sity): 168.8 (Mϩ, 100); Direct infusion MS (EI) m/z (rel.inten-
sity): 169.2 (M ϩ 1, 20), 153.3 (22), 138.4 (32), 110.6 (100), 96.7
(26), 82.3 (36).
(t, J = 7.4, 3H); 13C NMR (100 MHz, CDCl3): δ 12.1, 22.8, 23.2,
25.6, 26.0, 26.2, 27.8, 38.2, 48.5, 48.8, 49.2, 50.1, 50.6; tR = 2.2
min, ESI m/z (rel.intensity): 210.9 (Mϩ, 100); Direct infusion
MS (EI) m/z (rel.intensity): 211.2 (M ϩ 1, 100), 195.4 (42),
153.3 (42), 110.2 (58), 82.2 (30).
(1S,2R,4S,5R)-2-(Hydroxymethyl)-5-ethyl-1-azabicyclo-
[2.2.2]octane 7. QCD 2 was hydrogenated according to the
general procedure (half scale). (1S,2R,4S,5R)-2-(Hydroxy-
methyl)-5-ethyl-1-azabicyclo[2.2.2]octane 7 was isolated as a
colourless viscous oil (2.5 g; 98%). Spectral data were identical
to those reported in ref. 22.
Acknowledgements
Financial support from Vetenskapsrådet (The Swedish
Research Council), Ingegerd Berghs Stiftelse, SSF (The
Swedish Foundation for Strategic Research), and Solvias AG
is gratefully acknowledged. We also thank Dr C. von Riesen
(1S,2R,4S,5R)-2-(Aminomethyl)-5-ethyl-1-azabicyclo[2.2.2]-
octane 8. QCD-Amine 4 was hydrogenated according to the
general procedure. (1S,2R,4S,5R)-2-(Aminomethyl)-5-ethyl-1-
azabicyclo[2.2.2]octane 8 was isolated as a pale yellow viscous
oil (5.3 g, 98%). [α]Drt = ϩ152.9 (c = 1, CHCl3). IR (CHCl3, cmϪ1)
and Buchler GmbH-Chininfabrik Braunschweig for
a
generous gift of QCI, QCD, QCI-Amine, and QCD-Amine,
and Dr J. Frackenpohl for fruitful discussions.
1
2937, 2873, 1575, 1520, 1461, 1380, 1051, 929; H NMR (500
References
MHz, CDCl3): δ 2.95–2.76 (m, 3H), 2.74–2.66 (dd, J= 12.7 Hz,
J = 9.6 Hz, 1H), 2.56–2.64 (m, 1H), 2.51–2.46 (dd, J = 12.7 Hz,
J = 4.9 Hz, 1H), 2.37–2.31 (m, 1H), 1.68–1.30 (m, 7H), 1.27
(pent, 2H), 1.12–1.04 (m, 1H), 0.81 (t, J = 7.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ 12.4, 25.6, 26.9, 27.8, 29.0, 37.8,
40.8, 45.9, 57.9, 59.0; HPLC-MS: tR = 2.1 min, ESI m/z
(rel.intensity): 168.8 (Mϩ, 100); Direct infusion MS (EI)
m/z (rel.intensity): 169.2 (M ϩ 1, 30), 138.3 (52), 110.3 (100),
82.3 (62).
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(1S,2S,4S,5R)-2-(N-(Isopropyl)aminomethyl)-5-ethyl-1-aza-
bicyclo[2.2.2]octane 9. Sodium cyanoborohydride (0.189 g,
3.0 mmol), methanol (2.76 ml) and 4 Å molecular sieves (0.15 g)
were mixed. To the mixture was added acetone (0.44 ml,
6.0 mmol) and (1S,2S,4S,5R)-2-(aminomethyl)-5-ethyl-1-
azabicyclo[2.2.2]octane 6 (0.51 g, 3.0 mmol) in a solution of 2.8
ml methanol. The mixture was stirred for 24 h in room temper-
ature and then quenched with 3.3 ml water and 3.3 ml 10%
sodium hydroxide solution. The mixture was filtered and then
extracted three times with 15 ml dichloromethane. The com-
bined organic phases were washed with 10% aqueous sodium
hydroxide solution (3 × 15 ml), and subsequently extracted with
0.5 M aqueous hydrochloric acid (3 × 15 ml). The combined
water phases were made basic and then extracted three times
with dichloromethane. The organic phases were dried with
sodium sulfate and then concentrated under reduced pressure
to give (1S,2S,4S,5R)-2-(N-(isopropyl)aminomethyl)-5-ethyl-1-
azabicyclo[2.2.2]octane 9 a slightly yellowish oil (0.50 g, 78%).
[α]Drt = ϩ3.2 (c = 1, CHCl3). IR (CHCl3, cmϪ1) 2961, 2932, 2865,
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Dihydroxylation
– Discovery and Development, in Catalytic
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1
1520, 1455, 1383, 1339, 1126, 1051, 922; H NMR (500 MHz,
CDCl3): δ 3.15–3.08 (dd, J = 13.4 Hz, 9.5 Hz, 1H), 2.8–2.6 (m,
2H), 2.75 (sep, J = 6.2 Hz, 1H), 2.64–2.5 (m, 5H), 2.38 (m, 1H),
1.81 (m, 1H), 1.65 (m, 1H), 1.5–1.3 (m, 5H), 1.04 (dd, J = 6.9
Hz, J = 6.6 Hz, 6H), 0.85 (t, J = 7.4 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 12.1, 22.5, 23.3, 25.7, 27.3, 27.8, 28.5, 37.8,
40.8, 49.1, 51.2, 55.8, 57.5; HPLC-MS: tR = 2.2 min, ESI m/z
(rel.intensity): 210.9 (Mϩ, 100); Direct infusion MS (EI)
m/z (rel.intensity): 211.2 (M ϩ 1, 26), 153.3 (30), 110.3 (100),
82.3 (46).
(1S,2R,4S,5R)-2-(N-(Isopropyl)aminomethyl)-5-ethyl-1-aza-
bicyclo[2.2.2]octane 10. (1S,2R,4S,5R)-2-(Aminomethyl)-5-
ethyl-1-azabicyclo[2.2.2]octane
8 (0.5 g, 3.0 mmol) was
reductively alkylated with acetone following the same pro-
cedure as described for the QCI-amine 9. (1S,2R,4S,5R)-2-(N-
(isopropyl)aminomethyl)-5-ethyl-1-azabicyclo[2.2.2]octane 10
was isolated as a pale yellow oil (0.52 g, 83%). [α]Drt = ϩ191.1 (c =
1, CHCl3). IR (CHCl3, cmϪ1) 2961, 2935, 2873, 1463, 1382,
1
30 D. A. Alonso, P. Brandt, S. F. M. Nordin and P. G. Andersson,
J. Am. Chem. Soc., 1999, 121, 9580.
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1466.
32 D. A. Alonso, S. F. M. Nordin, P. Roth, T. Tarnai, P. G. Andersson,
M. Thommen and U. Pittelkow, J. Org. Chem., 2000, 65, 3116.
1339, 1082, 1055, 920; H NMR (500 MHz, CDCl3): δ 2.9–2.7
(m, 5H), 2.75–2.71 (t, J = 6.2 Hz, 1H), 2.56 (dd, J = 11.7 Hz,
J = 9.9 Hz, 1H), 2.48 (dd, J = 11.7 Hz, J = 4.6 Hz, 1H), 2.35 (m,
1H), 1.62–1.5 (m, 2H), 1.5–1.4 (m, 2H), 1.4–1.25 (m, 4H),
1.17–1.10 (m, 1H), 1.03 (dd, J = 9.1 Hz, J = 6.2 Hz, 6H), 0.83
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 5 2 2 – 2 5 2 6
2526