October 1998
SYNLETT
1119
temperature for 80 minutes before adding anhydrous magnesium
sulphate (1g) and stirring for a further 10 minutes. The solution
was filtered and the solvent removed under reduced pressure to
127.5, 128.5 (2C), 131.4, 131.9, 134.8, 137.0; m/z (EI) found
+
274.2172 [M + H], C
H
NO requires 274.2173.
18 27
(9) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835;
Bocoum, A.; Savoia, D.; Umani-Ronchi, A. Tetrahedron Lett.
1991, 32, 1367; Basile, T.; Bocoum, A.; Savoia, D.; Umani-
Ronchi, A. J. Org. Chem. 1994, 59, 7766; Alvaro, G.; Martelli, G.;
Savoia, D. J. Chem. Soc., Perkin Trans. 1, 1998, 775.
give imine ( ) as a pale yellow oil. The imine was used without
1b
further purification.
ν
(neat) 3261, 2956, 2868, 1636, 1618, 1478, 1051, 980, 958,
max
-1
749, 734, 691cm , δH (250 MHz, CDCl ) 0.94 (9H, s), 2.69 (1H,
3
br.s), 2.81-2.87 (1H, dd, J 8.1, 5Hz), 3.83-3.93 (2H, m), 6.86-6.90
(2H, m), 7.26-7.39 (5H, m), 7.94 (1H, d, J 7.8Hz); δC (100 MHz,
(10) Pridgen, L. N.; Mokhallalati, M. K.; Wu, M. J. J. Org. Chem.
1992, 57, 1237; Hashimoto, S.; Yamada, S.; Koga, K. J. Am.
CDCl ) 26.2, 27.0 (3C), 33.4, 62.2, 82.2, 127.2, 127.5, 128.7
3
Chem. Soc.
1976, 98, 7450.
+
(2C), 129.1, 137.0, 142.3, 164.7; m/z (EI) found 231.1624 [M
H], C NO requires 231.1623.
+
H
(11) General method for the amino-Cope rearrangement of amines (
-
2a
15 21
): The amine in dry THF was cooled to –78°C under an inert
e
(7) Scaldione, M. A.; Meyers, A. I. Tetrahedron Lett. 1994, 35, 7533;
Pridgen, L. N.; Mokhallalati, M. K.; Wu, M. J. J. Org. Chem.
1992, 57, 1237.
atmosphere and 2.5 equivalents of n-butyllithium was added
dropwise. After 10 minutes the reaction flask was allowed to
warm to room temperature and then heated to reflux for 2 hours.
The reaction was quenched by dropwise addition of a solution of
sodium acetate/acetic acid/water (1:1:2) and refluxed for a further
4 hours. The solution was allowed to cool to room temperature,
before addition of further 15ml of diethyl ether and washing with
sodium bicarbonate solution (2 x 10ml) and brine (2 x 10ml). The
organic phase was dried over anhydrous magnesium sulphate,
filtered and the solvent removed under reduced pressure. The
crude product was purified by flash column chromatography on
silica gel using an eluent mixture of light petroleum ether/diethyl
(8) General procedure for the synthesis of amines (2a – e):
Allylmagnesium bromide was prepared by the dropwise addition
of allyl bromide (1.62ml, 18.80mmol) to magnesium turnings
(0.45g, 18.80mmol) in dry diethyl ether (10ml) containing a
crystal of iodine. Imine ( ) was added to the Grignard reagent at
1b
0°C in a dropwise fashion over a 45 minute period. The reaction
mixture was then heated at reflux for 2 hours before being poured
onto ice water (20ml). Extraction into diethyl ether was followed
by subsequent washing with 2N NaOH (2 x 20ml), and brine (2 x
20ml). The organic extracts were dried over anhydrous
magnesium sulphate, filtered and evaporated under reduced
ether/acetone (10:2:1). Aldehyde ( ) was isolated as a pale yellow
4
oil.
pressure to yield the target amine ( ) as a pale yellow oil. The
2b
ν
(neat) 1724, 1640, 1602, 1494, 1453, 995, 916, 762, 701; δH
max
major diastereoisomer was isolated by crystallisation from
petroleum ether/diethyl ether (10:1).
(250 MHz, CDCl ) 2.36-2.44 (2H, m), 2.73-2.78 (2H, m), 3.27-
3
3.33 (1H, m), 4.98-5.05 (2H, m), 5.64-5.67 (1H, m), 7.18-7.34
ν
(neat) 3396, 2954, 1636, 1618, 1477, 991, 1051, 984, 915,
max
(5H, m), 9.67 (1H, t, J 1.91Hz); δC (100 MHz, CDCl ) 39.6, 40.9,
-1
3
750cm , δH (250 MHz, CDCl ) 0.85 (9H, s), 2.39-2.43 (3H, m),
3
49.3, 117.1, 126.6, 127.4 (2C), 128.6 (2C), 135.7, 143.0, 201.6; m/
3.27-3.33 (1H, m), 3.46-3.64 (2H, m), 5.07-5.16 (2H, m), 5.82-
5.91 (1H, m), 5.91-6.01 (1H, dd, J 15, 7.5Hz), 6.43 (1H, d, J
15Hz), 7.26-7.35 (5H, m), [OH, NH not visible]; δC (100 MHz,
+
z (EI) found 174.1044 [M ], C
H O requires 174.1045.
12 14
(12) Agami, C.; Meynier, F.; Berlan, J.; Besace, Y.; Brochard, L. J.
Org. Chem. 1986, 51, 73.
CDCl ) 27.3 (3C), 33.8, 40.9, 59.2, 59.5, 63.1, 117.5, 126.2 (2C),
3