1098
P.-F. Wang et al.
LETTER
J = 4.8 Hz, 1 H), 1.86 (m, 1 H), 1.63 (m, 1 H), 1.20–1.00 (m,
2 H), 1.14 (s, 3 H), 1.00 (s, 3 H), 0.88 (s, 3 H). 13C NMR (75
MHz, CDCl3): d = 168.11, 139.61, 128.70, 128.38, 126.62,
82.89, 77.52, 67.58, 61.49, 49.97, 49.07, 47.25, 39.82,
34.71, 23.55, 21.26, 20.02, 11.40. MS (EI): m/z (%) = 327
(17) [M+], 310 (0.5) [M – 17], 144 (11), 136 (8), 104 (100),
95 (23). HRMS (ESI): m/z calcd for C20H26NO3+ [M + 1]:
328.1907; found: 328.1908.
References and Notes
(1) For recent reviews, see: (a) Gothelf, K. V.; Jørgensen, K. A.
Chem. Commun. 2000, 1449. (b) Gothelf, K. V.; Jørgensen,
K. A. Chem. Rev. 1998, 98, 863. (c) Frederickson, M.
Tetrahedron 1997, 53, 403. (d) 1,3-Dipolar Cycloaddition
Chemistry, Vol. 2; Padwa, A., Ed.; General Heterocyclic
Chemistry Series, John Wiley and Sons: New York, 1984,
83.
(2) (a) Inouye, Y.; Takaya, K.; Kakisawa, H. Bull. Chem. Soc.
Jpn. 1983, 56, 3541. (b) Aurich, H. G.; Franzke, M.;
Kesselheim, H. P. Tetrahedron 1992, 48, 663. (c) LeBel, N.
A.; Balasubramanian, N. Tetrahedron Lett. 1985, 26, 4331.
(3) (a) Tamura, O.; Gotanda, K.; Terashima, R.; Kikuchi, M.;
Miyawaki, T.; Sakamoto, M. Chem. Commun. 1996, 1861.
(b) Tamura, O.; Gotanda, K.; Yoshino, J.; Morita, Y.;
Terashima, R.; Kikuchi, M.; Miyawaki, T.; Mita, N.;
Yamashita, M.; Ishibashi, H.; Sakamoto, M. J. Org. Chem.
2000, 65, 8544. (c) Katagiri, N.; Sato, H.; Okada, M.;
Morishita, Y.; Kaneko, C. Tetrahedron 1997, 53, 5727.
(d) Westermann, B.; Walter, A.; Flörke, U.; Altenbach, H.-
J. Org. Lett. 2001, 3, 1375. (e) Baldwin, S. W.; Long, A.
Org. Lett. 2004, 6, 1653. (f) Tamura, O.; Shiro, T.;
Ogasawara, M.; Toyao, A.; Ishibashi, H. J. Org. Chem.
2005, 70, 4569. (g) Long, A.; Baldwin, S. W. Tetrahedron
Lett. 2001, 42, 5343.
(4) (a) Xu, P.-F.; Lu, T.-J. J. Org. Chem. 2003, 68, 658. (b)Xu,
P.-F.; Chen, Y.-S.; Lin, S.-I.; Lu, T.-J. J. Org. Chem. 2002,
67, 2309.
(5) Catalytic hydrogenation of 4a in MeOH was also attempted.
However, the mixture of compound 5 and a by-product
which arised from transesterification of 4a and MeOH were
observed.
(6) (a) Murahashi, S.; Shiota, T.; Imada, Y. Org. Synth. 1992,
70, 265. (b) Murahashi, S.; Shiota, T. Tetrahedron Lett.
1987, 28, 2383.
(7) Typical Procedure for the Preparation of Nitrone 6.
To a solution of amine 5 (300 mg, 1.43 mmol) in CH2Cl2 (12
mL) was added a sat. aq Na2CO3 (18 mL). The resulting
mixture was stirred at 0 °C. During this period, a solution of
MCPBA (767 mg, 4.22 mmol) in CH2Cl2 (18 mL) was added
dropwise over 1 h. After further stirring at r.t. for 12 h, the
layers were separated, and the aqueous layer was extracted
with CH2Cl2. The combined organic layers were dried
(Na2SO4) and filtered. Evaporation of the solvents gave a
residue which was chromatographed over silica gel to afford
the nitrone 6; mp 126 °C (dec.); [a]D23 –280 (c 0.51, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.16 (br s, 1 H), 4.78 (d,
J = 8.1 Hz, 1 H), 3.86 (d, J = 8.1 Hz, 1 H), 2.30 (d, J = 4.8
Hz, 1 H), 1.89 (m, 1 H), 1.65 (m, 1 H), 1.30 (m, 1 H), 1.15
(m, 1 H), 1.15 (s, 3 H), 0.96 (s, 3 H), 0.91 (s, 3 H). 13C NMR
(75 MHz, CDCl3): d = 157.15, 124.56, 81.06, 75.48, 52.09,
50.38, 48.38, 36.46, 22.77, 21.82, 19.85, 12.66. MS (EI):
m/z (%) = 223 (2) [M+], 206 (3) [M – 15], 178 (88), 95 (100).
HRMS (ESI): m/z calcd for C12H18NO3+ [M + 1]: 224.1281;
found: 224.1277.
Compound 8b: mp 86–87 °C; [a]D17 +105 (c 0.62, CHCl3).
1H NMR (300 MHz, CDCl3): d = 4.43 (d, J = 8.4 Hz, 1 H),
4.40 (m, 1 H), 4.01 (dd, J = 12.3, 8.1 Hz, 1 H), 2.74 (d,
J = 8.4 Hz, 1 H), 2.28 (m, 1 H), 2.22 (m, 1 H), 2.03 (d,
J = 5.1 Hz, 1 H), 1.79 (m, 1 H), 1.70–1.40 (m, 3 H), 1.40–
1.20 (m, 4 H), 1.15–0.95 (m, 2 H), 1.07 (s, 3 H), 0.93 (s, 3
H), 0.88 (m, 3 H), 0.83 (s, 3 H). 13C NMR (75 MHz, CDCl3):
d = 168.66, 82.77, 76.08, 67.55, 60.88, 49.92, 48.90, 47.21,
36.37, 34.69, 34.19, 27.97, 23.52, 22.53, 21.23, 19.93,
13.90, 11.35. MS (EI): m/z (%) = 307 (14) [M+], 292 (0.5)
[M – 15], 250 (13), 222 (17), 136 (68), 95 (100). HRMS
(ESI): m/z calcd for C18H30NO3+ [M + 1]: 308.2220; found:
308.2215.
(9) (a) Baldwin, S. W.; McFayden, R. B.; Aube, J.; Wilson, J. D.
Tetrahedron Lett. 1991, 32, 4431. (b) Bonner, M. P.;
Thornton, E. R. J. Am. Chem. Soc. 1991, 113, 1299.
(10) Typical Procedure for the Preparation of Nitrone 10.
A mixture of an aq solution (50%) of glyoxylic acid (0.728
g, 4.92 mmol), 3-(hydroxyamino) isoborneol hydrochloride
(0.990 g, 4.47 mmol) and NaHCO3 (0.376 g, 4.47 mmol) in
CH2Cl2 was stirred for 30 min at r.t. The water of the mixture
was removed azeotropically for 4.5 h. Anhyd p-TsOH (0.387
g, 2.24 mmol) was added to the mixture, and the mixture was
heated at reflux for 14.5 h. After cooling, DCC (0.453 g, 2.24
mmol) was added, and the mixture was stirred for 4 h at r.t.
After cooling, the mixture was washed with H2O, and the
aqueous phase was extracted with CH2Cl2. The organic
phases were combined, dried (Na2SO4), and filtered. The
filtrate was concentrated in vacuo to give the residue, which
was purified by column chromatography on silica gel to
afford nitrone 10 (0.502 g, 50%) as a crystalline solid: mp
117 °C (dec.); [a]D14 +224 (c 1.80, CHCl3). 1H NMR (400
MHz, CDCl3): d = 7.16 (br s, 1 H), 4.53 (d, J = 8.8 Hz, 1 H),
3.92 (d, J = 8.8 Hz, 1 H), 2.68 (d, J = 4.4 Hz, 1 H), 1.92 (m,
1 H), 1.70 (m, 1 H), 1.20 (m, 2 H), 1.10 (s, 3 H), 0.91 (s, 3
H), 0.88 (s, 3 H). 13C NMR (100 MHz, CDCl3): d = 156.93,
124.47, 83.91, 72.32, 51.06, 48.63, 47.65, 32.41, 26.12,
21.63, 19.38, 10.81. MS (EI): m/z (%) = 223 (3) [M+], 206
(2) [M – 15], 162 (4), 135 (33), 95 (100). HRMS (ESI): m/z
calcd for C12H18NO3+ [M + 1]: 224.1281; found: 224.1285.
(11) Representative Spectroscopic Data.
Compound 15a: mp of 152–154 °C. [a]D 15 –156 (c 0.69,
CHCl3). 1H NMR (400 MHz, CDCl3): d = 7.32 (m, 5 H),
5.42 (dd, J = 10.0, 3.6 Hz, 1 H), 4.28 (m, 1 H), 4.25 (d,
J = 8.4 Hz, 1 H), 3.02 (d, J = 8.4 Hz, 1 H), 2.68 (m, 1 H),
2.52 (m, 1 H), 2.16 (d, J = 4.4 Hz, 1 H), 1.80 (m, 1 H), 1.62
(m, 1 H), 1.11 (m, 2 H), 1.04 (s, 6 H), 0.87 (s, 3 H). 13C NMR
(100 MHz, CDCl3): d = 167.95, 139.63, 128.67, 128.35,
126.45, 85.97, 77.93, 64.21, 61.37, 49.63, 49.56, 47.44,
39.36, 33.16, 25.63, 21.51, 20.14, 11.02. MS (EI): m/z
(%) = 327 (0.9) [M+], 283 (0.6), 104 (100), 95 (23). HRMS
(ESI): m/z calcd for C20H26NO3+ [M + 1]: 328.1907; found:
328.1908.
(8) Representative Experimental Procedure for
Cycloaddition Reactions with Nitrone 6.
A solution of nitrone 6 (50 mg, 0.224 mmol) and styrene 7a
(2.24 mmol) in 7 mL of toluene was heated at 60 °C for 8 h.
The mixture was then concentrated under reduced pressure;
the 1H NMR spectrum of the crude product indicated a
diastereomeric ratio of >99:1. An analytical sample 8a
crystallized from EtOAc–PE (1:1) had a mp of 197–199 °C;
[a]D18 +118 (c 1.10, CHCl3). 1H NMR (300 MHz, CDCl3):
d = 7.38–7.31 (m, 5 H), 5.41 (dd, J = 9.6, 3.6 Hz, 1 H), 4.53
(d, J = 8.4 Hz, 1 H), 4.34 (dd, J = 8.4, 7.8 Hz, 1 H), 2.93 (d,
J = 8.4 Hz, 1 H), 2.69 (m, 1 H), 2.57 (m, 1 H), 2.11 (d,
Compound 15b: oil; [a]D15 –107 (c 2.11, CHCl3). 1H NMR
(400 MHz, CDCl3): d = 4.45 (m, 1 H), 4.22 (d, J = 8.4 Hz, 1
H), 4.03 (dd, J = 12.0, 8.0 Hz, 1 H), 2.87 (d, J = 8.4 Hz, 1 H),
2.35 (m, 1 H), 2.27 (m, 1 H), 2.12 (d, J = 4.0 Hz, 1 H), 1.80
(m, 1 H), 1.60 (m, 3 H), 1.33 (m, 4 H), 1.09 (m, 2 H), 1.03
(s, 3 H), 0.99 (s, 3 H), 0.90 (t, J = 7.0 Hz, 3 H), 0.87 (s, 3 H).
Synlett 2006, No. 7, 1095–1099 © Thieme Stuttgart · New York