Stereoselective Nucleophilic Addition to a Novel Chiral Pyrroline N-Oxide
FULL PAPER
tion mixture was stirred at ambient temperature for 30 min, after
which it was cooled to 0 °C and a 10% aqueous solution of KOH
(5 mL) was added dropwise. After 1 h of additional stirring at am-
phy (Dowex 50 W) by elution with water and then with a 2 solu-
tion of NH4OH. After evaporation of the ammonia fraction under
reduced pressure, pure 1 (75 mg, 89%) was obtained as a white
bient temperature the resulting mixture was filtered through a pad solid. m.p. 195Ϫ197 °C. [ref.[3] m.p. 195Ϫ197 °C]. [α]2D0 ϭ Ϫ39 (c ϭ
of Celite. The precipitated salts were washed with Et2O and the
combined filtrates were dried (MgSO4) and rotary evaporated to
0.40, H2O). {ref.[4] [α]D ϭ Ϫ42.0 (c ϭ 1.30, H2O)}. 1H NMR
(D2O): δ ϭ 1.59 (s, 3 H, ϪCH3), 2.10Ϫ2.18 (m, 2 H, H4a and H4b),
3.40 (ddd, J ϭ 4.5, 7.3, 11.2 Hz, 1 H, H5a), 3.52 (dt, J ϭ 7.5,
give the crude mixture of hydroxylamines 8 and 14 in a 1:9 ratio
1
(measured by H NMR). Purification by column chromatography 11.2 Hz, 1 H, H5b), 3.85 (s, 1 H, H2) ppm. 13C NMR (D2O): δ ϭ
(hexane/EtOAc, 2:3) gave pure 14 (1.73 g, 90%) as an oil. [α]2D0
24.3, 39.9, 43.7, 70.1, 78.8, 171.2 ppm. C6H11NO3 (145.16): calcd.
C 49.65, H 7.64, N 9.65; found C 49.72, H 7.43, N 9.56.
Ϫ146 (c ϭ 0.28, CHCl3). 1H NMR (CDCl3): δ ϭ 1.41 (s, 3 H,
ϪCH3), 2.00 (ddd, J ϭ 3.3, 9.4, 13.6 Hz, 1 H, H4a), 2.25 (dt, J ϭ
8.5, 13.6 Hz, 1 H, H4b), 2.87 (pseudo q, J ϭ 9.6 Hz, 1 H, H5a),
3.18 (s, 3 H, ϪOCH2OCH3), 3.52 (td, J ϭ 3.7, 9.6 Hz, 1 H, H5b),
3.68 (s, 1 H, H2), 4.37 and 4.58 (AB system, J ϭ 7.7 Hz, 2 H), 5.51 Acknowledgments
(br. s, 1 H, ϪNOH), 6.31 (br. d, J ϭ 2.9 Hz, 1 H, furyl-H3), 6.36
For their support of our programs we thank: the Spanish Ministry
(dd, J ϭ 1.8, 3.3 Hz, 1 H, furyl-H4), 7.39 (br. s, 1 H, furyl-H5)
ppm. 13C NMR (CDCl3): δ ϭ 24.1, 33.3, 35.2, 54.6, 55.0, 81.5,
91.8, 108.6, 110.3, 142.1, 151.2 ppm. C11H17NO4 (227.26): calcd. C
58.14, H 7.54, N 6.16; found C 57.95, H 7.40, N 6.30.
of Science and Technology (MCYT), the FEDER Program (Project
CASANDRA, BQU2001Ϫ2428), and the Government of Aragon
(Project P116Ϫ2001); the Ministry of Instruction, University and
Scientific Research (MIUR Ϫ Italy, Cofin 2002); MCYT and
MIUR for a bilateral exchange project (2000Ϫ2001). J. R. was the
recipient of a fellowship under the Socrates/Erasmus student ex-
change program (Firenze-Zaragoza). The authors thank Professor
Zhu-Jun Yao (Shanghai Institute of Organic Chemistry, Shanghai,
China) for providing original NMR spectra of compound 1.
(2S,3R)-2-(2-Furyl)-3-methoxymethoxy-3-methylpyrrolidine
(15):
Treatment of 14 (1.8 g, 8.2 mmol) with In powder (1.15 g, 10 mmol)
under the conditions described above for the preparation of 9 gave
pyrrolidine 15 (1.3 g, 80%) as an oil sufficiently pure to be used in
the next reaction. 1H NMR (CDCl3): δ ϭ 1.23 (s, 3 H, ϪCH3),
2.01Ϫ2.13 (m, 2 H, H4a and ϪNH), 2.25 (ddd, J ϭ 5.5, 8.4,
13.5 Hz, 1 H, H4b), 3.01 (dt, J ϭ 4.4, 10.6 Hz, 1 H, H5a), 3.14Ϫ3.27
(m, 1 H, H5b), 3.20 (s, 3 H, ϪOCH2OCH3), 3.79 (s, 1 H, H2), 4.50
and 4.54 (AB system, J ϭ 7.3 Hz, 2 H, ϪOCH2OCH3), 6.20 (br.
d, J ϭ 2.8 Hz, 1 H, furyl-H3), 6.38 (dd, J ϭ 1.9, 3.4 Hz, 1 H, furyl-
H4), 7.36 (br. s, 1 H, furyl-H5) ppm.
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H, ϪCH3), 1.38 [s, 9 H, ϪOC(CH3)3], 1.88 (ddd, J ϭ 4.0, 7.7,
12.1 Hz, 1 H, H4a), 2.26 (dt, J ϭ 8.5, 12.1 Hz, 1 H, H4b), 2.94 (s,
3 H, ϪOCH2OCH3), 3.36 (dt, J ϭ 7.7, 10.3 Hz, 1 H, H5a), 3.54
(ddd, J ϭ 4.0, 8.5, 10.3 Hz, 1 H), H5b), 4.41 and 4.58 (AB system,
J ϭ 7.0 Hz, 2 H, ϪOCH2OCH3), 4.55 (s, 1 H, H2), 6.12 (br. d, J ϭ
3.3 Hz, 1 H, furyl-H3), 6.38 (dd, J ϭ 1.8, 2.9 Hz, 1 H, furyl-H4),
7.50 (br. s, 1 H, furyl-H5) ppm. 13C NMR (CDCl3): δ ϭ 23.3, 28.1,
34.8, 44.2, 55.2, 63.9, 79.3, 82.5, 91.9, 107.1, 110.7, 141.2 (2 C),
157.4 ppm. C16H25NO5 (311.37): calcd. C 61.72, H 8.09, N 4.50;
found C 61.83, H 7.95, N 4.40.
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(ddd, J ϭ 3.9, 6.8, 11.7 Hz, 1 H, H4a), 2.09 (dt, J ϭ 8.3, 11.7 Hz,
1 H, H4b), 3.41 (ddd, J ϭ 4.4, 10.0, 14.6 Hz, 1 H, H5a), 3.62 (dt,
J ϭ 9.8, 14.6 Hz, 1 H, H5b), 3.31 (s, 3 H, ϪOCH2OCH3), 4.60 and
4.62 (AB system, J ϭ 7.3 Hz, 2 H, ϪOCH2OCH3), 4.07 (s, 1 H,
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2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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