Cyclization-carbonylation-cyclization coupling reactions of propargyl acetates and amides with palladium(II)-bisoxazoline catalysts

Article abstract of DOI:10.1002/anie.201008139

Clever boxing: A cyclization-carbonylation-cyclization-coupling reaction of propargyl acetates 1 or amides 2 in the presence of a palladium(II)- bisoxazoline (box) catalyst afforded symmetrical ketones of types 3 and 4, respectively, containing two heterocyclic groups in moderate to excellent yields (see scheme; tfa=trifluoroacetate). Compounds 3 were converted into ketones containing two 3(2H)-furanone rings.

Full text of DOI:10.1002/anie.201008139

Communications
DOI: 10.1002/anie.201008139
Domino Reactions
Cyclization–Carbonylation–Cyclization Coupling Reactions of
Propargyl Acetates and Amides with Palladium(II)–Bisoxazoline
Catalysts
Sumie Yasuhara, Makiko Sasa, Taichi Kusakabe, Hiroyuki Takayama, Masayuki Kimura,
Tomoyuki Mochida, and Keisuke Kato*
3(2H)-Furanones and oxazoles are common structures in a
range of important pharmaceuticals.[1] Diaryl ketones are also
frequently found in natural products and pharmaceuticals,[2]
and they are good precursors for nonsteroidal antiestrogen
drugs, such as tamoxifen,[3] and diarylmethyl compounds, such
as histamine H1 antagonists,[4a] antitubercular compounds,[4b]
and inhibitors of tubulin polymerization.[4c] A variety of
carbo- and heterocycles can be synthesized by transition-
metal-catalyzed reactions of unsaturated systems.[5] Among
the available coupling methods, three-component carbon-
ylation reactions, such as the carbonylative Suzuki reaction,
Scheme 1. Our concept of a cyclization–carbonylation–cyclization cou-
pling reaction (CCC coupling reaction) of propargylic compounds.
the carbonylative Sonogashira reaction, and the carbonylative
Heck reaction, create interesting building blocks.[6,7] The vinyl
and aryl palladium intermediates are formed by the oxidative
addition of a carbon–halogen bond to palladium(0). In this
context, we propose a CCC coupling reaction: a cyclization–
carbonylation–cyclization coupling reaction of propargylic
compounds should afford symmetrical ketones with two
heterocyclic groups (Scheme 1).[8]
In this transformation, the triple bond of the substrate
coordinates to palladium(II) and undergoes nucleophilic
attack by the intramolecular nucleophile X followed by CO
insertion to produce the acyl palladium intermediate A.
Coordination of the triple bond of the second molecule
induces the second cyclization. Reductive elimination then
leads to the formation of a ketone with two heterocyclic
groups. We needed to avoid methanolysis of A during the
second cyclization step and anticipated that the p electrophi-
licity of the acyl palladium intermediate A would play an
important role. We believed that the use of bisoxazoline (box)
ligands would solve this problem.
ligand was absent, the second triple bond did not react. The
use of the box ligand caused a significant change in the course
of the reaction, and tandem carbonylative cyclization oc-
curred as a result of insertion of the second triple bond. We
believe that the box ligand enhances the p electrophilicity of
palladium(II)[9a–d] and thus promotes coordination of the
second triple bond in the second part of the tandem reaction.
Previously, we also reported that the palladium(II)-mediated
cyclization–carbonylation of propargyl acetates affords cyclic
orthoesters in the same type of reaction as that shown in
Equation (1) of Scheme 2.[9e,f] We believed the CCC coupling
reaction of propargyl acetates 1 (Scheme 3) to be an
intermolecular version of the tandem reaction in Equation (2)
of Scheme 2. On the basis of our earlier results, we
Recently, we reported a ligand-controlled tandem carbon-
ylative cyclization of propargyl acetates with 1,4-diyne[9a] and
1,5-diyne structures (Scheme 2).[9b] In these systems, if the box
[*] S. Yasuhara, M. Sasa, Dr. T. Kusakabe, Prof. Dr. K. Kato
Faculty of Pharmaceutical Sciences, Toho University
2-2-1 Miyama, Funabashi, Chiba 274-8510 (Japan)
Fax : (+81)474-721-825
E-mail: kkk@phar.toho-u.ac.jp
Dr. H. Takayama, Prof. Dr. M. Kimura
School of Pharmacy, Nihon Pharmaceutical University
10281, Komuro, Inamachi, Kita-Adachigun, Saitama (Japan)
Prof. Dr. T. Mochida
Department of Chemistry, Faculty of Sciences, Kobe University
Rokkodai, Nada, Kobe 657-8501 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201008139.
Scheme 2. Previous studies: ligand-controlled tandem carbonylative
cyclization of propargyl acetates. tfa=trifluoroacetate.
3912
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 3912 –3915

Table 1: CCC coupling (cyclization–carbonylation–cyclization coupling)
reaction of propargylic acetates 1.
Entry
R
Ligand
Yield of 3
Yield of 5
[%]
[%]
1[a] -(CH2)5-
2[a] -(CH2)5-
3[a] -(CH2)5-
(S)-Phbox
(L1)
(S)-iPrbox
(L2)
3a: 56
3a: 52
3a: 55
5a: 2
5a: 2
trace
(R)-Bnbox
(L3)
Scheme 3. [(box)Pd(tfa)2]-catalyzed CCC coupling reaction of propargyl
acetates 1 and amides 2.
4
-(CH2)5-
box (L4)[b]
none
3a: 63
3a: 11
3b: 62
3c: 59
3d: 85
5a: 3
5a: 37
trace
trace
–
5[a] -(CH2)5-
6
7
8
-(CH2)4-
-(CH2)6-
-(CH2)2-NBoc-
box (L4)[b]
box (L4)[b]
box (L4)[b]
hypothesized that the [(box)PdII] complexes should strongly
activate the triple bond of the second molecule and thus
enable the CCC coupling reaction of 1. Consequently, we
report herein the [(box)Pd(tfa)2]-catalyzed CCC coupling
reaction of propargyl acetates 1 and amides 2 (Scheme 3).
We previously reported the [(CH3CN)PdCl2]-catalyzed
cyclization–carbonylation of propargyl acetates 1 to form
monomeric esters 5 in 61–99% yield.[9e,f] In the present study,
we initially screened some box
(CH2)2-
Bn
9
box (L4)[b]
box (L4)[b]
box (L4)[b]
box (L4)[b]
3e: 85
3 f: 65
3g: 76
–
–
10
Et
trace
–
11
Me
H
12[a]
[a] The reaction was carried out at 08C for 24 h. [b] The isolated complex
[(L4)Pd(tfa)2] (5 mol%) was employed as the catalyst. Bn=benzyl,
Boc=tert-butoxycarbonyl.
ligands (Scheme 4) for the CCC
coupling reaction of 1a according
to our hypothesis. As expected, the
CCC coupling reaction occurred
smoothly in the presence of the box
ligands to afford 3a in 52–63% yield
together with trace amounts of 5a
(Table 1, entries 1–4). In our previ-
To demonstrate the value of compounds 3, we converted
the dimeric ketones into carbonyl difuranones 6 by a two-step
procedure (Table 2). Acid hydrolysis of 3 gave the corre-
sponding triketones, which were treated with a base to afford
6 in moderate to good yields through a Knoevenagel–Claisen-
type double condensation.
Scheme 4. Box ligands.
ous studies,[9a–d,g] substituents at the C4 position of the box
ligands played an important role in promoting the attempted
reactions. In this case, however, all box ligands exhibited
similar activity. Among them, the simple box ligand L4 gave
the best result (Table 1, entry 4). Pure 3a was readily obtained
by recrystallization from methanol, and the structure of 3a
was determined by X-ray crystallographic analysis.[10] In the
absence of a box ligand, the monomeric ester 5a was obtained
as the major product (Table 1, entry 5), in agreement with our
previous results with the catalyst [(CH3CN)2PdCl2].[9e,f] The
use of [{(ꢀ)-sparteine}Pd(tfa)2] and [(2,2’-bipyridine)PdCl2]
led to no reaction. Internal acetylenes also gave no reaction.
Furthermore, CH2Cl2 and N,N-dimethylformamide were not
suitable as solvents.
Having optimized the reaction conditions, we examined
the reaction of different substrates with the simple box ligand
L4. The cyclic substrates 1a–d and acyclic substrates 1e–g
were transformed in moderate to good yields (Table 1,
entries 4 and 6–11). The gem-dialkyl effect[11] plays a funda-
mental role in the success of the reaction: the CCC coupling
of simple propargyl acetate (1h) did not proceed (Table 1,
entry 12). Instead, the reaction afforded methyl (E)-4-ace-
toxy-3-methoxy-2-butenoate[12] in 4% yield through intermo-
lecular methoxycarbonylation.[9c]
Table 2: Conversion of dimeric ketones 3 into carbonyl difuranones 6.
Entry
R
t (step 1) [h]
t (step 2) [days]
Yield of 6 [%]
1
2
3
4
5
6
-(CH2)5-
-(CH2)4-
-(CH2)6-
Bn
Et
Me
0.5
0.5
0.5
72
0.5
0.5
3
5
3.5
1.5[a]
4
6a: 83
6b: 60
6c: 81
6e: 61
6 f: 69
6g: 62
5
[a] K2CO3 was used instead of NaHCO3.
Previously, Bacchi et al. reported that the palladium(II)-
catalyzed cyclization–carbonylation of propargyl amide 2c
afforded a mixture of the E and Z isomers of the 5-
((methoxycarbonyl)methylene)oxazoline
7c in 90% yield (E/Z 83:7) together with
the dimeric ketone 4c in 8% yield.[13,14]
Although the yield of 4c could be
Angew. Chem. Int. Ed. 2011, 50, 3912 –3915
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3913

Communications
increased by carrying out the reaction at higher concentra-
tions ((E)-7c: 30%, (Z)-7c: 7%, 4c: 43%), only this one
example of a CCC coupling product was presented.
To investigate the generality of the CCC coupling
reaction, we attempted the [(box)PdII]-catalyzed carbonyla-
tion of propargyl amides. As expected, the reaction pro-
ceeded smoothly in the presence of the (ꢁ )-Phbox ligand L1
to afford the dimeric ketones 4 in good to excellent yields
(Table 3).[15,16] For benzamides 2a–c and 4-substituted benza-
Steric hindrance in the acyl palladium intermediate also
seems to play an important role in the dimerization. The
reaction of internal acetylene 2z afforded the (Z)-5-
((methoxycarbonyl)methylene)oxazoline 7z in 52% yield
together with recovered starting material (39%; Scheme 5).
The configuration of (Z)-7z was confirmed by NOE experi-
ments to be that shown in Scheme 5.
Table 3: CCC coupling reaction of propargylic amides 2.
Scheme 5. Reaction of the internal acetylene 2z.
In conclusion, we have presented a cyclization–carbon-
ylation–cyclization coupling reaction (CCC coupling reac-
tion) of propargylic acetates and amides catalyzed by
[(box)PdII] complexes. Symmetrical ketones containing two
heterocyclic groups were obtained in moderate to excellent
yields. We believe that the box ligand enhances the p elec-
trophilicity of palladium(II)[9a–d] and thus promotes coordina-
tion of the triple bond of a second molecule to the acyl
palladium intermediate A to enable the dimerization reaction
to take place. We are currently investigating other new
tandem reactions based on the cyclization–carbonylation–
cyclization strategy presented herein for the synthesis of other
types of ketones containing two heterocyclic groups.
Entry
R1
R2
T [8C]
t [h]
Yield of
4 [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
Ph
Ph
Ph
H
0
0
0
0
12
3
2
6
11
5
6
5
5
5
5
5
3
24
24
3
24
24
3
4a: 90
4b: 97
4c: 99
4d: 90
4e: 92
4 f: 99
4g: 99
4h: 92
4i: 89
4j: 95
4k: 90
4l: 95
4m: 96
4n: 89
4o: 93
4p: 84
4q: 95
4r: 92
4s: 93
4t: 85
4u: 99
4v: 87
4w: 79
4x: 82
–
-(CH2)5-
Me
H
-(CH2)5-
Me
Me
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
3-furyl
3-furyl
2-furyl
2-indolyl
3-indolyl
CH2 CH
ꢀ10
ꢀ10
ꢀ10
H
0
-(CH2)5-
Me
H
-(CH2)5-
Me
-(CH2)5-
Me
Me
Me
-(CH2)5-
-(CH2)5-
Me
Me
Me
Me
-(CH2)5-
H
0
0
0
0
Received: December 23, 2010
Revised: January 27, 2011
Published online: March 22, 2011
0
ꢀ
Keywords: alkynes · bisoxazoline ligands · C O coupling ·
carbonylation · palladium
ꢀ30!ꢀ20
.
ꢀ20
0
ꢀ30!ꢀ20
ꢀ30!ꢀ20
[1] a) D. K. Dalvie, A. S. Kalgutkar, S. C. Khojasteh-Bakht, R. S.
Obach, J. P. OꢀDonnell, Chem. Res. Toxicol. 2002, 15, 269;
b) S. L. McGovern, E. Caselli, N. Grigorieff, B. K. Shoichet, J.
Med. Chem. 2002, 45, 1712; c) M. Murcia-Soler, F. Pꢁrez-
Gimꢁnez, F. J. Garcꢂa-March, M. T. Salabert-Salvador, W. Dꢂaz-
Villanueva, M. J. Castro-Bleda, A. Villanueva-Pareja, J. Chem.
Inf. Comput. Sci. 2004, 44, 1031; d) S. S. Shin, Y. Byun, K. M.
Lim, J. K. Choi, K.-W. Lee, J. H. Moh, J. K. Kim, Y. S. Jeong, J. Y.
Kim, Y. H. Choi, H.-J. Koh, Y.-H. Park, Y. I. Oh, M.-S. Noh, S.
Chung, J. Med. Chem. 2004, 47, 792; e) A. Carotti, A. Carrieri, S.
Chimichi, M. Boccalini, B. Cosimelli, C. Gnerre, A. Carotti, P.-A.
Carrupt, B. Testa, Bioorg. Med. Chem. Lett. 2002, 12, 3551; f) S.
Chimichi, M. Boccalini, B. Cosimelli, F. DallꢀAcqua, G. Viola,
Tetrahedron 2003, 59, 5215; g) T. Sasaki, J. Yamakoshi, M. Saito,
K. Kasai, T. Matsudo, M. Kikuchi, T. Koga, K. Mori, Biosci.
Biotechnol. Biochem. 1998, 62, 2145; h) R. A. Mack, W. I.
Zazulak, L. A. Radov, J. E. Baer, J. D. Stewart, P. H. Elzer,
C. R. Kinsolving, V. S. Georgiev, J. Med. Chem. 1988, 31, 1910.
[2] H. Neumann, A. Brennfꢃhrer, M. Beller, Chem. Eur. J. 2008, 14,
3645, and references therein.
=
0
0
0
=
CH2 CH
cinnamoyl
Me
3
3
70
70
12
24
ꢀ30!ꢀ10
ꢀ30!ꢀ10
ꢀ20
Et
cyclohexyl
Me
RT
mides 2d–g, the reaction proceeded well (Table 3, entries 1–
7). Br and Cl substituents were tolerated on the benzoic acid
moiety under the reaction conditions, and products 4h–m
were obtained in good to excellent yields (Table 3, entries 8–
13). Furan and indole derivatives 2n–r also underwent
conversion in good yields (Table 3, entries 14–18). Substrates
2s–u containing alkenyl groups as the R1 substituent were also
found to be suitable (Table 3, entries 19–21), as were the alkyl
amides 2v–x (Table 3, entries 22–24). The substituent at the
propargylic position was found to be important for this type of
reaction: the reaction of a-unsubstituted alkyl amide 2y gave
a complex mixture (Table 3, entry 25).
[3] a) A. Nguyen, S. Top, P. Pigeon, A. Vessiꢄres, E. A. Hillard, M.-
A. Plamont, M. Huchꢁ, C. Rigamonti, G. Jaouen, Chem. Eur. J.
2009, 15, 684; b) E. Y. H. Chao, J. L. Collins, S. Gaillard, A. B.
3914
www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 3912 –3915

Miller, L. Wang, L. A. Orband-Miller, R. T. Nolte, D. P.
McDonnell, T. M. Willson, W. J. Zuercher, Bioorg. Med. Chem.
Lett. 2006, 16, 821; c) R. K. Pandey, R. D. Wakharkar, P. Kumar,
Synth. Commun. 2005, 35, 2795; d) C. Olier-Reuchet, D. J.
Aitken, R. Bucourt, H.-P. Husson, Tetrahedron Lett. 1995, 36,
8221; e) P. L. Coe, C. E. Scriven, J. Chem. Soc. Perkin Trans. 1
1986, 475.
h) S. Ma, J. Zhang, L. Lu, Chem. Eur. J. 2003, 9, 2447; i) S. Ma, Z.
Yu, Chem. Eur. J. 2004, 10, 2078; j) S. Ma, Z. Yu, Z. Gu, Chem.
Eur. J. 2005, 11, 2351; k) Y. Deng, J. Li, S. Ma, Chem. Eur. J. 2008,
14, 4263; l) B. Alcaide, P. Almendros, T. Martꢂnez del Campo,
Eur. J. Org. Chem. 2007, 2844; m) B. Alcaide, P. Almendros, C.
Aragoncillo, Chem. Eur. J. 2009, 15, 9987.
[9] a) K. Kato, R. Teraguchi, S. Yamamura, T. Mochida, H. Akita,
T. A. Peganova, N. V. Vologdin, O. V. Gusev, Synlett 2007, 638;
b) K. Kato, R. Teraguchi, S. Motodate, A. Uchida, T. Mochida,
T. A. Peganova, N. V. Vologdin, H. Akita, Chem. Commun.
2008, 3687; c) K. Kato, S. Motodate, T. Mochida, T. Kobayashi,
H. Akita, Angew. Chem. 2009, 121, 3376; Angew. Chem. Int. Ed.
2009, 48, 3326; d) S. Motodate, T. Kobayashi, M. Fujii, T.
Mochida, T. Kusakabe, S. Katoh, H. Akita, K. Kato, Chem.
Asian J. 2010, 5, 2221; e) K. Kato, Y. Yamamoto, H. Akita,
Tetrahedron Lett. 2002, 43, 6587; f) K. Kato, H. Nouchi, K.
Ishikura, S. Takaishi, S. Motodate, H. Tanaka, K. Okudaira, T.
Mochida, R. Nishigaki, K. Shigenobu, H. Akita, Tetrahedron
2006, 62, 2545; g) T. Kusakabe, K. Kato, S. Takaishi, S.
Yamamura, T. Mochida, H. Akita, T. A. Peganova, N. V.
Vologdin, O. V. Gusev, Tetrahedron 2008, 64, 319.
[4] a) F. Schmidt, R. T. Stemmler, J. Rudolph, C. Bolm, Chem. Soc.
Rev. 2006, 35, 454; b) S. K. Das, G. Panda, V. Chaturvedi, Y. S.
Manju, A. K. Gaikwad, S. Sinha, Bioorg. Med. Chem. Lett. 2007,
17, 5586; c) C. ꢅlvarez, R. ꢅlvarez, P. Corchete, J. L. Lꢆpez, C.
Pꢁrez-Melero, R. Pelꢇez, M. Medarde, Bioorg. Med. Chem.
2008, 16, 5952.
[5] a) Handbook of Organopalladium Chemistry for Organic Syn-
thesis, Vol. II (Ed.: E. Negishi), Wiley, New York, 2002, p. 2309;
for reviews, see: b) R. Grigg, S. P. Mutton, Tetrahedron 2010, 66,
5515; c) K. C. Majumdar, B. Chattopadhyay, P. K. Maji, S. K.
Chattopadhyay, S. Samanta, Heterocycles 2010, 81, 795; d) K. C.
Majumdar, P. Debnath, B. Roy, Heterocycles 2009, 78, 2661; e) I.
Nakamura, Y. Yamamoto, Chem. Rev. 2004, 104, 2127; f) G.
Zeni, R. C. Larock, Chem. Rev. 2004, 104, 2285; g) B. C. G.
Soderberg, Coord. Chem. Rev. 2004, 248, 1085; h) S. A. Vizer,
K. B. Yerzhanov, A. A. A. Al Quntar, V. M. Dembitsky, Tetra-
hedron 2004, 60, 5499; i) J. Muzart, Tetrahedron 2005, 61, 5955;
j) N. Asao, Synlett 2006, 1645; k) S. Ma, Chem. Rev. 2005, 105,
2829; for the tandem dimerization and cyclization of acetylenic
compounds, see: l) A. Jeevanandam, K. Narkunan, Y.-C. Ling, J.
Org. Chem. 2001, 66, 6014; m) H. A. Wegner, S. Ahles, M.
Neuburger, Chem. Eur. J. 2008, 14, 11310; n) M. G. Auzias, M.
Neuburger, H. A. Wegner, Synlett 2010, 2443.
[6] For reviews on palladium-catalyzed carbonylation, see: a) A.
Brennfꢃhrer, H. Neumann, M. Beller, ChemCatChem 2009, 1,
28; b) C. Torborg, M. Beller, Adv. Synth. Catal. 2009, 351, 3027;
c) C. F. J. Barnard, Organometallics 2008, 27, 5402.
[7] A. Brennfꢃhrer, H. Neumann, M. Beller, Angew. Chem. 2009,
121, 4176; Angew. Chem. Int. Ed. 2009, 48, 4114, and references
therein.
[8] Recently, we reported a CCC coupling reaction of allenyl
ketones without a bisoxazoline ligand. The reactivity of allenyl
compounds is high enough to induce dimer formation: a) K.
Kato, T. Mochida, H. Takayama, M. Kimura, H. Moriyama, A.
Takeshita, Y. Kanno, Y. Inoue, H. Akita, Tetrahedron Lett. 2009,
50, 4744; for selected examples of dimerization or coupling
reactions of allenyl compounds, see: b) J. A. Marshall, E. D.
Robinson, J. Org. Chem. 1990, 55, 3450; c) J. A. Marshall, C. A.
Sehon, J. Org. Chem. 1995, 60, 5966; d) A. S. K. Hashmi, Angew.
Chem. 1995, 107, 1749; Angew. Chem. Int. Ed. Engl. 1995, 34,
1581; e) A. S. K. Hashmi, T. L. Ruppert, T. Knꢈfel, J. W. Bats, J.
Org. Chem. 1997, 62, 7295; f) A. S. K. Hashmi, L. Schwarz, J.-H.
Choi, T. M. Frost, Angew. Chem. 2000, 112, 2382; Angew. Chem.
Int. Ed. 2000, 39, 2285; g) S. Ma, L. Li, Org. Lett. 2000, 2, 941;
[10] CCDC 799108 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif. See the Supporting Information.
[11] P. G. Sammes, D. J. Weller, Synthesis 1995, 1205.
[12] L. Duc, J. F. McGarrity, T. Meul, A. Warm, Synthesis 1992, 391.
[13] For selected examples of palladium-catalyzed reactions of
propargyl amides, see: a) A. Bacchi, M. Costa, N. Della Cꢉ, B.
Gabriele, G. Salerno, S. Cassoni, J. Org. Chem. 2005, 70, 4971;
b) M. Costa, N. Della Cꢉ, B. Gabriele, C. Massera, G. Salerno,
M. Soliani, J. Org. Chem. 2004, 69, 2469; c) A. Arcadi, S. Cacchi,
V. Carnicelli, F. Marinelli, Tetrahedron 1994, 50, 437; d) A. Lei,
X. Lu, Org. Lett. 2000, 2, 2699; e) A. Arcadi, S. Cacchi, L. Cascia,
G. Fabrizi, F. Marinelli, Org. Lett. 2001, 3, 2501; f) E. M. Beccalli,
E. Borsini, G. Broggini, G. Palmisano, S. Sottocornola, J. Org.
Chem. 2008, 73, 4746; g) E. Merkul, T. J. J. Mꢃller, Chem.
Commun. 2006, 4817; h) A. Saito, A. Matsumoto, Y. Hanzawa,
Tetrahedron Lett. 2010, 51, 2247.
[14] A. Bacchi, M. Costa, B. Gabriele, G. Pelizzi, G. Salerno, J. Org.
Chem. 2002, 67, 4450. In this case, the carbonylation of 2a
afforded maleic diester derivatives (derived from oxidative
bisalkoxycarbonylation of the triple bond) in 69% yield together
with oxazole 7a (14%).
[15] For preliminary experiments, see the Supporting Information.
[16] The CCC cross-coupling reaction of amide 2v (1 equiv) with
acetate 1g (1 equiv) catalyzed by [(L4)Pd(tfa)2] (5 mol%) under
our reaction conditions (ꢀ108C, 24 h) afforded an unsymmet-
rical ketone in 18% yield together with dimeric ketones 4v
(37%) and 3g (7%).
Angew. Chem. Int. Ed. 2011, 50, 3912 –3915
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3915