1238
K. Fujiwara et al. / Tetrahedron Letters 50 (2009) 1236–1239
Tetrahedron 1994, 50, 3; (d) Shimizu, Y. Chem. Rev. 1993, 93, 1658; (e)
R1
CO2Me
OCb
H
H
Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1895; (f) Erickson, K. L.. In Marine
Natural Products, Chemical and Biological Perspectives; Scheuer, P. J., Ed.;
Academic Press: New York, 1983; Vol. 5, p 131; See also: (g) Blunt, J. W.;
Copp, B. R.; Munro, M. H. G.; Northcore, P. T.; Prinsep, M. R. Nat. Prod. Rep. 2001,
18, 1. and Ref. 3a.
O
O
Grubbs II
OCb
O
O
25
c — e
2. Recent reviews, see: (a) Fujiwara, K.. In Topics in Heterocyclic Chemistry; Gupta,
R. R., Kiyota, H., Eds.; Springer: Berlin, 2006; Vol. 5, p 97; (b) Nakamura, I.;
Yamamoto, Y. Chem. Rev. 2004, 104, 2127; (c) Elliot, M. C. J. Chem. Soc., Perkin
Trans. 1 2002, 2301; (d) Elliot, M. C.; Williams, E. J. Chem. Soc., Perkin Trans. 1
2001, 2303; (e) Yet, L. Chem. Rev. 2000, 100, 2963; (f) Hoberg, J. O. Tetrahedron
1998, 54, 12631; (g) Alverz, E.; Candenas, M.-L.; Perez, R.; Ravelo, J. L.; Martin, J.
D. Chem. Rev. 1995, 95, 1953.
3. Handbook of Metathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weinheim, 2003.
4. For early applications to medium-ring ethers, see: (a) Linderman, R. J.;
Siedlecki, J.; O’Neil, S. A.; Sum, H. J. Am. Chem. Soc. 1997, 119, 6919; (b)
Crimmins, M. T.; Choy, A. L. J. Org. Chem. 1997, 62, 7548.
NBoc
Me
OBn
OCb
O
Me
O
OBn
OCb
H
O
19: R1 = CO2Me
g
O
a, b
26: R1 = CH2OBn
O
H
OR2
27: R2 = H
28: R2 = Allyl
14
f
5. For recent applications to medium-ring ethers, see: (a) Marvin, C. C.; Voight, E.
A.; Suh, J. M.; Paradise, C. L.; Burke, S. D. J. Org. Chem. 2008, 73, 8452; (b) Oishi,
T.; Hasegawa, F.; Torikai, K.; Konoki, K.; Matsumori, N.; Murata, M. Org. Lett.
2008, 10, 3599; (c) Crimmins, M. T.; Ellis, J. M. J. Org. Chem. 2008, 73, 1649; (d)
Sato, K.; Sasaki, M. Angew. Chem., Int. Ed. 2007, 46, 2518; (e) Roberts, S. W.;
Rainier, J. D. Org. Lett. 2007, 9, 2227; (f) Clark, J. S.; Conroy, J.; Blake, A. J. Org.
Lett. 2007, 9, 2091; (g) Inoue, M.; Miyazaki, K.; Ishihara, Y.; Tatami, A.; Ohnuma,
Y.; Kawada, Y.; Komano, K.; Yamashita, S.; Lee, N.; Hirama, M. J. Am. Chem. Soc.
2006, 128, 9352; (h) Kadota, I.; Nishii, H.; Ishioka, H.; Takamura, H.; Yamamoto,
Y. J. Org. Chem. 2006, 71, 4183; (i) Crimmins, M. T.; McDougall, P. J.; Ellis, J. M.
Org. Lett. 2006, 8, 4079; (j) Ortega, N.; Martín, T.; Martín, V. S. Org. Lett. 2006, 8,
871.
6. For related stereoselective construction of b-hydroxy ethers for cyclic ether
synthesis: (a) Crimmins, M. T.; McDougall, P. J. Org. Lett. 2003, 5, 591; (b)
Crimmins, M. T.; She, J. Synlett 2004, 1371; (c) Crimmins, M. T.; McDougall, P. J.;
Emmitte, K. A. Org. Lett. 2005, 7, 4033.
7. (a) Fujiwara, K.; Goto, A.; Sato, D.; Kawai, H.; Suzuki, T. Tetrahedron Lett. 2005,
46, 3465; (b) Goto, A.; Fujiwara, K.; Kawai, A.; Kawai, H.; Suzuki, T. Org. Lett.
2007, 9, 5373; (c) Sato, D.; Fujiwara, K.; Kawai, H.; Suzuki, T. Tetrahedron Lett.
2008, 49, 1514.
Scheme 4. Reagents and conditions: (a) LiAlH4, THF, –20 °C, 1 h; (b) NaH, BnBr,
Bu4NI, THF, 0 °C?25 °C, 14 h, 87% from 19; (c) TFA–CH2Cl2 (1:2), 25 °C, 10 min; (d)
NaIO4, 1,4-dioxane–pH 7 buffer (1:1), 25 °C, 2 h; (e) NaBH4, CeCl3ꢀ7H2O, MeOH,
–78 °C, 10 min, 65% from 26; (f) NaH, allyl bromide, Bu4NI, THF, 0 °C?25 °C, 18 h,
87%; (g) (H2IMes)(PCy3)Cl2RuCHPh (cat.), CH2Cl2, reflux, 12 h, 96%.
thereby confirming the configurations of rearrangement products
19 and 20.
Construction of an oxane-fused seven-membered ring ether
from 19 was also carried out (Scheme 4). The immediate treatment
of 19 with second-generation Grubbs’ catalyst19 did not afford
RCM product 25 but gave only recovered starting material. This
suggested that steric congestion of the CbO- and the 3-Boc-2,2-di-
methyl-1,3-oxazoline-4-yl groups would inhibit the access of any
active ruthenium species to the internal olefin. Therefore, a step-
wise route from 19 including the removal of the oxazolinyl group
and a relay-RCM process,21 an effective method for the RCM of ste-
rically hindered substrates, was undertaken for the assembly of se-
ven-membered ring ether 14. After methyl ester 19 was converted
to benzyl ether 26 by reduction and subsequent benzylation (87%),
the 3-Boc-2,2-dimethyl-1,3-oxazoline-4-yl group of 26 was trans-
formed to an allyl alcohol group by the same three-step process
as described above (65%). The resulting alcohol 27 was allylated
under Williamson conditions to provide 28 (87%), which was cy-
clized with second-generation Grubbs’ catalyst19 to furnish 1420
in high yield (96%). Thus, a simple procedure was set up for the se-
ven-membered ring ether synthesis subsequent to the Ireland–Cla-
isen step.
8. McFarland, C. M.; McIntosh, M. C. In The Claisen Rearrangement; Hiersemann,
M., Nubbemeyer, U., Eds.; Wiley-VCH: Weinheim, 2007; p 117.
9. Acid 10 was prepared from known (2R,3S)-2-vinyltetrahydropyran-3-ol by a
two-step process [(i) tert-butyl bromoacetate, Bu4NHSO4, 50% NaOH–CH2Cl2
(2:1), 22 °C, 1.5 h, 54%; (ii) TFA–CH2Cl2 (1:2), 24 °C, 1.5 h, ꢁ100%]. The
synthesis of (2R,3S)-2-vinyltetrahydropyran-3-ol, see: (a) Nicolaou, K. C.;
Hwang, C. K.; Marron, B. E.; DeFrees, S. A.; Couladouros, E. A.; Abe, Y.; Carrol,
P. J.; Snyder, J. P. J. Am. Chem. Soc. 1990, 112, 3040–3054; (b) Alvarez, E.;
Delgado, M.; Diaz, M. T.; Hanxing, L.; Perez, R.; Martin, J. D. Tetrahedron Lett.
1996, 37, 2865.
10. Garner, P.; Park, J. M. Org. Synth. 1991, 70, 18.
11. Liang, X.; Andersch, J.; Bols, M. J. Chem. Soc., Perkin Trans. 1 2001, 2136.
12. Gralla, G.; Wibbeling, B.; Hoppe, D. Org. Lett. 2002, 4, 2193.
13. The presence of LiBr enhanced the yield of 12. In order to include LiBr in the
reaction solution conveniently, acetylene 11 was deprotonated with LDA
prepared from i-Pr2NH and a commercially available ether solution of MeLi
containing LiBr (Kanto Chemical Co. Ltd).
14. The compounds 15, 17, and 18 were stable enough to be purified by silica gel
column chromatography with 5% Et3 N containing eluent.
In conclusion, the asymmetric synthesis of an acyclic anti-b-alk-
oxy ether was achieved by the Ireland–Claisen rearrangement of
Z-3-alkoxy-2-propenyl glycolate ester, prepared from Garner’s
aldehyde, a glycolic acid derivative, and ethynyl N,N-diisopropylc-
arbamate. The resulting acyclic ether was facilely converted to
seven- and eight-membered cyclic ethers via processes involving
ring-closing olefin metatheses. Further improvement of the diaste-
reoselectivity of the rearrangement step and applications to the
synthesis of natural medium ring ethers are now in progress.
15. An excess amount of KHMDS was required to obtain reproducible yields of the
products. When 18 was treated with LDA, the terminal vinylic proton adjacent
to the carbamoyloxy group was selectively deprotonated and substituted by a
TMS group. LHMDS was unreactive to 18.
16. Hashimoto, N.; Aoyama, T.; Shioiri, T. Chem. Pharm. Bull. 1981, 29, 1457.
17. Gemal, A. L.; Luche, J.-L. J Am. Chem. Soc. 1981, 103, 5454.
18. (a) Movassaghi, M.; Ahmad, O. K. J. Org. Chem. 2007, 72, 1838; (b) Movassaghi,
M.; Piizzi, G.; Siegel, D. S.; Piersanti, G. Angew. Chem., Int. Ed. 2006, 45, 5859; (c)
Myers, A. G.; Zheng, B.; Movassaghi, M. J. Org. Chem. 1997, 62, 7507.
19. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953.
20. Selected spectral data: 13: ½a D25
ꢃ
+46 (c 0.035, CHCl3); IR (neat) mmax 3030, 2965,
2933, 2873, 2853, 1754, 1693, 1439, 1369, 1344, 1286, 1218, 1118, 1094, 1062,
1025, 769 cmꢂ1 1H NMR (400 MHz, C6D6) d 1.07 (6H, d, J = 6.8 Hz), 1.08 (6H, d,
;
Acknowledgments
J = 6.8 Hz), 1.19–1.38 (3H, m), 1.94–2.01 (1H, m), 2.52 (1H, ddd, J = 2.8, 6.7,
14.1 Hz), 2.67 (1H, dddd, J = 1.1, 3.5, 9.9, 14.1 Hz), 2.82–2.90 (1H, m), 3.12–3.20
(1H, m), 3.27–3.65 (1H, m), 3.40 (3H, s), 3.56–3.62 (1H, m), 3.71 (1H, br ddd,
J = 1.7, 5.0, 8.6 Hz), 3.80–4.20 (1H, m), 4.27 (1H, d, J = 9.9 Hz), 5.60–5.69 (1H,
m), 5.74 (1H, br td, J = 3.1, 9.9 Hz), 5.92 (1H, br dd, J = 5.0, 11.3 Hz); 13C NMR
(100 MHz, C6D6) d 20.8 (CH3 ꢄ 2), 21.3 (CH3 ꢄ 2), 25.7 (CH2), 30.1 (CH2), 31.5
(CH2), 45.6 (CH), 46.5 (CH), 51.6 (CH3), 67.0 (CH2), 73.7 (CH), 79.6 (CH), 79.9
(CH), 81.8 (CH), 125.1 (CH), 136.5 (CH), 154.2 (C), 171.2 (C); HR-EIMS calcd for
We thank Mr. Kenji Watanabe and Dr. Eri Fukushi (GC–MS and
NMR Laboratory, Graduate School of Agriculture, Hokkaido Univer-
sity) for the measurements of mass spectra. This work was sup-
ported by a Global COE Program (B01: Catalysis as the Basis for
Innovation in Materials Science) and a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japanese Government.
C19H31NO6 [M+]: 369.2151, found: 369.2169. Compound 23: ½a 2D5
ꢃ
+139 (c
0.050, CHCl3); IR (neat) mmax 3030, 2957, 2927, 2850, 1760, 1736, 1686, 1440,
1369, 1290, 1210, 1147, 1121, 1075, 1030, 949, 769 cm–1 1H NMR (400 MHz,
;
C6D6) d 1.00–1.42 (15H, m), 1.78–1.86 (1H, m), 1.92 (1H, tdd, J = 1.7, 7.3,
14.8 Hz), 2.81 (1H, ddd, J = 5.9, 8.2, 14.8 Hz), 2.92 (1H, br dt, J = 2.3, 12.0 Hz),
3.40–3.65 (4H, m), 3.45 (3H, s), 3.87 (1H, br s), 4.05–4.35 (1H, m), 5.67 (1H, br
d, J = 5.7 Hz), 5.69–5.77 (1H, m), 5.89 (1H, ddd, J = 1.7, 7.2, 10.9 Hz); 13C NMR
(75 MHz, CDCl3) d 20.6 (CH3 ꢄ 2), 21.3 (CH3 ꢄ 2), 26.0 (CH2), 27.3 (CH2), 31.0
(CH2), 45.3 (CH), 46.6 (CH), 52.4 (CH3), 67.9 (CH2), 74.6 (CH), 74.7 (CH), 76.4
References and notes
1. Reviews for natural cyclic ethers, see: (a) Yasumoto, T. Chem. Rec. 2001, 3, 228;
(b) Yasumoto, T.; Murata, M. Nat. Prod. Rep. 2000, 17, 293; (c) Scheuer, P. J.