S. Ma et al.
action was complete (monitored by TLC, petroleum ether/ethyl acetate
10:1), rotary evaporation and flash chromatography on silica gel (petro-
leum ether/ethyl ether 20:1) afforded 2a (32 mg, 68%) as a liquid.
1H NMR (300 MHz, CDCl3): d=5.57 (s, 2H), 4.20 (q, J=6.9 Hz, 2H),
2.92 (s, 4H), 2.17 (s, 3H), 1.25 ppm (t, J=6.9 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3): d=202.6, 172.8, 127.6, 65.3, 61.5, 39.1, 25.8,
13.9 ppm; IR (neat): n˜ =3062, 2983, 2928, 2856, 1716, 1626, 1446, 1358,
1237, 1157 cmÀ1; MS (ESI): m/z: 183 [M+H+]; HRMS (EI): m/z calcd
for C10H14O3: 182.0943 [M+]; found: 182.0935.
the 3-type allylated products 3a–h and the catalytically
active PdII. In the presence of relatively sterically hindered
allylic halides 7a–e, the related insertion is obviously slow.
However, in the presence of Pd0, the oxidative addition of
differently substituted allylic halides with Pd0 would afford
the thermodynamically more stable divalent p-allyl palladi-
um complex syn-13.[20] When this complex coordinated with
1, syn-14 was formed highly regioselectively due to the same
reason, which would also trigger the oxymetallation to pro-
duce syn-15.[12b] Subsequent highly regioselective reductive
elimination would form the carbon–carbon bond at the less-
substituted terminus of the allylic moiety to yield the prod-
ucts 3cb–if and regenerate Pd0. This also explains the regio-
and stereoselectivity demonstrated in Table 7.
Method B: Synthesis of 2-methyl-3-(ethoxycarbonyl)-5-(penta-1,4-dien-2-
yl)-4,5-dihydrofuran (3a): A mixture of 1a (28 mg, 0.15 mmol), [PdCl2-
A
mide (27 mg, 0.22 mmol) in MeCN (2 mL) was stirred at room tempera-
ture under Ar in a flame-dried Schlenk tube for 4 h. After the reaction
was complete (monitored by TLC, petroleum ether/ethyl acetate 10:1),
rotary evaporation and flash chromatography on silica gel (petroleum
ether/ethyl ether 20:1) afforded 3a (25 mg, 73%) as a liquid. 1H NMR
(300 MHz, CDCl3): d=5.90–5.75 (m, 1H), 5.20–4.95 (m, 4H), 4.91 (s,
1H), 4.15 (q, J=7.8 Hz, 2H), 3.10–2.95 (m, 1H), 2.90–2.75 (m, 2H),
2.75–2.65 (m, 1H), 2.21 (s, 3H), 1.27 ppm (t, J=6.9 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3): d=167.7, 166.0, 146.2, 135.2, 116.9, 111.5, 101.7, 83.8,
59.4, 35.6, 34.9, 14.4, 14.0 ppm; IR (neat): n˜ =3080, 2980, 2928, 2873,
1700, 1650, 1433, 1384, 1342, 1321, 1259, 1225, 1143, 1127, 1084 cmÀ1; MS
(EI): m/z (%): 223 (0.40) [M+H+], 222 (0.08) [M+], 194 (2.91)
[MÀEt+H+], 43 (100); HRMS (ESI): m/z calcd for C13H18O3: 222.1256
[M+H+]; found: 222.1265.
Conclusion
We have demonstrated two different types of cyclization re-
actions of 2-(2’,3’-allenyl)acetylacetates that enable highly
selective syntheses of substituted cyclopentenes with a qua-
ternary stereocenter[11] and 4,5-dihydrofuran derivatives by
Method C: Synthesis of 2-ethyl-3-(methoxycarbonyl)-5-(4-phenylpenta-
applying [AuCl
C-attack-5-endo cyclization reactions or by using catalytic
[Pd(dba)2] in O-attack-5-exo cyclization processes. The dif-
A
N
1,4-dien-2-yl)-4,5-dihydrofuran (3cb):
A
mixture of 1c (45 mg,
0.25 mmol), [Pd(dba)2] (7 mg, 0.0122 mmol), K2CO3 (42 mg, 0.30 mmol),
AHCTREUNG
R
and 7b (99 mg, 0.50 mmol) in MeCN (2 mL) was stirred in a flame dried
Schlenk tube at room temperature for 13 h. After the reaction was com-
plete (monitored by TLC, petroleum ether/ethyl acetate 10:1), rotary
evaporation and flash chromatography on silica gel (petroleum ether/di-
ethyl ether 50:1) afforded 3cb (43 mg, 59%) as a liquid. 1H NMR
(300 MHz, CDCl3): d=7.48–7.40 (m, 2H), 7.36–7.24 (m, 3H), 5.52 (s,
1H), 5.17 (s, 1H), 5.11 (s, 1H), 5.06 (dd, J=10.5, 8.7 Hz, 1H), 4.93 (s,
1H), 3.70 (s, 3H), 3.32 (d, J=16.5 Hz, 1H), 3.23 (d, J=16.5 Hz, 1H),
3.05 (dd, J=14.4, 11.7 Hz, 1H), 2.85–2.60 (m, 3H), 1.15 ppm (t, J=
7.2 Hz, 3H); 13C NMR (CDCl3, 75.4 MHz): d=172.7, 166.3, 145.4, 144.3,
140.3, 128.3, 127.5, 126.0, 115.4, 112.7, 100.3, 83.6, 50.8, 37.2, 34.8, 21.2,
11.2 ppm; IR (neat): n˜ =3083, 2975, 2947, 1704, 1642, 1435, 1247, 1136,
1096 cmÀ1; MS (EI): m/z (%): 298 (7.00) [M+], 43 (100); HRMS (EI):
m/z calcd for C19H22O3: 298.1569 [M+]; found: 298.1577.
ferent cyclization modes are probably due to the steric and
electronic effects of the substrates and catalysts. In the [Pd-
A
selectivity for the unsymmetric allylic halides is very high,
affording products with the allylic substituent at the termi-
nal position of the (E)-carbon–carbon double bond in the
products. In view of the easy availability of the starting ma-
terials and the catalysts, these types of transformations may
be useful in organic synthesis. Further studies, such as the
asymmetric variants of these cyclization reactions are being
conducted in our laboratory.
Experimental Section
Acknowledgements
General: 1H (300 MHz) and 13C (75.4 MHz) spectra were recorded in
CDCl3 with a Varian Mercury 300 MHz spectrometer. Chemical shifts
are reported in ppm with reference to the signals of the residual CHCl3
in CDCl3 (1H NMR (d=7.26 ppm) and 13C NMR (d=77.0 ppm)). Mass
spectra of the products were obtained by using a HP 5989A instrument.
IR spectra were obtained with a Perkin–Elmer 983 instrument. Elemen-
tal analyses were carried out by using a Vario EL III system and high-res-
olution (HR) MS analyses were performed by using a Finnigan MAT
8430 instrument. Thin-layer chromatography (TLC) was carried out by
using plates coated with 0.15–0.20 mm thick silica gel (Huanghai, Yantai,
China), and column chromatography was performed by using silica gel H
(Huanghai, Yantai, China). DCM and MeCN were distilled over CaH2
before use. All of the reactions were carried out under a dry argon at-
mosphere. The starting materials 2-(2’,3’-allenyl)acetylacetates were syn-
thesized by SN2 substitution reactions of acetylacetates with 2,3-allenyl
bromide.[21]
Financial support from the National Natural Science Foundation of
China (20423001, and 20732005) and the State Key Basic Research &
Development Program (2006CB06105) is greatly appreciated. We thank
Mr. Y. Liu in our research group for reproducing the reactions of 2b, 3b,
2e, 3e, 2g, and 3g in Table 2.
[1] For reviews on the chemistry of allenes, see: a) R. Zimmer, C. U.
ladium Chemistry for Organic Synthesis, (Ed.: E. Negishi), Wiley,
New York, 2002, 1491–1523; e) R. Bates, V. Satcharoen, Chem. Soc.
Topics in Organometallic Chemistry (Ed.: J. Tsuji), Springer, Heidel-
berg, 2005, 183–210; l) S. Ma, Aldrichimica Acta 2007, 40, 91.
Method A: Synthesis of 4-acetyl-4-(ethoxycarbonyl)cyclopentene (2a):[22]
A mixture of 1a (47 mg, 0.26 mmol), [AuCl(PPh3)] (6 mg, 0.0121 mmol),
A
and AgSbF6 (3 mg, 0.0117 mmol) in CH2Cl2 (2 mL) was stirred under Ar
in a flame-dried Schlenk tube at room temperature for 1 h. After the re-
8576
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Chem. Eur. J. 2008, 14, 8572 – 8578