A palladium catalyzed efficient synthesis of γ-methylene-α, β-unsaturated γ-lactones via cyclization of 3,4-alkadienoic acids

Article abstract of DOI:10.1016/j.tet.2005.06.063

An efficient method was developed for the synthesis of γ-methylene- α,β-unsaturated γ-lactones from the Pd-catalyzed cyclization of 3,4-alkadienoic acids. Control experiment shows that the reaction should be carried out under a N₂ atmosphere to ensure the high purity of the products.

Full text of DOI:10.1016/j.tet.2005.06.063

Tetrahedron 61 (2005) 9896–9901
A palladium catalyzed efficient synthesis of g-methylene-
a,b-unsaturated g-lactones via cyclization of 3,4-alkadienoic acids
*
Shengming Ma and Fei Yu
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 1 March 2005; revised 19 April 2005; accepted 10 June 2005
Available online 14 July 2005
Abstract—An efficient method was developed for the synthesis of g-methylene-a,b-unsaturated g-lactones from the Pd-catalyzed
cyclization of 3,4-alkadienoic acids. Control experiment shows that the reaction should be carried out under a N2 atmosphere to ensure the
high purity of the products.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
PhI, 5-methylene-2(5H)-furanone 3a was afforded under
the catalysis of PdCl2(PPh3)2 (entry 2, Table 1). However,
the product was contaminated by other inseparable
by-products. Furthermore, it is lucky for us to observe that
when the reaction was conducted under a N2 atmosphere, 3a
was isolated as the single product in 88% yield with a very
high purity (entry 3, Table 1). When CuBr2 was used instead
of CuCl2, the reaction was complicated (entry 4, Table 1). In
the presence of H2O or O2, the purity of the product was also
not high (entries 2, 5, and 6, Table 1). When a less amount of
CuCl2 was applied, the yield of 3a was obviously lower
(entries 7 and 8, Table 1). Thus, after screening several
commonly used catalyst, PdCl2(PPh3)2 appeared to be the
best (compare entries 9–11 with entry 3, Table 1). The
reaction could proceed in the absence of PdCl2(PPh3)2 albeit
in much lower yield (entry 12, Table 1). Obviously this
cyclization reaction can also be mediated by CuCl2 (entry
13, Table 1). In the absence of the base the yield was also
low (entry 14, Table 1). When only 3 equiv of K2CO3 were
added, the product isolated was not pure (entry 15, Table 1).
When 5 equiv of CuCl2 were applied, no obvious
improvement was observed (entry 16, Table 1). From
these results we concluded the best reaction conditions:
Recently, the chemistry of allenes has been attracting the
attention of more and more chemists.1,2 During the course of
our studies on the chemistry of allenes,3,4 we have
developed some new methodologies for the synthesis of
butenolides from a-allenoic acids (Scheme 1).5
Scheme 1.
2. Results and discussion
When we turned our attention from the a-allenoic acids to
the b-allenoic acids 1a, we found that under the catalysis of
Pd(0)/AgC the reaction of 2-methyl-3-(n-butyl)-3,4-penta-
dienoic acid with iodobenzene in MeCN afforded not only
the coupling-cyclization product 2a but also 5-methylene-
2(5H)-furanone 3a (Scheme 2). Recently, the g-alkylidene-
a,b-unsaturated g-lactones6 has also attracted the attention
of many organic chemists because of their biological
activities7,8 and versatile use in organic synthesis.9 When
we found product 3a was obtained in 29% yield in DMF
under the catalysis of Pd(PPh3)4 (entry 1, Table 1), we went
on to search a set of reaction conditions for the sole
formation of 3a. When 4 equiv CuCl2 were used instead of
Keywords: 3,4-Alkadienoic acids; Palladium; CuCl2; Cyclization.
*
Corresponding author. Tel.: C86 21 6416 3300; fax: C86 21 6416 7510;
e-mail: masm@mail.sioc.ac.cn
Scheme 2.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.063

S. Ma, F. Yu / Tetrahedron 61 (2005) 9896–9901
9897
Table 1. Pd-catalyzed cyclization reaction of 2-methyl-3-(n-butyl)penta-3,4-dienoic acid 1a
Entry
Catalyst (5 mol%)
Additive (equiv)
Time (h)
Yield of 3a (%)
1
Pd(PPh3)4
PhI (1.5)
24
12
12
24
12
12
24
24
24
24
24
24
12
12
12
12
29
2a
3
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2
CuCl2 (4)
CuCl2 (4)
CuBr2 (5)
CuCl2 (4)
CuCl2 (4)
CuCl2 (2.5)
CuCl2 (0.8)
CuCl2 (4)
CuCl2 (4)
CuCl2 (4)
CuCl2 (4)
CuCl2 (1)
CuCl2 (4)
CuCl2 (4)
CuCl2 (4)
!87b
88
4
complicated
5c
6d
7
!50b
!70b
75
8
9
22
54
40
34
60
18
70
10
11
12
13
14e
15f
16g
Pd(OAc)2
PdCl2(CH3CN)2
—
—
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
!87b
89
a The reaction was exposed to air.
b The product is not pure.
c The reaction was conducted under 1 atm of pure O2.
d Four equivalents H2O was added.
e No K2CO3 was used.
f
Three equivalents K2CO3 were used.
g Five equivalents K2CO3 were used.
5 mol% PdCl2(PPh3)2, 4 equiv of CuCl2, 4 equiv of K2CO3
in DMF at 70 8C for 12 h under N2.
yield of 3k (protoanemonin)7 is 31% by NMR (entry 11,
Table 2).
A palladium catalyzed mechanism was proposed for this
reaction: endo-mode cyclic anti-oxypalladation of the non-
terminal carbon–carbon double bonds in the 3,4-allenoic
acids would form 4, which would afford the products 3
via syn-b-H elimination, which may be facilitated by the
presence of the base and the electron-withdrawing carbonyl
group in 4. The in situ generated palladium hydride species
would form Pd(0) species upon its action with K2CO3. The
catalytically active Pd(II) species would be regenerated via
the oxidation with CuCl2 (Scheme 3).
b-Allenoic acids can be conveniently prepared from the
hydrolysis of the corresponding b-allenoic acid esters.10
Subsequently, we studied the scope of this cyclization
reaction of b-allenoic acids (Table 2). From the data listed in
Table 2, it is obvious that the scope of the reactant is broad:
R1 can be H, alkyl, allyl, Bn or t-Bu and R2 can be H or
alkyl. With simple unsubstituted pentadienoic acid, the
Table 2. PdCl2(PPh3)2-catalyzed cyclization reaction of b-allenoic acids 1
In conclusion, we have described a convenient method for
the preparation of the valuable g-methylene-2(5H)-fura-
nones from 3,4-allenoic acids in high yield. The reaction
demonstrated high efficiency and regioselectivity. Further
studies in this area are being conducted in our laboratory.
Entry
R1
R2
Yield of 3
(%)
3. Experimental
1
2
3
4
5
6
7
8
n-Bu
n-Bu
n-Bu
n-Bu
Me
n-C7H15
t-Bu
Allyl
Bn
Me
H
Et
(1a)
(1b)
(1c)
(1d)
(1e)
(1f)
(1g)
(1h)
(1i)
88 (3a)
78 (3b)
81 (3c)
84 (3d)
64 (3e)
84 (3f)
71 (3g)
66 (3h)
89 (3i)
51 (3j)
31 a(3k)
3.1. General procedure for the synthesis of b-allenoic
acids 1
n-Pr
Me
Me
Me
Me
Me
n-Pr
H
Conditions A. A solution of the corresponding b-allenoic
acid ethyl ester10 (6 mmol), and LiOH (288 mg, 12 mmol)
was stirred in the mixed solvent of 12 mL of H2O and 24 mL
of MeOH at 30 8C for 3 days. After acidification with 1 N
HCl, extraction with ether, drying over anhydrous Na2SO4,
and evaporation, the mixture was submitted to flash
9
10
11
H
H
(1j)
(1k)
a The yield was determined by NMR using p-methoxyiodobenzene as the
internal standard.

9898
S. Ma, F. Yu / Tetrahedron 61 (2005) 9896–9901
Scheme 3.
chromatography on silica gel (CH2Cl2/MeOHZ10/1) to
produce compound 1.
7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) d 207.1, 178.0,
96.7, 76.1, 38.5, 31.2, 29.4, 22.2, 13.8; IR (neat) 1961,
1740 cmK1; MS (m/z) 154 (MC, 11.97), 41 (100); HRMS
calcd for C9H14O2(MC) 154.09938; Found 154.10058.
Conditions B. A solution of the corresponding b-allenoic
acid ethyl ester10 (6.6 mmol) was stirred in the mixed
solvent of 27 mL of 20% hydrochloric acid, 20 mL of 1,4-
dioxane, and 7 mL of THF at 30 8C for 3 days. After
extraction with ether, drying over anhydrous Na2SO4, and
evaporation, the mixture was submitted to flash chroma-
tography on silica gel (CH2Cl2/MeOHZ10/1) to produce
compound 1.
3.1.3. 2-Ethyl-3-(n-butyl)penta-3,4-dienoic acid (1c). The
reaction of the corresponding allenoic acid ester (3654 mg,
17.4 mmol) with LiOH (945 mg, 39.4 mmol) afforded
3060 mg (97%) of 1c under conditions A: liquid; 1H
NMR (300 MHz, CDCl3) d 11.52 (br s, 1H), 4.84–4.79 (m,
2H), 2.77 (t, JZ7.5 Hz, 1H), 2.08–1.92 (m, 2H), 1.85–1.71
(m, 1H), 1.69–1.56 (m, 1H), 1.48–1.25 (m, 4H), 0.94 (t, JZ
7.5 Hz, 3H), 0.89 (t, JZ7.2 Hz, 3H); 13C NMR (75.4 MHz,
CDCl3) d 206.2, 180.7, 101.8, 77.8, 49.9, 30.3, 29.5, 23.5,
3.1.1. 2-Methyl-3-(n-butyl)penta-3,4-dienoic acid (1a).
The reaction of the corresponding allenoic acid ester
(1044 mg, 5.3 mmol) with LiOH (250 mg, 10.4 mmol)
afforded 817 mg (91%) of 1a under conditions A: liquid;
1H NMR (300 MHz, CDCl3) d 11.64 (br s, 1H), 4.85–4.81
(m, 2H), 3.05–2.95 (m, 1H), 2.08–1.93 (m, 2H), 1.47–1.30
(m, 4H), 1.27 (d, JZ7.2 Hz, 3H), 0.89 (t, JZ7.2 Hz, 3H);
13C NMR (75.4 MHz, CDCl3) d 205.9, 181.3, 103.3, 78.3,
42.1, 30.2, 29.6, 22.3, 15.8, 13.9; IR (neat) 1958, 1711,
1459, 1222 cmK1; MS (m/z) 168 (MC, 4.83), 111 (100);
HRMS calcd for C10H16O2(MC) 168.11503; Found
168.11785.
22.3, 13.9, 12.0; IR (neat) 1957, 1707, 1460, 1219 cmK1
;
MS (m/z) 182 (MC, 1.59), 153 (100); HRMS calcd for
C11H18O2Na(MNaC) 205.1223; Found 205.1219.
3.1.4. 2-n-(Propyl)-3-n-(butyl)penta-3,4-dienoic acid
(1d). The reaction of the corresponding allenoic acid ester
(4613 mg, 20.6 mmol) with LiOH (1198 mg, 50 mmol)
afforded 3300 mg (82%) of 1d under conditions A: liquid;
1H NMR (300 MHz, CDCl3) d 11.50 (br s, 1H), 4.84–4.76
(m, 2H), 2.87 (t, JZ7.5 Hz, 1H), 2.06–1.92 (m, 2H), 1.63–
1.52 (m, 1H), 1.45–1.25 (m, 4H), 1.49–1.25 (m, 6H), 0.91
(t, JZ6.9 Hz, 3H), 0.89 (t, JZ7.2 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) d 206.2, 180.9, 102.0, 77.8, 48.0, 32.4,
30.2, 29.5, 22.3, 20.6, 13.9, 13.8; IR (neat) 1957, 1708,
1466, 1210 cmK1; MS (m/z) 196 (MC, 1.19), 153 (100);
HRMS calcd for C12H20O2Na(MNaC) 219.1355; Found
219.1377.
3.1.2. 3-(n-Butyl)penta-3,4-dienoic acid (1b). The reaction
of the corresponding allenoic acid ester (1.132 g, 6.2 mmol)
with LiOH (314 mg, 13 mmol) afforded 275 mg (29%) of
1b under conditions A: liquid; 1H NMR (300 MHz, CDCl3)
d 10.83 (br s, 1H), 4.78–4.70 (m, 2H), 3.03 (t, JZ2.4 Hz,
2H), 2.08–1.99 (m, 2H), 1.48–1.25 (m, 4H), 0.89 (t, JZ

S. Ma, F. Yu / Tetrahedron 61 (2005) 9896–9901
9899
3.1.5. 2,3-Dimethylpenta-3,4-dienoic acid (1e). The
reaction of the corresponding allenoic acid ester (1.541 g,
10 mmol) with LiOH (480 mg, 20 mmol) afforded 639 mg
(51%) of 1e under conditions A: liquid; 1H NMR (300 MHz,
CDCl3) d 11.77 (br s, 1H), 4.79–4.72 (m, 2H), 3.08–2.96 (m,
1H), 1.76 (t, JZ3.3 Hz, 3H), 1.28 (d, JZ6.9 Hz, 3H); 13C
NMR (75.4 MHz, CDCl3) d 206.5, 181.1, 98.0, 76.3, 42.9,
17.1, 15.5; IR (neat) 1962, 1712, 1456, 1223 cmK1; MS
(m/z) 126 (MC, 7.53), 111 (100); HRMS calcd for
C7H10O2(MC) 126.06635; Found 126.06681.
(1693 mg, 10 mmol) afforded 453 mg (33%) of 1j under
conditions B: liquid; H NMR (300 MHz, CDCl3) d 11.60
1
(br s, 1H), 5.20 (q, JZ3.6 Hz, 1H), 4.80 (d, JZ6.9 Hz, 2H),
3.03 (q, JZ8.1 Hz, 1H), 1.83–1.72 (m, 1H), 1.64–1.55 (m,
1H), 1.43–1.34 (m, 2H), 0.92 (t, JZ7.5 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) d 208.5, 180.8, 88.7, 76.5, 44.9, 33.9,
20.2, 13.7; IR (neat) 1958, 1709, 1415, 1286, 1208 cmK1
;
MS (m/z) 141 (MCC1, 4.15), 97 (100); HRMS calcd for
C8H11O(MCKOH) 123.08099; Found 123.08177.
3.1.11. Penta-3,4-dienoic acid (1k).11 The reaction of the
corresponding allenoic acid ester (2038 mg, 16.2 mmol)
afforded 1360 mg (86%) of 1k under conditions B: liquid;
1H NMR (300 MHz, CDCl3) d 11.91 (br s, 1H), 5.23 (pentet,
JZ6.9 Hz, 1H), 4.79–4.71 (m, 2H), 3.12–3.04 (m, 2H); 13C
NMR (75.4 MHz, CDCl3) d 209.3, 178.1, 82.7, 75.9, 33.9;
IR (neat) 1960, 1713, 1440 cmK1; MS (m/z) 98 (MC,
15.03), 97 (MCK1, 40.04), 70 (100).
3.1.6. 2-Methyl-3-(n-heptyl)penta-3,4-dienoic acid (1f).
The reaction of the corresponding allenoic acid ester
(1.357 g, 5.7 mmol) with LiOH (297 mg, 12.4 mmol)
afforded 639 mg (53%) of 1f under conditions A: liquid;
1H NMR (300 MHz, CDCl3) d 11.43 (br s, 1H), 4.86–4.81
(m, 2H), 3.08–2.95 (m, 1H), 2.14–1.92 (m, 2H), 1.48–1.26
(m, 13H), 0.88 (d, JZ7.2 Hz, 3H); 13C NMR (75.4 MHz,
CDCl3) d 205.9, 181.3, 103.4, 78.2, 42.1, 31.8, 30.5, 29.2,
29.1, 27.4, 22.6, 15.8, 14.1; IR (neat) 1958, 1709, 1459,
1221 cmK1; MS (m/z) 210 (MC, 3.75), 111 (100); HRMS
calcd for C13H22O2(MC) 210.16198; Found 210.16407.
The reaction of 1a (86 mg, 5.0 mmol), PhI (85 ml,
7.5 mmol), K2CO3 (273 mg, 2.0 mmol), AgNO3 (8 mg,
0.05 mmol), and Pd(PPh3)4 (30 mg, 0.025 mmol) in 3 mL of
CH3CN at 70 8C for 33 h produced 30 mg (24%) of 2a and
9 mg (11%) of 3a via separation with chromatography on
silica gel (petroleum ether/etherZ5/1).
3.1.7. 2-Methyl-3-(tert-butyl)penta-3,4-dienoic acid (1g).
The reaction of the corresponding allenoic acid ester
(538 mg, 2.7 mmol) with LiOH (145 mg, 5.5 mmol)
afforded 143 mg (31%) of 1g under conditions A: solid;
3.1.12. 3-Methyl-4-(n-butyl)-5-benzyl-2(5H)-furanone
(2a). Liquid; H NMR (300 MHz, CDCl3) d 7.32–7.17 (m,
1
mp 44 8C (ether); H NMR (300 MHz, CDCl3) d 4.86 (s,
2H), 3.06 (q, JZ6.9 Hz, 1H), 1.29 (d, JZ7.2 Hz, 3H), 1.08
1
5H), 5.09–4.97 (m, 1H), 3.15 (dd, JZ3.6, 14.1 Hz, 1H),
2.75 (dd, JZ7.5, 14.1 Hz, 1H), 2.53–2.40 (m, 1H), 2.30–
2.22 (m, 1H), 1.74 (s, 3H), 1.52–1.22 (m, 4H), 0.92 (t, JZ
7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) d 174.3, 162.5,
135.6, 129.2, 128.3, 126.8, 123.9, 82.1, 38.6, 29.7, 26.4,
22.5, 13.6, 8.5; IR (neat) 1754, 1675, 1455 cmK1; MS (m/z)
244 (MC, 0.62), 84 (100); HRMS calcd for C16H20O2(MC)
244.14633; Found 244.14523.
(s, 9H); 13C NMR (75.4 MHz, CDCl3) d 205.3, 181.6, 112.8,
79.1, 37.6, 33.6, 29.0, 18.4; IR (neat) 1950, 1707, 1233 cmK1
;
MS (m/z) 169 (MCC1, 93.02), 168 (MC, 20.46), 153 (100).
Anal. Calcd for C10H16O2: C, 71.39; H, 9.59. Found C,
71.46; H, 9.31.
3.1.8. 2-Methyl-3-allylpenta-3,4-dienoic acid (1h). The
reaction of the corresponding allenoic acid ester (2745 mg,
15.2 mmol) with LiOH (719 mg, 30 mmol) afforded 553 mg
(24%) of 1h under conditions A: liquid; 1H NMR
(300 MHz, CDCl3) d 10.57 (br s, 1H), 5.88–5.71 (m, 1H),
5.12–5.02 (m, 2H), 4.88–4.83 (m, 2H), 3.09–2.98 (m, 1H),
2.90–2.73 (m, 2H), 1.28 (d, JZ6.6 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) d 206.3, 180.9, 135.1, 116.5, 101.6,
3.2. General procedure for PdCl2(PPh3)2-catalyzed
cyclization reaction of b-alleneoic acids 1
Under N2 atmosphere a solution of 1 (0.5 mmol),
PdCl2(PPh3)2 (18 mg, 5 mol%), anhydrous CuCl2
(270 mg, 2 mmol), and K2CO3 (276 mg, 2 mmol) was
stirred in 3 mL of anhydrous DMF at 70 8C for 12 h. The
reaction mixture was diluted with ether (50 mL), washed
with brine, and dried over anhydrous Na2SO4. After
evaporation, the residue was submitted to column chroma-
tography on silica gel (petroleum ether/etherZ10/1) to
produce 3.
78.3, 41.2, 35.7, 15.7; IR (neat) 1958, 1712, 1641 cmK1
;
MS (m/z) 153 (MCC1, 38.90), 152 (MC, 14.13), 107 (100);
HRMS calcd for C9H12O2(MC) 152.08373; Found
152.08326.
3.1.9. 2-Methyl-3-benzylpenta-3,4-dienoic acid (1i). The
reaction of the corresponding allenoic acid ester (1.798 g,
7.8 mmol) with LiOH (402 mg, 16.8 mmol) afforded
1
1.179 g (75%) of 1i under conditions A: liquid; H NMR
3.2.1. 3-Methyl-4-(n-butyl)-5-methylene-2(5H)-furanone
(3a). The reaction of 1a (84 mg, 0.5 mmol), CuCl2 (266 mg,
2.0 mmol), K2CO3 (277 mg, 2.0 mmol), and Pd(PPh3)4
(5 mol%) in 3 mL of DMF at 70 8C for 12 h produced 73 mg
(88%) of 3a: liquid; 1H NMR (300 MHz, CDCl3) d 5.06 (d,
JZ2.7 Hz, 1H), 4.81 (d, JZ2.7 Hz, 1H), 2.44 (t, JZ7.5 Hz,
2H), 1.91 (s, 3H), 1.56–1.46 (m, 2H), 1.41–1.30 (m, 2H),
0.93 (t, JZ7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) d
170.7, 155.2, 150.9, 126.0, 92.5, 31.1, 24.5, 22.6, 13.8, 8.8;
IR (neat) 1773, 1648, 1459, 1287 cmK1; MS (m/z) 167
(MCC1, 10.40), 166 (MC, 10.40), 124 (100); HRMS calcd
for C9H11O2(MCKCH3) 151.0759; Found 151.0785.
(300 MHz, CDCl3) d 11.78 (br s, 1H), 7.38–7.15 (m, 5H),
4.87 (br s, 2H), 3.52 (d, JZ15.0 Hz, 1H), 3.41 (d, JZ
15.0 Hz, 1H), 3.03–2.92 (m, 1H), 1.28 (d, JZ7.2 Hz, 3H);
13C NMR (75.4 MHz, CDCl3) d 206.9, 181.1, 138.7, 129.1,
128.2, 126.4, 102.9, 78.1, 40.6, 38.2, 15.9; IR (neat) 1958,
1705, 1455, 1226 cmK1; MS (m/z) 202 (MC, 2.59), 129
(100); HRMS calcd for C13H14O2(MC) 202.09938; Found
202.09801.
3.1.10. 2-(n-Propyl)penta-3,4-dienoic acid (1j). The
reaction of the corresponding allenoic acid ester

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S. Ma, F. Yu / Tetrahedron 61 (2005) 9896–9901
3.2.2. 5-Methylene-4-(n-butyl)-2(5H)-furanone (3b). The
reaction of 1b (74 mg, 0.5 mmol), CuCl2 (267 mg,
2.0 mmol), K2CO3 (276 mg, 2.0 mmol), and Pd(PPh3)4
(5 mol%) in 3 mL of DMF at 70 8C for 12 h produced 57 mg
1466, 1287 cmK1; MS (m/z) 208 (MC, 6.83), 124 (100);
HRMS calcd for C13H20O2(MC) 208.14633; Found
208.14484.
1
(78%) of 3b: liquid; H NMR (300 MHz, CDCl3) d 5.95–
3.2.7. 3-Methyl-4-(tert-butyl)-5-methylene-2(5H)-fura-
none (3g). The reaction of 1g (77 mg, 0.46 mmol), CuCl2
(250 mg, 1.85 mmol), K2CO3 (262 mg, 1.90 mmol), and
Pd(PPh3)4 (5 mol%) in 3 mL of DMF at 70 8C for 12 h
5.92 (m, 1H), 5.13–5.10 (m, 1H), 4.91–4.89 (m, 1H), 2.45
(dt, JZ1.2, 7.5 Hz, 2H), 1.66–1.52 (m, 2H), 1.46–1.31 (m,
2H), 0.92 (t, JZ7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d 169.2, 159.3, 155.9, 116.6, 94.1, 29.9, 25.7, 22.2, 13.6; IR
(neat) 1763, 1651, 1467, 1261 cmK1; MS (m/z) 153 (MCC
1, 21.12), 152 (MC, 12.22), 110 (100); HRMS calcd for
C9H12O2(MC) 152.08373; Found 152.08498.
1
produced 53 mg (71%) of 3g: liquid; H NMR (300 MHz,
CDCl3) d 5.21 (d, JZ2.1 Hz, 1H), 5.09 (d, JZ2.1 Hz, 1H),
2.08 (s, 3H), 1.39 (s, 9H); 13C NMR (75.4 MHz, CDCl3) d
170.9, 155.5, 154.0, 125.4, 97.0, 34.7, 30.9, 11.3; IR (neat)
1770, 1639, 1464, 1274 cmK1; MS (m/z) 166 (MC, 59.06),
123 (100); HRMS calcd for C10H14O2Na(MNa)C189.0886;
Found 189.0894.
3.2.3. 3-Ethyl-4-(n-butyl)-5-methylene-2(5H)-furanone
(3c). The reaction of 1c (92 mg, 0.5 mmol), CuCl2
(282 mg, 2.0 mmol), K2CO3 (286 mg, 2.0 mmol), and
Pd(PPh3)4 (5 mol%) in 3 mL of DMF at 70 8C for 12 h
1
produced 74 mg (81%) of 3c: liquid; H NMR (300 MHz,
3.2.8. 3-Methyl-4-allyl-5-methylene-2(5H)-furanone
(3h). The reaction of 1h (77 mg, 0.5 mmol), CuCl2
(269 mg, 2.0 mmol), K2CO3 (280 mg, 2.0 mmol), and
Pd(PPh3)4 (5 mol%) in 3 mL of DMF at 70 8C for 12 h
CDCl3) d 5.04 (d, JZ2.7 Hz, 1H), 4.79 (d, JZ2.4 Hz, 1H),
2.42 (t, JZ7.5 Hz, 2H), 2.32 (q, JZ7.5 Hz, 2H), 1.57–1.46
(m, 2H), 1.44–1.30 (m, 2H), 1.10 (t, JZ7.5 Hz, 3H), 0.91 (t,
JZ6.9 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) d 170.1,
155.1, 150.4, 131.3, 92.5, 31.7, 24.3, 22.6, 17.2, 13.7, 12.7;
IR (neat) 1772, 1648, 1463, 1296, 1256 cmK1; MS (m/z)
181 (MCC1, 100); HRMS calcd for C11H16O2Na(MNa)C
203.1042; Found 203.1041.
1
produced 50 mg (66%) of 3h: liquid; H NMR (300 MHz,
CDCl3) d 5.86–5.72 (m, 1H), 5.15–5.08 (m, 3H), 4.84 (d,
JZ3.0 Hz, 1H), 3.21 (d, JZ6.0 Hz, 2H), 1.92 (s, 3H); 13C
NMR (75.4 MHz, CDCl3) d 170.4, 154.8, 147.7, 132.4,
127.1, 117.5, 93.1, 28.9, 8.8; IR (neat) 1782, 1650, 1441,
1287 cmK1; MS (m/z) 150 (MC, 36.37), 79 (100); HRMS
calcd for C9H10O2Na(MNaC) 173.0573; Found 173.0580.
3.2.4. 3-(n-Propyl)-4-(n-butyl)-5-methylene-2(5H)-fura-
none (3d). The reaction of 1d (98 mg, 0.5 mmol), CuCl2
(272 mg, 2.0 mmol), K2CO3 (278 mg, 2.0 mmol), and
Pd(PPh3)4 (5 mol%) in 3 mL of DMF at 70 8C for 12 h
3.2.9. 3-Methyl-4-benzyl-5-methylene-2(5H)-furanone
(3i). The reaction of 1i (101 mg, 0.5 mmol), CuCl2
(264 mg, 2.0 mmol), K2CO3 (282 mg, 2.0 mmol), and
Pd(PPh3)4 (5 mol%) in 3 mL of DMF at 70 8C for 12 h
1
produced 81 mg (84%) of 3d: liquid; H NMR (300 MHz,
CDCl3) d 5.03 (d, JZ2.4 Hz, 1H), 4.79 (d, JZ2.7 Hz, 1H),
2.41 (t, JZ7.5 Hz, 2H), 2.26 (t, JZ7.5 Hz, 2H), 1.58–1.46
(m, 4H), 1.40–1.30 (m, 2H), 0.91 (t, JZ7.5 Hz, 6H); 13C
NMR (75.4 MHz, CDCl3) d 170.2, 155.0, 150.9, 129.9,
92.5, 31.6, 25.7, 24.4, 22.7, 21.4, 13.9, 13.7; IR (neat) 1718,
1648, 1465, 1284 cmK1; MS (m/z) 195 (MCC1, 32.35),
194 (MC, 15.12), 123 (100); HRMS calcd for
C12H18O2(MC) 194.13068; Found 194.13200.
1
produced 90 mg (89%) of 3i: liquid; H NMR (300 MHz,
CDCl3) d 7.32–7.13 (m, 5H), 5.08 (d, JZ2.7 Hz, 1H), 4.81
(d, JZ2.7 Hz, 1H), 3.82 (s, 2H), 1.94 (s, 3H); 13C NMR
(75.4 MHz, CDCl3) d 170.3, 154.9, 148.4, 136.5, 128.8,
128.1, 127.4, 126.9, 93.7, 30.6, 9.0; IR (neat) 1770, 1648,
1496, 1454, 1287 cmK1; MS (m/z) 200 (MC, 41.10), 84
(100); HRMS calcd for C13H12O2Na(MNaC) 223.0729;
Found 223.0737.
3.2.5. 3,4-Dimethyl-5-methylene-2(5H)-furanone (3e).
The reaction of 1e (63 mg, 0.5 mmol), CuCl2 (270 mg,
2.0 mmol), K2CO3 (281 mg, 2.0 mmol), and Pd(PPh3)4
(5 mol%) in 3 mL of DMF at 70 8C for 12 h produced 40 mg
(64%) of 3e: solid; mp 80–81 8C (ether); 1H NMR
(300 MHz, CDCl3) d 5.03 (d, JZ2.7 Hz, 1H), 4.79 (d, JZ
2.7 Hz, 1H), 2.04 (s, 3H), 1.89 (s, 3H); 13C NMR
(75.4 MHz, CDCl3) d 170.6, 155.8, 146.6, 126.2, 92.2,
9.9, 8.7; IR (neat) 1763, 1651, 1439, 1285, 1260 cmK1; MS
(m/z) 124 (MC, 100); HRMS calcd for C7H8O2(MC)
124.05243; Found 124.05262.
3.2.10. 3-(n-Propyl)-5-methylene-2(5H)-furanone (3j).
The reaction of 1j (70 mg, 0.5 mmol), CuCl2 (270 mg,
2.0 mmol), K2CO3 (286 mg, 2.0 mmol), and Pd(PPh3)4
(5 mol%) in 3 mL of DMF at 70 8C for 12 h produced 36 mg
(51%) of 3j: liquid; 1H NMR (300 MHz, CDCl3) d 7.02 (s,
1H), 5.08 (dd, JZ1.2, 2.4 Hz, 1H), 4.76 (d, JZ2.4 Hz, 1H),
2.38–2.28 (m, 2H), 1.66–1.54 (m, 2H), 0.95 (t, JZ6.9 Hz,
3H); 13C NMR (75.4 MHz, CDCl3) d 170.5, 153.9, 136.4,
128.5, 96.5, 27.1, 20.7, 13.6; IR (neat) 1767, 1465 cmK1
;
MS (m/z) 138 (MC, 24.48), 84 (100); HRMS calcd for
3.2.6. 3-Methyl-4-(n-heptyl)-5-methylene-2(5H)-fura-
none (3f). The reaction of 1f (105 mg, 0.5 mmol), CuCl2
(277 mg, 2.0 mmol), K2CO3 (282 mg, 2.0 mmol), and
Pd(PPh3)4 (5 mol%) in 3 mL of DMF at 70 8C for 12 h
C8H10O2Na(MNa)C 161.0573; Found 161.0581.
3.2.11. 5-Methylene-2(5H)-furanone (3k).12 The reaction
of 1k (98 mg, 1.0 mmol), CuCl2 (545 mg, 4.0 mmol),
K2CO3 (550 mg, 4.0 mmol), and Pd(PPh3)4 (5 mol%) in
3 mL of DMF at 70 8C for 12 h produced 3k (31%)
(determined by NMR using p-methoxyiodobenzene as the
internal standard).
1
produced 90 mg (84%) of 3f: liquid; H NMR (300 MHz,
CDCl3) d 5.03 (d, JZ2.1 Hz, 1H), 4.78 (d, JZ2.7 Hz, 1H),
2.40 (t, JZ7.5 Hz, 2H), 1.88 (s, 3H), 1.53–1.46 (m, 2H),
1.30–1.21 (m, 8H), 0.84 (t, JZ6.9 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) d 170.7, 155.2, 151.0, 126.0, 92.5, 31.6,
29.4, 29.0, 28.9, 24.8, 22.5, 14.0, 8.8; IR (neat) 1774, 1648,

S. Ma, F. Yu / Tetrahedron 61 (2005) 9896–9901
9901
6. (a) Dean, F. M. Naturally Occurring Oxygen Ring Com-
pounds; Butterworth: London, 1963. (b) Lu, X.; Huang, X.;
Ma, S. Tetrahedron Lett. 1993, 34, 5963. (c) Kotora, M.;
Negishi, E. Synthesis 1997, 121.
References and notes
1. For some of the most typical recent reports, see: (a) Kang, S.;
Ha, Y.; Ko, B.; Lim, Y.; Jung, J. Angew. Chem., Int. Ed. 2002,
41, 343. (b) Lee, K.; Seomoon, D.; Lee, P. Angew. Chem., Int.
Ed. 2002, 41, 3901. (c) Brummond, K.; Chen, H.; Sill, P.; You,
L. J. Am. Chem. Soc. 2002, 124, 15186. (d) Franzen, J.;
Backvall, J. J. Am. Chem. Soc. 2003, 125, 6056. (e) Trost, B.;
Jakel, C.; Plietrker, B. J. Am. Chem. Soc. 2003, 125, 4438. (f)
Ohno, H.; Miyamura, K.; Takeoka, Y.; Tanaka, T. Angew.
Chem., Int. Ed. 2003, 42, 2647. (g) Yang, F.; Shanmuga-
sundaram, M.; Chuang, S.; Ku, P.; Wu, M.; Cheng, C. J. Am.
Chem. Soc. 2003, 125, 12576.
7. Keiji, I.; Wataru, T.; Hisashi, T.; Katsumi, K. Agric. Biol.
Chem. 1987, 51, 1045.
8. (a) Stromgarad, K.; Nakanishi, K. Curr. Org. Chem. 1999, 3,
577. (b) Roupioz, Y.; Lhomme, J.; Kotero, M. J. Am. Chem.
Soc. 2002, 124, 9129.
9. (a) Franciseo, S. S.; Serafin, V.; Bernardo, H. Tetrahedron:
Asymmetry 1996, 7, 3209. (b) Rao, Y. S. Chem. Rev. 1976, 76,
625. (c) Kido, F.; Noda, Y.; Yoshikoshi, A. J. Am. Chem. Soc.
1982, 104, 5509. (d) Nardo, C. D.; Jeroncic, L. O.; Lederkremer,
R. M.; Varela, O. J. Org. Chem. 1996, 61, 4007. (e) Harrowven,
D. C.; Wilden, J. D.; Tyte, M. J.; Hursthouse, M. B.; Coles, S.
J. Tetrahedron Lett. 2001, 42, 1193.
2. Modern Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.;
Wiley-VCH: Weinheim, 2004.
3. For accounts, see: (a) Ma, S. Acc. Chem. Res. 2003, 36, 701.
(b) Ma, S.; Li, L. Synlett 2001, 1206.
10. (a) Lai, G.; Anderson, W. K. Synth. Commun. 1995, 25, 4087.
(b) Ralph, L.; Carsten, T.; Arne, L.; Frank, G.; Peter, Z.
J. Mater. Chem. 1997, 7, 1713. (c) Brown, R. F. C.; Coulston,
K. J.; Easteood, F. W.; Hill, M. P. Aust. J. Chem. 1988, 41,
215.
4. For some of our most recent reports, see: (a) Ma, S.; Yu, Z.
Angew. Chem., Int. Ed. 2002, 41, 1775. (b) Ma, S.; Yu, F.;
Gao, W. J. Org. Chem. 2003, 68, 5943. (c) Ma, S.; Wu, B.; Shi,
Z. J. Org. Chem. 2004, 69, 1429. (d) Ma, S.; He, Q. Angew.
Chem., Int. Ed. 2004, 43, 988.
11. Crowlev, K. J. J. Am. Chem. Soc. 1963, 85, 1210.
12. Okabe, M.; Sun, R.; Tam, S.; Todaro, T. L.; Coffen, D. L.
J. Org. Chem. 1988, 53, 4780.
5. (a) Ma, S.; Shi, Z. J. Org. Chem. 1998, 63, 6387. (b) Ma, S.;
Duan, D.; Shi, Z. Org. Lett. 2000, 2, 1419.