J. B. Sweeney et al. / Tetrahedron 62 (2006) 11506–11512
11511
1
15.8, 115.9, 138.4, 171.0, 171.1; m/z (CI) 294.2421
M +H, C H NO requires 294.2433), 156 (14%), 131
aqueous layer was further extracted with diethyl ether
+
(
(
(4ꢃ20 ml). The combined extracts were dried (MgSO )
1
8
32
2
4
12), 110 (100), 69 (7).
and the solvent was removed in vacuo to leave a yellow oil,
which was purified by column chromatography, eluting
with diethyl ether/petrol (1:2), to give (2R,3R)-N-methyl-
2-(1R,2S,5R)-8-phenylmenthyloxycarbonyl-3-ethenylpyrro-
lidine (120 mg, 29%) and (2S,3S)-N-methyl-2-(1R,2S,5R)-
8-phenylmenthyloxycarbonyl-3-ethenylpyrrolidine (99 mg,
24%) both as colourless oil.
(
0
2
1S,2R,5S)-Menthyl-3-aza-3-methyl-octa-5,7-dienoate: Rf
.46 (diethyl ether/petrol 1:2); nmax/cm 2955, 2923 and
871 (NR ), 1736, 1686 and 1643; d (CDCl ) 0.75 (3H,
ꢂ1
3
H
3
d, J 6.9), 0.86 (3H, d, J 6.9), 0.88 (3H, d, J 6.9), 0.95–1.05
2H), 1.11 (1H, m), 1.27 (1H, m), 1.31 (1H, m), 1.59 (1H,
m), 1.66 (1H, m), 1.84 (1H, m), 1.97 (1H, m), 2.41 (3H,
(
s), 3.26 (2H, s), 3.35 (2H, d, J 7.3), 4.76 (1H, ddd, J 4.4,
(2S,3S)-N-Methyl-2-(1R,2S,5R)-8-phenylmenthyloxycar-
bonyl-3-ethenylpyrrolidine: R 0.33 (diethyl ether/petrol
1
5
0.9, 10.9), 5.16 (1H, d, J 10.09), 5.25 (1H, d, J 16.8),
.55 (1H, dt, J 10.6, 7.3), 6.18 (1H, dd, J 10.6, 11.2), 6.65
f
2
0
ꢂ1
1:2); [a]D ꢂ13.04 (c 1.3, CH Cl ); nmax/cm
2955,
2876 and 2789 (NR ), 1735, 1684 and 1653; d (CDCl )
2
2
(
1H, dddd, J 10.09, 11.2, 16.8, 1.1); dC (CDCl ): 16.2,
3
3
H
3
2
5
2
0.7, 22.0, 23.3, 26.2, 31.4, 34.2, 40.9, 42.3, 46.9, 53.4,
7.7, 74.4, 118.7, 128.2, 131.7, 132.5, 170.4; m/z (CI)
0.78 (1H, m), 0.84 (3H, d, J 6.2), 0.88 (1H, m), 0.96
(1H, m), 1.22 (3H, s), 1.34 (3H, s), 1.43 (1H, m), 1.50
(1H, m), 1.83 (1H, m), 1.92 (1H, m), 1.95 (1H, m), 2.07
(2H, m), 2.33 (3H, s), 2.48 (1H, m), 2.92 (1H, m),
+
94.2443 (M +H, C H NO requires 294.2433), 156
2
1
8
32
(
13%), 110 (64), 96 (53), 67 (12).
2
.96 (1H, m), 3.07 (1H, m), 4.74 (1H, ddd, J 4.03,
4.9. N-Methyl-N-((1R)-8-phenylmenthyloxycarbonyl)-
methyl-3,4-didehydropiperidinium bromide 6
10.9, 10.9), 5.03 (1H, dd, J 1.8, 9.9), 5.07 (1H, dd,
J 1.8, 17.2), 5.67 (1H, ddd, J 9.4, 9.9, 17.2), 7.15 (1H,
m), 7.26 (2H, m), 7.28 (2H, m); d (CDCl ) 21.2, 24.3,
C
3
(
1R,2S,5R)-8-Phenylmenthyl bromoacetate (0.5 g, 1.41
27.2, 29.0, 30.3, 31.3, 34.6, 40.2, 41.8, 46.1, 50.5, 54.9,
71.6, 74.4, 116.3, 125.2, 125.7, 128.0, 138.4, 151.1,
171.9; m/z (CI) 370.2744 (M +H, C H NO requires
370.2740), 282 (9%), 197 (11), 156 (15), 110 (100),
69 (12).
mmol) was added dropwise over 5 min to a stirred solution
of N-methyl-3,4-didehydropiperidine (0.14 g, 1.41 mmol)
in THF (10 ml) under argon. The reaction mixture was
heated under reflux for 12 h resulting in the precipitation
of the title compound, which was filtered and washed with
diethyl ether (2ꢃ15 ml) under argon to give N-methyl-
N-(8-phenylmenthyloxycarbonyl)methyl-3,4-didehydro-
piperidinium bromide 6 (503 mg, 79%) as a colourless
+
2
4
36
2
(2R,3R)-N-Methyl-2-(1R,2S,5R)-8-phenylmenthyloxycar-
bonyl-3-ethenylpyrrolidine: R 0.17 (diethyl ether/petrol
f
2
0
ꢂ1
1:2); [a]D ꢂ10.77 (c 0.9, CH Cl ); nmax/cm 2955, 2876
2
2
ꢀ
deliquescent solid; mp 169.9–170.2 C (CH Cl /petrol);
2
nmax/cm (CH Cl ) 2958, 2935 and 2875, 1735, 1685,
2
and 2789 (NR ), 1735, 1684 and 1653; d (CDCl ) 0.82
3 H 3
2
ꢂ1
(1H, m), 0.84 (3H, d, J 6.5), 0.87 (1H, m), 1.06 (1H, m),
1.31 (3H, s), 1.43 (3H, s), 1.57 (1H, m), 1.59 (1H, m),
1.67 (1H, m), 1.72 (1H, m), 1.87 (1H, m), 2.01 (2H, m),
2.34 (3H, s), 2.43 (1H, m), 2.94 (1H, m), 2.96 (1H, m),
3.14 (1H, m), 4.82 (1H, ddd, J 4.3, 10.7, 10.7), 4.89 (1H,
dd, J 1.8, 10.1), 4.94 (1H, dd, J 1.8, 17.0), 5.67 (1H, ddd,
J 9.6, 10.1, 17.03) 7.15 (1H, m), 7.27 (2H, m), 7.34 (2H,
2
1
d, J 6.9), 0.91 (1.5H, d), 0.97 (1H, m), 1.09 (1H, m), 1.18
(
(
(
653 and 1636 (aromatic C]C); d (CDCl ) 0.87 (1.5H,
H 3
3H, m), 1.23 (1H, m), 1.29 (3H, m), 1.47 (1H, m), 1.71
1H, m), 1.85 (1H, m), 1.94 (1H, m), 2.16 (1H, m), 2.33
1H, br m), 2.50 (1H, br m), 3.49 (3H, s), 3.87 (1H, m),
.98 (1H, m), 4.14 (1H, br m), 4.29 (1H, m), 4.38 (1H, m),
.44 (1H, d, J 17.9), 4.86 (1H, m), 5.69 (1H, br m), 6.01
3
4
m); dC (CDCl ) 15.3, 21.8, 26.7, 29.7, 30.3, 31.2, 34.6,
3
(
(
1H, br m), 7.17 (1H, m), 7.31 (2H, m), 7.34 (2H, m); dC
CDCl ) 21.1, 21.2, 21.5, 22.2, 22.5, 22.5, 25.9, 26.0, 28.1,
39.8, 42.1, 45.9, 50.1, 55.2, 70.8, 74.6, 115.7, 125.0,
125.4, 128.1, 138.9, 151.7, 170.5; m/z (CI) 370.2744
3
+
2
5
1
1
3
8.9, 30.1, 30.3, 34.0, 41.1, 41.2, 48.4, 48.7, 49.2, 49.3,
6.9, 57.7, 58.8, 59.2, 59.3, 60.2, 118.8, 119.1, 124.3,
24.6, 125.1, 125.2, 125.3, 128.2, 151.6, 151.8, 163.4,
(M +H, C H NO requires 370.2740), 282 (9%), 197
2
4
36
2
(11), 156 (15), 110 (100), 69 (12).
+
63.5; m/z (CI) 370.2763 (M ꢂBr, C H NO requires
2
4
36
2
Acknowledgements
70.2746), 156 (19%), 110 (100).
We acknowledge the financial support of the EPSRC, Smith-
KlineBeecham (A.T.) and F. Hofmann La Roche (Basel)
(J.A.W.). We also acknowledge the contributions of Mr.
Kenneth Matheson.
4
.10. (2R,3R)-N-methyl-2-(1R)-8-phenylmenthyloxycar-
bonyl-3-ethenylpyrrolidine and (2S,3S)-N-methyl-2-
1R)-8-phenylmenthyloxycarbonyl-3-ethenylpyrroli-
dine 6
(
Sodium hydride (26.6 mg, 1.11 mmol) was added to a
suspension of N-methyl-N-((1R,2S,5R)-8-phenylmenthyl-
oxycarbonyl)methyl-3,4-didehydropiperidinium bromide
References and notes
1. Workman, J. A.; Garrido, N. P.; San c¸ on, J.; Roberts, E.; Wessel,
H. P.; Sweeney, J. B. J. Am. Chem. Soc. 2005, 127, 1066; for a
related reaction, see: Bild, J.; Panknin, M.; Somfai, P. J. Am.
Chem. Soc. 2005, 127, 9353.
2. Fora review, see: Mark ꢀo , I. E. Comp. Org. Synth. 1991, 3, 913;for
other leading references: Baldwin, J. E.; Hackler, R. E.; Kelly,
D. P. J. Am. Chem. Soc. 1968, 90, 4758; Blackburn, G. M.;
Ollis, W. D.; Smith, C.; Sutherland, I. O. J. Chem. Soc., Chem.
(
(
0.50 g, 1.11 mmol) and powdered molecular sieves
200 mg) in THF (20 ml), vigorously stirred under argon.
The reaction mixture was heated under reflux for 16 h, after
which it was cooled and quenched by careful addition of
methanol. Solvents were removed in vacuo to give a solid,
which was partitioned between water (20 ml) and diethyl
ether (20 ml). The organic layer was separated and the