Unusual formation of cyclic-orthoesters by Pd(II)-mediated cyclization-carbonylation of propargylic acetates

Article abstract of DOI:10.1016/S0040-4039(02)01438-7

The oxidative cyclization-methoxycarbonylation of propargylic acetates 1 in the presence of (CH₃CN)₂PdCl₂/p-benzoquinone in methanol under carbon monoxide atmosphere (balloon) afforded (E)-cyclic-orthoesters 5 in moderate

Full text of DOI:10.1016/S0040-4039(02)01438-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6587–6590
Unusual formation of cyclic-orthoesters by Pd(II)-mediated
cyclization–carbonylation of propargylic acetates
Keisuke Kato,a,* Yasuhiro Yamamotob and Hiroyuki Akitaa,*
aSchool of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
bDepartment of Chemistry, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
Received 14 June 2002; accepted 12 July 2002
Abstract—The oxidative cyclization–methoxycarbonylation of propargylic acetates 1 in the presence of (CH3CN)2PdCl2/p-benzo-
quinone in methanol under carbon monoxide atmosphere (balloon) afforded (E)-cyclic-orthoesters 5 in moderate yields. © 2002
Elsevier Science Ltd. All rights reserved.
The reaction of carbon monoxide with alkynes medi-
ated by palladium is a useful method for the synthesis
of acetylene carboxylate,1 g-lactones,2 benzofurans3 and
b-alkoxy acrylates.4 Propargylic esters undergo a num-
ber of palladium-catalyzed, synthetically useful trans-
formations,5 such as preparation of enynes6 and
allenes,7 nucleophilic substitution,8 oxidative rearrange-
ment,9 and carbonylation reactions.10 Recently, Oku-
moto et al.10a reported the palladium-mediated
carbonylation of propargylic acetates 1 afforded g-ace-
toxy-b-methoxyacrylates 3 via the direct attack of
MeOH to the triple bond of the coordinated intermedi-
ate A (Scheme 1(a)). On the other hand, Utimoto et
al.11 reported the regioselective hydration of alkynes
controlled by neighboring group participation of the
carbonyl group. In addition, we have reported oxida-
tive cyclization–carbonylation of 4-yn-1-ones 2 using a
Pd(II)/p-benzoquinone catalytic system afforded cyclic-
ketals 4 via the cyclic intermediate B (Scheme 1(b),
X=carbon).12 We considered that similar neighboring
group participation of the carbonyl group in propar-
gylic acetates is important for the carbonylation of
propargylic acetate 1. Now we wish to report here the
unusual formation of cyclic-orthoesters 5 by the
cyclization–carbonylation of propargylic acetates medi-
ated by palladium (II) (Scheme 1(b), X=oxygen).
The oxidative cyclization–carbonylation of propargylic
acetate 1a–d13 in the presence of (CH3CN)2PdCl2/p-
benzoquinone in methanol at 0°C–room temperature
under carbon monoxide atmosphere (balloon) afforded
(E)-cyclic-orthoesters 5a–d in moderate yields (Table 1,
entries 1–4).14 In our case, methoxyacrylates 3 were not
obtained.15 The reaction of TBDMS ether 1e did not
Scheme 1.
* Corresponding author. Fax: +047-472-1825; e-mail: kkk@phar.toho-u.ac.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01438-7

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K. Kato et al. / Tetrahedron Letters 43 (2002) 6587–6590
Table 1. Cyclization–carbonylation of propargylic acetate 1
proceed under similar reaction conditions, which sug-
gested that the presence of neighboring group participa-
tion of the carbonyl group is indispensable for initiating
the reaction (entry 5). The substrate 1f, bearing two
phenyl groups in propargylic position, afforded differ-
ent products 6 (36%) and 7 (23%) from those of entries
1–4 (entry 6). These products 6 and 7 should be pro-
duced by SN1-type substitution of the acetoxy group
with MeOH and by oxidative rearrangement of propar-
gylic acetate,9 respectively. The reaction of internal
acetylene 1g did not proceed and the substrate was
recovered (entry 7). Next, we examined the reaction of
three kinds of acyl substrates 1hꢀj. When the benzoate
1h was subjected to similar reaction conditions, the
yield of the product 5h was improved in comparison
with acetate 5a (entry 8). However, in the case of
p-nitrobenzoate 1i having an electron-withdrawing
group, the reaction scarcely proceeded and 5i was
obtained in 21% yield together with recovery of the
substrate (65%) (entry 9). The use of p-methoxyben-
zoate 1j bearing an electron-donating group gave b-
ketoester 8 in 83% yield. In addition, a similar reaction
of 1c in the absence of CO and p-benzoquinone was
examined as shown in Scheme 2. Treatment of propar-
gylic acetate 1c with 5 mol% of (CH3CN)2PdCl2 in
methanol at room temperature under air atmosphere
provided hydroxy ketone 9 and its dimethyl ketal 10 in
49 and 39% yield, respectively. On the other hand, the
reaction of TBDMS ether 1e did not proceed under the
same reaction conditions, and the substrate 1e was
recovered quantitatively. These results suggested that
the neighboring group participation of the carbonyl
group in acetates plays an important role in the Pd(II)-
mediated reaction of propargylic acetates.
Selected data of NMR spectra measured in CD3COCD3
of 5a are shown in Fig. 1. The quaternary carbon of
orthoester appeared in 124 ppm and its HMBC correla-
tions with proton of the methyl group (1.6 ppm) and
with proton of the methoxy group (3.24 ppm) were
clearly observed. These results indicated the presence of
an orthoester structure. The stereochemistry of 5a was
confirmed by NOE experiment after conversion into
allyl alcohol 11 by reduction with DIBAL-H as shown
in Fig. 2. The plausible mechanism of the present
reactions would be proposed as shown in Scheme 3.
Propargylic acetate 1 reacts with Pd(II) to generate
vinyl palladium intermediate C, which was subjected to
Figure 1. Selected data of 1H and 13C NMR and HMBC
spectra of 5a.
Figure 2. NOE correlation of 11.
Scheme 2.

K. Kato et al. / Tetrahedron Letters 43 (2002) 6587–6590
6589
Scheme 3.
Figure 3.
3. Nan, Y.; Miao, H.; Yang, Z. Org. Lett. 2000, 2, 297.
the nucleophilic attack of MeOH on the carbon atom
of the carbonyl group followed by CO insertion to
provide the orthoester products 5. In the case of benzo-
ate 1h and p-methoxybenzoate 1j, the cationic inter-
4. (a) Gabriele, B.; Salerno, G.; Pascali, F. D.; Costa, M.;
Chiusoli, G. P. J. Organomet. Chem. 2000, 593–594, 409;
(b) Marshall, J. A.; Yanik, M. M. Tetrahedron Lett. 2000,
41, 4717; (c) Kato, K.; Nishimura, A.; Yamamoto, Y.;
Akita, H. Tetrahedron Lett. 2001, 42, 4203; (d) Kato, K.;
Nishimura, A.; Yamamoto, Y.; Akita, H. Tetrahedron
Lett. 2002, 43, 643; (e) Kato, K.; Tanaka, M.;
Yamamoto, Y.; Akita, H. Tetrahedron Lett. 2002, 43,
1511.
5. (a) Labrosse, J.-R.; Lhoste, P.; Snou, D. J. Org. Chem.
2001, 66, 6634; (b) Condon-Gueugnot, S.; Linstrumelle,
G. Tetrahedron 2000, 56, 1851; (c) Ackermann, L.;
Bruneau, C.; Dixneuf, H. P. Synlett 2001, 397.
6. Mandai, T.; Tsujiguchi, Y.; Matsuoka, S.; Tsuji, J. Tetra-
hedron Lett. 1993, 34, 7615.
mediate
C (R3=Ph and p-MeO-Ph) should be
stabilized by an electron-donating group, and nucleo-
philicity of the carbonyl oxygen should be increased.
Therefore, the yield of the products could be improved.
While the electron-withdrawing effect of the nitro
group caused decreased nucleophilicity of the carbonyl
oxygen in 1i, the reaction scarcely proceeded. In the
case of p-methoxybenzoate 1j, the orthoester bond of 5
(R3=p-MeO-Ph) should be easily cleaved, to afford
b-ketoester 8 in good yield.16
In summary, we have presented a new type of cycliza-
tion–carbonylation of propargylic acetates 1 using a
Pd(II)/p-benzoquinone catalytic system under mild con-
ditions. The neighboring group participation of the
carbonyl group in acetates plays an important role in
the Pd(II)-mediated reaction of propargylic acetates.
7. Tanaka, H.; Takeuchi, H.; Ren, Q.; Torii, S. Electroanaly-
sis 1996, 8, 769.
8. (a) Ehud, K.; Eric, B. J. Org. Chem. 1986, 51, 4006; (b)
Tsuji, J.; Watanabe, H.; Minami, I.; Shimizu, I. J. Am.
Chem. Soc. 1985, 107, 2196.
9. Kataoka, H.; Watanabe, K.; Goto, K. Tetrahedron Lett.
1990, 31, 4181.
10. (a) Okumoto, H.; Nishihara, S.; Nakagawa, H.; Suzuki,
A. Synlett 2000, 217; (b) Mandai, T.; Tsujiguchi, Y.;
Matsuoka, S.; Saito, S.; Tsuji, J. J. Organomet. Chem.
1995, 488, 127; (c) Mandai, T.; Tsujiguchi, Y.; Tsuji, J.;
Saito, S. J. Am. Chem. Soc. 1993, 115, 5865.
11. (a) Imi, K.; Imai, K.; Utimoto, K. Tetrahedron Lett.
1987, 28, 3127; (b) Utimo, K. Pure Appl. Chem. 1983, 55,
1845; (c) Fukuda, Y.; Shiragami, H.; Utimoto, K.;
Nozaki, H. J. Org. Chem. 1991, 56, 5816.
References
1. Tsuji, J.; Takahashi, M.; Takahashi, T. Tetrahedron Lett.
1980, 21, 849.
2. (a) Tamaru, Y.; Hojo, M.; Yoshida, Z. J. Org. Chem.
1991, 56, 1099; (b) Ali, B. E.; Alper, H. J. Org. Chem.
1991, 56, 5357; (c) Consorti, S. C.; Ebeling, G.; Dupont,
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K. Kato et al. / Tetrahedron Letters 43 (2002) 6587–6590
12. (a) Kato, K.; Yamamoto, Y.; Akita, H. Tetrahedron Lett.
2002, 43, 4915; (b) Pd(II) catalyzed cyclization of alkynyl
aldehydes via the hemiacetal intermediate have reported
by Yamamoto et al. See: Asao, N.; Nogami, T.; Taka-
hashi, K.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124,
764.
13. Compounds 1a, 1c and 1d are the same substrates as
those of reported by Okumoto et al. (Scheme 1(a), Ref.
10a).
14. At first, some kinds of palladium catalysts were examined
in cyclization–carbonylation of 1a. Among them, bis(ace-
tonitrile)dichloropalladium(II) gave good results. General
procedure: A 30 mL two-necked round-bottomed flask,
containing a magnetic stirring bar, (CH3CN)2PdCl2 (0.01
mmol), p-benzoquinone (0.22 mmol) and MeOH (4 mL)
was fitted with a rubber septum and three-way stopcock
connected to a balloon filled with carbon monoxide. The
apparatus was purged with carbon monoxide by pump-
ing–filling via the three-way stopcock. A solution of the
substrate 1 (0.2 mmol) in MeOH (2 mL) was added
dropwise to the stirred mixture via a syringe at 0°C. After
being stirred for the period of time, the mixture was
diluted with CH2Cl2 (30 mL), washed with 5% NaOH aq.
(40 mL), and dried over MgSO4. The crude product was
purified by column chromatography on silica-gel. The
fraction eluted with hexane/ethyl acetate (50/1–30/1)
afforded 5 as a colorless oil. Satisfactory analytical data
1
were obtained for all new compounds. Compound 5a: H
NMR (400 MHz, CD3COCD3): l 1.33–1.41 (1H, m),
1.60 (3H, s), 1.56–1.70 (6H, m), 1.75–1.81 (1H, m),
2.48–2.57 (1H, m), 2.69–2.71 (1H, m), 3.24 (3H, s,
orthoester), 3.61 (3H, s, ester), 5.27 (1H, s); 13C NMR
(400 MHz, CD3COCD3): l 22.5, 22.7, 25.2, 25.2, 32.1,
33.2, 49.7 (OMe of orthoester), 51.1 (CO2Me), 87.4 (qua-
ternary, O-C
orthoester), 167.0 (ester), 174.6 (OC
C, 61.22; H, 8.12. Calcd. for C13H20O5: C, 60.92; H,
7.87%.
6
), 89.2 (OC=C
6
H), 124.1 (quaternary,
6
ꢀCH). Anal. found:
15. We also examined the carbonylation reaction of 1c by
using
a PdCl2/CuCl2 catalytic system, and 5c was
obtained in 70% yield.
16. The b-keto ester 12 was obtained in 83% yield by acid
treatment of orthoester product 5c (Fig. 3).