meso-Phbox-Pd(II) catalyzed tandem carbonylative cyclization of 1-ethynyl-1-propargyl acetate

Article abstract of DOI:10.1039/b806207b

Palladium(II) catalyzed carbonylation of 1-ethynyl-1-propargyl acetate 1 is described; in the absence of the bisoxazoline (box) ligand, the second triple bond did not react, affording cyclic orthoesters 3 and 4. The use of meso-Phbox-Pd(II) strikingly changed the course of the reaction, yielding bicyclic lactone 2 by tandem carbonylative cyclization as a result of insertion of the second triple bond. The Royal Society of Chemistry.

Full text of DOI:10.1039/b806207b

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meso-Phbox-Pd(II) catalyzed tandem carbonylative cyclization
of 1-ethynyl-1-propargyl acetatew
Keisuke Kato,*a Ryuhei Teraguchi,a Satoshi Motodate,a Akira Uchida,c
Tomoyuki Mochida,b Tat’yana A. Peganova,d Nikolai V. Vologdind and
Hiroyuki Akita*a
Received (in College Park, MD, USA) 11th April 2008, Accepted 14th May 2008
First published as an Advance Article on the web 23rd June 2008
DOI: 10.1039/b806207b
Palladium(II) catalyzed carbonylation of 1-ethynyl-1-propargyl acet-
ate 1 is described; in the absence of the bisoxazoline (box) ligand, the
second triple bond did not react, affording cyclic orthoesters 3 and 4.
The use of meso-Phbox-Pd(II) strikingly changed the course of the
Scheme 1 1,4-Enynes: Rautenstrauch3a and Toste and co-workers.3b
reaction, yielding bicyclic lactone 2 by tandem carbonylative cycliza-
tion as a result of insertion of the second triple bond.
The transition metal-catalyzed reaction of unsaturated sys-
tems has recently proven to be a powerful method for the
construction of a variety of carbo- and heterocycles.1 A large
number of reactions of propargylic esters mediated by transi-
tion metal catalysts have been recently reported.2 For exam-
ple, Rautenstrauch3a and Toste and co-workers3b reported
palladium and gold catalyzed cycloisomerizations of pro-
pargylic acetates having a 1,4-enyne structure (Scheme 1).
Recently, we reported the gold catalyzed cycloisomerization
of propargylic acetates having a 1,5-allenyne structure,4a and
also the gold catalyzed double Wacker-type reaction4b of
propargylic acetates having a 1,4-diyne structure (Scheme 2).
In addition, we reported the palladium complex catalyzed
carbonylation of 1,4-diynes (Scheme 3).4c In the absence of the
Phbox ligand, orthoesters are predominantly formed. How-
ever, the use of the Phbox ligand afforded functionalized
4-cyclopentene-1,3-diones as major products. Clearly, the
Phbox ligand plays an important role in product selectivity.
Although box ligands are among the most popular classes of
chiral ligands in asymmetric chemistry, examples where the
box ligand changes the course of the reaction are rare. During
the course of our studies,4a–c we became interested in the
palladium catalyzed carbonylation of propargylic acetates
having a 1,5-diyne structure 1. Herein, we report a meso-
Phbox/Pd(TFA)2 catalyzed tandem carbonylative cyclization
of 1,2-diethynyl acetates 1 (Scheme 4).5
Scheme 2 1,5-Allenynes and 1,4-diynes (Au cat.): Kato et al.4a,b
Scheme 3 1,4-Diynes (Pd cat.): Kato et al.4c
Initially, we selected 1a as a standard substrate to search for
potential catalysts (Scheme 5, Table 1). The reaction of 1a with
(CH3CN)2PdCl2 (5 mol%) in the presence of p-benzoquinone
(1.2 equiv.) in methanol under carbon monoxide atmosphere
(balloon) generated the expected4c–e product 3a in 57% yield
as a mixture of diastereomers (ratio = 2.5 : 1) along with a
small amount (11%) of bicyclic lactone 2a (Table 1, entry 1).
As mentioned previously,4c,f,g the phosphine ligand seemed to
be ineffective for reactions of this type, i.e., a palladium
complex of (S)-BINAP gave a complex mixture (entry 2),
and (Ph3P)2PdCl2 (entry 3) and BPPFA6 did not show cata-
lytic activity. In addition, the use of (2,20-bipyridine)dichloro-
palladium(II) and (ꢀ)-sparteine/Pd(TFA)2 resulted in no
a Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama,
Funabashi, Chiba, 274-8510, Japan. E-mail: kkk@phar.toho-u.ac.jp;
Fax: (+81)474-721-825; Tel: (+81)474-721-825
b Department of Chemistry, Faculty of Science, Kobe University,
Rokkodai, Nada, Kobe, 657-8501, Japan
c Department of Chemistry, Faculty of Science, Toho University, 2-2-1
Miyama, Funabashi, Chiba, 274-8510, Japan
d A.N. Nesmeyanov Institute of Organoelement Compounds of the
Russian Academy of Sciences, Vavilov St.28, 119991 Moscow,
Russia
w Electronic supplementary information (ESI) available: Experimental
section. CCDC 685066. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/b806207b
Scheme 4 1,5-Diynes: this work.
ꢁc
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Chem. Commun., 2008, 3687–3689 | 3687

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Scheme 5
reaction. In the case of Pd(TFA)2, the second triple bond did
not react at all, affording cyclic orthoesters 3 and 4 in 57–72%
total yield (entries 4–8).
Fig. 1
Table 2 Carbonylation of 1 in the presence of box ligand (Scheme 4)
Yield 2b
Next, we used the box ligand depicted in Fig. 1 according to
our previous results (Scheme 3).4c Although the use of (S)-i-
Prbox and (S)-Bnbox resulted in the formation of the bicyclic
lactone 2a in 34–43% yield together with an unidentified
mixture (Scheme 4, Table 2, entries 1 and 2), (S)-Phbox and
(ꢂ)-Phbox accelerated the reaction, and the yield improved to
86–87% (entries 3 and 4). However, the reaction of 1d having a
bulky cyclohexyl group was sluggish and the yield of 2d was
reduced to 51%. Dihydroxybenzaldehyde 5 (Fig. 1) was also
produced as a by-product (entry 5). We then used the meso-
Phbox ligand7 depicted in Fig. 1. The yields of 2a catalyzed by
the palladium complexes of meso-Phbox and (ꢂ)-Phbox were
almost identical (entries 4 and 6). However, the use of the
meso-Phbox ligand improved the yield of 2d (entry 7) and the
products 2b, 2c and 2e having octyl, hexyl and Ph groups were
obtained in 82–86% yields (entries 8–10). Unfortunately, the
internal acetylene 1f was inert under the reaction conditions
(Fig. 1). Product 2 contained a small amount of the corres-
ponding acetate, and the structure of 2a was determined by X-
ray crystallographic analysisw after recrystallization (Fig. 2).
Although the box ligands used in entries 1–3 were optically
active, the products were almost racemic (2–9% ee).
Entry
Catalysta
R
t/h
(%)
1
2
3
4
5
6
7
8
9
10
a
(S)-i-Prbox/Pd(TFA)2
(S)-Bnbox/Pd(TFA)2
(S)-Phbox/Pd(TFA)2
(ꢂ)-Phbox/Pd(TFA)2
(ꢂ)-Phbox/Pd(TFA)2
meso-Phbox/Pd(TFA)2
meso-Phbox/Pd(TFA)2
meso-Phbox/Pd(TFA)2
meso-Phbox/Pd(TFA)2
meso-Phbox/Pd(TFA)2
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
c-Hexyl
PhCH2CH2
c-Hexyl
Octyl
22
20
4
5
8
2
2
2
2
2a: 43
2a: 34c
2a: 87d
2a: 86
2d: 51e
2a: 86
2d: 75f
2b: 82
2c: 86
2e: 83
Hexyl
Ph
2
b
Pd(TFA)2 (5 mol%), ligand (7.5 mol%). A small amount of the
c
corresponding acetate of 2 was present (17 : 1 to 7 : 1). 9% ee.
d
e
f
2% ee. Aldehyde 5 was obtained in 15% yield. 5: 1 Mixture of 2d
and the corresponding acetate.
A plausible mechanism for the present reaction is shown in
Scheme 6. 1,2-Diethynyl acetate 1 coordinates to Pd(II) and this
intermediate undergoes nucleophilic attack by MeOH to pro-
duce the vinyl palladium intermediate. This is followed by CO
insertion or protonolysis to provide acyl palladium intermedi-
ate A1 and enol ether 4, respectively. In the absence of the
Phbox ligand, the second triple bond does not react at all,
suggesting that it does not coordinate to the palladium. The
coordination of MeOH to A1 leads to methoxy carbonylation
to give ester product 3. In the presence of the meso-Phbox
ligand (Scheme 7), the bicyclic lactone 2 is the sole product,
implying that the meso-Phbox ligand induces the coordination
of the second triple bond to the palladium. As a result, the
racemic substrate 1 produces two acyl palladium intermediates,
Fig. 2 X-Ray crystal structure of 2a.
A2 and A3. Insertion of the second triple bond then occurs,
followed by carbonylative lactonization and subsequent hydro-
lysis of the acetate, producing the bicyclic lactone 2.
Although the precise mechanism of the reaction selectivity is
still an open question, it might be ascribed to the different
coordination sphere of palladium species A. The coordination
Table 1 Carbonylation of 1 in the absence of box ligand (Scheme 5)
Entry
Catalyst
t/h
Yield 2 (%)
Yield 3 (%) (ratioa)
3a: 57 (2.5 : 1)
Yield of 4 (%) (ratioa)
1
2
3
4
5
6
7
8
a
(CH3CN)2PdCl2
(S)-BINAP/Pd(TFA)2
(Ph3P)2PdCl2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
10
48
72
4
3
1.5
5
2a: 11
Complex mixture
N.R.
—
—
—
—
—
—
3a: 22 (1.9 : 1)
3b: 13 (1.9 : 1)
3c: 15 (1.9 : 1)
3d: 22 (3.1 : 1)
3e: 33 (1 : 1)
4a: 50 (1.8 : 1)
4b: 48 (1.9 : 1)
4c: 51 (2.3 : 1)
4d: 34 (6.6 : 1)
4e: 25 (2.1 : 1)
Pd(TFA)2
Pd(TFA)2
27
Mixture of diastereomers.
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steric and/or electronic repulsion in the acyl palladium inter-
mediates [A2 and A3 for meso-Phbox (Scheme 7) and A4 and
A5 for (ꢂ)-Phbox (Scheme 8)].
In the case of A4 and A5, steric and/or electronic repulsion
between the phenyl ring and the cyclohexyl group inhibits the
insertion of the second triple bond, allowing methoxy pallada-
tion of A4 and/or A5, followed by reductive elimination to
give intermediate B (Scheme 8). Hydrolysis of the enol ether
moiety in intermediate B and subsequent aromatization
afforded dihydroxybenzaldehyde 5 as a by-product. However,
no considerable steric and/or electronic repulsion exists in the
intermediates A2 and A3 (Scheme 7).
Scheme 6 Plausible mechanism (I): in the absence of Phbox ligand.
In conclusion, the meso-Phbox ligand strikingly changes the
course of the carbonylation of 1-ethynyl-1-propargyl acetate 1.
Pd(TFA)2 catalyzed single cyclization afforded cyclic ortho-
esters 3 and 4, whereas the meso-Phbox-Pd(TFA)2 complex
catalyzed tandem carbonylative cyclization leading to bicyclic
lactone 2.
Notes and references
1 (a) Handbook of Organopalladium Chemistry for Organic Synthesis,
ed. E. Negishi, Wiley, New York, 2002, vol. II, p. 2309; for recent
reviews, see: (b) I. Nakamura and Y. Yamamoto, Chem. Rev.,
2004, 104, 2127; (c) G. Zeni and R. C. Larock, Chem. Rev., 2004,
104, 2285; (d) B. C. G. Soderberg, Coord. Chem. Rev., 2004, 248,
1085; (e) S. A. Vizer, K. B. Yerzhanov, A. A. A. A. Quntar and V.
M. Dembitsky, Tetrahedron, 2004, 60, 5499; (f) J. Muzart, Tetra-
hedron, 2005, 61, 5955; (g) N. Asao, Synlett, 2006, 1645.
Scheme 7 Plausible mechanism (II): in the presence of meso-Phbox
ligand.
2 (a) N. Marion, S. Diez-Gonzalez, P. Fremont, A. R. Noble and S.
P. Nolan, Angew. Chem., Int. Ed., 2006, 45, 3647; (b) S. Wang and
L. Zhang, J. Am. Chem. Soc., 2006, 128, 8414; (c) B. G. Pujanauski,
B. A. B. Prasad and R. Sarpong, J. Am. Chem. Soc., 2006, 128,
6786; (d) L. Zhang and S. Wang, J. Am. Chem. Soc., 2006, 128,
1442; (e) J. Zhao, C. O. Hughes and F. D. Toste, J. Am. Chem. Soc.,
2006, 128, 7436; (f) L. Zhang, J. Am. Chem. Soc., 2005, 127, 16804;
(g) M. J. Johansson, D. J. Gorin, S. T. Staben and F. D. Toste, J.
Am. Chem. Soc., 2005, 127, 18002; (h) K. Cariou, E. Mainetti, L.
Fensterbank and M. Malacria, Tetrahedron, 2004, 60, 9745.
3 (a) V. Rautenstrauch, J. Org. Chem., 1984, 49, 950; (b) X. Shi, D. J.
Gorin and F. D. Toste, J. Am. Chem. Soc., 2005, 127, 5802.
4 (a) K. Kato, T. Kobayashi, T. Fujinami, S. Motodate, T. Kusa-
kabe, T. Mochida and H. Akita, Synlett, 2008, 1081; (b) K. Kato,
R. Teraguchi, T. Kusakabe, S. Motodate, S. Yamamura, T.
Mochida and H. Akita, Synlett, 2007, 63; (c) K. Kato, R.
Teraguchi, S. Yamamura, T. Mochida, H. Akita, T. A. Peganova,
N. V. Vologdin and O. V. Gusev, Synlett, 2007, 638; (d) K. Kato,
Y. Yamamoto and H. Akita, Tetrahedron Lett., 2002, 43, 6587; (e)
K. Kato, H. Nouchi, K. Ishikura, S. Takaishi, S. Motodate, H.
Tanaka, K. Okudaira, T. Mochida, R. Nishigaki, K. Shigenobu
and H. Akita, Tetrahedron, 2006, 62, 2545; (f) K. Kato, C.
Matsuba, T. Kusakabe, H. Takayama, S. Yamamura, T. Mochida,
H. Akita, T. A. Peganova, N. V. Vologdin and O. V. Gusev,
Tetrahedron, 2006, 62, 9988; (g) T. A. Kusakabe, K. Kato, S.
Takaishi, S. Yamamura, T. A. Mochida, H. Akita, T. A.
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Scheme
plausible mechanism for the generation of by-product 5.
8
Possible acyl palladium complex of (ꢂ)-Phbox and
sphere of palladium in A1 contains one acyl ligand, one TFAꢀ,
and presumably two MeOH molecules, whereas A2/A3 con-
tain one acyl ligand and one Phbox ligand (two N-donor
atoms) and the triple bond. Therefore, a cationic Pd(II) center
with a C, N, N coordination will clearly be more electrophilic
and thus more prone to bind the triple bond than a neutral
Pd(II) center with a C, TFAꢀ, MeOH coordination. Moreover,
the structures of A2 and A3 are more rigid than that of A1 and
this rigidity places the triple bond in a better position to bind
to palladium than can be expected in the more flexible A1.
Such factors may be playing an important role for the reaction
selectivity. The difference in reactivity between the meso-
Phbox and the (ꢂ)-Phbox ligands is believed to be caused by
5 Recent examples of carbonylative cyclization: (a) S. Sugawara, K.
Uemura, N. Tsukada and Y. Inoue, J. Mol. Catal. A: Chem., 2003,
195, 55; (b) A. Kamitani, N. Chatani and S. Murai, Angew. Chem.,
Int. Ed., 2003, 42, 1397; (c) R. Schiller, M. Pour, H. Fakova, J.
Kunes and I. Cisarova, J. Org. Chem., 2004, 69, 6761; (d) Y.
Harada, Y. Fukumoto and N. Chatani, Org. Lett., 2005, 7, 4385.
6 T. Hayashi, T. Mise, M. Fukushima, M. Kagotani, N. Nagashima,
Y. Hamada, M. Akira, S. Kawakami, M. Konishi, K. Yamamoto
and M. Kumada, Bull. Chem. Soc. Jpn., 1980, 53, 1138.
7 C. Foltz, B. Stecker, G. Marconi, S. Bellemin-Laponnaz, H.
Wadepohl and L. H. Gade, Chem.–Eur. J., 2007, 13, 9912.
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Chem. Commun., 2008, 3687–3689 | 3689