Z)-en-2′-yl)furan-2(5H)-one derivatives Z-5 and Pd(0). The in-situ formed Pd(0) was efficiently
converted to the catalytically active Pd(II) species by benzoquinone in HOAc. The functional groups, such
as malonate, acetoxyl, and phthalic amide in allene 3, are tolerable under the current conditions. High
efficiency of chirality transfer was observed when optically active 2,3-allenoic acids were used, which reveals
that the formation of the intermediates 2 was a highly stereoselective anti-oxypalladation process. The
highly selective formation of Z-isomer may be explained by face-selective coordination of allene 3 with the
palladium atom in intermediate 2: the palladium atom coordinates to the terminal CdC double bond of
allene 3 from the face opposite to the substituent group to avoid the steric congestion. The products Z-5
could be further elaborated via the SN2 nucleophilic substitution with amine or sodium benzenesulfinate,
the reduction of the C-Br bond by NaBH4, and the CuBr‚SMe2-catalyzed SN2′-substitution with CH3MgBr.
Introduction
for the synthesis of a wide variety of biologically active
compounds and complex natural products.4 Despite these
achievements, the development of efficient synthetic methods
leading to the formation of this class of compounds with a new
structural feature readily for further elaboration is still of current
interest.
On the other hand, the transition metal-catalyzed cyclization
reaction of functionalized allenes has caught the attention of
many synthetic chemists due to its unique reactivity and
stereoselectivity.5-7 Recently, much attention has been paid to
the reactions involving two same or different allenes (Scheme
1). Three type of reactions have been observed in the ho-
Butenolides [2(5H)-furanones], a unit occurring in a large
number of natural products,1 have caught the attention of both
organic and bioorganic chemists because many of the buteno-
lide-containing compounds may be considered as potential
insecticides, bactericides, fungicides, and phospholiphase A2
inhibitors, etc.2,3 Butenolides are also versatile building blocks
(1) Brown, S. P.; Goodwin, N. C.; MacMillan, D. W. C. J. Am. Chem. Soc.
2003, 125, 1192.
(2) For some of the most recent examples, see: (a) Chia, Y.; Chang, F.; Wu,
Y. Tetrahedron Lett. 1999, 40, 7513. (b) Evidente, A.; Sparapano, L. J.
Nat. Prod. 1994, 57, 1720. (c) Damtoft, S.; Jensen, S. R. Phytochemistry
1995, 40, 157. (d) Este´vez-Reyes, R.; Este´vez-Braun, A.; Gonza´lez, A. G.
J. Nat. Prod. 1993, 56, 1177. (e) Seki, T.; Satake, M.; Mackenzie, L.;
Kaspar, H. F.; Yasumoto, T. Tetrahedron Lett. 1995, 36, 7093. (f) Cambie,
R. C.; Bergquist, P. R.; Karuso, P. J. Nat. Prod. 1988, 51, 1014.
(3) (a) Deshong, P.; Sidler, D. R.; Slough, G. A. Tetrahedron Lett. 1987, 28,
2233. (b) Marshall, J. A.; Wolf, M. A. J. Org. Chem. 1996, 61, 3238. (c)
Xiao, W.; Alper, H. J. Org. Chem. 1997, 62, 3422. (d) Cowell, A.; Stille,
J. K. Tetrahedron Lett. 1979, 20, 133. (e) Marshall, J. A.; Bartley, G. S.;
Wallace, E. M. J. Org. Chem. 1996, 61, 5729. (f) Clough, J. M.; Pattenden,
G.; Wight, P. G. Tetrahedron Lett. 1989, 30, 7469. (g) Yoneda, E.; Kaneko,
T.; Zhang, S.; Onitsuka, K.; Takahashi, S. Org. Lett. 2000, 2, 441. (h)
Renurd, M.; Ghosez, L. A. Tetrahedron 2001, 57, 2597. (i) Linclau, B.;
Boydell, A. J.; Clarke, P. J.; Horan, R.; Jacquet, C. J. Org. Chem. 2003,
68, 1821. (j) Hakimelahi, G. H.; Mei, N.-W.; Moosavi-Movahedi, A. A.;
Davari, H.; Hakimelahi, S.; King, K.-Y.; Ru Hwu, J.; Wen, Y.-S. J. Med.
Chem. 2001, 44, 1749. (k) Marshall, J. A.; Piettre, A.; Paige, M. A.;
Valeriote, F. J. Org. Chem. 2003, 68, 1780. (l) Ma, S.; Lu, L.; Lu, P. J.
Org. Chem. 2005, 70, 1063. (m) Ma, S.; Gu, Z.; Deng, Y. Chem. Commun.
2006, 94. (n) Ma, S.; Duan, D.; Shi, Z. Org. Lett. 2000, 2, 1419.
(4) (a) Renard, M.; Ghosez, L. A. Tetrahedron 2001, 57, 2597. (b) Feringa,
B. L.; de Lange, B.; Jansen, J. F. G. A.; de Jong, J. C.; Lubben, M.; Faber,
W.; Schudde, E. P. Pure Appl. Chem. 1992, 64, 1865. (c) Dehoux, C.;
Gorrichon, L.; Baltas, M. Eur. J. Org. Chem. 2001, 1105-1113. (d) Jauch,
J. Angew. Chem., Int. Ed. 2000, 39, 2764-2765. (e) Kedar, T. E.; Miller,
M. W.; Hegedus, L. S. J. Org. Chem. 1996, 61, 6121.
(5) (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., Ed. The Chemistry of the Allenes; Academic Press:
London, 1982; Vol. 1. (d) Krause, N., Hashmi, A. S. K., Eds. Modern
Allene Chemistry; Wiley-VCH: Weinheim, 2004; Vols. 1-2.
(6) (a) Zimmer, R. C.; Dinesh, U.; Nandanan, E.; Khan, F. A. Chem. ReV.
2000, 100, 3067. (b) Hoffmann-Ro¨der, A.; Krause, N. Angew. Chem., Int.
Ed. 2004, 43, 1196. (c) Reissig, H.-U.; Schade, W.; Amombo, M. O.; Pulz,
R.; Hausherr, A. Pure Appl. Chem. 2002, 74, 175. (d) Ma, S. Chem. ReV.
2005, 105, 2829 and references therein. (e) Ma, S. Acc. Chem. Res. 2003,
36, 701.
9
10948
J. AM. CHEM. SOC. 2007, 129, 10948-10956
10.1021/ja072790j CCC: $37.00 © 2007 American Chemical Society

Cyclization Reaction of 2,3-Allenoic Acids
A R T I C L E S
Scheme 1. The Reaction Patterns Involving Two Functionalized
Allenes: (a) Intermolecular Homodimerization Reaction of
Functionalized Allenes; (b) Intermolecular Heterodimerization
Reaction of Functionalized Allenes
Scheme 2. The Proposed Reaction Pathways for the Cyclization
of 2,3-Allenoic Acids in the Presence of Simple Allenes
of allenes, at least one allene cyclized and the catalyst was
regenerated via â-heteroatom elimination or protonolysis with
the aid of the second functionalized allenes. To the best of our
knowledge, there is no report on the cross-coupling cyclization
reaction between a functionalized allene and a non-functional-
ized simple allene.
With this notion in mind, we proposed the following path to
realize this type of reaction (Scheme 2). First, the interaction
of 2,3-allenoic acids 1 with Pd(OAc)2 would form intermediate
2 via cyclic oxypalladation.6e Next, regioselective carbopalla-
dation of simple allene 3 with 2 would give a π-allylic
intermediate 4,14 which may undergo â-elimination15 or nu-
cleophilic substitution14 to yield different products and Pd(0).
Thus, the challenge here would be the regeneration of the
catalyst, match of the reactivities of these two very different
types of allenes, and the control of regio- and stereochemistry.
Herein, we report a protocol for the cyclization reaction of 2,3-
allenoic acids in the presence of alkyl- or aryl-substituted allenes
with the nice control of the regio- and stereoselectivity.
modimerization reaction of functionalized allenes (Scheme
1a): The first palladium-catalyzed homodimerization reaction
of 1,2-allenyl ketones has been reported by Hashmi et al. in
1995, which led to the formation of the monocyclic 3-(3′-oxo-
1′-alkenyl)-substituted furan derivatives.8 Interestingly, 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.9 In 2003, we have reported the homodimerization
of 2,3-allenoic acids affording bicyclic bibutenolides.10 In the
area of heterodimerization (Scheme 1b), we have successfully
realized the reactions between 2,3-allenoic acids or 2,3-
allenamides and 1,2-allenyl ketones, in which both allenes were
cyclized to form products with two different rings.11 However,
it is interesting to observe that in the palladium-catalyzed
cyclization of 2,3-allenoic acids in the presence of 2,3-allenols
the 2,3-allenoic acids were cyclized while 2,3-allenols formed
the 1,3-dienyl units via â-hydroxide elimination.12 Recently,
Alcaide and co-workers also reported the similar cross-coupling
cyclization reaction of R-allenols in the presence of 2,3-allenyl
carboxylates.13 In these reactions involving two different classes
Results and Discussion
Our efforts in this area started with the reaction of 2,3-allenoic
acid 1a and hepta-1,2-diene 3a. After some screening, it was
observed that the reaction of 1a with 3a in the presence of 5
mol % Pd(OAc)2, 110 mol % of benzoquinone (BQ),16 and 200
mol % of LiBr‚H2O in HOAc afforded Z-5aa in 53% yield
(Table 1, entry 1). The yield dropped when only 1.5 equiv of
3a was used (Table 1, entry 2). The reaction with 1.5 equiv of
BQ gave 67% yield of Z-5aa (Table 1, entry 3). Other solvent,
such as CH3CN, CH2Cl2, or mixed solvent of trifluoroacetic
acid (TFA) and HOAc, was not better than HOAc (Table 1,
entries 3-5). At a higher reaction temperature, the reaction gave
Z-5aa in relatively higher yield (compare entries 6-8, Table
1). Almost the same yield was observed when the loading of
Pd(OAc)2 was reduced to 2 mol % (Table 1, entry 9). It is
important to note that a noncyclic CdC double bond in the
(7) For some of the typical reactions of allenes, see: (a) Chang, K.-J.;
Rayabarapu, D. K.; Yang, F.-Y.; Cheng, C.-H. J. Am. Chem. Soc. 2005,
127, 126. (b) Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2005, 127, 7320.
(c) Hamaguchi, H.; Kosaka, S.; Ohno, H.; Tanaka, T. Angew. Chem., Int.
Ed. 2005, 44, 1513. (d) Winkler, J. D.; Ragains, J. R. Org. Lett. 2006, 8,
4031. (e) Trost, B. M.; Xie, J. J. Am. Chem. Soc. 2006, 128, 6044. (f)
Yoshino, T.; Ng, F.; Danishefsky, S. J. J. Am. Chem. Soc. 2006, 128, 14185.
(8) (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.
(9) Hashmi, A. S. K.; Schwarz, L.; Choi, J. H.; Frost, T. M. Angew. Chem.,
Int. Ed. 2000, 39, 2285.
(14) (a) Shimizu, I.; Tsuji, J. Chem. Lett. 1984, 233. (b) Yamamoto, Y.;
Radhakrishnan, U. Chem. Soc. ReV. 1999, 28, 199.
(10) (a) Ma, S.; Yu, Z. Org. Lett. 2003, 5, 1507; 2003, 5, 2581. (b) Ma, S.; Yu,
Z.; Gu, Z. Chem.-Eur. J. 2005, 11, 2351.
(15) (a) Tsuji, J.; Yamakawa, T.; Kaito, M.; Mandai, T. Tetrahedron Lett. 1978,
19, 2075. (b) Fu, C.; Ma, S. Org. Lett. 2005, 9, 1707. (c) Chang, H.-M.;
Cheng, C.-H. J. Org. Chem. 2000, 65, 1767. (d) Grigg, R.; Brown, S.;
Sridharan, V.; Uttley, M. D. Tetrahedron Lett. 1998, 39, 3247.
(16) (a) Grennberg, H.; Gogoll, A.; Ba¨ckvall, J.-E. Organmetallics 1993, 12,
1790. (b) Albe´niz, A. C.; Espinet, P.; Mart´ın-Ruiz, B. Chem.-Eur. J. 2001,
7, 2481.
(11) (a) Ma, S.; Yu, Z. Angew. Chem., Int. Ed. 2002, 41, 1775. (b) Ma, S.; Gu,
Z.; Yu, Z. J. Org. Chem. 2005, 70, 6291.
(12) Ma, S.; Gu, Z. J. Am. Chem. Soc. 2005, 127, 6182.
(13) Alcaide, B.; Almendros, P.; Campo, T. M. Angew. Chem., Int. Ed. 2006,
45, 4501.
9
J. AM. CHEM. SOC. VOL. 129, NO. 35, 2007 10949

A R T I C L E S
Gu et al.
Table 1. The Cyclization Reaction of 2,3-Allenoic Acid 1a in the
Presence of 1,2-Heptadiene 3aa
Table 2. The Cross-Coupling Cyclization Reaction of 1 in the
Presence of 3aa
1
time
(h)
yield of Z-5
entry
R1
R2
R3
(%)
1
2b
3
4
5
6
7
Ph
Ph
Ph
Me
H (1a)
H (1b)
H (1c)
H (1d)
H (1e)
H (1f)
Et (1g)
6
7
7
6
9
7
8
70 (Z-5aa)
59 (Z-5ba)
44 (Z-5ca)
51 (Z-5da)
54 (Z-5ea)
56 (Z-5fa)
60 (Z-5ga)
n-Pr
i-Bu
n-Pr
n-Bu
Me
BQ
time/temp
(h/˚C)
yield of Z-5aa
entry
(equiv)
solvent
(%)b
pBrC6H4
pClC6H4
R-naphthyl
Ph
1
1.1
1.1
1.1
1.1
1.1
1.5
1.5
1.5
1.5
HOAc
HOAc
CH3CN
CH2Cl2
HOAc/TFAe
HOAc
HOAc
HOAc
HOAc
25/35
13/35
13/35
10/35
31/35
11.5/35
36.5/rt
5.5/60
6/60
53
44
16
trace
19
67
43
70
70
2c
3d
4d
5
Me
8
Ph
H (1h)
10
45 (Z-5ha)
6
7
a The reaction was carried out using 0.25 mmol of 1, 0.50 mmol of 3a,
2 mol % of Pd(OAc)2, 0.50 mmol of LiBr‚H2O, and 0.375 mmol of BQ in
2 mL of HOAc in a Schlenk tube with a screw cap. b 4 mol % of Pd(OAc)2
was used.
8
9f
a The reaction was carried out using 0.25 mmol of 1a, 0.50 mmol of 3a,
2.0 equiv of LiBr‚H2O, 5 mol % of Pd(OAc)2, and BQ in 2 mL of solvent
in a Schlenk tube with a screw cap. b Isolated yields. c 0.375 mmol of 3a
was used. d 2.0 equiv of HOAc was added. e HOAc:trifluoroacetic acid
(TFA) ) 10:1. f 2 mol % of Pd(OAc)2 was used.
1
major product was formed in its Z-form. H NMR analysis of
the crude mixture reveals that the Z:E ratio of 5aa is >50:1.
There exists a little amount of cycloisomerization product 7a.
No significant amounts of branched-product 6aa and homodi-
meric bicyclic product 8a were detected. The product Z-5aa
may be contaminated with about 10% of the corresponding chlor-
ide when LiBr‚H2O used contains LiCl. This problem could be
solved when LiBr‚H2O of a higher purity17 was used. The pres-
ence of chloride Z-5AA was confirmed by LC-MS analysis. The
treatment of Z-5aa with LiCl in THF/H2O afforded a 1:1 mixture
of Z-5aa and Z-5AA in quantitative yield (eq 1), which further
confirmed the presence of the chloride Z-5AA in the product.
Figure 1. ORTEP representation of Z-5fa.
We also tested the reaction of 2,3-allenoic acids in the
presence of other substituted alkyl- and aryl-substituted allenes;
the yields are from moderate to good (Table 3). With R4 being
1°-alkyl (Table 3, entries 1-3, and 7-9), 2°-alkyl (Table 3,
entry 4), aryl (Table 3, entry 5), and benzyl group (Table 3,
entry 6), the reaction underwent smoothly to give the corre-
sponding products.
With this protocol in hand, we studied the generality of this
cyclization reaction of substituted 2,3-allenoic acids in the
presence of hepta-1,2-diene 3a. With R1 being phenyl (Table
2, entries 1-3), p-halophenyl (Table 2, entries 4 and 5), or
R-naphthyl group (Table 2, entry 6), the reaction could afford
the corresponding products smoothly. The fully substituted 2,3-
allenoic acid 1g could also react with 3a to give Z-5ga in 60%
yield (Table 2, entry 7). The reaction is also tolerable for the
cyclopropanyl group (Table 2, entry 8). The structure of the
products was further determined by the X-ray diffraction studies
of Z-5fa (Figure 1).18
The reaction is also tolerable for some functional groups in
the simple allenes, such as malonate (Table 4, entries 1 and 2),
acetoxyl (Table 4, entries 3 and 4), and phthalic amide (Table
4, entry 5), which provides opportunity for further synthetic
elaboration.
Furthermore, the cyclization reaction of optically active 2,3-
allenoic acid [R-(-)-1a] in the presence of allene 3 afforded
the product R-(-)-Z-5 in high enantiopurity, where the R group
may be an alkyl (Table 5, entries 1 and 2), an alkyl group with
an ester functionality (Table 5, entry 3), and phenyl group (Table
4, entry 4). The high efficiency of the chirality transfer presented
in Table 5 indicated that the formation of furanonyl palladium
(17) LiBr‚H2O contains less than 0.01% of chlorides.
(18) Crystal data for compound 5fa: C22H23O2Br, MW 399.31, monoclinic, P2-
(1)/c, Mo KR, final R indices [I > 2σ(I)], R1 ) 0.0685, wR2 ) 0.2031, a
) 12.3128 (18) Å, b ) 8.8210 (13) Å, c ) 18.775 (13) Å, R ) 90°, â )
106.790 (3)°, γ ) 90°, V ) 1952.2 (5) Å3, T ) 293 (2) K, Z ) 4, reflections
collected/unique 11 159/4229 (Rint ) 0.1412), number of observations [>2σ-
(I)] 1623, parameters 222. Supplementary crystallographic data have been
deposited at the Cambridge Crystallographic Data Center. CCDC 626363.
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10950 J. AM. CHEM. SOC. VOL. 129, NO. 35, 2007

Cyclization Reaction of 2,3-Allenoic Acids
A R T I C L E S
Table 3. The Coupling Cyclization Reaction of 2,3-Allenoic Acids
1 in the Presence of Simple Allenes 3a
Table 5. The Coupling Cyclization Reaction of R-(-)-1a in the
Presence of Simple Allenes 3a
yield of R-(
−)-Z-5
1
3
time
(h)
yield of Z-5
entry
R
(%)
% ee of Z-5
entry
R1
R2
R4
(%)
1
2
3
4
n-C4H9 (3a)
n-C6H13 (3b)
CH2CH2OAc (3j)
Ph (3f)
63 (R-(-)-Z-5aa)
67 (R-(-)-Z-5ab)
70 (R-(-)-Z-5aj)
80 (R-(-)-Z-5af)
98
98
98
97
1
2
3b
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
4-BrC6H4
Ph
Ph
Me (1a)
Me (1a)
Me (1a)
Me (1a)
Me (1a)
Me (1a)
n-Pr (1d)
Et (1i)
n-C6H13 (3b)
n-C7H15 (3c)
n-C8H17 (3d)
c-C6H11 (3e)
Ph (3f)
10.5
6.5
8
62 (Z-5ab)
59 (Z-5ac)
60 (Z-5ad)
70 (Z-5ae)
88 (Z-5af)
61 (Z-5ag)
57 (Z-5db)
50 (Z-5ic)
56 (Z-5jd)
7
6.5
5.5
6
18.5
10
a The reaction was carried out using 0.25 mmol of R-(-)-1a, 0.50 mmol
of 3, 2 mol % of Pd(OAc)2, 0.50 mmol of LiBr‚H2O, and 0.375 mmol of
BQ in 2 mL of HOAc in a Schlenk tube with a screw cap.
Bn (3g)
n-C6H13 (3b)
n-C7H15 (3c)
n-C8H17 (3d)
allyl (1j)
Scheme 3. The Rationale for the Stereoselectivity
a For the reaction conditions, see footnote a, Table 2. b 4 mol % of
Pd(OAc)2 was used.
Table 4. The Coupling Cyclization Reaction of 1a and 1f in the
Presence of Allenes 3h-k with a Functional Groupa
palladium atom may account for the stereoselectivity ob-
served: the palladium atom coordinates with the terminal Cd
C double bond of monosubstituted allene from the face opposite
to the substituent R4 favorably to avoid the steric congestion,
which results in the formation of a π-allylpalladium species
anti-9 with the R4 group anti to the relatively bulky furanone
moiety. Furthermore, the π-allylic palladium intermediate anti-9
is more favorable than syn-9 due to the steric hindrance.19g,20
Further nucleophilic attack of anti-9 by Br- affords Z-5 and
Pd(0).14 BQ was acting as the oxidant to regenerate the
catalytically active species Pd(II) (Scheme 3).16
The synthetic utilities of these cross-coupling products Z-5
were demonstrated by the representative transformation of the
product Z-5aa or Z-5fa. As it is known that the highly regio-
and stereoselective synthesis of 4-(stereodefined multi-substi-
tuted alkenyl)-2(5H)-furanone derivatives is still challenging via
the known methods, the chemistry presented in Scheme 4 may
be of high synthetic interest. The reaction of Z-5aa with Et2-
NH would give allylic amine Z-10 in moderate yield. Z-5aa
was also easily nucleophilically attacked by sodium benzene-
sulfinate to afford Z-11 as the only product in excellent yield
at -22 °C in DMF.21 Furthermore, in the presence of NaBH4
the C-Br bond of Z-5aa may be reduced to afford E-12 in 71%
yield (E/Z g 22/1) with a regioselectivity of 15/1.22 In these
cases, the substitution reaction occurred at the less-substituted
a The reaction was carried out using 0.25 mmol of 1, 0.50 mmol of 3, 2
mol % of Pd(OAc)2, 0.50 mmol of LiBr‚H2O, and 0.375 mmol of BQ in 2
mL of HOAc in a Schlenk tube with a screw cap.
intermediate 2 in Scheme 2 is a highly stereoselective anti-
oxypalladation process.6e
The highly selective formation of Z-isomer is remarkable in
view of the fact that most carbopalladation reactions of
monosubstituted allenes reported gave a mixture of E and Z
isomeric products with low selectivity.19 A plausible mechanism
based on the face-selective coordination of allenes with the
(19) For the stereoselectivity of carbometallation of allenes, see: (a) Larock,
R. C.; Tu, C.; Pace, P. J. Org. Chem. 1998, 63, 6859. (b) Larock, R. C;
He, Y.; Long, W. W.; Han, X.; Refvik, M. D.; Zenner, J. M. J. Org. Chem.
1998, 63, 2154. (c) Ma, S.; Negishi, E. I. J. Am. Chem. Soc. 1995, 117,
6345. (d) Gamez, P.; Ariente, C.; Gore´, J.; Cazes, B. Tetrahedron 1998,
54, 14825. (e) Al-Masum, M.; Yamamoto, Y. J. Am. Chem. Soc. 1998,
120, 3809. (f) Jonasson, C.; Ba¨ckvall, J.-E. Tetrahedron Lett. 1998, 39,
3601. (g) Yang, F.; Wu, M.; Cheng, C.-H. J. Am. Chem. Soc. 2000, 122,
7122. (h) Wu, M.; Rayabarapu, D. K.; Cheng, C.-H. J. Am. Chem. Soc.
2003, 125, 12426. (i) Zhao, C.; Han, L.; Tanaka, M. Organometallics 2000,
19, 4196.
(20) Aakermark, B.; Hansson, S.; Vitagliano, A. J. Am. Chem. Soc. 1990, 112,
4587.
(21) Nilsson, Y. I. M.; Andersson, P. G.; Ba¨ckvall, J.-E. J. Am. Chem. Soc.
1993, 115, 6609.
(22) Corey, E. J.; Kirst, H. A.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1970,
92, 6314.
9
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A R T I C L E S
Gu et al.
Scheme 4. The Synthetic Utilities of Z-5
1.23 (m, 2H), 1.18-1.02 (m, 2H), 0.79 (t, J ) 7.5 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) δ 10.2, 13.7, 22.0, 26.9, 27.8, 30.7, 83.3, 124.5,
127.5, 128.5, 128.8, 129.4, 134.9, 141.9, 157.9, 174.4; MS(EI) m/z (%)
351 [M+(81Br) + 1, 0.67], 349 [M+(79Br) + 1, 0.84], 105 (100); IR
(neat) 2957, 1758, 1637, 1456, 1380, 1209, 1095 cm-1; HRMS
(MALDI/DHB) calcd for C18H22O2Br [M+(79Br) + 1], 349.0798; found,
349.0808.
allylic terminal. However, in the presence of 5 mol % of CuBr‚
SMe2, the reaction of Z-5aa and Z-5fa with CH3MgBr led to
predominant formation of branched product 13a and 13b with
very high regioselectivity and diastereoselectivity.23 The relative
stereochemistry of the two chiral centers in 13 was determined
by the single-crystal X-ray diffraction study of 14bb (eq 2), one
of the two isomeric dibromination products of 13b (Figure 2).24
(2) Synthesis of 3-Propyl-4-(1′-bromohept-2′(Z)-en-2′-yl)-5-phen-
ylfuran-2(5H)-one (Z-5ba). A mixture of 1b (51 mg, 0.25 mmol), 3a
(48 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol), benzoquinone
(41 mg, 0.375 mmol), and Pd(OAc)2 (2 mg, 0.009 mmol) in 2 mL of
HOAc was stirred at 60 °C for 7 h to afford Z-5ba (56 mg, 59%): oil,
1H NMR (300 MHz, CDCl3) δ 7.38-7.30 (m, 3H), 7.22-7.18 (m,
2H), 5.92 (s, 1H), 5.60 (t, J ) 7.8 Hz, 1H), 3.96 (d, J ) 10.8 Hz, 1H),
3.90 (d, J ) 10.8 Hz, 1H), 2.50-2.30 (m, 2H), 2.20-2.05 (m, 2H),
1.72-1.58 (m, 2H), 1.34-1.22 (m, 2H), 1.22-1.10 (m, 2H), 1.00 (t,
J ) 7.5 Hz, 3H), 0.83 (t, J ) 7.5 Hz, 3H); 13C NMR (75.4 MHz,
CDCl3) δ 13.7, 14.2, 21.9, 22.0, 26.7, 27.1, 27.7, 30.7, 83.3, 127.4,
128.1, 128.8, 129.2, 129.3, 134.8, 141.0, 158.9, 174.0; MS(ESI) m/z
379 [M+(81Br) + 1], 377 [M+(79Br) + 1]; IR (neat) 2959, 1757, 1634,
1458, 1005 cm-1; HRMS (MALDI/DHB) calcd for C20H26O2Br [M+(79-
Br) + 1], 377.1111; found, 377.1105.
Conclusion
We have developed a cyclization reaction of 2,3-allenoic acids
in the presence of simple allenes, in which a lactone ring was
formed from 2,3-allenoic acid and the simple allene yielded the
stereodefined allylic bromide moiety, which is ready for further
elaboration. A rationale was proposed to explain the stereose-
lectivity observed. Further studies in this area are being carried
out in our laboratory.
Experimental Section
Palladium-Catalyzed Cyclization of 2,3-Allenoic Acids 1 in the
Presence of Simple Allenes 3. (1) Synthesis of 3-Methyl-4-(1′-
bromohept-2′(Z)-en-2′-yl)-5-phenylfuran-2(5H)-one (Z-5aa). Typical
Procedure. A mixture of 1a (44 mg, 0.25 mmol), 3a (48 mg, 0.50
mmol), LiBr‚H2O (53 mg, 0.50 mmol), benzoquinone (41 mg, 0.375
mmol), and Pd(OAc)2 (1 mg, 0.0045 mmol, 2 mol %) in 2 mL of HOAc
was stirred at 60 °C for 6 h in a Schlenk tube with a screw cap. After
the complete consumption of the starting material as monitored by TLC,
the solvent was evaporated, and the crude product was analyzed by 1H
NMR spectra. The residue was purified via flash chromatography on
(3) Synthesis of 3-Isobutyl-4-(1′-bromohept-2′(Z)-en-2′-yl)-5-
1
silica gel to afford Z-5aa (63 mg, 71%): oil, H NMR (300 MHz,
CDCl3) δ 7.38-7.30 (m, 3H), 7.22-7.18 (m, 2H), 5.92 (q, J ) 1.5
Hz, 1H), 5.67 (t, J ) 7.8 Hz, 1H), 4.01 (d, J ) 10.8 Hz, 1H), 3.93 (d,
J ) 10.8 Hz, 1H), 2.20-2.07 (m, 2H), 2.08 (d, J ) 1.5 Hz, 3H), 1.32-
(23) (a) Minnaard, A. J.; Feringa, B. L. Acc. Chem. Res. 2007, 40, 179. (b)
Lo´pez, F.; van Zijl, A. W.; Minnaard, A. J.; Feringa, B. L. Chem. Commun.
2006, 409.
(24) Crystal data for compound 14bb: C23H26Br2O2, MW 494.26, triclinic, P-1,
Mo KR, final R indices [I > 2σ(I)], R1 ) 0.0603, wR2 ) 0.1625, R indices
(all data), R1 ) 0.0871, wR2 ) 0.1837, a ) 7.8406(10) Å, b ) 11.7468-
(15) Å, c ) 12.4428(16) Å, R ) 76.331(2)°, â ) 75.280(2)°, γ ) 89.708-
(2)°, V ) 1075.2(2) Å3, T ) 293(2) K, Z ) 2, reflections collected/unique
6145/4361 (Rint ) 0.0891), number of observations [>2σ(I)] 2600,
parameters 255. Supplementary crystallographic data have been deposited
at the Cambridge Crystallographic Data Center. CCDC 651341.
Figure 2. ORTEP representation of 14bb.
9
10952 J. AM. CHEM. SOC. VOL. 129, NO. 35, 2007

Cyclization Reaction of 2,3-Allenoic Acids
A R T I C L E S
phenylfuran-2(5H)-one (Z-5ca). A mixture of 1c (51 mg, 0.236 mmol),
3a (48 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol), benzoquinone
(41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045 mmol, 2 mol %)
in 2 mL of HOAc was stirred at 60 °C for 7 h to afford Z-5ca (41 mg,
44%): oil, 1H NMR (300 MHz, CDCl3) δ 7.38-7.30 (m, 3H), 7.22-
7.18 (m, 2H), 5.92 (s, 1H), 5.67 (t, J ) 7.8 Hz, 1H), 3.97 (d, J ) 10.8
Hz, 1H), 3.93 (d, J ) 10.8 Hz, 1H), 2.40-2.28 (m, 2H), 2.20-2.06
(m, 3H), 1.32-1.24 (m, 2H), 1.20-1.12 (m, 2H), 0.96 (d, J ) 6.9 Hz,
3H), 0.95 (d, J ) 6.9 Hz, 3H), 0.83 (t, J ) 7.5 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) δ 13.7, 22.0, 22.66, 22.70, 27.3, 27.4, 27.7, 30.6,
33.4, 83.4, 127.4, 127.9, 128.3, 128.8, 129.3, 134.7, 141.0, 159.7, 174.1;
MS(ESI) m/z 393 [M+(81Br) + 1], 391[M+(79Br) + 1]; IR (neat) 2957,
1759, 1667, 1456, 1009 cm-1; HRMS (MALDI/DHB) calcd for
C21H28O2Br [M+(79Br) + 1], 391.1267; found, 391.1278.
mmol), 3a (48 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 8 h to
afford Z-5ga (53 mg, 60%): oil, 1H NMR (300 MHz, CDCl3) δ 7.40-
7.20 (m, 5H), 5.31 (t, J ) 7.5 Hz, 1H), 3.91 (d, J ) 10.8 Hz, 1H),
3.33 (d, J ) 10.8 Hz, 1H), 2.50-2.32 (m, 1H), 2.25-2.06 (m, 3H),
1.93 (s, 3H), 1.40-1.20 (m, 4H), 0.95-0.85 (m, 6H); 13C NMR (75.4
MHz, CDCl3) δ 7.6, 9.9, 13.8, 22.3, 27.4, 27.8, 28.6, 30.7, 90.3, 125.7,
125.8, 128.0, 128.4, 128.6, 137.7, 141.0, 163.6, 174.2; MS(ESI) m/z
420 [M(81Br) + K+], 418 [M(79Br) + K+], 396 [M(81Br) + NH4+],
394 [M(79Br) + NH4+], 379 [M+(81Br) + 1], 377 [M+(79Br) + 1]; IR
(neat) 2928, 1757, 1448, 1210, 1079 cm-1; HRMS (MALDI/DHB)
calcd for C20H25O2BrNa [M(79Br) + Na+], 399.0930; found, 399.0936.
(8) Synthesis of 4-(1′-Bromohept-2′(Z)-en-2′-yl)-3-cyclopropyl-
methenyl-5-phenylfuran-2(5H)-one (Z-5ha). A mixture of 1h (54 mg,
0.252 mmol), 3a (48 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 10 h to
afford Z-5ha (44 mg, 45%): oil, 1H NMR (300 MHz, CDCl3) δ 7.40-
7.30 (m, 3H), 7.27-7.17 (m, 2H), 5.94 (s, 1H), 5.61 (t, J ) 7.5 Hz,
1H), 3.96 (d, J ) 11.4 Hz, 1H), 3.93 (d, J ) 11.4 Hz, 1H), 2.45-2.27
(m, 2H), 2.20-2.00 (m, 2H), 1.37-1.20 (m, 2H), 1.20-0.98 (m, 3H),
(4) Synthesis of 3-Propyl-4-(1′-bromohept-2′(Z)-en-2′-yl)-5-(4′′-
bromophenyl)-furan-2(5H)-one (Z-5da). A mixture of 1d (70 mg,
0.25 mmol), 3a (48 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 6 h to
1
afford Z-5da (58 mg, 51%): oil, H NMR (300 MHz, CDCl3) δ 7.47
(d, J ) 6.6 Hz, 2H), 7.08 (d, J ) 6.6 Hz, 2H), 5.88 (s, 1H), 5.57 (t, J
) 7.8 Hz, 1H), 3.97 (d, J ) 10.8 Hz, 1H), 3.90 (d, J ) 10.8 Hz, 1H),
2.40 (t, J ) 7.8 Hz, 2H), 2.20-2.05 (m, 2H), 1.78-1.56 (m, 2H), 1.38-
1.22 (m, 2H), 1.22-1.10 (m, 2H), 0.98 (t, J ) 7.5 Hz, 3H), 0.85 (t, J
) 7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 13.8, 14.2, 21.8, 22.1,
26.6, 27.0, 27.8, 30.7, 82.4, 123.4, 127.9, 129.0, 129.4, 132.0, 133.9,
141.2, 158.5, 173.7; MS(MALDI) m/z 481 [M(81Br81Br) + Na+], 479
[M(81Br79Br) + Na+], 477 [M(79Br79Br) + Na+], 459 [M+(81Br81Br) +
1], 457 [M+(81Br79Br) + 1], 455 [M+(79Br79Br) + 1]; IR (neat) 2959,
1753, 1637, 1489, 1006 cm-1; HRMS (MALDI/DHB) calcd for
C20H25O2Br2 [M+(79Br) + 1], 455.0216; found, 455.0216.
(5) Synthesis of 4-(1′-Bromohept-2′(Z)-en-2′-yl)-3-butyl-5-(4′′-
chlorophenyl)-furan-2(5H)-one (Z-5ea). A mixture of 1e (63 mg, 0.25
mmol), 3a (48 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 9 h to
afford Z-5ea (58 mg, 54%): oil, 1H NMR (300 MHz, CDCl3) δ 7.34-
7.28 (m, 2H), 7.16-7.10 (m, 2H), 5.89 (s, 1H), 5.58 (t, J ) 7.8 Hz,
1H), 3.97 (d, J ) 10.8, 1H), 3.89 (d, J ) 10.8, 1H), 2.41 (t, J ) 8.4
Hz, 2H), 2.24-2.03 (m, 2H), 1.70-1.48 (m, 2H), 1.46-1.26 (m, 4H),
1.26-1.08 (m, 2H), 0.93 (t, J ) 7.5 Hz, 3H), 0.84 (t, J ) 7.5 Hz, 3H);
13C NMR (75.4 MHz, CDCl3) δ 13.7, 13.8, 22.1, 22.8, 24.5, 27.0, 27.8,
30.6, 30.7, 82.3, 128.0, 128.8, 129.1, 129.6, 133.4, 135.3, 141.2, 158.2,
173.7; MS(ESI) m/z 429 [M+(37Cl81Br) + 1], 427 [M+(35Cl81Br + 37Cl79-
Br) + 1], 425 [M+(35Cl79Br) + 1]; IR (neat) 2957, 1758, 1493, 1084,
1010 cm-1; HRMS (MALDI/DHB) calcd for C21H27O2BrCl [M+(35Cl79-
Br) + 1], 425.0878; found, 425.0884.
0.82 (t, J ) 7.2 Hz, 3H), 0.55-0.41 (m, 2H), 0.35-0.17 (m, 2H); 13
C
NMR (75.4 MHz, CDCl3) δ 4.7, 4.8, 10.0, 13.7, 22.0, 27.2, 27.7, 28.9,
30.6, 83.4, 127.4, 128.0, 128.8, 129.3, 134.7, 141.1, 158.9, 174.2; MS-
(EI) m/z (%) 391 [M+(81Br) + 1, 5.34], 389 [M+(79Br) + 1, 5.43], 91
(100); IR (neat) 1758, 1634, 1497, 1456, 1209, 1014 cm-1; HRMS
(EI) calcd for C21H25O2Br [M+(79Br)], 388.1038; found, 388.1035.
(9) Synthesis of 4-(1′-Bromonon-2′(Z)-en-2′-yl)-3-methyl-5-phen-
ylfuran-2(5H)-one (Z-5ab). A mixture of 1a (44 mg, 0.25 mmol), 3b
(62 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol), benzoquinone
(41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045 mmol, 2 mol %)
in 2 mL of HOAc was stirred at 60 °C for 10.5 h to afford Z-5ab (59
1
mg, 62%): oil, H NMR (300 MHz, CDCl3): δ 7.38-7.30 (m, 3H),
7.22-7.18 (m, 2H), 5.92 (q, J ) 1.8 Hz, 1H), 5.67 (t, J ) 7.5 Hz,
1H), 4.01 (d, J ) 10.8 Hz, 1H), 3.93 (d, J ) 10.8 Hz, 1H), 2.20-2.08
(m, 2H), 2.09 (d, J ) 1.8 Hz, 3H), 1.36-1.04 (m, 8H), 0.84 (t, J ) 7.5
Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 10.2, 14.0, 22.4, 26.9, 28.0,
28.48, 28.53, 31.4, 83.2, 124.5, 127.5, 128.4, 128.8, 129.3, 134.9, 141.9,
157.8, 174.3; MS(ESI) m/z 396 [M(81Br) + NH4+], 394 [M(79Br) +
NH4+], 379 [M+(81Br) + 1], 377 [M+(79Br) + 1]; IR (neat) 2927, 1757,
1637, 1456, 1096 cm-1; HRMS (MALDI/DHB) calcd for C20H26O2Br
[M+(79Br) + 1], 377.1111; found, 377.1107.
(10) Synthesis of 4-(1′-Bromodec-2′(Z)-en-2′-yl)-3-methyl-5-phen-
ylfuran-2(5H)-one (Z-5ac). A mixture of 1a (44 mg, 0.25 mmol), 3c
(69 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol), benzoquinone
(41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045 mmol, 2 mol %)
in 2 mL of HOAc was stirred at 60 °C for 6.5 h to afford Z-5ac (58
(6) Synthesis of 4-(1′-Bromohept-2′(Z)-en-2′-yl)-3-methyl-5-
(naphth-1′-yl)furan-2(5H)-one (Z-5fa). A mixture of 1f (56 mg, 0.25
mmol), 3a (48 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 7 h to
1
mg, 59%): oil, H NMR (300 MHz, CDCl3) δ 7.40-7.30 (m, 3H),
7.22-7.18 (m, 2H), 5.93 (q, J ) 1.8 Hz, 1H), 5.67 (t, J ) 7.5 Hz,
1H), 4.01 (d, J ) 10.8 Hz, 1H), 3.93 (d, J ) 10.8 Hz, 1H), 2.22-2.08
(m, 2H), 2.10 (d, J ) 1.8 Hz, 3H), 1.38-1.04 (m, 10H), 0.87 (t, J )
7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 10.2, 14.0, 22.5, 26.9,
28.0, 28.5, 28.8, 28.9, 31.6, 83.2, 124.5, 127.5, 128.5, 128.8, 129.4,
134.9, 141.9, 157.8, 174.3; MS(EI) m/z (%) 393 [M+(81Br) + 1, 1.39],
391 [M+(79Br) + 1, 1.52], 105 (100); IR (neat) 2926, 1758, 1636, 1456,
1095 cm-1; HRMS (MALDI/DHB) calcd for C21H28O2Br [M+(79Br)
+ 1], 391.1267; found, 391.1280.
(11) Synthesis of 4-(1′-Bromoundec-2′(Z)-en-2′-yl)-3-methyl-5-
phenylfuran-2(5H)-one (Z-5ad). A mixture of 1a (44 mg, 0.25 mmol),
3d (76 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol), benzoquinone
(41 mg, 0.375 mmol), and Pd(OAc)2 (2 mg, 0.009 mmol) in 2 mL of
HOAc was stirred at 60 °C for 8 h to afford Z-5ad (61 mg, 60%): oil,
1H NMR (300 MHz, CDCl3) δ 7.38-7.30 (m, 3H), 7.22-7.18 (m,
2H), 5.92 (q, J ) 1.5 Hz, 1H), 5.67 (t, J ) 7.8 Hz, 1H), 4.01 (d, J )
10.8 Hz, 1H), 3.93 (d, J ) 10.8 Hz, 1H), 2.20-2.08 (m, 2H), 2.10 (d,
1
afford Z-5fa (56 mg, 56%): solid, mp 89-90 °C (ethyl acetate); H
NMR (300 MHz, CDCl3) δ 8.19 (d, J ) 8.1 Hz, 1H), 7.88 (t, J ) 8.7
Hz, 2H), 7.64-7.50 (m, 2H), 7.40 (t, J ) 7.5 Hz, 1H), 7.27 (d, J )
6.3 Hz, 1H), 6.79 (q, J ) 1.5 Hz, 1H), 5.77 (t, J ) 7.5 Hz, 1H), 4.04
(d, J ) 10.8 Hz, 1H), 3.87 (d, J ) 10.8 Hz, 1H), 2.19 (d, J ) 1.5 Hz,
3H), 2.20-2.08 (m, 2H), 1.28-1.16 (m, 2H), 1.12-1.00 (m, 2H), 0.77
(t, J ) 7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 10.6, 13.8, 22.2,
26.9, 28.0, 31.0, 78.9, 122.6, 125.1, 125.4, 125.7, 126.1, 127.0, 128.9,
129.1, 130.1, 130.8, 131.8, 133.8, 142.2, 157.3, 174.3; MS(EI) m/z (%)
400 [M+(81Br) + 1, 4.96], 398 [M+(79Br) + 1, 4.24], 319 (100); IR
(KBr) 2957, 1753, 1635, 1458, 1097 cm-1; HRMS (MALDI/DHB)
calcd for C22H24O2Br [M+(79Br) + 1], 399.0954; found, 399.0951.
(7) Synthesis of 4-(1′-Bromohept-2′(Z)-en-2′-yl)-3-methyl-5-ethyl-
5-phenylfuran-2(5H)-one (Z-5ga). A mixture of 1g (47 mg, 0.233
9
J. AM. CHEM. SOC. VOL. 129, NO. 35, 2007 10953

A R T I C L E S
Gu et al.
J ) 1.5 Hz, 3H), 1.16-1.04 (m, 12H), 0.87 (t, J ) 7.5 Hz, 3H); 13C
NMR (75.4 MHz, CDCl3) δ 10.2, 14.0, 22.6, 26.9, 28.0, 28.5, 28.9,
29.1, 29.2, 31.7, 83.2, 124.5, 127.5, 128.5, 128.8, 129.4, 134.9, 141.9,
157.8, 174.3; MS(EI) m/z (%) 407 [M+(81Br) + 1, 1.38], 405 [M+(79-
Br) + 1, 1.50], 105 (100); IR (neat) 2926, 1758, 1636, 1456, 1094
cm-1; HRMS (MALDI/DHB) calcd for C22H30O2Br [M+(79Br) + 1],
405.1424; found, 405.1441.
1634, 1489, 1207, 1006 cm-1; HRMS (MALDI/DHB) calcd for
C22H29O2Br2 [M+(79Br) + 1], 483.0529; found, 483.0535.
(16) Synthesis of 4-(1′-Bromodec-2′(Z)-en-2′-yl)-3-ethyl-5-phen-
ylfuran-2(5H)-one (Z-5ic). A mixture of 1i (47 mg, 0.25 mmol), 3c
(69 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol), benzoquinone
(41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045 mmol) in 2 mL of
HOAc was stirred at 60 °C for 18.5 h to afford Z-5ic (50 mg, 50%):
oil, 1H NMR (300 MHz, CDCl3) δ 7.38-7.30 (m, 3H), 7.22-7.18 (m,
2H), 5.90 (s, 1H), 5.60 (t, J ) 7.8 Hz, 1H), 3.95 (d, J ) 10.8 Hz, 1H),
3.89 (d, J ) 10.8 Hz, 1H), 2.56-2.40 (m, 2H), 2.18-2.08 (m, 2H),
1.38-1.08 (m, 13H), 0.87 (t, J ) 7.5 Hz, 3H); 13C NMR (75.4 MHz,
CDCl3) δ 13.2, 14.0, 18.1, 22.6, 27.1, 28.0, 28.6, 28.87, 28.95, 31.6,
83.2, 127.4, 128.2, 128.8, 129.3, 130.6, 134.7, 141.0, 158.3, 173.8;
MS(EI) m/z (%) 407 [M+(81Br) + 1, 1.46], 405 [M+(79Br) + 1, 1.63],
105 (100); IR (neat) 2927, 1758, 1639, 1458, 1004 cm-1; HRMS
(MALDI/DHB) calcd for C22H30O2Br [M+(79Br) + 1], 405.1424; found,
405.1426.
(12) Synthesis of 4-(1′-Bromo-3′-cyclohexylprop-2′(Z)-en-2′-yl)-
3-methyl-5-phenylfuran-2(5H)-one (Z-5ae). A mixture of 1a (43 mg,
0.25 mmol), 3e (61 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 7 h to
afford Z-5ae (65 mg, 70%): oil, 1H NMR (300 MHz, CDCl3) δ 7.38-
7.30 (m, 3H), 7.22-7.18 (m, 2H), 5.92 (q, J ) 1.8 Hz, 1H), 5.47 (d,
J ) 9.9 Hz, 1H), 4.01 (d, J ) 10.5 Hz, 1H), 3.95 (d, J ) 10.5 Hz,
1H), 2.35-2.20 (m, 1H), 2.07 (d, J ) 1.8 Hz, 3H), 1.70-1.43 (m,
5H), 1.37-0.90 (m, 5H); 13C NMR (75.4 MHz, CDCl3) δ 10.2, 25.1,
25.5, 27.2, 31.9, 32.0, 37.3, 83.3, 124.4, 126.4, 127.4, 128.7, 129.3,
134.8, 146.9, 158.1, 174.4; MS(ESI) m/z 394 [M(81Br) + NH4+], 392
[M(79Br) + NH4+], 377 [M+(81Br) + 1], 375 [M+(79Br) + 1]; IR (neat)
2926, 1756, 1448, 1207, 1094 cm-1; HRMS (MALDI/DHB) calcd for
C20H24O2Br [M+(79Br) + 1], 375.0954; found, 375.0968.
(17) Synthesis of 3-Allyl-4-(1′-bromoundec-2′(Z)-en-2′-yl)-5-phen-
ylfuran-2(5H)-one (Z-5jd). A mixture of 1j (52 mg, 0.26 mmol), 3d
(76 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol), benzoquinone
(41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045 mmol, 2 mol %)
in 2 mL of HOAc was stirred at 60 °C for 10 h to afford Z-5jd (62
1
mg, 56%): oil, H NMR (300 MHz, CDCl3) δ 7.38-7.30 (m, 3H),
(13) Synthesis of 4-(1′-Bromo-3′-phenylprop-2′(Z)-en-2′-yl)-3-
methyl-5-phenylfuran-2(5H)-one (Z-5af). A mixture of 1a (43 mg,
0.25 mmol), 3f (58 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol) in 2 mL of HOAc was stirred at 60 °C for 6.5 h to afford Z-5af
(80 mg, 88%): oil, 1H NMR (300 MHz, CDCl3) δ 7.42-7.22 (m, 10H),
6.69 (s, 1H), 6.07 (q, J ) 1.8 Hz, 1H), 4.17 (d, J ) 10.8 Hz, 1H), 4.04
(d, J ) 10.8 Hz, 1H), 2.18 (d, J ) 1.8 Hz, 3H); 13C NMR (75.4 MHz,
CDCl3) δ 10.5, 29.2, 83.1, 126.3, 127.5, 128.70, 128.73, 128.8, 129.0,
129.4, 129.6, 134.3, 134.5, 137.9, 157.7, 174.0; MS(ESI) m/z 388
[M(81Br) + NH4+], 386 [M(79Br) + NH4+], 371 [M+(81Br) + 1], 369
[M+(79Br) + 1]; IR (neat) 1754, 1622, 1496, 1455, 1091 cm-1; HRMS
(MALDI/DHB) calcd for C20H18O2Br [M+(79Br) + 1], 369.0485; found,
369.0483.
7.22-7.18 (m, 2H), 6.03-5.90 (m, 2H), 5.71 (t, J ) 7.5 Hz, 1H), 5.16
(s, 1H), 5.14-5.10 (m, 1H), 3.99 (d, J ) 10.8 Hz, 1H), 3.92 (d, J )
10.8 Hz, 1H), 3.27-3.23 (m, 2H), 2.20-2.04 (m, 2H), 1.38-1.08 (m,
12H), 0.88 (t, J ) 6.9 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 14.0,
22.6, 26.9, 28.1, 28.5, 28.8, 28.9, 29.1, 29.2, 31.7, 83.3, 116.5, 126.5,
127.5, 128.0, 128.9, 129.4, 133.9, 134.7, 142.0, 159.6, 173.6; MS(ESI)
m/z 433 [M+(81Br) + 1], 431 [M+(79Br) + 1]; IR (neat) 2926, 1760,
1639, 1456, 1013 cm-1; HRMS (MALDI/DHB) calcd for C24H31O2-
BrNa [M(79Br) + Na+], 453.1400; found, 453.1394.
(18) Synthesis of 4-(1′-Bromo-5′,5′-dimethoxylcarbonylpenta-2′-
(Z)-en-2′-yl)-3-methyl-5-phenylfuran-2(5H)-one (Z-5ah). A mixture
of 1a (43 mg, 0.25 mmol), 3h (92 mg, 0.50 mmol), LiBr‚H2O (53 mg,
0.50 mmol), benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1
mg, 0.0045 mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C
for 6 h to afford a mixture of Z-5ah and hydroquinone. The mixture
was then dissolved in 30 mL of CH2Cl2, washed with water (5 mL ×
3), and dried over Na2SO4. The solvent was evaporated to afford pure
(14) Synthesis of 4-(1′-Bromo-4′-phenylbuta-2′(Z)-en-2′-yl)-3-
methyl-5-phenylfuran-2(5H)-one (Z-5ag). A mixture of 1a (43 mg,
0.25 mmol), 3g (65 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol) in 2 mL of HOAc was stirred at 60 °C for 5.5 h to afford Z-5ag
(58 mg, 61%): oil, 1H NMR (300 MHz, CDCl3) δ 7.42-7.30 (m, 3H),
7.28-7.17 (m, 5H), 6.96-6.87 (m, 2H), 5.96 (q, J ) 1.8 Hz, 1H),
5.83 (t, J ) 7.5 Hz, 1H), 4.11 (d, J ) 10.8 Hz, 1H), 4.03 (d, J ) 10.8
Hz, 1H), 3.60-3.43 (m, 2H), 2.10 (d, J ) 1.8 Hz, 3H); 13C NMR (75.4
MHz, CDCl3): δ 10.2, 26.6, 34.0, 83.2, 125.1, 126.6, 127.5, 128.2,
128.6, 128.9, 129.2, 129.4, 134.7, 137.7, 139.0, 157.7, 174.2; MS(ESI)
m/z 385 [M+(81Br) + 1], 383 [M+(79Br) + 1]; IR (neat) 1755, 1638,
1602, 1495, 1454, 1095, 1014 cm-1; HRMS (MALDI/DHB) calcd for
C21H20O2Br [M+(79Br) + 1], 383.0641; found, 383.0654.
1
Z-5ah (63 mg, 58%): oil, H NMR (300 MHz, CDCl3) δ 7.39-7.30
(m, 3H), 7.22-7.13 (m, 2H), 5.89 (q, J ) 1.8 Hz, 1H), 5.60 (t, J ) 7.5
Hz, 1H), 4.01 (d, J ) 11.1 Hz, 1H), 3.90 (d, J ) 11.1 Hz, 1H), 3.66
(s, 3H), 3.61 (s, 3H), 3.38 (t, J ) 7.2 Hz, 1H), 2.72 (dd, J ) 7.8, 7.8
Hz, 2H), 2.03 (d, J ) 1.8 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ
10.1, 26.1, 27.2, 50.2, 52.7, 52.8, 83.1, 125.7, 127.4, 128.8, 129.4, 131.2,
134.4, 135.1, 157.4, 168.4, 173.9; MS(ESI) m/z (%) 461 [M(81Br) +
Na+], 459 [M(79Br) + Na+], 439 [M+(81Br) + 1], 437 [M+(79Br) + 1];
IR (neat) 1755, 1650, 1498, 1456, 1436, 1274, 1210, 1158, 1094, 1014
cm-1; HRMS (MALDI/DHB) calcd for C20H22O6Br [M+(79Br) + 1],
437.0594; found, 437.0590.
(15) Synthesis of 4-(1′-Bromonon-2′(Z)-en-2′-yl)-5-(4′′-bromophen-
yl)-3-propyl-furan-2(5H)-one (Z-5db). A mixture of 1d (70 mg, 0.25
mmol), 3b (62 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 6 h to
(19) Synthesis of 4-(1′-Bromo-5′,5′-diethoxylcarbonylpenta-2′(Z)-
en-2′-yl)-3-methyl-5-phenylfuran-2(5H)-one (Z-5ai). A mixture of 1a
(44 mg, 0.25 mmol), 3i (106 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50
mmol), benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg,
0.0045 mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 6
1
1
afford Z-5db (69 mg, 57%): oil, H NMR (300 MHz, CDCl3) δ 7.46
h to afford Z-5ai (71 mg, 60%): oil, H NMR (300 MHz, CDCl3) δ
(d, J ) 8.7 Hz, 2H), 7.07 (d, J ) 8.7 Hz, 2H), 5.88 (s, 1H), 5.57 (t, J
) 7.8 Hz, 1H), 3.97 (d, J ) 10.8 Hz, 1H), 3.90 (d, J ) 10.8 Hz, 1H),
2.40 (t, J ) 7.5 Hz, 2H), 2.20-2.04 (m, 2H), 2.72-1.54 (m, 2H), 1.38-
1.04 (m, 8H), 0.97 (t, J ) 7.5 Hz, 3H), 0.85 (t, J ) 7.5 Hz, 3H); 13C
NMR (75.4 MHz, CDCl3) δ 14.0, 14.2, 21.8, 22.5, 26.6, 27.0, 28.0,
28.5, 28.6, 31.4, 82.3, 123.4, 127.9, 129.0, 129.3, 132.0, 133.9, 141.2,
158.4, 173.6; MS(ESI) m/z 504 [M(81Br81Br) + NH4+], 502 [M(81Br79-
Br) + NH4+], 500 [M(79Br79Br) + NH4+], 487 [M+(81Br81Br) + 1],
485 [M+(81Br79Br) + 1], 483 [M+(79Br79Br) + 1]; IR (neat) 2928, 1758,
7.40-7.25 (m, 3H), 7.25-7.13 (m, 2H), 5.89 (s, 1H), 5.62 (t, J ) 7.5
Hz, 1H), 4.23-3.96 (m, 5H), 3.90 (d, J ) 10.8 Hz, 1H), 3.33 (t, J )
7.2 Hz, 1H), 2.72 (t, J ) 7.5 Hz, 2H), 2.03 (s, 3H), 1.27-1.15 (m,
6H); 13C NMR (75.4 MHz, CDCl3) δ 10.1, 13.92, 13.93, 26.2, 27.2,
50.6, 61.69, 61.75, 83.1, 125.7, 127.4, 128.8, 129.4, 131.1, 134.5, 135.4,
157.4, 168.0, 168.1, 174.0; MS(ESI) m/z 489 [M(81Br) + Na+], 487
[M(79Br) + Na+], 467 [M+(81Br) + 1], 465 [M+(79Br) + 1]; IR (neat)
1755, 1456, 1370, 1269, 1095, 1017 cm-1; HRMS (MALDI/DHB) calcd
for C22H26O6Br [M+(79Br) + 1], 465.0907; found, 465.0898.
9
10954 J. AM. CHEM. SOC. VOL. 129, NO. 35, 2007

Cyclization Reaction of 2,3-Allenoic Acids
A R T I C L E S
(20) Synthesis of 4-(1′-Bromo-5′-acetoxylpenta-2′(Z)-en-2′-yl)-3-
methyl-5-phenylfuran-2(5H)-one (Z-5aj). A mixture of 1a (44 mg,
0.25 mmol), 3j (63 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 6 h to
afford Z-5aj (64 mg, 67%): oil, 1H NMR (300 MHz, CDCl3) δ 7.40-
7.27 (m, 3H), 7.24-7.15 (m, 2H), 5.91 (q, J ) 1.5 Hz, 1H), 5.63 (t, J
) 7.8 Hz, 1H), 4.02 (t, J ) 6.0 Hz, 2H), 3.96 (d, J ) 10.8 Hz, 1H),
3.90 (d, J ) 10.8 Hz, 1H), 2.58-2.38 (m, 2H), 2.06 (d, J ) 1.5 Hz,
3H), 1.92 (s, 3H); 13C NMR (75.4 MHz, CDCl3) δ 10.1, 20.7, 26.4,
27.5, 62.1, 83.2, 125.4, 127.4, 128.8, 129.4, 130.9, 134.6, 135.9, 157.4,
170.6, 174.0; MS(EI) m/z (%) 381 [M+(81Br) + 1, 1.27], 379 [M+(79Br)
+ 1, 1.06], 299 (M+ - Br, 12.83), 43 (100); IR (neat) 1755, 1652,
1497, 1456, 1239, 1095, 1036 cm-1; HRMS (EI) calcd for C18H19O4
[M+ - Br], 299.1283; found, 299.1280.
0.0045 mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 6
h in a Schlenk tube with a screw cap to afford R-(-)-Z-5ab (60 mg,
63%, 98% ee). HPLC conditions: OD-H column; rate, 0.7 mL/min;
eluent, hexane/i-PrOH 80/20. λ ) 230 nm. [R]D20 ) -166° (c ) 0.900,
CHCl3).
(3) Synthesis of R-(-)-3-Methyl-4-(1′-bromo-5′-acetoxylpenta-
2′(Z)-en-2′-yl)-5-phenylfuran-2(5H)-one (R-(-)-Z-5aj). A mixture of
R-(-)-1a (43 mg, 0.25 mmol, 98%ee), 3j (63 mg, 0.50 mmol), LiBr‚
H2O (53 mg, 0.50 mmol), benzoquinone (41 mg, 0.375 mmol), and
Pd(OAc)2 (1 mg, 0.0045 mmol, 2 mol %) in 2 mL of HOAc was stirred
at 60 °C for 6 h to afford R-(-)-Z-5aj (66 mg, 70%, 98% ee). HPLC
conditions: OD-H column; rate, 0.5 mL/min; eluent, hexane/i-PrOH
20
70/30. λ ) 254 nm. [R]D ) -187° (c ) 1.300, CHCl3).
(4) Synthesis of R-(-)-3-Methyl-4-(1′-bromo-3′-phenylprop-2′-
(Z)-en-2′-yl)-5-phenylfuran-2(5H)-one (R-(-)-Z-5af). A mixture of
R-(-)-1a (44 mg, 0.25 mmol, 98%ee), 3f (58 mg, 0.50 mmol), LiBr‚
H2O (53 mg, 0.50 mmol), benzoquinone (41 mg, 0.375 mmol), and
Pd(OAc)2 (1 mg, 0.0045 mmol, 2 mol %) in 2 mL of HOAc was stirred
at 60 °C for 6 h to afford R-(-)-Z-5af (75 mg, 80%, 97% ee). HPLC
conditions: ODH column; rate, 0.7 mL/min; eluent, hexane/i-PrOH
(21) Synthesis of 4-(1′-Bromo-5′-acetoxylpenta-2′(Z)-en-2′-yl)-3-
methyl-5-(r-naphthyl)-furan-2(5H)-one (Z-5fj). A mixture of 1f (56
mg, 0.25 mmol), 3j (62 mg, 0.49 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 10 h to
1
20
afford Z-5fj (69 mg, 64%): oil, H NMR (300 MHz, CDCl3) δ 8.17
95/5. λ ) 230 nm. [R]D ) -487° (c ) 0.710, CHCl3).
(d, J ) 8.1 Hz, 1H), 7.86 (t, J ) 8.1 Hz, 2H), 7.63-7.49 (m, 2H),
7.38 (t, J ) 7.8 Hz, 1H), 7.24 (d, J ) 6.6 Hz, 1H), 6.78 (q, J ) 1.8
Hz, 1H), 5.74 (t, J ) 7.5 Hz, 1H), 4.05-3.88 (m, 3H), 3.83 (d, J )
11.1 Hz, 1H), 2.52-2.38 (m, 2H), 2.17 (d, J ) 1.8 Hz, 3H), 1.82 (s,
3H); 13C NMR (75.4 MHz, CDCl3) δ 10.5, 20.6, 26.4, 27.5, 62.0, 78.8,
122.4, 125.1, 125.6, 126.1, 126.3, 127.1, 128.9, 130.2, 130.4, 131.4,
131.6, 133.7, 136.2, 156.8, 170.6, 174.0; MS(ESI) m/z 431 [M+(81Br)
+ 1], 429 [M+(79Br) + 1]; IR (neat) 1751, 1598, 1638, 1450, 1239,
1095, 1035 cm-1; HRMS (MALDI/DHB) calcd for C22H21O4BrNa
[M(79Br) + Na+], 451.0515; found, 451.0517.
The Reaction of Z-5aa with LiCl. A mixture of Z-5aa (100 mg,
0.29 mmol), LiCl (49 mg, 1.16 mmol), THF (4 mL), and distilled H2O
(4 mL) was stirred at 40 °C for 5.5 h to afford 101 mg of Z-5aa and
Z-5AA with a ratio of 1:1.
Synthetic Application of Z-5aa. (1) Synthesis of 3-Methyl-4-(1′-
diethylaminohepta-2′(Z)-en-2′-yl)-5-phenyl-furan-2(5H)-one (Z-10).
Under an argon atmosphere, a mixture of Z-5aa (59 mg, 0.17 mmol),
Et2NH (25 mg, 0.34 mmol), K2CO3 (47 mg, 0.34 mmol), and DMF (2
mL) was stirred in a Schlenk tube with a screw cap at room temperature
for 6 h. After the complete consumption of the starting material as
monitored by TLC, the reaction mixture was quenched with H2O (5
mL) and extracted with 50 mL of ether. The organic layer was washed
with brine and dried over Na2SO4. The solvent was evaporated, and
the crude product was analyzed by 1H NMR spectra. The residue was
purified via flash chromatography on silica gel to afford Z-10 (38 mg,
66%): 1H NMR (300 MHz, CDCl3) δ 7.38-7.28 (m, 3H), 7.25-7.15
(m, 2H), 6.15 (q, J ) 1.5 Hz, 1H), 5.64 (t, J ) 7.2 Hz, 1H), 3.04 (d,
J ) 14.1 Hz, 1H), 2.90 (d, J ) 14.1 Hz, 1H), 2.58-2.41 (m, 2H),
2.31-2.18 (m, 2H), 2.18-2.00 (m, 2H), 1.99 (d, J ) 1.5 Hz, 3H),
1.35-1.22 (m, 2H), 1.22-1.03 (m, 2H), 0.95 (t, J ) 7.2 Hz, 6H), 0.81
(t, J ) 7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 10.0, 11.5, 13.8,
22.0, 27.6, 31.4, 46.3, 51.1, 83.6, 122.6, 127.8, 128.6, 129.0, 130.9,
135.4, 138.2, 163.1, 175.2; MS(EI) m/z (%) 341 [M+, 3.84], 58 (100);
IR (neat) 1756, 1654, 1455, 1090 cm-1; HRMS calcd for C22H31NO2
[M+], 341.2355; found, 341.2362.
(22) Synthesis of 4-(1′-Bromo-5′-phthalamidopenta-2′(Z)-en-2′-
yl)-3-methyl-5-(r-naphthyl)furan-2(5H)-one (Z-5ak). A mixture of
1a (44 mg, 0.25 mmol), 3k (106 mg, 0.50 mmol), LiBr‚H2O (53 mg,
0.50 mmol), benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1
mg, 0.0045 mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C
for 6 h in a Schlenk tube with a screw cap. After the complete
consumption of the starting material as monitored by TLC, the solvent
was evaporated, and the residue was dissolved in 50 mL of CH2Cl2,
then washed with water (5 mL × 4), and dried over Na2SO4. The solvent
was evaporated, and the residue was purified via flash chromatography
1
on silica gel to afford Z-5ak (87 mg, 74%): oil, H NMR (300 MHz,
CDCl3) δ 7.88-7.77 (m, 2H), 7.77-7.63 (m, 2H), 7.30-7.18 (m, 3H),
7.18-7.10 (m, 2H), 5.85 (s, 1H), 5.71 (t, J ) 7.5 Hz, 1H), 3.89 (d, J
) 10.8 Hz, 1H), 3.82 (d, J ) 10.8 Hz, 1H), 3.80-3.61 (m, 2H), 2.69-
2.47 (m, 2H), 2.02 (s, 3H); 13C NMR (75.4 MHz, CDCl3) δ 10.1, 26.2,
27.3, 36.3, 83.1, 123.3, 125.5, 127.3, 128.8, 129.4, 131.4, 131.7, 134.1,
134.5, 136.1, 157.1, 168.1, 174.0; MS(ESI) m/z 506 [M(81Br) + K+],
504 [M(79Br) + K+], 490 [M(81Br) + Na+], 488 [M(79Br) + Na+],
468 [M+(81Br) + 1], 466 [M+(79Br) + 1]; IR (neat) 1755, 1710, 1396,
1361, 1097, 1007 cm-1; HRMS (MALDI/DHB) calcd for C24H21NO4-
Br [M+(79Br) + 1], 466.0649; found, 466.0645.
(2) Synthesis of 3-Methyl-4-(1′-phenylsulfonylhepta-2′(Z)-en-2′-
yl)-5-phenyl-furan-2(5H)-one (Z-11). Under an argon atmosphere, a
mixture of Z-5aa (54 mg, 0.15 mmol), PhSO2Na‚2H2O (60 mg, 0.30
mmol), and DMF (2 mL) was stirred at -22 °C for 2.5 h. After the
complete consumption of the starting material as monitored by TLC,
the mixture was diluted with 60 mL of ether and washed sequentially
with H2O and brine. The organic layer was dried over Na2SO4. The
Typical Procedure for the Cyclization of Optically Active 2,3-
Allenoic Acids R-(-)-1a in the Presence of Simple Allenes 3. (1)
Synthesis of R-(-)-3-Methyl-4-(1′-bromohept-2′(Z)-en-2′-yl)-5-phen-
ylfuran-2(5H)-one (R-(-)-Z-5aa). A mixture of R-(-)-1a (44 mg, 0.25
mmol, 98%ee), 3a (48 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50 mmol),
benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg, 0.0045
mmol, 2 mol %) in 2 mL of HOAc was stirred at 60 °C for 6 h to
afford R-(-)-Z-5aa (59 mg, 67%, 98% ee). HPLC conditions: OD-H
column; rate, 0.5 mL/min; eluent, hexane/i-PrOH 70/30. λ ) 230 nm.
1
solvent was evaporated, and the crude product was analyzed by H
NMR spectra. The residue was purified via flash chromatography on
silica gel to afford Z-11 (59 mg, 93%): 1H NMR (300 MHz, CDCl3)
δ 7.72 (d, J ) 7.5 Hz, 2H), 7.63 (t, J ) 7.5 Hz, 1H), 7.50 (t, J ) 7.5
Hz, 2H), 7.38-7.28 (m, 3H), 7.22-7.13 (m, 2H), 5.96 (q, J ) 1.5 Hz,
1H), 5.81 (t, J ) 7.5 Hz, 1H), 3.94 (d, J ) 14.7 Hz, 1H), 3.75 (d, J )
14.7 Hz, 1H), 2.01 (d, J ) 1.5 Hz, 3H), 1.80-1.67 (m, 1H), 1.66-
1.50 (m, 1H), 1.11-0.89 (m, 4H), 0.71 (t, J ) 6.9 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) δ 10.7, 13.6, 21.9, 28.1, 30.3, 55.7, 83.0, 119.8,
124.1, 127.8, 128.2, 128.9, 129.2, 129.4, 134.1, 134.2, 137.9, 145.8,
158.7, 174.1; MS(EI) m/z (%) 410 (M+, 3.45), 268 (100); IR (neat)
1754, 1634, 1585, 1447, 1320, 1156, 1086, 1016 cm-1; HRMS calcd
for C24H26O4S [M+], 410.1552; found, 410.1568.
20
[R]D ) -215° (c ) 0.590, CHCl3).
(2) Synthesis of R-(-)-3-Methyl-4-(1′-bromonon-2′(Z)-en-2′-yl)-
5-phenylfuran-2(5H)-one (R-(-)-5ab). A mixture of R-(-)-1a (43 mg,
0.25 mmol, 98%ee), 3b (62 mg, 0.50 mmol), LiBr‚H2O (53 mg, 0.50
mmol), benzoquinone (41 mg, 0.375 mmol), and Pd(OAc)2 (1 mg,
9
J. AM. CHEM. SOC. VOL. 129, NO. 35, 2007 10955

A R T I C L E S
Gu et al.
(3) Synthesis of 3-Methyl-4-(hepta-2′(E)-en-2′-yl)-5-phenylfuran-
2(5H)-one (E-12). Under an argon atmosphere, a mixture of Z-5aa
(69 mg, 0.20 mmol), NaBH4 (15 mg, 0.40 mmol), and DMSO (3 mL)
was stirred at 18 °C for 50 min. After the complete consumption of
the starting material as monitored by TLC, the mixture was diluted
with 60 mL of ether and washed sequentially with H2O and brine. The
organic layer was dried over Na2SO4. The solvent was evaporated, and
130.5, 131.8, 133.8, 146.6, 161.3, 174.5; MS(EI) m/z (%) 334 (M+,
13.00), 141 (100); IR (neat) 1758, 1512, 1456, 1379, 1319, 1096 cm-1
HRMS calcd for C23H26O2 [M+], 334.1933; found, 334.1934.
;
(6) Synthesis of (5S*,2′R*,3′R*)-3-Methyl-4-(3′-methyl-1′,2′-dibro-
mohept-2′-yl)-5-(r-naphthyl)furan-2(5H)-one(14ba)and(5S*,2′S*,3′R*)-
3-Methyl-4-(3′-methyl-1′,2′-dibromohept-2′-yl)-5-(r-naphthyl)furan-
2(5H)-one (14bb). To a stirred solution of 13b (30 mg, 0.09 mmol) in
2 mL of CH2Cl2 was added Br2 (0.36 mL, 0.50 mol/L in CH2Cl2), which
was followed by stirring at room temperature for 5 h. After complete
consumption of the starting material as monitored by TLC, a minimal
amount of aqueous saturated solution of Na2S2O3 was added until the
disappearance of the deep color of the excess Br2. The mixture was
extracted with 30 mL of CH2Cl2, and the organic layer was dried over
anhydrous Na2SO4. After evaporation of the solvent, the residue was
purified via flash chromatography on silica gel (eluent: petroleum ether/
ethyl acetate ) 20:1) to afford 14ba (less polar, 6 mg, 14%) and 14bb
1
the crude product was analyzed by H NMR spectra (regiolectivity:
1/15, E/Z g 22/1). The residue was purified via flash chromatography
on silica gel to afford pure E-12 (38 mg, 71%): 1H NMR (300 MHz,
CDCl3) δ 7.40-7.29 (m, 3H), 7.23-7.14 (m, 2H), 5.87 (q, J ) 1.5
Hz, 1H), 5.57 (t, J ) 7.2 Hz, 1H), 2.13-1.92 (m, 5H), 1.72 (s, 3H),
1.35-1.19 (m, 2H), 1.19-1.03 (m, 2H), 0.80 (t, J ) 7.2 Hz, 3H); 13
C
NMR (75.4 MHz, CDCl3) δ 10.4, 13.8, 15.4, 22.0, 27.7, 31.0, 83.4,
121.7, 127.3, 127.4, 128.6, 129.0, 135.6, 137.0, 161.9, 175.0; MS(EI)
m/z (%) 271 [M+ + 1, 24.67], 270 [M+, 56.45], 105 (100); IR (neat)
1755, 1640, 1456, 1331, 1092, 1003 cm-1; HRMS calcd for C18H22O2
[M+], 270.1620; found, 270.1630.
1
(more polar, 34 mg, 77%). 14ba: oil, H NMR (300 MHz, CDCl3) δ
8.33 (d, J ) 8.7 Hz, 1H), 7.98-7.88 (m, 2H), 7.66-7.40 (m, 4H),
7.14 (q, J ) 1.5 Hz, 1H), 3.69 (d, J ) 10.2 Hz, 1H), 3.28 (d, J ) 10.2
Hz, 1H), 2.52-2.38 (m, 1H), 2.33 (d, J ) 1.5 Hz, 3H), 1.58-1.22 (m,
6H), 1.00 (d, J ) 6.0 Hz, 3H), 0.94 (t, J ) 7.2 Hz, 3H); MS(ESI) m/z
(%) 514 [M(2 × 81Br) + NH4+], 512 [M(2 × 79Br81Br) + NH4+], 510
[M(2 × 79Br) + NH4+], 497 [M(2 × 81Br)+ + 1], 495 [M(2 × 79Br81-
(4) Synthesis of (5S*,3′R*)-3-Methyl-4-(3′-methylhepta-1′-en-2′-
yl)-5-phenylfuran-2(5H)-one (13a). Under an argon atmosphere, a
mixture of Z-5aa (70 mg, 0.20 mmol), CuBr‚SMe2 (2 mg, 0.01 mmol),
and DCM (4 mL) was cooled to -78 °C. A solution of CH3MgBr
[0.36 mL, 1.4 mol/L in toluene/THF (75/25), 0.50 mmol] was carefully
added to the mixture via a syringe at this temperature. After being stirred
for 30 min at -78 °C, 0.5 mL of H2O was added to the reaction mixture
at this temperature, and then the reaction mixture was warmed to room
temperature. The reaction mixture was filtered via a short column of
silica gel, evaporated, and analyzed by 1H NMR spectra (regioselectivity
) 18/1, dr ) 25/1). The residue was purified via flash chromatography
on silica gel to afford 13a (51 mg, 90%): 1H NMR (300 MHz, CDCl3)
δ 7.38-7.27 (m, 3H), 7.21-7.12 (m, 2H), 5.85 (q, J ) 1.8 Hz, 1H),
5.15 (s, 1H), 4.95 (s, 1H), 2.19-2.00 (m, 1H), 1.98 (d, J ) 1.8 Hz,
3H), 1.42-1.30 (m, 1H), 1.28-0.98 (m, 5H), 0.86 (d, J ) 7.2 Hz,
3H), 0.79 (t, J ) 7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 10.0,
13.9, 20.1, 22.6, 29.3, 34.2, 37.2, 83.7, 116.4, 124.1, 127.3, 128.6, 129.1,
134.7, 146.0, 162.0, 174.6; MS(EI) m/z (%) 285 [M+ + 1, 56.84], 284
[M+, 20.07], 91 (100); IR (neat) 1759, 1656, 1456, 1319, 1091, 1003
cm-1; HRMS calcd for C19H24O2 [M+], 284.1776; found, 284.1783.
(5) Synthesis of (5S*,3′R*)-3-Methyl-4-(3′-methylhepta-1′-en-2′-
yl)-5-(r-naphthyl)furan-2(5H)-one (13b). Under an argon atmosphere,
to a mixture of Z-5fa (54 mg, 0.135 mmol) and CuBr‚SMe2 (1 mg,
0.005 mmol) in DCM (3 mL) was added CH3MgBr (0.24 mL, 1.4 mol/L
in toluene/THF (75/25), 0.34 mmol) carefully via a syringe at -78 °C.
After the mixture was stirred for 30 min at -78 °C, 0.5 mL of H2O
was added to the reaction mixture at this temperature, and then the
reaction mixture was warmed to room temperature. The reaction mixture
was filtered via a short column of silica gel, evaporated, and analyzed
Br)+ + 1], 493 [M(2 × 79Br)+ + 1]; IR (neat) 1762, 1512, 1459, 1379,
79
1313, 1100, 1020 cm-1; HRMS calcd for C23H26O2Br2Na [M(2 ×
-
Br) + Na+], 515.0192; found, 515.0187. 14bb: solid, mp 107-109
°C (ethyl acetate/ether/petroleum ether), H NMR (300 MHz, CDCl3)
1
δ 8.34 (d, J ) 8.4 Hz, 1H), 7.91 (d, J ) 9.0 Hz, 2H), 7.68-7.50 (m,
2H), 7.50-7.35 (m, 2H), 7.18 (bs, 1H), 3.82 (d, J ) 11.4 Hz, 1H),
3.73 (d, J ) 11.4 Hz, 1H), 2.48-2.20 (m, 1H), 2.29 (d, J ) 1.8 Hz,
3H), 1.59-1.42 (m, 2H), 1.42-1.20 (m, 2H), 1.18 (d, J ) 6.6 Hz,
3H), 1.15-0.95 (m, 2H), 0.88 (t, J ) 7.5 Hz, 3H); 13C NMR (75.4
MHz, CDCl3) δ 12.5, 14.0, 15.9, 22.8, 30.7, 32.7, 43.5, 79.6, 122.7,
124.9, 125.3, 126.1, 126.9, 129.0, 130.0, 130.4, 130.6, 131.4, 134.0,
158.2, 173.6; MS(ESI) m/z (%) 514 [M(2 × 81Br) + NH4+], 512 [M(2
×
79Br81Br) + NH4+], 510 [M(2 × 79Br) + NH4+], 497 [M(2 × 81Br)+
+ 1], 495 [M(2 × 79Br81Br)+ + 1], 493 [M(2 × 79Br)+ + 1]; IR (neat)
1759, 1512, 1464, 1380, 1312, 1100, 1018 cm-1; HRMS calcd for
C23H26O2Br2Na [M(2 × 79Br) + Na+], 515.0192; found, 515.0189.
Acknowledgment. Financial support from the National
Natural Science Foundation of China (20121202, 20332060, and
20423001), the State Basic and Research Development Program
(Grant No. 2006CB806105), and the Shanghai Municipal
Committee of Science and Technology is greatly appreciated.
We thank Mr. Jinbo Zhao for reproducing the results presented
in entry 7 of Table 2, entry 7 of Table 3, entry 1 of Table 4,
and 13a in Scheme 4.
1
by H NMR spectra (regioselectivity >25/1, dr >50/1). The residue
was purified via flash chromatography on silica gel to afford 13b (36
mg, 80%): 1H NMR (300 MHz, CDCl3) δ 8.15 (d, J ) 8.1 Hz, 1H),
7.87 (t, J ) 8.7 Hz, 2H), 7.63-7.48 (m, 2H), 7.40 (t, J ) 7.5 Hz, 1H),
7.28 (d, J ) 6.3 Hz, 1H), 6.70 (q, J ) 1.8 Hz, 1H), 5.24 (s, 1H), 5.16
(s, 1H), 2.09 (d, J ) 1.8 Hz, 3H), 2.00 (q, J ) 6.9 Hz, 1H), 1.35-1.22
(m, 1H), 1.22-1.03 (m, 1H), 1.03-0.75 (m, 7H), 0.65 (t, J ) 6.9 Hz,
3H); 13C NMR (75.4 MHz, CDCl3) δ 10.4, 13.8, 20.4, 22.4, 29.1, 34.3,
37.1, 79.6, 116.9, 122.7, 125.0, 125.6, 125.9, 126.0, 126.8, 128.9, 130.0,
Supporting Information Available: 1H/13C NMR spectra of
all new compounds, chiral HPLC results of the optically active
compounds, and X-ray data (CIF) of Z-5fa and 14bb. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JA072790J
9
10956 J. AM. CHEM. SOC. VOL. 129, NO. 35, 2007