Chelation-accelerated sequential decarbonylation of formate and alkoxycarbonylation of aryl halides using a combined Ru and Pd catalyst

Article abstract of DOI:10.1021/jo026591o

An efficient cooperative catalyst system for the coupling of a wide range of organic electrophiles with chelated formate is reported to afford aryl and alkenyl esters by the simultaneous employment of Ru and Pd catalyst, in which ruthenium first promotes chelation-accelerated decarbonylation of formate to release CO and carbinol that are presumed to be transferred, still chelated to Ru, into Pd catalyst, which catalyzes alkoxycarbonylation of the organic electrophiles.

Full text of DOI:10.1021/jo026591o

TABLE 1. Cou p lin g of Iod oben zen e w ith F or m a te 1a
Ch ela tion -Acceler a ted Sequ en tia l
Deca r bon yla tion of F or m a te a n d
Alk oxyca r bon yla tion of Ar yl Ha lid es Usin g
a Com bin ed Ru a n d P d Ca ta lyst
Sangwon Ko,† Chongmok Lee,† Moon-Gun Choi,‡
entry
Ru (3 mol %)
Pd (2 mol %)
yieldb (%)
Youngim Na,§ and Sukbok Chang*,§
1
2
3
4
5
6
7
Ru3(CO)12
-
Ru3(CO)12
Ru3(CO)12
Ru3(CO)12
Ru3(CO)12
Ru3(CO)12
-
PdCl2
PdCl2
Pd(OAc)2
Pd(PPh3)4
Pd2(dba)3
Pd/C
<5
<5
94
79
88
93
86
Department of Chemistry, Ewha Womans University,
Seoul 120-750, Korea, Department of Chemistry, Yonsei
University, Seoul 120-749, Korea, and Center for Molecular
Design and Synthesis (CMDS), Department of Chemistry,
Korea Advanced Institute of Science and Technology
(KAIST), Daejeon 305-701, Korea
a
sbchang@mail.kaist.ac.kr
Iodobenzene (0.4 mmol), formate 1 (0.2 mmol), NaHCO3 (0.3
mmol), and indicated catalysts in DMF (0.2 mL). b Refer to isolated
yield.
Received October 21, 2002
Abstr a ct: An efficient cooperative catalyst system for the
coupling of a wide range of organic electrophiles with
chelated formate is reported to afford aryl and alkenyl esters
by the simultaneous employment of Ru and Pd catalyst, in
which ruthenium first promotes chelation-accelerated de-
carbonylation of formate to release CO and carbinol that are
presumed to be transferred, still chelated to Ru, into Pd
catalyst, which catalyzes alkoxycarbonylation of the organic
electrophiles.
observed that, with bulky substrates such as tri- and
tetrasubstituted olefins, decarbonylation of 1 was a major
source of low product yields. The Ru-catalyzed decarbo-
nylation of 1 became almost dominant, especially in the
absence of organic acceptors such as alkenes and alkynes,
which is believed to be accelerated presumably due to
chelation.6 For example, treatment of 2-pyridylmethyl
formate (1) with Ru3(CO)12 complex (5 mol %) resulted
in complete decarbonylation (DMF, 1 h, 135 °C), generat-
ing 2-pyridinemethanol and CO in quantitative yields.
In contrast, benzyl formate was not affected by the same
catalyst and was completely recovered unchanged, indi-
cating that the facile decarbonylation of formate 1 is
driven by chelation between ruthenium and the pyridyl
group of 1 (vide infra).7
This observation led us to test a possibility that the in
situ generated carbinol and CO could be sequentially
utilized to couple with organic electrophiles in the pres-
ence of a suitable second metal catalyst. As a test reac-
tion, iodobenzene was allowed to react with 2-pyridyl-
methyl formate (1) under a variety of catalytic condi-
tions (Table 1).8 Whereas no coupled product was gen-
erated with the action of any single metal species alone
(Ru, Rh, Pd, etc.), we were pleased to discover that
simultaneous employment of both Ru and Pd catalyst, in
Transition-metal catalysis has made significant con-
tributions to synthetic chemistry, especially in the past
decades, and this trend will continue in the future.1
Whereas a single metal species is employed to carry out
a specified transformation in most cases, some recent
examples have shown that one-pot tandem conversions
could be achieved by the right combination of multiple
catalysts, in which sequential catalytic processes are in
action by the use of different metal species at the same
time.2 In the context of studies on metal catalyzed
reactions,3 we recently reported a novel chelation-assisted
approach toward Ru-catalyzed hydroesterfication of ole-
fins.4 In this regard, we describe herein an efficient
coupling protocol of a chelating formate with aryl and
alkenyl (pseudo)halides on the basis of two sequential
catalytic processes; decarbonylation of pyridylmethyl
formate by Ru catalyst, and subsequent Pd-catalyzed
alkoxycarbonylation of organic electrophiles (eq 1).5
(3) (a) Na, Y.; Chang, S. Org. Lett. 2000, 2, 1887. (b) Lee, M.; Ko,
S.; Chang, S. J . Am. Chem. Soc. 2000, 122, 12011. (c) Chang, S.; Lee,
M.; Kim, S. Synlett 2001, 1557. (d) Chang, S.; Na, Y.; Choi, E.; Kim,
S. Org. Lett. 2001, 3, 2089. (e) Chang, S.; Yang, S. H.; Lee, P. H.
Tetrahedron Lett. 2001, 42, 4833. (f) Yang, S. H.; Chang, S. Org. Lett.
2001, 3, 4209. (g) Choi, E.; Lee, C.; Na, Y.; Chang, S. Org. Lett. 2002,
4, 2369.
(4) Ko, S.; Na, Y.; Chang, S. J . Am. Chem. Soc. 2002, 124, 750.
(5) Although efficiency was generally low (<36% yield), a bimetallic
catalytic system of Pd/Ru was previously utilized for the conversion of
halobenzenes into aromatic acids with aqueous methyl formate under
biphasic conditions at 160 °C, see: J enner, G.; Taleb, A. B. J .
Organomet. Chem. 1994, 470, 257.
(6) For recent examples of chelation-assisted strategy in metal
catalyzed reactions, see: (a) Itami, K.; Mitsudo, K.; Kamei, T.; Koike,
T.; Nokami, T.; Yoshida, J . J . Am. Chem. Soc. 2000, 122, 12013. (b)
Ishiyama, T.; Hartwig, J . J . Am. Chem. Soc. 2000, 122, 12043. (c)
Chatani, N.; Tatamidani, H.; Ie, Y.; Kakiuchi, F.; Murai, S. J . Am.
Chem. Soc. 2001, 123, 4849. (d) J un, C.-H.; Lee, H.; Moon, C. W.; Hong,
H.-S. J . Am. Chem. Soc. 2001, 123, 8600.
In the hydroesterification reaction of alkenes with 2-
pyridylmethyl formate (1) using Ru3(CO)12 catalyst,4 we
† Ewha Womans University.
‡ Yonsei University.
§ Korea Advanced Institute of Science and Technology.
(1) (a) Transition Metals for Organic Synthesis; Beller, M., Bolm,
C., Eds.; Wiley-VCH: Weinheim, 1998. (b) Tsuji, J . Transition Metal
Reagents and Catalysts; J ohn Wiley & Sons, Ltd.: London, 2000. (c)
Applied Homogeneous Catalysis with Organometallic Compounds;
Cornils, B., Herrmann, W. A., Eds.; Wiley-VCH: Weinheim, 2002.
(2) For selected recent examples, see: (a) Barnhart, R. W.; Banzan,
G. C.; Mourey, T. J . Am. Chem. Soc. 1998, 120, 1082. (b) J eong, N.;
Seo, S. D.; Shin, J . Y. J . Am. Chem. Soc. 2000, 122, 10220. (c) Lee, P.
H.; Sung, S.-y.; Lee, K. Org. Lett. 2001, 3, 3201. (d) Son, S. U.; Park,
K. H.; Chung, Y. K. J . Am. Chem. Soc. 2002, 124, 6838.
(7) Ru3(CO)12 has been known to catalyze decarbonylation of alkyl
formates in the presence of phosphines or N-oxide ligands, see: (a)
Kondo, T.; Tantayanon, S.; Tsuji, Y.; Watanabe, Y. Tetrahedron Lett.
1989, 30, 4137. (b) J enner, G.; Nahmed, E. M.; Leismann, H. J .
Organomet. Chem. 1990, 387, 315.
10.1021/jo026591o CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/18/2003
J . Org. Chem. 2003, 68, 1607-1610
1607

TABLE 2. Rea ction of F or m a te 1 w ith Va r iou s Or ga n ic
Electr op h ilesa
the presence of an inorganic base (NaHCO3), afforded
2-pyridinemethyl benzoate (2a ) in high yield. Whereas
Ru3(CO)12 was the only effective Ru species among vari-
ous complexes tested, choice of a Pd partner was more
flexible. Although certain Pd catalysts exhibited rather
similar efficiency on the coupling in the presence of Ru3-
(CO)12 catalyst (entries 3-6), PdCl2 was chosen as the
Pd catalyst for practical reasons. In addition to the ho-
mogeneous Pd catalysts, Pd/C (entry 7) turned out to be
also effective for the reaction.9 DMF (94%, entry 3) was
the most effective medium for the reaction compared with
other tested solvents such as toluene (72%), THF (61%),
or dioxane (59%).10 Although a bimetallic catalytic system
of Rh/Pd was previously known to perform formate-halide
carbonylation reactions,11 the carbonylation did proceed
only under pressurized CO atmosphere implying that
formate ester carbonyl is not the source of the generated
carbonylated products.
The sequential Ru/Pd bimetallic catalytic protocol could
be successfully applied to a large array of aryl and alken-
yl (pseudo)halides with formate 1 under the conditions
established above (Table 2). In general, 2-5 mol % of
each PdCl2 and Ru3(CO)12 catalyst were sufficient to ob-
tain satisfactory yields in DMF (135 °C) in the presence
of NaHCO3 (1.5 equiv). Whereas free hydroxyl group was
tolerant to the reaction conditions (entry 4), steric hin-
drance near the reaction site slowed the conversion to
some extent (entry 6). Chemoselective coupling on iodo
group in the presence of bromo was observed (entry 7).
However, with longer reaction times, bromobenzene itself
was also reacted with higher loadings of both Pd (5 mol
%) and Ru (5 mol %) catalyst (entry 8). For 1-iodonaph-
thalene, K2CO3 (73%) turned out to be a more effective
base than NaHCO3 (36%). An aryl triflate was smoothly
reacted with 1 to afford benzoate in moderate yield (entry
10). Alkenyl iodides were also readily coupled with for-
mate 1 under the standard conditions and conjugated
esters were obtained in high yields (entries 11 and 12).
In addition, allylic carbonate turned out to be another
coupling partner to afford allylic ester (entry 13).12 No
isomerization of the olefinic geometry was observed with
alkenyl substrates.
a
Substrates (0.8 mmol), 1 (0.4 mmol), and NaHCO3 (0.6 mmol)
in DMF (0.4 mL). Isolated yield after chromatography. c Pd and
Ru were each used (5 mol %). K2CO3 (1.5 equiv) was used instead
of NaHCO3.
b
d
into imidoyl carboxylates have not been reported using
the conventional Pd-catalyzed carbonylation of iodoben-
zenes with alcohols even in the presence of high pressuric
CO atmosphere.15 As shown in our previous paper,4 the
stable formate 1 is readily prepared with excellent yields
(>95%) in large scales (>15 g) by a simple formylation
of 2-pydidinemethanol. In addition, hydrolysis of the pro-
duced carboxylates under mild conditions gives pyridyl-
carbinol and the corresponding carboxylic acids in quan-
titative yields. Therefore, this protocol could be used as
an attractive alternative to the Pd-catalyzed carbonyla-
tion reaction.
Notably, imidoyl triflates were also coupled with for-
mate 1 under the employed conditions (DMF, 135 °C),
and cyclic imidoyl carboxylates with variable ring sizes
(2l-2o) were readily produced in 12-24 h (eq 2).13 It
should be mentioned that this could be potentially
developed into an easy route for preparation of unnatural
chiral amino acids upon stereoselective reduction of the
imidoyl double bond.14 The conversion of imidoyl triflates
(8) Pd-catalyzed alkoxycarbonylation of aryl halides with alkyl
formates in the presence of sodium alkoxides was previously reported,
in which sodium alkoxide decarbonylates stoichiometrically formates
to provide carbon monoxide, see: Carpentier, J .-F.; Castanet, Y.;
Brocard, J .; Mortreux, A.; Petit, F. Tetrahedron Lett. 1991, 32, 4705.
(9) Recently, it has been revealed that Pd/C is a source of soluble
homogeneous catalyst in carbonylation reaction, see: Davies, I. W.;
Matty, L.; Hughes, D. L.; Reider, P. J . J . Am. Chem. Soc. 2001, 123,
10139.
(10) On the basis of this result, a possibility that DMF acts as a CO
source through decomposition of DMF could be ruled out, for reference;
see: Wan, Y.; Altermann, M.; Larhed, M.; Hallberg, A. J . Org. Chem.
2002, 67, 6232.
Although further studies have to be carried out to
elucidate detailed aspects of this reaction, it is believed
(13) Imidoyl triflates were prepared in 70-90% yields starting from
the corresponding lactams: J acobi, P. A.; Liu, H. J . Am. Chem. Soc.
1999, 121, 1958.
(14) Blaser, H.-U.; Spindler, F. In Comprehensive Asymmetric
Catalysis I; J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-
Verlag: Heidelberg, 1999; Vol. 1, Chapter 6.2.
(11) Buchan, C.; Hamel, N.; Woell, J . B.; Alper, H. J . Chem. Soc.,
Chem. Commun. 1986, 167.
(12) However, chlorobenzene did not react under the present condi-
tions.
(15) Organopalladium Chemistry for Organic Synthesis; Negishi, E.,
Ed.; Wiley-Interscience: New York, 2002; Vol. 2, Part VI.
1608 J . Org. Chem., Vol. 68, No. 4, 2003

pheric CO environment (1 atm), PdCl2 (2 mol %) catalyst
performed the stoichiometric coupling reaction between
iodobenzene and 3 producing benzoate ester (2a ) in 43%
yield in the presence of NaHCO3 (1.5 equiv) even at lower
temperatures (80 °C, 2 h) compared with the catalytic
conditions. Reaction of 2-pyridinemethanol with iodo-
benzene (2 equiv) under atmospheric CO was sluggish
with Pd species alone in the absence of Ru catalyst and
provided benzoate in low yield (33%) of benzoate with
PdCl2 catalyst (2 mol %) in DMF (80 °C, 2 h, 42% con-
version). However, the same reaction proceeded much
faster in the presence of Ru3(CO)12 (2 mol %), and result-
ed in complete conversion with 91% isolated yield under
otherwise identical conditions. This implies that the
transfer of 2-pyridinemethanol into the Pd-catalyzed
alkoxycarbonylation cycles is greatly accelerated by che-
lation with Ru. Therefore, it is believed that the ruthen-
ium catalyst has dual roles; it catalyzes decarbonylation
of chelating formate 1 and facilitates chelation-assisting
transfer of the in situ formed carbinol to Pd-catalyzed
carbonylation pathways.
In summary, an efficient cooperative catalytic system
for coupling a range of organic electrophiles with chelat-
ing formate has been achieved to afford aryl and alkenyl
esters by the one-pot employment of Ru and Pd catalysts.
In the processes, chelation plays a key role on the
efficiency of both sequences of ruthenium-catalyzed de-
carbonylation of formate and palladium-catalyzed alkoxy-
carbonylation of aryl and alkenyl (pseudo)halides. Imi-
doyl carboxylates can be readily obtained from the
corresponding imidoyl triflates. The merit of this protocol
in comparison with Pd-catalyzed carbonylation is obvious
such that it does not employ high pressuric CO atmo-
sphere, which can potentially lead to an easy way of
introducing a labeled carbonyl into products without need
of using expensive labeled gaseous CO.19
F IGURE 1. Molecular structure of 3. Selected bond lengths
(Å) and angles (deg): Ru(1)-Ru(2) 2.7841(7), Ru(2)-Ru(3)
3.0197(9), Ru(1)-Ru(3) 2.7693(8), Ru(2)-O(1) 2.088(3), Ru-
(2)-O(2) 2.147(3), Ru(2)-N(1) 2.171(4); Ru(1)-Ru(2)-Ru(3)
56.825(18), Ru(2)-O(1)-Ru(3) 91.11(12), O(1)-Ru(2)-N(1)
77.81(13).
SCHEME 1. P r op osed Mech a n ism for th e Ru /
P d -Ca ta lyzed Rea ction
Exp er im en ta l Section
Gen er a l Meth od s. 1H and 13C NMR spectra were recorded
on
a 250 and 62.5 MHz NMR spectrometer, respectively.
Chemical shifts are reported in δ, parts per million (ppm)
downfield from tetramethylsilane, or in ppm relative to the
singlet at 7.26 ppm of chloroform-d or to a center line of a pentet
at 2.50 ppm of DMSO-d6. Splitting patterns are designated as
follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet;
td, triple of doublet; dd, double of doublet; b, broad. 13C NMR
data are reported in ppm relative to the center line of a triplet
at 77.0 ppm of chlorofom-d or to a center line of a heptet at 39.5
ppm of DMSO-d6. IR and mass spectra were obtained from the
Center for Molecular Design and Synthesis (CMDS) at KAIST.
Column chromatography was carried out using silica gel 60
(230-400 mesh, Merck). Solvents were purified by standard
procedures. Commercially obtained chemicals including Ru and
Pd complexes were purchased from a commercial supplier and
used as obtained without further purification.
to proceed via two sequential catalytic executions (Scheme
1): decarbonylation of formate 1 by Ru3(CO)12 complex
followed by Pd-catalyzed alkoxycarbonylation of organic
electrophiles.
Treatment of 2-pyridylmethyl formate (1) with stoichio-
metric amounts of Ru3(CO)12 gave a brownish solid (3),
the IR spectrum of which showed five detectable CO
stretches: 2071, 2024, 1994, 1971, and 1932 cm-1. Crystal
structure of 3 reveals that it is a triruthenium cluster
coordinated with eight carbon monoxides and two mol-
ecules of 2-pyridinemethanol which are generated via
decarbonylation of formate 1 (Figure 1).16 Whereas tri-
nuclear Ru species were proposed previously as key inter-
mediates in some organic transformations involving C-H
activation,17 to the best of our knowledge, this is the first
example of a ruthenium cluster containing five-mem-
bered N,O-heteroatom chelation.18 Under the atmos-
Rep r esen ta tive P r oced u r e for th e Cou p lin g Rea ction .
To a solution of 2-pyridylmethyl formate 14 (54.8 mg, 0.4 mmol)
in DMF (0.4 mL) was added iodobenzene (163.2 mg, 0.8 mmol)
(17) Fukuyama, T.; Chatani, N.; Tatsumi, J .; Kakiuchi, F.; Murai,
S. J . Am. Chem. Soc. 1998, 120, 11522.
(18) For a previous report of a crystal structure of a ruthenium
cluster with phenanthroline ligand, see: Fish, R. H.; Kim, T.-J .;
Stewart, J . L.; Bushweller, J . H.; Rosen, R. K.; Dupon, J . W. Organo-
metallics 1986, 5, 2193.
(19) Recently, the use of aldehyde as a CO source in catalytic
Pauson-Khand reaction has been reported, see: (a) Morimoto, T.; Fuji,
K.; Tsutsumi, K.; Kakiuchi, K. J . Am. Chem. Soc. 2002, 124, 3806. (b)
Shibata, T.; Toshida, N.; Takagi, K. Org. Lett. 2002, 4, 1619.
(16) For full data of crystal 3, see the Supporting Information.
Selected data of crystal 3: crystal dimension 0.28 × 0.26 × 0.16 mm,
V ) 2376.0(10) Å3, monoclinic, space group P2(1)/c, a ) 13.097(3) Å, b
) 9.137(2) Å, c ) 20.287(5) Å, measured 17585, R(int) ) 0.0519, wR2
(all data) ) 0.0754, GOF ) 1.180, Z ) 11.
J . Org. Chem, Vol. 68, No. 4, 2003 1609

followed by Ru3(CO)12 (7.7 mg, 3 mol %), PdCl2 (1.4 mg, 2 mol
%) and NaHCO3 (50.4 mg, 0.6 mmol). The reaction mixture was
stirred at 135 °C for 6 h in a sealed vial. After removal of the
solvent under reduced pressure, the residue was purified by flash
column chromatography on silica gel (15% EtOAc/hexane) to
afford the 2-pyridylmethyl benzoate (2a ) as a yellowish liquid:
1H NMR (CDCl3, 250 MHz) δ 8.61 (d, 1H, J ) 4.3 Hz), 8.12 (d,
2H, J ) 8.3 Hz), 7.70 (td, 1H, J ) 7.7, 1.7 Hz), 7.56 (dd, 1H, J
) 7.7, 1.5 Hz), 7.43 (m, 3H), 7.24 (m, 1H), 5.49 (s, 2H); 13C NMR
(CDCl3, 62.5 MHz) δ 166.6, 156.4, 149.9, 137.2, 133.6, 130.2,
128.9, 123.3, 122.1, 67.6; IR (neat) 3066, 3015, 2949, 1971, 1916,
1719, 1595, 1438 cm-1; HRMS (EI) calcd for C13H11NO2 213.0790
(M+), found 213.0794.
2-P yr id ylm eth yl 4-m eth ylben zoa te (2b): 1H NMR (CDCl3,
250 MHz) δ 8.62 (d, 1H, J ) 4.3 Hz), 8.00 (d, 2H, J ) 8.2 Hz),
7.72 (td, 1H, J ) 7.7, 1.7 Hz), 7.45 (d, 1H, J ) 7.8 Hz), 7.26 (d,
3H, J ) 7.3 Hz) 5.48 (s, 2H), 2.42 (s, 3H); 13C NMR (CDCl3, 62.5
MHz) δ 166.7, 156.5, 149.8, 144.4, 137.2, 130.2, 129.6, 127.5,
123.2, 122.0, 67.4, 22.1; IR (neat) 2948, 1930, 1720, 1612, 1438,
1276, 1108, 753 cm-1; HRMS (EI) calcd for C14H13NO2 227.0947
(M+), found 227.0948.
Hz), 7.37 (d, 1H, J ) 7.8 Hz), 7.23 (m, 1H), 7.07 (dt, 1H, J )
15.6, 7.8 Hz), 5.93 (d, 1H, J ) 15.6 Hz), 5.30 (s, 2H), 2.24 (q,
1H, J ) 6.6 Hz), 1.49-1.29 (m, 4H), 0.91 (t, 3H, J ) 7.1 Hz); 13
C
NMR (CDCl3, 62.5 MHz) δ 166.8, 156.5, 151.1, 149.9, 137.2,
123.2, 122.2, 121.0, 67.0, 32.4, 30.4, 22.6, 14.3; IR (neat) 2961,
1726, 1439, 1170, 1047, 732 cm-1; HRMS (EI) calcd for C13H17
NO2 219.1260 (M+), found 219.1260.
-
2-P yr id ylm eth yl 2-bu tyla cr yla te (2j): 1H NMR (CDCl3, 250
MHz) δ 8.60 (d, 1H, J ) 4.7 Hz), 7.71 (td, 1H, J ) 7.7, 1.6 Hz),
7.37 (d, 1H, J ) 7.8 Hz), 7.23 (m, 1H), 6.25 (s, 1H), 5.06 (s, 1H),
5.32 (s, 2H), 2.36 (t, 2H, J ) 7.8 Hz), 1.51-1.30 (m, 4H), 0.91 (t,
3H, J ) 7.1 Hz); 13C NMR (CDCl3, 62.5 MHz) δ 167.3, 156.5,
149.8, 140.9, 137.2, 125.6, 123.2, 121.9, 67.3, 32.0, 30.9, 22.7,
14.3; IR (neat) 2959, 2871, 1722, 1595, 1438, 1282, 1155, 947,
757 cm-1; HRMS (EI) calcd for C13H17NO2 219.1260 (M+), found
219.1262.
2-P yr id ylm eth yl (E)-4-p h en yl-3-bu ten oa te (2k ): 1H NMR
(CDCl3, 250 MHz) δ 8.60 (d, 1H, J ) 4.5 Hz), 7.73 (td, 1H, J )
7.6, 1.6 Hz), 7.51 (d, 1H, J ) 7.8 Hz), 7.44-7.20 (m, 6H), 6.70
(d, 1H, J ) 15.9 Hz), 6.40 (dt, 1H, J ) 15.9, 6.1 Hz), 4.73 (s,
2H), 4.32 (dd, 2H, J ) 6.0, 1.0 Hz); 13C NMR (CDCl3, 62.5 MHz)
δ 158.5, 149.1, 136.6, 132.8, 128.5, 127.7, 126.5, 125.7, 122.3,
121.4, 73.1, 71.5; IR (neat) 3462, 2986, 1746, 1447, 1375, 1245,
1048, 918, 735 cm-1; HRMS (EI) calcd for C16H15NO2 253.1104
(M+), found 253.1109.
2-P yr id ylm eth yl 1-p yr r olin e-2-ca r boxyla te (2l): 1H NMR
(CDCl3, 250 MHz) δ 8.60 (d, 1H, J ) 4.8 Hz), 8.40 (bs, 1H), 7.77
(td, 1H, J ) 7.8, 1.6 Hz), 7.32 (d, 2H, J ) 7.4 Hz), 5.31 (s, 2H),
3.47 (m, 2H), 2.62 (t, 2H, J ) 6.5 Hz), 2.11-2.00 (m, 2H); 13C
NMR (CDCl3, 62.5 MHz) δ 172.9, 155.3, 149.6, 137.8, 123.7,
122.8, 122.3, 117.7, 66.1, 43.8, 32.3, 25.6; IR (neat) 3058, 2887,
1741, 1599, 1441, 1375, 1191, 1080, 983, 743 cm-1; HRMS (EI)
calcd for C11H12N2O2 204.0899 (M+), found 204.0878.
2-P yr id ylm et h yl-3,4,5,6-t et r a h yd r op yr id in eca r b oxyl-
a te (2m ): 1H NMR (CDCl3, 250 MHz) δ 8.60 (d, 1H, J ) 4.8
Hz), 7.74 (td, 1H, J ) 7.7, 1.6 Hz), 7.56 (bs, 1H), 7.35 (d, 1H, J
) 7.8 Hz), 7.29-7.26 (m, 1H), 5.20 (s, 2H), 3.33 (m, 2H), 2.48 (t,
2H, J ) 6.4 Hz), 1.83-1.65 (m, 4H); 13C NMR (CDCl3, 62.5 MHz)
δ 173.5, 155.4, 149.7, 137.8, 123.8, 122.8, 117.7, 66.9, 43.8, 33.9,
29.9, 21.3; IR (neat) 3021, 2871, 1738, 1601, 1483, 1368, 1223,
1084, 762 cm-1; HRMS (EI) calcd for C12H14N2O2 218.1056 (M+),
found 218.1056.
2-P yr id ylm eth yl 4-m eth oxylben zoa te (2c): yellowish solid;
1
mp 49-50 °C dec; H NMR (CDCl3, 250 MHz) δ 8.61 (d, 1H, J
) 4.4 Hz), 8.08 (d, 2H, J ) 8.9 Hz), 7.72 (td, 1H, J ) 7.7, 1.6
Hz), 7.44 (d, 1H, J ) 7.8 Hz), 7.24 (m, 1H), 6.93 (d, 2H, J ) 8.9
Hz), 5.46 (s, 2H), 3.86 (s, 3H); 13C NMR (CDCl3, 62.5 MHz) δ
166.4, 164.0, 156.7, 149.9, 137.2, 132.3, 123.2, 122.6, 122.0, 114.1,
67.4, 55.9; IR (neat) 3387, 2977, 2938, 1705, 1608, 1295, 1104,
1020, 757 cm-1; HRMS (EI) calcd for C14H13NO3 243.0896 (M+),
found 243.0894.
2-P yr id ylm eth yl 4-h yd r oxylben zoa te (2d ): yellowish solid;
1
mp 167-170 °C dec; H NMR (DMSO-d6, 250 MHz) δ 10.47 (s,
1H), 8.57 (d, 1H, J ) 4.3 Hz), 7.90 (d, 2H, J ) 8.7 Hz), 7.84 (t,
1H, J ) 7.7 Hz), 7.48 (d, 1H, J ) 7.8 Hz), 7.35 (m, 1H), 6.88 (d,
2H, J ) 8.6 Hz), 5.36 (s, 2H); 13C NMR (DMSO-d6, 75 MHz) δ
165.2, 162.2, 155.9, 149.0, 137.2, 131.7, 123.0, 121.5, 120.0, 115.4,
66.1; IR (neat) 3460, 2936, 1715, 1671, 1388, 1260, 1096, 771
cm-1; HRMS (EI) calcd for C13H11NO3 229.0739 (M+), found
229.0740.
2-P yr id ylm eth yl 4-a cetylben zoa te (2e): yellowish solid; mp
88-89 °C dec; 1H NMR (CDCl3, 250 MHz) δ 8.63 (d, 1H, J ) 4.6
Hz), 8.20 (d, 2H, J ) 8.3 Hz), 8.02 (d, 2H, J ) 8.3 Hz), 7.75 (t,
1H, J ) 7.7 Hz), 7.46 (d, 1H, J ) 7.8 Hz), 7.28 (m, 1H), 5.51 (s,
2H), 2.65 (s, 3H); 13C NMR (CDCl3, 62.5 MHz) δ 197.9, 165.8,
155.9, 150.0, 140.8, 137.3, 134.0, 130.5, 128.7, 123.5, 122.3, 68.1,
27.4; IR (neat) 3056, 2961, 1972, 1729, 1689, 1274 cm-1; HRMS
(EI) calcd for C15H13NO3 255.0896 (M+), found 255.0887.
2-P yr id ylm et h yl 2,6-d im et h ylb en zoa t e (2f): 1H NMR
(CDCl3, 250 MHz) δ 8.61 (d, 1H, J ) 4.8 Hz), 7.71 (td, 1H, J )
7.7, 1.7 Hz), 7.45 (d, 1H, J ) 7.8 Hz), 7.27-7.16 (m, 2H), 7.03
(d, 2H, J ) 7.5 Hz), 5.48 (s, 2H), 2.33 (s, 6H); 13C NMR (CDCl3,
62.5 MHz) δ 170.0, 156.0, 150.0, 137.2, 135.6, 133.8, 130.0, 128.0,
123.4, 122.6, 67.8, 20.3; IR (neat) 3438, 3055, 2962, 1730, 1595,
2-P yr idylm eth yl 1-aza-1-cycloh epten e-2-car boxylate (2n ):
1H NMR (CDCl3, 250 MHz) δ 8.58 (d, 1H, J ) 4.9 Hz), 7.74 (td,
1H, J ) 7.7, 1.6 Hz), 7.37 (d, 1H, J ) 7.8 Hz), 7.29-7.26 (m,
1H), 7.15 (bs, 1H), 5.20 (s, 2H), 3.34 (m, 2H), 2.44 (t, 2H, J )
6.9 Hz), 1.73-1.59 (m, 4H), 1.50-1.40 (m, 2H); 13C NMR (CDCl3,
62.5 MHz) δ 173.7, 155.6, 149.6, 137.7, 123.7, 123.1, 122.8, 117.7,
67.1, 44.2, 34.0, 29.8, 25.6. 24.2; IR (neat) 2949, 2868, 1746, 1600,
1440, 1372, 1183, 1046, 758 cm-1; HRMS (EI) calcd for
C
13H16N2O2 232.1213 (M+), found 232.1216.
2-P yr idylm eth yl 1-aza-1-cyclon on en e-2-car boxylate (2o):
1H NMR (CDCl3, 400 MHz) δ 8.55 (d, 1H, J ) 4.5 Hz), 7.69 (td,
1H, J ) 7.7, 1.7 Hz), 7.34 (d, 1H, J ) 7.8 Hz), 7.22 (m, 1H), 6.17
(bs, 1H), 5.19 (s, 2H), 3.26 (t, 2H, J ) 7.1 Hz), 2.39 (t, 2H, J )
7.4 Hz), 1.67-1.53 (m, 4H), 1.31 (m, 6H); 13C NMR (CDCl3, 62.5
MHz) δ 173.4, 155.6, 149.6, 137.0, 123.0, 122.2, 66.6, 44.3, 34.0,
30.0, 28.6, 28.3, 25.8, 24.5; IR (neat) 2935, 1735, 1598, 1438,
1374, 1146, 763 cm-1; HRMS (EI) calcd for C15H20N2O2 260.1526
(M+), found 260.1531.
1468, 1271, 1116, 1075, 736 cm-1; HRMS (EI) calcd for C15H15
NO2 241.1104 (M+), found 241.1103.
-
2-P yr id ylm eth yl 3-br om oben zoa te (2g): 1H NMR (CDCl3,
250 MHz) δ 8.63 (d, 1H, J ) 4.7 Hz), 8.24 (s, 1H), 8.04 (dd, 1H,
J ) 7.8, 1.0 Hz), 7.73-7.68 (m, 2H), 7.43 (d, 1H, J ) 7.8 Hz),
7.35 (d, 1H, J ) 7.9 Hz), 7.26 (m, 1H), 5.48 (s, 2H); 13C NMR
(CDCl3, 62.5 MHz) δ 165.3, 156.0, 150.0, 137.3, 136.6, 133.1,
132.1, 130.4, 128.8, 123.5, 122.9, 122.3, 68.0; IR (neat) 3432,
3069, 2950, 1720, 1572, 1425, 1252, 1122, 998, 747 cm-1; HRMS
(EI) calcd for C13H10NO2Br 290.9895 (M+), found 290.9885.
2-P yr idylm eth yl 1-n aph th alen ecar boxylate (2h ): 1H NMR
(CDCl3, 250 MHz) δ 8.99 (d, 1H, J ) 8.6 Hz), 8.63 (d, 1H, J )
4.7 Hz), 8.31 (d, 1H, J ) 7.3 Hz), 8.03 (d, 1H, J ) 8.2 Hz), 7.88
(d, 1H, J ) 8.2 Hz), 7.71 (td, 1H, J ) 7.7, 1.6 Hz), 7.61-7.47 (m,
4H), 7.24 (m, 1H), 5.57 (s, 2H); 13C NMR (CDCl3, 62.5 MHz) δ
167.4, 156.5, 150.0, 137.3, 134.3, 134.2, 131.9, 131.0, 129.0, 128.4,
127.0, 126.7, 126.2, 125.0, 123.3, 122.2, 67.7; IR (neat) 3056,
2951, 1715, 1594, 1438, 1278, 1133, 1016, 783, 735 cm-1; HRMS
(EI) calcd for C17H13NO2 263.0947 (M+), found 263.0939.
Ack n ow led gm en t. This research was supported by
Korea Science & Engineering Foundation (Grant No.
R02-2002-000-00140-0) through the Basic Research
Program.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR of all 2-pyridylmethyl carboxylates prepared (2a -o) and
crystal/refinement data of 3. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
2-P yr id ylm eth yl (E)-2-h ep ten oa te (2i): H NMR (CDCl3,
250 MHz) δ 8.60 (d, 1H, J ) 4.7 Hz), 7.71 (td, 1H, J ) 7.7, 1.6
J O026591O
1610 J . Org. Chem., Vol. 68, No. 4, 2003