Direct reaction of dibromoacetic acid with aldehydes promoted by samarium diiodide: An easy, efficient, and rapid synthesis of (E)-α,β- unsaturated carboxylic acids with total stereoselectivity

Article abstract of DOI:10.1021/jo052236x

A promoted SmI₂ direct reaction of dibromoacetic acid with different aldehydes, followed by an elimination reaction also promoted by samarium diiodide, affords (E)-α,β-unsaturated carboxylic acids 2 with total stereoselectivity. A mechanism to explain this transformation is proposed.

Full text of DOI:10.1021/jo052236x

Direct Reaction of Dibromoacetic Acid with
Aldehydes Promoted by Samarium Diiodide: An
Easy, Efficient, and Rapid Synthesis of
prepare compounds of biological relevance such as tetrahy-
dromyricoid or the antibacterial reutericyclin.
7
8
However, the methods to directly transform aldehydes into
(
E)-R,â-unsaturated carboxylic acids, through sequential addition
(
E)-r,â-Unsaturated Carboxylic Acids with Total
9
and elimination reactions, are scarce and present some draw-
backs. So, the Knoevenagel reaction with malonic acid gave
low yields with enolizable aldehydes. The use of (trimethyl-
silyl)acetic acid dianion (Peterson olefination) and the cy-
cloaddition of (trimethylsilyl)ketene suffered from a lack of
stereoselectivity. No application of the Wittig-Horner reaction
†
Stereoselectivity
10
1
1
1
2
Jos e´ M. Concell o´ n* and Carmen Concell o´ n
1
3
Departamento de Qu ´ı mica Org a´ nica e Inorg a´ nica, Facultad de
Qu ´ı mica, UniVersidad de OViedo, Juli a´ n ClaVer ´ı a, 8,
14
with highly enolizable aldehydes has been described, and, in
general, this method required fairly stringent conditions to isolate
3
3071 OViedo, Spain
1
4b
the R,â-unsaturated acids.
unsaturated carboxylic acids by the reaction of C,O,O-tris-
trimethylsilyl)ketene acetal with enolizable aldehydes took
Finally, the synthesis of R,â-
jmcg@fq.unioVi.es
(
1
5
place in low yield, and to prepare the starting ketene acetal
from (trimethylsilyl)acetic ester, three steps are necessary.
ReceiVed October 27, 2005
For these reasons, to obtain R,â-unsaturated carboxylic acids,
sometimes it is preferable to carry out a condensation reaction
16
of esters with aldehydes, followed by hydrolysis (deprotection
of acid function), instead of the direct synthesis of R,â-
unsaturated carboxylic acids. Consequently, a direct synthesis
of R,â-unsaturated carboxylic acids from commercially available
compounds, obviating the protection-deprotection steps of the
carboxylic function, would be very interesting.
2
A promoted SmI direct reaction of dibromoacetic acid with
different aldehydes, followed by an elimination reaction also
promoted by samarium diiodide, affords (E)-R,â-unsaturated
carboxylic acids 2 with total stereoselectivity. A mechanism
to explain this transformation is proposed.
Previously, we have described the highly diastereoselective
17
18
preparation of (E)-R,â-unsaturated esters or amides by the
treatment of 2-halo-3-hydroxyesters or amides with SmI2. No
generalization of this methodology to the synthesis of R,â-
unsaturated carboxylic acids could be performed as a result of
the difficulty in obtaining the starting 2-halo-3-hydroxyacids.
Most recently, we have also reported the synthesis of R,â-
unsaturated esters by a promoted SmI2 reaction of aldehydes
The synthetic applications of dianions derived from carboxylic
acids are limited, probably a result of the low solubility of these
1
dianions in organic solvents. In particular, no generation of
bromo- or chloroacetic acid dianions (Li, Na, K, Mg, Zn) have
been described to the best of our knowledge. Also, synthetic
1
9
with ethyl dibromoacetate.
2
applications of acetic dianion are very scarce.
(6) Cho, H.; Ueda, M.; Tamaoka, M.; Hamaguchi, M.; Aisaka, K.; Kiso,
Regarding the application of SmI2 in organic synthesis, except
3
Y.; Inoue, T.; Ogino, R.; Tatsuoka, T.; Ishihara, T.; Noguchi, T.; Morita,
pinacol coupling reactions, no CsC bond formation from using
I.; Murota, S. J. Med. Chem. 1991, 34, 1503-1505.
carboxylic acids (without protection of the acid function) and,
(7) Song, J.; Hesse, M. Tetrahedron 1993, 49, 6797-6804.
consequently, from the R-condensation of acetic acid has been
(8) Marquardt, U.; Schmid, D.; Jung, G. Synlett 2000, 1131-1132.
(9) No synthesis of R, â-unsaturated carboxylic acids by using the Wittig
reaction is possible: (a) Denney, D. B.; Smith, L. C. J. Org. Chem. 1962,
described to date.4
In addition, (E)-R,â-unsaturated carboxylic acids are present
2
7, 3404-3408. (b) Considine, W. J. J. Org. Chem. 1962, 27, 647-649.
in some natural products (i.e., the secretion juice of the honeybee
(10) Jones, G. Org. React. 1997, 15, 204-213.
5
6
(11) House, H. O. In Modern Synthetic Reactions; Benjamin, W. A.,
queen and caffeic acid ) and are also versatile building blocks
in organic syntheses. For example, they have been used to
Ed.; Benjamin-Cummings Publishing Co.: Menlo Park, CA, 1972; p 649.
12) Grieco, P. A.; Wang, C. L.; Burke, S. D. J. Chem. Soc., Chem.
(
Commun. 1975, 537-539.
†
Dedicated to Professor Miguel Yus on the occasion of his 59th birthday.
1) For reviews of dianions of carboxylic acids, see: (a) Petragnani, N.;
(13) (a) Concepci o´ n, A. B.; Maruoka, K.; Yamamoto, H. Tetrahedron
1995, 51, 4011-4020. (b) Black, T. H.; Zhang, Y.; Huang, J.; Smith, D.
C.; Yates, B. E. Synth. Commun. 1995, 25, 15-20.
(
Yonashiro, M. Synthesis 1982, 521-578. (b) Thompson, C. M.; Green, D.
L. C. Tetrahedron 1991, 47, 4223-4285.
(14) (a) Koppel, G. A.; Kinnick, M. D. Tetrahedron Lett. 1974, 711-
713. (b) Coutrot, P.; Snoussi, M.; Savignac, P. Synthesis 1978, 133-134.
(c) Lombargo, L.; Taylor, R. J. K. Synthesis 1978, 131-132. (d) Sano, S.;
Takemoto, Y.; Nagao, Y. ARKIVOC 2003, 8, 93-101.
(15) (a) Bellassoued, M.; Gaudemar, M. Tetrahedron Lett. 1988, 29,
4551-4554. (b) Lensen, N.; Mouelhi, S.; Bellassoued, M. Synth. Commun.
2001, 31, 1007-1011.
(
2) Yus, M.; Pastor, I. M. Tetrahedron Lett. 2000, 41, 5335-5339 and
references therein.
3) (a) Nami, J. L.; Souppe, J.; Kagan, H. B. Tetrahedron Lett. 1983,
4, 765-766. (b) Souppe, J.; Danon, L.; Namy, J. L.; Kagan, H. B. J.
Organomet. Chem. 1983, 250, 227-236.
4) For recent reviews of synthetic applications of SmI2, see: (a)
(
2
(
Molander, G. A.; Harris, C. R. Chem. ReV. 1996, 96, 307-338. (b)
Molander, G. A.; Harris, C. R. Tetrahedron 1998, 54, 3321-3354. (c) Krief,
A.; Laval, A. M. Chem. ReV. 1999, 99, 745-777. (d) Steel, P. G. J. Chem.
Soc., Perkin Trans. 1 2001, 2727-2751. (e) Kagan, H. B. Tetrahedron 2003,
(16) To see a synthesis of (E)-R,â-unsaturated esters by the reaction of
dichloroacetates with aldehydes or ketones promoted by Zn/TMSCl, see:
Ishino, Y.; Mihara, M.; Nishihama, S.; Nishiguchi, I. Bull. Chem. Soc. Jpn.
1998, 71, 2669-2672.
(17) Concell o´ n, J. M.; P e´ rez-Andr e´ s, J. A.; Rodr ´ı guez-Solla, H. Angew.
Chem. 2000, 112, 2866-2868; Angew. Chem., Int. Ed. 2000, 39, 2773-
2775.
5
9, 10351-10372. (f) Concell o´ n, J. M.; Rodr ´ı guez-Solla, H. Chem. Soc.
ReV. 2005, 33, 599-609.
5) Callow, R. K.; Johnston, N. C. Bee World 1960, 41, 152-153.
(
10.1021/jo052236x CCC: $33.50 © 2006 American Chemical Society
1
728
J. Org. Chem. 2006, 71, 1728-1731
Published on Web 01/20/2006

SCHEME 1. SmI
Carboxylic Acids
2
-Mediated Synthesis of r,â-Unsaturated
SCHEME 2. Mechanism and Chair Transition State Model
TABLE 1. Synthesis of r,â-Unsaturated Carboxylic Acids 2
entry
2
R1
yieldb,c (%)
1
2
3
4
2a
2b
2c
2c
2d
2d
2e
2e
2f
n-C7H15
n-C7H15
Cy
70
83
75
d
Cy
76
c
5
(CH3)2CHCH2
(CH3)2CHCH2
PhCH2
PhCH2
PhCH(CH3)
Ph2CH
78
75
d
6
7
8
9
93
89
d
71
84
10
2g
a
All reactions were carried out using 5 equiv of SmI2 and with a reaction
b
time of 120 min. Diastereoisomeric excess (de) in all reactions was >98%
and was determined by CGL/MS and 300 MHz H and C NMR analysis
of the crude products 2. Isolated yield after column chromatography on
the basis of compound 1. These reactions were carried out using 5 equiv
1
13
c
d
of SmI2 generated in situ and with a reaction time of 120 min.
iodomethane.22 In the latter cases (Table 1, entries 4, 6, and 8),
negligible effects on the reaction outcome were appreciable;
the corresponding R,â-unsaturated carboxylic acids were ob-
tained with similar yields and with total E selectivity.
Now we describe the first SmI2-mediated method to obtain
E)-R,â-unsaturated carboxylic acids with total stereoselectivity
(
by using commercially available dibromoacetic acid and alde-
hydes. This transformation takes place through a sequential
process: an aldol-type reaction (without the protection of the
acid function) in the first step, followed by a â-elimination
reaction in the second step. (Scheme 1). In addition, the reaction
can be carried out with easily enolizable aldehydes.
Several comments are worth mentioning: (1) Aliphatic
(linear, branched, or cyclic) (E)-R,â-unsaturated carboxylic acids
2 can be prepared; starting from aromatic or cinnamaldehyde
aldehydes, the corresponding pinacol compounds were obtained
instead of the R,â-unsaturated carboxylic acids. (2) In opposition
to other previously described syntheses of R,â-unsaturated acid
derivatives, this preparation of R,â-unsaturated carboxylic acids
can be carried out by using easily enolizable aldehydes (Table
1, entries 7, 9, and 10). (3) To the best of our knowledge, this
sequential CsC bond formation/elimination reaction constitutes
the first example described in the literature in which a new Cs
C bond is performed by SmI2 with a nonprotected carboxylic
acid. (4) This synthesis of R,â-unsaturated acids is very simple
(especially when SmI2 is generated in situ) and requires
considerably less time, effort, and material than other classical
methods. First, the synthesis is based on a sequential reaction,
and second, no protection-deprotection of the carboxylic
function is necessary. (5) The synthesis of R,â-unsaturated acids
can be carried out on a bigger scale (2e was obtained starting
from 4 mmol of 1e).
The reaction of different aldehydes (1 equiv) with dibro-
moacetic acid (1.5 equiv) in the presence of a solution of SmI2
(
5 equiv) in THF over a period of 2 h at room temperature
afforded the corresponding (E)-R,â-unsaturated carboxylic acids
after hydrolysis, with total stereoselectivity and in good to
2
excellent yields. Table 1 presents the results obtained.
3,4
The presence of a single diastereoisomer was determined on
1
the crude reaction mixtures by GC-MS and H NMR spectros-
copy.
The E stereochemistry of the double CdC bond of the R,â-
unsaturated acids 2 was assigned on the basis of the following:
(
a) the NOESY experiments of compounds 2b, 2c, and 2e; (b)
1
the value of the H NMR coupling constant of the olefinic
protons; and (c) the comparison of the H NMR data of
compounds 2a, 2b, 2e, and 2f with those previously reported.
2
0
1
2
1
The obtention of the compounds 2 might be explained
assuming a sequential process (Scheme 2). Thus, the reaction
of 2 equiv of SmI2 with dibromoacetic acid generates a
samarium enolate 3 rapidly. The reaction of this enolate with
the aldehyde afforded the corresponding 2-bromoacid 4, which
could be hydrolyzed to afford the samarium-carboxylate 5.
Metalation of 5 with 2 equiv of samarium diiodide gives another
enolate intermediate 6, which suffers a spontaneous elimination
reaction before it is hydrolyzed, yielding, after workup hydroly-
sis, the corresponding R,â-unsaturated carboxylic acid. Chelation
of the Sm(III) center with the oxygen atom of the alcohol group
The same transformation can be carried out by using SmI2
generated in situ from a mixture of samarium and di-
(
18) Concell o´ n, J. M.; P e´ rez-Andr e´ s, J. A.; Rodr ´ı guez-Solla, H. Chem.s
Eur. J. 2001, 7, 3062-3068.
19) Concell o´ n, J. M.; Concell o´ n, C.; M e´ jica, C. J. Org. Chem. 2005,
0, 6111-6113.
20) The coupling constants between the olefinic protons of compounds
(
7
(
2
a-f, ranging between 15.7 and 15.4 Hz, were assigned according to the
average literature values. Silverstein, R. M.; Bassler, G. C.; Morrill, T. C.
Spectrometric Identification of Organic Compounds; John Wiley and
Sons: New York, 1991.
2
3
(
21) (a) Karlsson, S.; H o¨ gberg, H.-E. Org. Lett. 1999, 10, 1667-1669.
b) Bellassoued, M.; Lensen, N.; Bakasse, M.; Mouelhi, S. J. Org. Chem.
998, 63, 8785-8789. (c) Effenberger, F.; Obwald, S. Tetrahedron:
Asymmetry 2001, 12, 2581-2587.
22) Concell o´ n, J. M.; Rodr ´ı guez-Solla, H.; Bardales, E.; Huerta, M. Eur.
J. Org. Chem. 2003, 1775-1778.
leads to the formation of a six-membered ring. Tentatively,
we propose a chairlike transition state model I with the group
R in the equatorial orientation (to avoid 1,3-diaxial interactions).
Elimination from I affords (E)-R,â-unsaturated carboxylic acids
2.
(
1
(
J. Org. Chem, Vol. 71, No. 4, 2006 1729

SCHEME 3. Mechanism and Nonchelated Transition State
Model
added to a suspension of Sm powder (2.5 mmol), dibromoacetic
acid (0.75 mmol), and the aldehyde (0.5 mmol). After stirring the
reaction at room temperature for 2 h, it was quenched with aqueous
HCl (0.1 M) before the organic material was extracted with
2 4
dichloromethane. The combined extracts were dried over Na SO ,
and the solvent was removed under reduced pressure. Purification
by flash chromatography on silica gel (hexane/ethyl acetate, 5:1)
afforded pure products 2.
The most questionable aspect of this mechanism is the
proposition of a samarium enolate derived from the bromoacetic
acid 3. We do not have direct evidence for the existence of
such an intermediate. However, a radical mechanism could be
rejected, considering that no differences were observed in the
course and result of the reaction when it was performed in the
dark or in the presence of AIBN. Possibly, after enolate
formation, the tautomeric form I2SmCHBrCO2H might evolve
to the most stable counterpart BrCHdC(OH)OSmI2. This could
be argued considering the high oxophilic character exhibited
by the Sm(III) ions.24 In this sense, the tautomer BrCHdC(OH)-
OSmI2 is capable of coexisting in the presence of a hydroxyl
group. To reinforce this argument, â-hydroxy samarium enolates
were previously generated by the treatment of the corresponding
1
(E)-Hept-2-enoic Acid (2a). H NMR (300 MHz, CDCl
3
): 7.08
(
(
(
dt, J ) 6.8, 15.7 Hz, 1H), 5.83 (d, J ) 15.7 Hz, 1H), 2.35-2.18
13
m, 2H), 1.64-1.26 (m, 4H), 0.92 (t, J ) 7.3 Hz, 3H). C NMR
3
75 MHz, CDCl ): δ 171.5 (C), 152.2 (CH), 120.5 (CH), 31.9
(CH ), 29.9 (CH ), 22.1 (CH ), 13.7 (CH ). IR (neat): 2680, 1697,
1651 cm . R ) 0.3 (hexane/EtOAc, 3:1). Anal. Calcd for
C
2
2
2
3
-
1
f
H
7 12
2
O : C, 65.60; H, 9.44. Found: C, 65.10; H, 9.21.
1
(E)-Dec-2-enoic Acid (2b). Pale orange oil. H NMR (300 MHz,
CDCl
3
): 7.08 (dt, J ) 7.0, 15.4 Hz, 1H), 5.82 (dt, J ) 1.6, 15.4
Hz, 1H), 2.35-2.18 (m, 2H), 1.46-1.25 (m, 10H), 0.88 (t, J )
13
5.2 Hz, 3H). C NMR (75 MHz, CDCl
20.5 (CH), 32.2 (CH ), 31.6 (CH ), 29.6 (CH
CH ), 22.5 (CH ), 13.9 (CH ). MS (70 eV, EI, %) m/z: 170 (M ,
1), 152 (13), 123 (25), 73 (100). HRMS (70 eV): [M ] calcd for
, 170.1307; found, 170.1287. IR (neat): 2676, 1698, 1652
3
): δ 172.1 (C), 152.4 (CH),
1
2
2
2
), 29.0 (CH ), 27.8
2
+
(
2
2
3
+
<
10
cm 1. R
C
H
18
O
2
17
18
2-chloro-3-hydroxyesters or amides with samarium diiodide
-
f
) 0.3 (hexane/EtOAc, 3:1). Anal. Calcd for C10H O :
18 2
to afford, after a â-elimination reaction, the corresponding R,â-
unsaturated ester or amide and byproducts such as those
generated from the hydrolysis of the enolate by the alcohol
function, which were not detected.
Another alternative nonchelated model to explain the E
stereochemistry is shown in Scheme 3. In this model, recently
proposed by Mioskowski and co-workers25 to explain an
elimination reaction promoted by Cr(II), the steric interactions
between the samarium enolate and the R group are minimized
in transition state B to give the observed E isomer.
In conclusion, in this paper we have presented an easy, simple,
general, and efficient methodology for the preparation of R,â-
unsaturated carboxylic acids starting from commercially avail-
able aldehydes and dibromoacetic acid and being promoted by
samarium diiodide. The elimination reaction proceeds with total
or high E diastereoselectivity. A mechanism to explain the total
stereoselectivity has been proposed. This reaction constitutes
the first example of a CsC bond formation promoted by SmI2
with carboxylic acids. Different SmI2-promoted reactions to
form CsC bonds from carboxylic acids or other compounds
with active hydrogens are currently under investigation within
our laboratory.
C, 70.55; H, 10.66. Found: C, 70.34; H, 10.57.
1
(E)-Cyclohexylprop-2-enoic Acid (2c). H NMR (300 MHz,
CDCl
3
): δ 7.04 (dd, J ) 6.9, 15.7 Hz, 1H), 5.78 (dd, J ) 1.60,
5.8 Hz, 1H), 2.2-1.2 (m, 11H). 13C NMR (50 MHz, CDCl
): δ
72.4 (C), 156.9 (CH), 118.2 (CH), 40.4 (CH), 31.4 (2 × CH ),
5.8 (CH ), 14.0 (CH ). MS (70 eV, EI, %) m/z:
), 25.5 (2 × CH
54 (M , 3), 136 (21), 94 (40), 82 (100). HRMS (70 eV): [M ]
1
1
2
1
3
2
2
2
3
+
+
calcd for C H O , 154.0994; found, 154.0984. IR (neat): 2920,
9
14
2
-
1
1686 cm . R ) 0.2 (hexane/EtOAc, 3:1). Anal. Calcd for
f
C H
9
14
O
2
: C, 70.10; H, 9.15. Found: C, 70.21; H, 9.01.
(E)-5-Methylhex-2-enoic Acid (2d). 1H NMR (300 MHz,
CDCl ): δ 7.12-7.02 (ddt, J ) 1.5, 7.4, 15.7 Hz, 1H), 5.82 (dd,
3
J ) 1.4, 15.7 Hz, 1H), 2.13 (dd, J ) 6.9, 7.4 Hz, 2H), 1.78 (sept,
J ) 6.8 Hz, 1H), 0.94 (d, J ) 6.54 Hz, 3H), 0.92 (d, J ) 6.54 Hz,
3
H). 13C NMR (75 MHz, CDCl
3
): δ 171.9 (C), 151.5 (CH), 121.4
). R ) 0.6 (hexane/
7 12 2
H O : C, 65.60; H, 9.44. Found:
(
CH), 41.4 (CH
2
), 27.67 (CH), 22.2 (2 × CH
3
f
EtOAc, 3:1). Anal. Calcd for C
C, 65.48; H, 9.50.
(
E)-4-Phenylbut-2-enoic Acid (2e). 1H NMR (300 MHz,
CDCl
1
3
): δ 7.33-7.17 (m, 6H), 5.86-5.79 (dt, J ) 1.41, 15.6 Hz,
H), 3.57-3.54 (dd, J ) 1.41, 6.81 Hz, 2H). 13C NMR (75 MHz,
CDCl
3
): δ 171.6 (C), 150.0 (CH), 137.2 (C), 128.7 (2 × CH),
1
28.6 (2 × CH), 126.7 (CH), 121.5 (CH), 38.4 (CH
2
). MS (70 eV,
+
EI, %) m/z: 162 (M , 64), 144 (21), 117 (100), 115 (58). HRMS
Experimental Section
+
(
(
70 eV): [M ] calcd for C10
10 2
H O , 162.0681; found, 162.0683. IR
) 0.2 (hexane/EtOAc, 3:1). Anal.
neat): 2921, 1697 cm-1. R
f
General Procedure for the Synthesis of r,â-Unsaturated
Carboxylic Acids (2). SmI (2.5 mmol) was added to a stirred
2
suspension of dibromoacetic acid (0.75 mmol) and the correspond-
ing aldehyde (0.5 mmol) in THF (2 mL). When the reaction was
2 2 2
performed by using SmI generated in situ, CH I (2.5 mmol) was
Calcd for C10
10 2
H O : C, 74.06; H, 6.21. Found: C, 73.90; H, 6.90.
1
(
E)-4-Phenylpentan-2-enoic Acid (2f). H NMR (300 MHz,
CDCl
3.71-3.62 (m, 1H), 1.46 (d, J ) 7.2 Hz, 3H). C NMR (75 MHz,
CDCl
): δ 171.9 (C), 155.1 (CH), 142.8 (C), 128.6 (2 × CH),
27.2 (2 × CH), 126.7 (CH), 119.4 (CH), 42.0 (CH), 20.0 (CH ).
MS (70 eV, EI, %) m/z: 176 (M , 32), 130 (100), 115 (38). HRMS
3
): δ 7.37-7.20 (m, 6H), 5.83 (dd, J ) 1.6, 15.6 Hz, 1H),
13
3
1
3
(
23) A similar model involving a chairlike transition state has been
proposed to explain the selectivity observed in other reactions with SmI2:
a) Molander, G. A.; Etter, J. B.; Zinke, P. W. J. Am. Chem. Soc. 1987,
+
(
1
(
70 eV): [M ] calcd for C11
+
2
H O , 176.0837; found, 176.0848. IR
12
-1
09, 453-463. (b) Urban, D.; Skrydstrup, T.; Beau, J. M. J. Org. Chem.
(
neat): 2974, 1694, 1643 cm . R ) 0.2 (hexane/EtOAc, 3:1). Anal.
f
1
998, 63, 2507-2516. (c) Enemrke, R. J.; Larsen, J.; Hjollund, G. H.;
Calcd for C11
H
12
O
2
: C, 74.98; H, 6.86. Found: C, 74.69; H 6.74.
Skrydstrup, T.; Daasbjerg, K. Organometallics 2005, 24, 1252-1262. (d)
Davis, T. A.; Chopade, P. R.; Milmersson, G.; Flowers, R. A. Org. Lett.
1
(E)-4,4-Diphenylbut-2-enoic Acid (2g). H NMR (300 MHz,
2
005, 7, 119-122.
24) Molander, G. A. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Schreiber, S. L., Eds.; Pergamon: Cambridge, 1991; Vol.
, p 252.
25) Barma, D. K.; Kundu, A.; Zhang, H.; Mioskowski, C.; Falck, J. R.
J. Am. Chem. Soc. 2003, 125, 3218-3219.
CDCl
3
): δ 7.57-7.49 (m, 1H), 7.35-7.16 (m, 10H), 5.77-5.72
(
13
(
m, 1H), 4.90 (d, J ) 7.11 Hz, 1H). C NMR (75 MHz, CDCl ):
3
δ 171.7 (C), 152.6 (CH), 141.0 (2 × C), 128.6 (4 × CH), 128.5 (4
1
×
CH), 126.9 (2 × CH), 122.1 (CH), 53.4 (CH). MS (70 eV, EI,
(
+
%) m/z: 238 (M , 30), 220 (9), 192 (100), 178 (31), 114 (83).
1
730 J. Org. Chem., Vol. 71, No. 4, 2006

+
HRMS (70 eV): [M ] calcd for C16
2
H
14
O
2
, 238.0994; found,
Note Added after ASAP Publication. There was an error
in the dedication line in the version published ASAP January
0, 2006; the corrected version was published ASAP February
, 2006.
-
1
38.0966. IR (neat): 2923, 1693, 1648 cm . R
EtOAc, 3:1). Anal. Calcd for C16
C, 70.99; H, 5.71.
f
) 0.2 (hexane/
14 2
H O : C, 80.65; H, 5.92. Found:
2
1
Acknowledgment. We thank Ministerio de Ciencia y
Tecnolog ´ı a (CTQ2004-1191/BQU) for financial support and
Vicente del Amo for his revision of the English. C.C. thanks
the Ministerio de Ciencia y Tecnolog ´ı a for a predoctoral grant,
and J.M.C. thanks Carmen Fern a´ ndez-Fl o´ rez for her time.
Supporting Information Available: General methods and
spectroscopic data of 2. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO052236X
J. Org. Chem, Vol. 71, No. 4, 2006 1731