Palladium-catalyzed allylic acyloxylation of terminal alkenes in the presence of a base

Article abstract of DOI:10.1021/jo902587u

"Chemical Equation Presentation" The efficiency and the selectivity of the Pd-catalyzed oxidation, in carboxylic acids, of terminal alkenes are strongly improved in the presence of a base. The methodology is particularly well adapted for the oxidation of homoallylic alcohols, for which the resulting acyloxylated products are obtained selectively as E-isomers in fair to good yields. 2010 American Chemical Society.

Full text of DOI:10.1021/jo902587u

pubs.acs.org/joc
products were selectively obtained depending on the reaction
Palladium-Catalyzed Allylic Acyloxylation of
Terminal Alkenes in the Presence of a Base
conditions.3 This methodology has been applied in the total
synthesis of 6-deoxyerythronolide B, through a C-H oxida-
tive macrolactonization, increasing the overall efficiency of
the synthesis and providing stereochemical control at a key
lactone position.4 Kaneda and co-workers described a re-
gioselective process leading to linear allylic acetates using
N,N-dimethylacetamide (DMA) as solvent and molecular
oxygen as the sole oxidant, high pressures of O2 (6 atm) being
required, however.5 Bipyrimidines as ligands were also
found to improve the allylic acetoxylation of olefins.6 The
proposed mechanism of such transformations generally in-
volves π-allyl-Pd(II) intermediates.3f,6,7 Surprisingly, the
influence of additives, such as acetate salts, has not received
so much attention for the oxidation of terminal olefins.8
Such compounds could act as bases to facilitate the forma-
tion of π-allyl complexes,9 and as nucleophiles on such
complexes. Herein, we disclose our results on the use of
bases for the Pd-catalyzed oxidation of terminal alkenes.
The oxidation of allylbenzene (1a) in the presence of
Pd(OAc)2 (0.05 equiv) and BQ (2.0 equiv) in AcOH at 40
°C for 24 h led to a high conversion, but as observed before,3g
to a low yield of cinnamyl acetate (2a) (Table 1, entry 1). The
use of DMSO or DMA as the cosolvent improved the
selectivity of the reaction, but dropped the conversion
(entries 2 and 3). Almost full conversion was observed with
CH3CN as cosolvent, leading to 2a in 54% yield (entry 4).
CH2Cl2 was not an efficient cosolvent (entry 5). In AcOH
containing NaOAc as additive, 2a can be produced in high
yields but the results were inconsistent (entry 6). In contrast,
reproducible results were obtained in EtCO2H containing
Emilie Thiery, Chahinez Aouf, Julien Belloy,
Dominique Harakat, Jean Le Bras,* and Jacques Muzart
ꢀ
Institut de Chimie Moleculaire de Reims, UMR 6229 CNRS-
Universite de Reims Champagne-Ardenne, UFR des Sciences
ꢀ
exactes et naturelles, BP 1039, 51687 REIMS Cedex 2,
France
jean.lebras@univ-reims.fr
Received December 7, 2009
The efficiency and the selectivity of the Pd-catalyzed
oxidation, in carboxylic acids, of terminal alkenes are
strongly improved in the presence of a base. The metho-
dology is particularly well adapted for the oxidation of
homoallylic alcohols, for which the resulting acyloxylated
products are obtained selectively as E-isomers in fair to
good yields.
LiOH H2O as a base,10 affording 3a in up to 75% yield, with
3
Palladium(II)-catalyzed allylic oxidation of internal or
cyclic olefins in acetic acid is an efficient process for the
synthesis of allylic acetates.1 On the other hand, terminal
olefins generally yield mixtures of allylic acetates, vinyl
acetates, and ketones.2 Recently, two important progresses
have been achieved toward more selective transformations.
White et al. demonstrated that the association of Pd(OAc)2,
benzoquinone (BQ), and DMSO or a bis(sulfoxide) ligand
promoted the regio- and stereoselective allylic acetoxylation
of terminal alkenes. In addition, either linear or branched
high regioselectivity and good stereoselectivity (entries 7 and
8). The use of MnO2, MnO2/BQ, O2/Cu(OAc)2, or O2 as
oxidizing agents led to lower conversions and yields, but in
some cases to higher L/B and E/Z ratios (entries 9-12).
The scope of the process was then examined, under the
experimental conditions of entry 8 of Table 1 (namely after-
ward, method A). An electron donating group on the arene
decreases the regioselectivity of the oxidation (Table 2, 3b
and 3c), while an electron withdrawing group did not affect it
(3d). The methodology was found to be particularly well
adapted to homoallylic alcohols and their derivatives. A
protected homoallylic alcohol, such as 1-phenylbut-3-enyl
acetate (1e), was regio- and stereoselectively oxidized into
(1) (a) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S.
Chem. Rev. 2007, 107, 5318. (b) Frison, J.-C.; Legros, J.; Bolm, C. Copper- and
Palladium-Catalyzed Allylic Acyloxylations; Wiley-VCH Verlag GmbH & Co:
€
Weinheim, Germany, 2005; Vol. 2. (c) Grennberg, H.; Backvall, J.-E. Allylic
oxidations: palladium-catalyzed allylic oxidation of olefins; Wiley-VCH Verlag
GmbH & Co: Weinheim, Germany, 2004; Vol. 2. (d) Muzart, J. Bull. Soc. Chim.
Fr. 1986, 65.
(2) (a) Tsuji, J. Palladium Reagents and Catalysts: New Perspectives for the
21st Century; Wiley and Sons: New York, 2004. (b) Åkermark, B.; Larsson,
E. M.; Oslob, J. D. J. Org. Chem. 1994, 59, 5729. (c) Kitching, W.; Rappoport, Z.;
Winstein, S.; Yong, W. G. J. Am. Chem. Soc. 1966, 88, 2054.
(3) (a) Covell, D. J.; White, M. C. Angew. Chem., Int. Ed. 2008, 47, 6448.
(b) Fraunhoffer, K. J.; Prabagaran, N.; Sirois, L. E.; White, M. C. J. Am.
Chem. Soc. 2006, 128, 9032. (c) Delcamp, J. H.; White, M. C. J. Am. Chem.
Soc. 2006, 128, 15076. (d) Covell, D. J.; Vermeulen, N. A.; Labenz, N. A.;
White, M. C. Angew. Chem., Int. Ed. 2006, 45, 8217. (e) Fraunhoffer, K. J.;
Bachovchin, D. A.; White, M. C. Org. Lett. 2005, 7, 223. (f) Chen, M. S.;
Prabagaran, N.; Labenz, N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127,
6970. (g) Chen, M. S.; White, M. C. J. Am. Chem. Soc. 2004, 126, 1346.
(4) Stang, E. M.; White, M. C. Nat. Chem. 2009, 1, 547.
(5) Mitsudome, T.; Umetani, T.; Nosaka, N.; Mori, K.; Mizugaki, T.;
Ebitani, K.; Kaneda, K. Angew. Chem., Int. Ed. 2006, 45, 481.
(6) Lin, B.-L.; Labinger, J. A.; Bercaw, J. E. Can. J. Chem. 2009, 87, 264.
€
(7) Grennberg, H.; Backvall, J.-E. Chem.;Eur. J. 1998, 4, 1083.
(8) A noncoordinating base was recently used as additive, but its exact
role is unclear, see ref 3d. AcO- anions accelerate the reaction of Pd(OAc)2
with alkenes in apolþar solvents, due to better solubility of Pd(II) species in the
presence of (R4N) AcO-, see: Kozitsyna, N. Y.; Bukharkina, A. A.;
Martens, M. V.; Vargaftik, M. N.; Moiseev, I. I. J. Organomet. Chem.
2001, 636, 69.
(9) Trost, B. M; Strege, P. E.; Weber, L.; Fullerton, T. J.; Dietsche, T. J.
J. Am. Chem. Soc. 1978, 100, 3407.
(10) NaOH and LiOH H2O afforded similar results, but the latter which
3
is less hygroscopic was used for easier handling.
DOI: 10.1021/jo902587u
r
Published on Web 02/09/2010
J. Org. Chem. 2010, 75, 1771–1774 1771
2010 American Chemical Society

Thiery et al.
JOCNote
TABLE 1. Optimization of the Oxidation of Allylbenzene (1a)a
entry
RCO2H/cosolvent
Pd(OAc)2, %
Ox (equiv)
BQ (2.0)
BQ (2.0)
BQ (2.0)
BQ (2.0)
BQ (2.0)
BQ (2.0)
BQ (2.0)
BQ (2.0)
base
conv.,b %
yield,c %
(12)
(25)
(18)
(54)
(<5)
60-76 (70-86)
(65)
75 (86)
57 (67)
60 (71)
61 (71)
15 (24)
L/B, E/Zd
1
2
3
4
5
6
7
8
9
AcOH
5
5
5
5
5
70
38
29
97
50
80-100
78
100
80
AcOH/DMSO, 1:1
AcOH/DMA, 1:1
AcOH/CH3CN, 1:1
AcOH/CH2Cl2, 1:1
AcOH
EtCO2H
EtCO2H
EtCO2H
EtCO2H
5
5
NaOAc
LiOH H2O
99.9, 21
3
10
10
10
10
10
LiOH H2O
LiOH H2O
99.9, 21
99.9, 25
99.9, 14
99.9, 50
99.9, 14
3
MnO2 (2.0)
BQ (0.05), MnO2 (2.0)
Cu(OAc)2 (0.5), O2
3
10
11
12
LiOH H2O
LiOH H2O
92
85
45
3
e
EtCO2H
EtCO2H
3
e
O2
LiOH H2O
3
a1a (1.0 mmol), Pd(OAc)2 (0.05 or 0.1 mmol), oxidant (0.5 or 2.0 mmol), base (0 or 2.0 mmol), RCO2H/cosolvent (2.0 mL), 40 °C, 24 h. bDetermined
by GC. cGC yield in parentheses. dDetermined by GC on isolated products. eGas bag.
E-3e in medium yield. Interestingly, unprotected alcohols
1f-o have been directly oxidized into corresponding linear
(E)-4-hydroxy-esters 3f-o. No Z, or branched isomers were
detected by GC analysis. The allylic alcohol group is pre-
served, its oxidation or isomerization into a ketone function
not being observed. Halogenated compounds (1g-j) were
effectively oxidized allowing the possible elaboration of more
complex compounds through further coupling reactions.
While most products were isolated in fair to good yields
(60-78%), 3k and 3l were obtained in low yields (∼10%).
The oxidation of ether 1p into E-3p was improved from 48%
to 74% when the reaction was performed at rt for 72 h.
Oxidation of 1-decene (1s) in EtCO2H led to the expected
product 3s in good yield (Table 3, entry 1), but with low regio-
and stereoselectivity (L/B and E/Z < 10%). In addition, the
product was contaminated with 10% of the homoallylic deri-
vative. We have observed that the use of a higher carboxylic
acid as solvent can improve the selectivity, but has a detrimental
effect on the conversion, i-PrCO2H leading to only 62%
conversion (entry 2). Interestingly, the addition of a cosolvent
such as CH3CN to i-PrCO2H gave almost full conversion
leading to 4s in good yield, regio- and stereoselectivity, the
amount of homoallylic derivative remaining relatively un-
changed (entry 3), however. Medium conversion was obtained
with t-BuCO2H/CH3CN, even in prolonging the reaction time
to 72 h (entries 4 and 5), but the use of MnO2 as oxidizing agent
improved the conversion (entry 6), particularly when asso-
ciated with BQ (entry 7). This latter acts probably as an
electron-transfer mediator between the catalyst and the oxi-
dant, and facilitates the overall transformation.11
estingly, 1k and 1l could be thus oxidized in high yields and
regio- and stereoselectivities (5k, 80%; 5l, 72%). Ethers were
obtained in fair yields with method B (Table 2) in 72 (5q) or
24 h (5r). The oxidation of 1e was slightly improved (3e, 55%;
5e, 60%), but method B was less efficient than method A with
allylarenes (5a, 60%; 5c, 51%).
ESI-MS and the tandem version ESI-MS(/MS) are well
adapted to the observation of short-lived molecular ions issued
from metallocatalyzed reactions, and proposed species can
be characterized from high resolution (HRMS) and ESI-
MS(/MS) fragmentation.12 The analysis by ESI/MS(þ) of a
mixture of Pd(OAc)2 (0.1 mmol) and LiOH H2O (2.0 mmol)
3
in EtCO2H (2 mL) has shown two clusters at m/z 419.0661
and 499.1119, attributed to monomeric palladium species
[Li2Pd(EtCO2)4,Li]þ and [Li2Pd(EtCO2)4,EtCO2Li,Li]þ,
respectively. After addition of BQ and 1a, and45minofstirring,
two new clusters were observed at m/z 457.1002 and 537.1454,
and were assigned to [LiPd(1a)(EtCO2)3,Li]þ and [LiPd(1a)-
(EtCO2)3,EtCO2Li,Li]þ, respectively (Figures S1-S6, Sup-
porting Information). Palladium acetate exists as a trimer in
the solid state, in which the Pd(OAc)2 units are joined by double
OAc bridges.13 According to the ESI/MS studies, the acetate
anion of the salt can act as a ligand for palladium leading to
M2Pd(OAc)4 (A),14 then coordination of 1 to A affords B
-
(Scheme 1). The liganted RCO2 in B can act as a base,
facilitating the formation of π-allyl complex C.9,15 Carefull
(12) (a) Santos, L. S. Eur. J. Org. Chem. 2008, 235. (b) Svennebring, A.;
€
Sjoberg, P. J. R.; Larhed, M.; Nilsson, P. Tetrahedron 2008, 64, 1808.
(c) Thiery, E.; Harakat, D.; Le Bras, J.; Muzart, J. Organometallics 2008,
27, 3996. (d) Thiery, E.; Chevrin, C.; Le Bras, J.; Harakat, D.; Muzart, J. J.
Org. Chem. 2007, 72, 1859. (e) Chevrin, C.; Le Bras, J.; Roglans, A.; Harakat,
D.; Muzart, J. New J. Chem. 2007, 31, 121. (f) Markert, C.; Neuburger, M.;
Kuliche, K.; Meuwly, M.; Pfaltz, A. Angew. Chem., Int. Ed. 2007, 46, 5892.
(g) Taccardi, N.; Paolillo, R.; Gallo, V.; Mastrorilli, P.; Nobile, C. F.;
5s-v were obtained in fair yields (59-69%) with good
regio- and stereoselectivities (L/B 21-34, E/Z 12-18), and
were contaminated with only low amounts of the homallylic
derivatives (Tables 2 and 3). The new procedure, based on
the conditions of Table 3, entry 7 (called method B), is well
adapted to the oxidation of homoallylic alcohols. Indeed, the
efficiency of the oxidation of 1f and 1g was improved
(Table 2: 3f, 64%; 5f, 78%; 3g, 60%; 5g, 77%), and inter-
€
€
Raisanen, M.; Repo, T. Eur. J. Inorg. Chem. 2007, 4645. (h) Santos, L. S.;
Rosso, G. B.; Pilli, R. A.; Eberlin, M. J. Org. Chem. 2007, 72, 5809. (i) Neto,
B. A. D.; Alves, M. B.; Lapis, A. A. M.; Nachtigall, F. M.; Eberlin, M. N.;
Dupont, J.; Suarez, P. A. Z. J. Catal. 2007, 249, 154. (j) Masllorens, J.;
ꢀ
Gonzalez, I.; Roglans, A. Eur. J. Org. Chem. 2007, 158.
(13) Skapski, A. C.; Smart, M. L. J. Chem. Soc., Chem. Commun. 1970,
658.
(14) Pandey, R. N.; Henry, P. M. Can. J. Chem. 1974, 52, 1241.
(15) Tsuji, J. Palladium Reagents and Catalysts; Wiley: Chichester, UK,
1995; p 62.
€
(11) Piera, J.; Backvall, J.-E. Angew. Chem., Int. Ed. 2008, 47, 3506.
1772 J. Org. Chem. Vol. 75, No. 5, 2010

Thiery et al.
JOCNote
TABLE 2. Oxidations with Method A or Ba
aMethod A: 1 (1.0 mmol), Pd(OAc)2 (0.1 mmol), BQ (2.0 mmol), LiOH H2O (2.0 mmol), EtCO2H (2 mL), 40 °C, 24 h. Method B: 1 (1.0 mmol),
3
Pd(OAc)2 (0.1 mmol), BQ (0.05 mmol), MnO2 (2.0 mmol), LiOH H2O (2.0 mmol), t-BuCO2H (2 g), CH3CN (1 mL), 40 °C, 72 h. bRoom temperature,
3
72 h. c24 h. dPresence of 1-3% of homoallylic derivatives.
TABLE 3. Oxidation of 1-Decenea
entry
R
cosolvent
Ox (equiv)
BQ (2.0)
BQ (2.0)
BQ (2.0)
BQ (2.0)
BQ (2.0)
MnO2 (2.0)
BQ (0.05), MnO2 (2.0)
time, h
conv.,b %
yield, %
L/Bc
E/Zc
Hc
1
2
3
4
5
6
7
Et
i-Pr
i-Pr
t-Bu
t-Bu
t-Bu
t-Bu
24
24
24
24
72
72
72
88
62
94
49
66
76
90
80
42
74
33
43
54
61
8
25
17
50
43
27
29
7
22
19
17
15
20
18
10
11
10
4
4
3
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
3
a1s (1.0 mmol), Pd(OAc)2 (0.1 mmol), LiOH H2O (2.0 mmol), RCO2H (2.0 mL or 2.0 g), cosolvent (1.0 mL), 40 °C. bDetermined by GC. cDetermined
by GC on isolated products (H: homoallylic derivative).
3
analysis of the ESI/MS spectra did not show the presence of
clusters which could be attributed to C, suggesting that such
a complex evolves rapidly under the reaction conditions.
An intramolecular acetoxylation could lead to products 3-5
and D. The reoxidation of Pd(0) would then complete the
catalytic cycle.
In conclusion, the use of a base for the Pd-catalyzed allylic
oxidation of terminal alkenes in carboxylic acids as solvents
J. Org. Chem. Vol. 75, No. 5, 2010 1773

Thiery et al.
JOCNote
SCHEME 1. Proposed Mechanism
9.1, 27.5, 64.1, 74.0, 124.7, 126.3, 127.7, 128.5, 136.2, 142.6,
174.4; IR (film) 3445, 2982, 2942, 1738, 1454, 1382, 1349, 1276,
1186, 1083, 1009, 974, 759, 701. Anal. Calcd for C13H16O3: C,
70.89; H, 7.32. Found: C, 70.63; H, 7.45.
(E)-4-Hydroxy-4-phenylbut-2-enyl pivalate (5f): colorless oil,
78%, L/B and E/Z > 99.9; 1H NMR (250 MHz, CDCl3) δ 1.11
(s, 9H), 2.72 (br s, 1H), 4.46 (d, 2H, J = 4.6 Hz), 5.10 (d, 1H, J =
4.9 Hz), 5.80 (m, 2H), 7.21 (m, 5H); 13C NMR (63 MHz, CDCl3)
δ 27.6, 39.2, 64.5, 74.6, 125.5, 126.8, 128.2, 129.0, 136.2, 143.0,
178.8; IR (film) 3455, 2975, 1728, 1480, 1373, 1283, 1156, 1045,
971, 701; ESHRMS calcd for C15H20O3Na 271.1310, found
271.1304.
(E)-4-(4-Chlorophenyl)-4-hydroxybut-2-enyl propionate (3h):
pale yellow oil, 78%, L/B and E/Z > 99.9; 1H NMR (250 MHz,
CDCl3) δ 1.09 (t, 3H, J = 7.3 Hz), 2.30 (q, 2H, J = 7.3 Hz), 3.19
(br s, 1H), 4.53 (d, 2H, J = 4.0 Hz), 5.12 (d, 1H, J = 4.1 Hz),
5.84 (m, 2H), 7.25 (m, 4H); 13C NMR (63 MHz, CDCl3) δ 8.9,
27.3, 63.8, 73.2, 125.0, 127.6, 128.5, 133.2, 135.6, 140.8, 174.2;
IR (film) 3417, 2979, 1731, 1491, 1383, 1187, 1090, 1014, 911,
735; ESHRMS calcd for C13H15O3NaCl 277.0607, found
277.0614.
(E)-4-(2-Bromophenyl)-4-hydroxybut-2-enyl propionate (3j):
pale yellow oil, 74%, L/B and E/Z > 99.9; 1H NMR (250
MHz, CDCl3) δ 0.88 (t, 3H, J = 7.6 Hz), 2.08 (q, 2H, J = 7.5
Hz), 3.11 (br, 1H), 4.31 (m, 2H), 5.35 (s, 1H), 5.66 (m, 2H), 6.89
(dt, 1H, J = 1.5 Hz, J = 7.9 Hz), 7.08 (dd, 1H, J = 4.6 Hz, J =
9.6 Hz), 7.28 (m, 2H); 13C NMR (63 MHz, CDCl3) δ 8.9, 27.3,
64.0, 72.1, 122.1, 125.0, 127.6, 127.7, 128.9, 132.5, 134.0, 141.3,
174.2; IR (film) 3436, 2980, 1729, 1465, 1349, 1190, 1084, 1016,
910, 733; ESHRMS calcd for C13H15O3NaBr 321.0102, found
321.0095.
(E)-4-Hydroxy-4-p-tolylbut-2-enyl pivalate (5k): colorless oil,
80%, L/B and E/Z > 99.9; 1H NMR (250 MHz, CDCl3) δ 1.08
(s, 9H), 2.21 (s, 3H), 3.23 (br s, 1H), 4.41 (d, 2H, J = 4.8 Hz),
5.00 (d, 1H, J = 4.4 Hz), 5.71 (td, 1H, J = 4.9 Hz, J = 15.6 Hz),
5.79 (dd, 1H, J = 5.2 Hz, J = 15.7 Hz), 7.01 (d, 2H, J = 7.6 Hz),
7.10 (d, 2H, J = 7.8 Hz); 13C NMR (63 MHz, CDCl3) δ 20.8,
27.0, 38.5, 64.0, 73.5, 124.3, 126.0, 128.9, 135.8, 137.0, 139.5,
178.1; IR (film) 3439, 2973, 1728, 1480, 1397, 1283, 1156, 1088,
970, 819; ESHRMS calcd for C16H22O3Na 285.1467, found
285.1457.
(E)-4-(4-Chlorophenyl)-4-methoxybut-2-enyl pivalate (5q):
colorless oil, 64%, L/B and E/Z > 99.9; 1H NMR (250 MHz,
CDCl3) δ 1.13 (s, 9H), 3.23 (s, 3H), 4.53 (m, 3H), 5.74 (m, 2H),
7.21 (m, 4H); 13C NMR (63 MHz, CDCl3) δ 27.0, 38.5, 56.2,
63.6, 82.5, 126.6, 128.0, 128.5, 133.2, 133.5, 139.0, 177.8; IR
(film) 2976, 1729, 1482, 1462, 1282, 1152, 1090, 1015, 968, 824;
ESHRMS calcd for C16H21O3NaCl 319.1077, found 319.1082.
improved the efficiency and the selectivity of the process. The
methodology is particularly convenient for the oxidation of
homoallylic alcohols, corresponding E-acyloxylated pro-
ducts being obtained in fair to good yields.
Experimental Section
Method A for the Oxidation of 1. A round-bottomed flask was
charged with LiOH H2O (2.0 mmol, 84 mg) and EtCO2H
3
(1 mL) and the mixture was heated (oil bath, 40 °C) for 10 min.
BQ (2.0 mmol, 216 mg), Pd(OAc)2 (0.1 mmol, 22.4 mg), and
EtCO2H (1 mL) were added, and the mixture was stirred at rt for
15 min. 1 (1.0 mmol) was added, and the mixture was heated (oil
bath, 40 °C) for 24 h. After cooling to rt, the mixture
was filtered through a SiO2 pad, which was washed with Et2O
(50 mL). NaOH (2 M, 25 mL) was added, and the mixture was
stirred for 15 min. The organic phase was washed with H2O
(25 mL). The aqueous combined phases were extracted with
Et2O (25 mL). The combined organic phases were dried over
MgSO4, and then evaporated to dryness. Flash chromatography
(petroleum ether/EtOAc, 95:5-60:40) led to 3.
Method B for the Oxidation of 1. A round-bottomed flask was
charged with LiOH.H2O (2.0 mmol, 84 mg) and t-BuCO2H
(2 g), and the mixture was heated (oil bath, 40 °C) for 10 min. BQ
(0.05 mmol, 5.5 mg), MnO2 (2.0 mmol, 174 mg), Pd(OAc)2
(0.1 mmol, 22.4 mg), and CH3CN (1 mL) were added, and the
mixture was stirred at rt for 15 min. 1 (1.0 mmol) was added, and
the mixture was heated (oil bath, 40 °C) for 72 h. After cooling to
rt, the mixture was filtered through a SiO2 pad, which was
washed with Et2O (50 mL). NaOH (2 M, 25 mL) was added, and
the mixture was stirred for 15 min. The organic phase was
washed with H2O (25 mL). The aqueous combined phases were
extracted with Et2O (25 mL). The combined organic phases were
dried over MgSO4, and then evaporated to dryness. Flash
chromatography (petroleum ether/EtOAc, 95:52-60:40) led
to 5.
Acknowledgment. We are indebted to “Ville de Reims” for
a Ph.D. studentship to E.T. and to the CNRS for financial
support through the program “CPDD, Chimie et
ꢀ
Developpement Durables”.
Supporting Information Available: General information,
analytical data of compounds 3a-3e, 3g, 3i, 3m-3p, 5a, 5c, 5e,
5g, 5l, and 5r-5v, ESI/MS(þ) spectra (Figures S1-S6), and the
copies of 1H NMR and 13C NMR. This material is available free
of charge via the Internet at http://pubs.acs.org.
(E)-4-Hydroxy-4-phenylbut-2-enyl propionate (3f): pale yel-
low oil, 64%, L/B and E/Z > 99.9; 1H NMR (250 MHz, CDCl3)
δ 1.00 (t, 3H, J = 7.6 Hz), 2.20 (q, 2H, J = 7.5 Hz), 3.05 (br s,
1H), 4.43 (d, 2H, J = 5.0 Hz), 5.05 (d, 1H, J = 5.2 Hz),
5.65-5.85 (m, 2H), 7.21 (m, 5H); 13C NMR (63 MHz, CDCl3) δ
1774 J. Org. Chem. Vol. 75, No. 5, 2010