Intramolecular PIFA-mediated alkyne amidation and carboxylation reaction

Article abstract of DOI:10.1021/jo062320s

(Chemical Equation Presented) The hypervalent iodine reagent PIFA promotes the intramolecular electrophilic cyclization of easily accessible alkynylamides and alkynyl carboxylic acids, leading to the formation of pyrrolidinone and lactone skeletons, respe

Full text of DOI:10.1021/jo062320s

SCHEME 1. Preparation and Reactivity of Alkynylamides
Intramolecular PIFA-Mediated Alkyne
Amidation and Carboxylation Reaction
4a-i and Synthesis of 5-Aroylpyrrolidinones 5a-ia
Imanol Tellitu,* Sonia Serna,† M. Teresa Herrero,
Isabel Moreno, Esther Dom´ınguez,* and Raul SanMartin
Departamento de Qu´ımica Orga´nica II, Facultad de Ciencia y
Tecnolog´ıa, UniVersidad del Pa´ıs Vasco/Euskal Herriko
Unibertsitatea (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain
imanol.tellitu@ehu.es
ReceiVed NoVember 10, 2006
a Reagents and conditions: (i) H2SO4 (c), EtOH, room temperature
(94%); (ii) (a) RI, Pd(PPh3)4, CuI, Et2NH, CH2Cl2, room temperature; (b)
KOH, dioxane, room temperature (55-62% two steps); (iii) R′NH2, HOBt,
EDC‚HCl, Et3N, CH2Cl2, 0 °C to room temperature (63-98%); (iv) PIFA,
CF3CH2OH, 0 °C (50-88%).
The hypervalent iodine reagent PIFA promotes the intramo-
lecular electrophilic cyclization of easily accessible alkynyl-
amides and alkynyl carboxylic acids, leading to the formation
of pyrrolidinone and lactone skeletons, respectively, in a very
efficient way. A synthetic study and a mechanistic proposal
for these transformations are presented.
electrophilic reagents,6 molecular iodine and IPy2BF4 (Barlu-
enga’s reagent), inter alia, has been reported in the efficient
syntheses of nitrogen-containing heterocycles such as isoin-
dolinones, indoles, and isoquinolinones.7
In a recent communication,1 we have reported a novel
approach to the synthesis of 5-aroylpyrrolidinones based on the
action of the trivalent iodine reagent PIFA [phenyliodine(III)-
bis(trifluoroacetate)] on properly substituted alkynyl-N-aryla-
mides. The key feature of this transformation relies on the
generation of an electrophilic acyl-nitrenium intermediate,
stabilized by the donating properties of the aryl ring, that suffers
the intramolecular attack of the alkyne moiety to afford
efficiently the final heterocyclic products. As a metal-free
protocol, this PIFA-mediated intramolecular addition of a
nitrogen functionality across a carbon-carbon multiple bond
shows superiority over other established metal-based methods
in terms of economy, sustainability, stability of the I(III) reagents
to air and moisture, and its tolerance to different functional
groups. In this context, the employment of alkaline metals,2
transition metal complexes,3 lanthanides,4 and actinides5 as
catalysts describes a representative overview of the research in
this area. On the other hand, and although less exploited, the
reaction of alkynylamines with electrophilic reagents toward
this end has the advantage of the experimental simplicity and
the possibility to get functionalized products. Additionally, these
functionalities allow further manipulations toward the synthesis
of more complex structures. As a result, the use of different
By analogy with previous observations in our group on the
PIFA-mediated olefin amidation reaction,8 it was originally
assumed by us that the presence of an aryl group onto the
nitrogen able to stabilize the deficient intermediate was a
fundamental structural requirement for the success of the
reaction.9 Continuous research carried out by our group has
proven lately that this assumption happens to be untrue, an
observation that enriches the scope of the presented protocol.
As a consequence, an extension of this methodology to the
preparation of differently N-substituted 5-aroylpyrrolidinones,
and also 5-aroylfuranones, is presented in this paper.
Our study started with the synthesis of amides 4a-i that were
differently substituted both at the terminal position of the triple
bond and at the nitrogen (see Scheme 1). This could be easily
accomplished by esterification of commercially available 4-pen-
tynoic acid (1), followed by treatment of the resulting ethyl ester
(3) Early transition metals: (a) Bystschkov, I.; Doye, S. Eur. J. Org.
Chem. 2003, 935-946. (b) Ackermann, L.; Bergman, R. G.; Loy, R. N. J.
Am. Chem. Soc. 2003, 125, 11956-11963. (c) Tillack, A.; Garcia Castro,
I.; Hartung, C. G.; Beller, M. Angew. Chem., Int. Ed. 2002, 41, 2541-
2543. Palladium: (d) Yamamoto, Y.; Kadota, I.; Lutete, L. M. J. Am. Chem.
Soc. 2004, 126, 1622-1623. (e) Shimada, T.; Yamamoto, Y. J. Am. Chem.
Soc. 2002, 124, 12670-12671. (f) Jacobi, P. A.; Brielmann, H. L.; Hauck,
S. I. J. Org. Chem. 1996, 61, 5013-5023. Ruthenium: (g) Tokunaga, M.;
Eckert, M.; Wakatsuki, Y. Angew. Chem., Int. Ed. 1999, 38, 3222-3225.
Rhodium: (h) Hartung, C. G.; Tillack, A.; Trauthwein, H.; Beller, M. J.
Org. Chem. 2001, 66, 6339-5343. Silver: (i) Koseki, Y.; Kusano, S.; Ichi,
D.; Yoshida, K.; Nagasaka, T. Tetrahedron 2000, 56, 8855-8865.
(4) (a) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673-683. (b)
Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1998, 120, 1757-1771. (c) Li, Y.;
Marks, T. J. Organometallics 1996, 15, 3770-3772.
* To whom correspondence should be addressed. Phone: (34) 94 601 5438.
Fax: (34) 94 601 2748.
† Present address: Planta Piloto de Qu´ımica Fina, Universidad de Alcala´,
28871 Alcala´ de Henares, Spain.
(1) Serna, S.; Tellitu, I.; Dom´ınguez, E.; Moreno, I.; SanMartin, R. Org.
Lett. 2005, 7, 3073-3076.
(2) (a) Cid, M. M.; Dom´ınguez, D.; Castedo, L.; Va´zquez-Lo´pez, E. M.
Tetrahedron 1999, 55, 5599-5610. (b) Tzalis, D.; Koradin, C.; Knochel,
P. Tetrahedron Lett. 1999, 40, 6193-6195.
(5) (a) Stubbert, B. D.; Stern, C. L.; Marks, T. J. Organometallics 2003,
22, 4836-4838. (b) Straub, T.; Haskel, A.; Neyround, T. G.; Kapon, M.;
Botoshansky, M.; Eisen, M. S. Organometallics 2001, 20, 5017-5035.
10.1021/jo062320s CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/18/2007
1526
J. Org. Chem. 2007, 72, 1526-1529

SCHEME 2. Proposed Mechanisms for the PIFA-Mediated Intramolecular Alkyne Amidation on N-Arylamides (pathway A)
and N-Alkylamides (pathway B)
2 under standard Sonogashira10 cross-coupling reaction condi-
tions to place different aryl groups at the terminal position of
the triple bond.11 The basic hydrolysis of the intermediate esters
produced the desired carboxylic acids 3a-d in good overall
yields.12 Finally, the synthesis of amides 4a-i was effectively
achieved employing HOBt and EDC‚HCl as activating re-
agents.13
(1.5 equiv of PIFA in CF3CH2OH at 0 °C)15 to find that not
only the N-aryl-substituted amide 4a reacted to afford the
expected heterocyclic product 5a but also N-methyl, N-allyl,
N-benzyl, and N-cyclohexylamides 4b-i afforded the corre-
sponding pyrrolidinones 5b-i in very good yields and short
reaction times (typically less than 60 min).16 Consequently, we
must give an explanation to this pleasant but unexpected result.
Originally, and on the base of previously accepted mechanisms,9
we proposed that the presented cyclization would exclusively
take place on N-aryl-substituted amides as the only way to
stabilize the positively charged nitrenium intermediate B gener-
ated (see Scheme 2, pathway A). Thus, nitrenium B reacts
intramolecularly with the alkyne residue to form a new
intermediate C. Reaction of C with a free trifluoroacetate ligand
delivered by PIFA results in the formation of a nonisolable ester
D, which, after basic hydrolysis during the workup, affords the
substituted pyrrolidinone skeleton E. Conversely (see Scheme
2, pathway B), the success on the cyclization of N-alkynylamides
of type F, where a positive charge on nitrogen would not be
adequately stabilized, led us to propose an alternative mechanism
Next, the series of amides 4a-i14 was treated with the
hypervalent iodine reagent PIFA under optimized conditions
(6) I2: (a) Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 1432-1437.
KMnO4: (b) Hayashi, Y.; Shoji, M.; Yamaguchi, S.; Mukaiyama, T.;
Yamaguchi, J.; Kakeya, H.; Osada, H. Org. Lett. 2003, 5, 2287-2290.
(7) (a) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2006, 71, 62-69.
(b) Yue, D.; Larock, R. C. Org. Lett. 2004, 6, 1037-1040. (c) Cherry, K.;
Thibonnet, J.; Ducheˆne, A.; Parrain, J.-L.; Abarbri, M. Tetrahedron Lett.
2004, 45, 2063-2066. (d) Amjad, M.; Knight, D. W. Tetrahedron Lett.
2004, 45, 539-541. (e) Barluenga, J.; Trincado, M.; Rubio, E.; Gonza´lez,
J. M. Angew. Chem., Int. Ed. 2003, 42, 2406-2409. (f) Huang, Q.; Hunter,
J. A.; Larock, R. C. J. Org. Chem. 2002, 67, 3437-3444. (g) Kobayashi,
K.; Hase, K.; Hashimoto, K.; Fujita, S.; Tanmatsu, M.; Morikawa, O.;
Konishi, H. Synthesis 2006, 2493-2496.
(8) (a) Tellitu, I.; Urrejola, A.; Serna, S.; Moreno, I.; Herrero, M. T.;
Dom´ınguez, E.; SanMartin, R.; Correa, A. Eur. J. Org. Chem. 2007, 437-
444. (b) Serna, I.; Tellitu, I.; Dom´ınguez, E.; Moreno, I.; SanMartin, R.
Tetrahedron Lett. 2003, 44, 3483-3486.
(9) N-Methoxyamides and N-phthalimidoamides are also known to
generate stable acyl-nitrenium intermediates. (a) Falvey, D. E.; Kung, A.
C. J. Org. Chem. 2005, 70, 3127-3132. (b) Kikugawa, Y.; Nagashima,
A.; Sakamoto, T.; Miyazama, E.; Shiiya, M. J. Org. Chem. 2003, 68, 6739-
6744. (c) Prata, J. V.; Clemente, D. T. S.; Prabhakar, S.; Lobo, A. M.;
Mourato, I.; Branco, P. S. J. Chem. Soc., Perkin Trans. 1 2002, 513-528.
(d) Glover, S. A.; Goosen, A.; McCleland, C. W.; Schoonraad, J. L.
Tetrahedron 1987, 43, 2577-2592.
(10) (a) Tykwinski, R. R. Angew. Chem., Int. Ed. 2003, 42, 1566-1568.
(b) Sonogashira, K. J. Organomet. Chem. 2002, 653, 46-49.
(11) It is known that terminal triple bonds react with PIFA to render
R-hydroxyketones. Therefore, in our case, that position must be blocked
for a successful transformation. Tamura, Y.; Yakura, T.; Haruta, J.-I.; Kita,
Y. Tetrahedron Lett. 1985, 26, 3837-3840.
(12) (a) Amides 4e and 4i were directly prepared from the ethyl ester of
acid 3a by treatment with Me3Al and the corresponding amine. (b) For the
preparation of carboxylic acid 3b, see: Arcadi, A.; Cacchi, S.; Delmastro,
M.; Marinella, F. Synlett 1991, 409-411.
(13) For a recent review on amide bond formation, see: Montalbetti, C.
A. G. N.; Falque, V. Tetrahedron 2005, 61, 10827-10852.
(14) The preparation and cyclization of amide 4a to afford pyrrolidinone
5a has already been performed (see ref 1). It is included here for comparative
purposes.
(15) The employment of a highly polar non-nucleophilic solvent, such
as CF3CH2OH, was crucial for the success of the reaction. For a revision
about the chemical properties and synthetic uses of trifluoroethanol and
other related solvents, see: Be´gue´, J.-P.; Bonnet-Delpon, D.; Crousse, B.
Synlett 2004, 18-29.
(16) (a) It is noteworthy that the present access to 5-aroylpyrrolidines
of type 5 offers many advantages over other alternatives described in the
literature that involve multistep syntheses (chlorination plus Friedel-Craft
acylation) starting from pyroglutamic acid or related derivatives, a process
that lacks of regioselectivity when substituted arenes are employed. Rigo,
B.; El Ghammarti, S.; Gautret, P.; Couturier, D. Synth. Commun. 1994, 24,
2597-2607. (b) It was additionally verified that the formation of a related
pyrrolidine derivative by application of the cyclization conditions to
N-methyl-4-pentenamide was not possible. Instead, a 5-hydroxymethyl-4,5-
dihydrofuranone was the only identified product. Examples of this type of
transformation can be found in: Takahata, H.; Suzuki, T.; Maruyama, M.;
Moriyama, K.; Mozumi, M.; Takamatsu, T.; Yamazaki, T. Tetrahedron
1988, 44, 4777-4786.
J. Org. Chem, Vol. 72, No. 4, 2007 1527

SCHEME 3. Preparation of Furanones 6a-da
29.1, 63.9, 128.2, 128.9, 130.0, 133.9, 175.3, 196.3; IR (KBr) ν
1690; MS (EI) m/z (%) 203 (M+, 1), 98 (100); HRMS calcd for
C12H13NO2 203.0946, found 203.0952.
1-Allyl-5-benzoylpyrrolidin-2-one (5c). According to the typical
procedure, pyrrolidinone 5c was obtained from amide 4c in 81%
yield as a colorless oil after purification by flash chromatography
(EtOAc): 1H NMR (CDCl3) δ 1.96-2.01 (m, 1H), 2.39-2.42 (m,
3H), 3.39 (dd, J ) 15.0, 7.9 Hz, 1H), 4.45-4.51 (m, 1H), 5.02-
5.15 (m, 3H), 5.55-5.78 (m, 1H), 7.45-7.63 (m, 3H), 7.91 (d, J
) 7.1 Hz, 2H); 13C NMR (CDCl3) δ 23.0, 29.4, 44.2, 60.6, 118.6,
128.2, 128.9, 132.3, 133.9, 134.0, 175.0, 196.8; IR (film) ν 1694;
MS (EI) m/z (%) 229 (M+, 1), 124 (100), 105 (23); HRMS calcd
for C14H15NO2 229.1103, found 229.1111.
a Reagents and conditions: (i) PIFA, CF3CH2OH, 0 °C.
5-Benzoyl-1-benzylpyrrolidin-2-one (5d). According to the
typical procedure, pyrrolidinone 5d was obtained from amide 4d
in 71% yield as colorless oil after purification by flash chroma-
tography (EtOAc). All spectroscopic data were in agreement with
those reported in the literature.19
that includes activation of the triple bond by PIFA (instead of
nitrogen oxidation)17 to give an electrophilic intermediate that
reacts intramolecularly with the nucleophilic amide. Analogous
steps would render the final N-alkylpyrrolidinones of type J.
Therefore, in order to get more information to support the
second mechanistic alternative (pathway B in Scheme 2), we
envisaged that the behavior of carboxylic acids, as the nucleo-
philic component of this PIFA-mediated cyclization, might be
coherent with the obtained results on the cyclization of
N-alkylamides. To carry out this study, carboxylic acids 3a-d
were also submitted to the action of PIFA (1.5 equiv of PIFA
and CF3CH2OH as solvent at 0 °C), and in all cases, we verified
the formation of the expected furanones 6a-d in moderate to
good yields (see Scheme 3).18 Consequently, these results not
only increase the synthetic applicability of the described
methodology but they also support the previously proposed
alternative mechanism shown in Scheme 2.
In summary, the fact that N-alkyl (and not only N-aryl)-
substituted alkynylamides can be transformed into the corre-
sponding pyrrolidinones by the action of PIFA led us to propose
that this hypervalent iodine reagent can also activate alkyne
moieties toward the intramolecular nucleophilic attack of the
amide functional group. This suggestion is reinforced by the
verification that the treatment of a series of alkynylcarboxylic
acids with PIFA leads to the formation of the corresponding
furanones under the same reaction conditions in moderate to
good yields.
5-Benzoyl-1-cyclohexylpyrrolidin-2-one (5e). According to the
typical procedure, pyrrolidinone 5e was obtained from amide 4e
in 50% yield as a white solid after purification by flash chroma-
tography (hexanes/EtOAc, 4:6) followed by triturating in hexanes:
1
mp 102-103 °C (hexanes); H NMR (CDCl3) δ 0.82-1.00 (m,
2H), 1.10-1.41 (m, 3H), 1.52-1.78 (m, 5H), 1.86-2.00 (m, 1H),
2.24-2.56 (m, 3H), 3.87-3.97 (m, 1H), 5.18-5.21 (m, 1H), 7.48-
7.52 (m, 2H), 7.58-7.63 (m, 1H), 7.93-7.97 (m, 2H); 13C NMR
(CDCl3) δ 24.6, 25.4, 25.5, 25.6, 29.9, 30.8, 31.4, 52.0, 58.9, 128.1,
129.0, 133.8, 134.0, 175.3, 198.0; IR (KBr) ν 1681; MS (EI) m/z
(%) 272 (M+ + 1, 5), 271 (M+, 1), 167 (41), 166 (93), 105 (100),
84 (91), 77 (99), 69 (44), 55 (82), 51 (94); HRMS calcd for C17H21-
NO2 271.1572, found 271.1569.
1-Benzyl-5-(4-methoxybenzoyl)pyrrolidin-2-one (5f). Accord-
ing to the typical procedure, pyrrolidinone 5f was obtained from
amide 4f in 88% yield as a white solid after purification by flash
chromatography (EtOAc). All spectroscopic data were in agreement
with those reported in the literature.20
1-Benzyl-5-(1-naphthoyl)pyrrolidin-2-one (5g). According to
the typical procedure, pyrrolidinone 5g was obtained from amide
4g in 78% yield as colorless oil after purification by flash
chromatography (EtOAc): 1H NMR (CDCl3) δ 1.86-1.98 (m, 1H),
2.12-2.28 (m, 1H), 2.40-2.66 (m, 2H), 3.96 (d, J ) 15.0 Hz,
1H), 4.91 (dd, J ) 9.5, 3.9 Hz, 1H), 5.29 (d, J ) 15.0 Hz, 1H),
7.20-7.61 (m, 9H), 7.84-8.00 (m, 2H), 8.45 (d, J ) 8.7 Hz, 1H);
13C NMR (CDCl3) δ 22.5, 29.4, 45.5, 62.6, 124.1, 125.0, 126.7,
127.5, 127.8, 128.3, 128.4, 128.5, 128.7, 130.3, 132.8, 133.4, 133.7,
135.9, 175.3, 200.5; IR (film) ν 1685; MS (EI) m/z (%) 329 (M+,
1), 174 (100), 127 (15), 91 (95); HRMS calcd for C22H19NO2
329.1416, found 329.1413.
1-Benzyl-5-(thiophene-2-carbonyl)pyrrolidin-2-one (5h). Ac-
cording to the typical procedure, pyrrolidinone 5h was obtained
from amide 4h in 82% yield as a colorless oil after purification by
flash chromatography (EtOAc): 1H NMR (CDCl3) δ 1.95-2.07
(m, 1H), 2.12-2.65 (m, 3H), 3.75 (d, J ) 15.0 Hz, 1H), 4.66-
4.72 (m, 1H), 5.17 (d, J ) 15.0 Hz, 1H), 7.08-7.24 (m, 6H), 7.54
(d, J ) 3.6 Hz, 1H), 7.69 (d, J ) 4.7 Hz, 1H); 13C NMR (CDCl3)
δ 23.4, 29.4, 45.2, 62.2, 127.6, 128.3, 128.4, 128.6, 132.4, 134.9,
135.7, 140.8, 175.1, 190.3; IR (film) ν 1685; MS (EI) m/z (%) 285
(M+, 1), 174 (68), 91 (100); HRMS calcd for C16H15NO2S
285.0824, found 285.0825.
5-Benzoyl-1-(2-bromophenyl)pyrrolidin-2-one (5i). According
to the typical procedure, pyrrolidinone 5i was obtained from amide
4i in 54% yield as a white solid after purification by flash
chromatography (hexanes/EtOAc, 7:3): mp 124-126 °C (hexanes);
1H NMR (CDCl3) δ 2.18-2.26 (m, 1H), 2.56-2.83 (m, 3H), 5.75
Experimental Section
Typical Procedure for the PIFA-Mediated Alkyne Amidation.
Synthesis of 5-Benzoyl-1-methylpyrrolidin-2-one (5b). A solution
of amide 4b (100 mg, 0.53 mmol) in CF3CH2OH (5 mL) was cooled
to 0 °C, and a solution of PIFA (142 mg, 0.78 mmol) in CF3CH2-
OH (6 mL) was added dropwise. The reaction mixture was stirred
at 0 °C until completion was observed by TLC (1 h). Aqueous
Na2CO3 10% (5 mL) was added and extracted with CH2Cl2 (3 ×
10 mL). The combined organic extracts were washed with brine,
dried over Na2SO4, and the solvent evaporated. Purification of the
crude by flash chromatography (EtOAc/MeOH, 96:4), followed by
crystallization from hexanes, afforded pyrrolidinone 5b as a white
1
solid (84 mg, 78%): mp 97-98 °C (hexanes); H NMR (CDCl3)
δ 1.93-2.08 (m, 1H), 2.36-2.57 (m, 3H), 2.83 (s, 3H), 5.05-
5.10 (m, 1H), 7.49 (dd, J ) 8.3, 7.3 Hz, 2H), 7.61 (t, J ) 7.3 Hz,
1H), 7.94 (d, J ) 8.3 Hz, 2H); 13C NMR (CDCl3) δ 22.9, 28.9,
(17) N-Alkylnitrenium ions would not be stable enough to exist.
(18) Some selected examples of alkyne electrophilic cyclization employ-
ing oxygenated nucleophiles: (a) Arcadi, A.; Cacchi, S.; Di Giuseppe, S.;
Fabrizi, G.; Marinelli, F. Org. Lett. 2002, 4, 2409-2412. (b) Gulias, M.;
Rodr´ıguez, J. R.; Castedo, L.; Mascaren˜as, J. L. Org. Lett. 2003, 5, 1975-
1977. (c) Liu, Y.; Zhou, S. Org. Lett. 2005, 7, 4609-4611. (d) Yue, D.;
Della Ca´, N.; Larock, R. C. J. Org. Chem. 2006, 71, 3381-3388.
(19) Deskus, J.; Fan, D.; Smith, M. B. Synth. Commun. 1998, 28, 1649-
1659.
(20) Yaguang, L. U.S. Patent US6486169, 2002; Chem. Abstr. 2002, 137,
363098.
1528 J. Org. Chem., Vol. 72, No. 4, 2007

(dd, J ) 9.4, 2.3 Hz, 1H), 7.14-7.19 (m, 1H), 7.32-7.37 (m, 2H),
7.48 (t, J ) 7.6 Hz, 2H), 7.58-7.66 (m, 3H), 7.92 (d, J ) 7.7 Hz,
1H); 13C NMR (CDCl3) δ 24.0, 29.2, 63.4, 121.9, 128.2, 128.3,
128.9, 129.6, 132.3, 133.8, 133.9, 136.3, 175.3, 196.3; IR (film) ν
1708; MS (EI) m/z (%) 241 (10), 238 (84), 184 (68), 159 (83), 130
(83), 105 (98), 77 (100), 51 (94); HRMS calcd for C17H14NO2Br
343.0208, found 343.0208.
5-Benzoyl-4,5-dihydrofuran-2(3H)-one (6a). According to the
typical procedure, furanone 6a was obtained from carboxylic acid
3a in 55% yield as a white solid after purification by flash
chromatography (hexanes/EtOAc, 7:3). All spectroscopic data were
in agreement with those reported in the literature.21
13C NMR (CDCl3) δ 25.2, 26.8, 79.4, 124.2, 125.2, 126.8, 128.6,
128.9, 130.5, 131.3, 133.9, 134.1, 176.4, 197.9; IR (KBr) ν 1781,
1685; MS (EI) m/z (%) 240 (M+, 5), 155 (100), 127 (46); HRMS
calcd for C15H12O3 240.0786, found 240.0787.
5-(Thiophene-2-carbonyl)-4,5-dihydrofuran-2(3H)-one (6d).
According to the typical procedure, furanone 6d was obtained from
carboxylic acid 3d in 58% yield as a white solid after purification
by flash chromatography (hexanes/EtOAc, 9:1) followed by crystal-
lization from n-pentane: mp 79-80 °C (n-pentane); 1H NMR
(CDCl3) δ 2.41-2.68 (m, 4H), 5.53-5.59 (m, 1H), 7.15-7.19 (m,
1H), 7.75 (d, J ) 5.1 Hz, 1H), 7.93 (d, J ) 3.6 Hz, 1H); 13C NMR
(CDCl3) δ 25.4, 26.8, 79.1, 128.6, 133.9, 135.6, 140.0, 176.1, 187.9;
IR (KBr) ν 1781, 1667; MS (EI) m/z (%) 196 (M+, 8), 110 (100),
85 (20); HRMS calcd for C9H8O3S 196.0194, found 196.0191.
5-(4-Methoxybenzoyl)-4,5-dihydrofuran-2(3H)-one (6b). Ac-
cording to the typical procedure, furanone 6b was obtained from
carboxylic acid 3b in 65% yield as a white solid after purification
by flash chromatography (hexanes/EtOAc, 9:1). All spectroscopic
data were in agreement with those reported in the literature.22
5-(1-Naphthoyl)-4,5-dihydrofuran-2(3H)-one (6c). According
to the typical procedure, furanone 6c was obtained from carboxylic
acid 3c in 61% yield as a white solid after purification by flash
chromatography (hexanes/EtOAc, 9:1) followed by crystallization
Acknowledgment. Financial support from the University of
the Basque Country (9/UPV 41.310-13656/2001) and the
Spanish Ministry of Science and Technology (MCYT BQU
2001-0313 and MEC CTQ2004-03706/BQU) is gratefully
acknowledged. S.S. thanks the Basque Government for a
predoctoral scholarship.
1
from n-pentane: mp 72-74 °C (n-pentane); H NMR (CDCl3) δ
2.34-2.75 (m, 4H), 5.82-5.87 (m, 1H), 7.50-7.65 (m, 3H), 7.88-
7.94 (m, 2H), 8.06 (d, J ) 8.3 Hz, 1H), 8.62 (d, J ) 8.3 Hz, 1H);
Supporting Information Available: Experimental details and
1H and 13C NMR spectra of all new compounds are included. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(21) Bourguignon, J.-J.; Maitre, M.; Klotz, E.; Schmitt, M.; Gobaille,
S.; Macher, J.-P. Patent WO2002042250, 2002; Chem. Abstr. 2002, 136,
401535.
(22) Hou, R.-S.; Wang, H.-M.; Lin, Y.-C.; Chen, L.-C. Heterocycles
2005, 65, 649-656.
JO062320S
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