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THF (4 mL). The boron triuoride-etherate (5.0 mL, 40 mmol) Preparation and analysis of diastereomeric amides
was added, the mixture was heated under reux and, as a result,
General procedure. The racemic carboxylic acid (0.1 mmol)
was added to a vial containing 0.016 g (0.1 mmol) of 1,1 -car-
bonyldiimidazole CDI in 3 mL of dry THF. To this solution,
.015 g (0.1 mmol) of (ꢁ)-4e was added and stirred for 1 h. In
a clear solution formed in 20 min. To this solution, bor-
ondimethylsulde (3.0 mL, 30 mmol, or 90 mmol in THF) was
added drop wise over a period of 15 min. The liberated dimethyl
sulde and ether were distilled off as formed and collected.
Aer 20 min, the solvents were removed under suction. Ethyl
ether (EE, 20 mL) was added, followed by tetramethylethylene-
diamide (3.75 mL, 25 mmol). The reaction mixture was stirred
for 90 min at room temperature. The solid was separated,
washed with ethyl ether (2 ꢃ 15 mL). The combined EE layers
0
0
those cases where the acid was a solid, the acid (0.1 mmol) and
CDI (0.1 mmol) were weighed into a vial and dissolved in 3 mL
of THF, followed by the addition of (ꢁ)-4e. One mL of the THF
solution of the resulting diastereomeric amides was injected
directly into a gas chromatograph tted with an appropriate
capillary column maintained isothermally at the required
temperature. The diastereomeric amides revealed a 1 : 1 corre-
spondence with the corresponding retention times.
were dried over anhydrous MgSO . Purication by ash chro-
4
0
matography and removal of the solvent gave the diamine, N,N -
d
bis(isopinocampheyl)ethylenediamine
( IpcNHCH
2
CH
¼ ꢁ28.7I. MS m/
z 332 (M ); IR: 2960, 2780, 1475, 1035; H NMR (CDC1 ): d 0.96
s, 6H, –2CH ); 0.99 (2s, 12H, –4CH ); 1.41 (dd, 2H, –CH,
cyclohexane); 1.42 (dd, 2H, –CH, cyclohexane); 1.49 (dd, 2H,
2
NH-
General procedure for the enantioselective nitroaldol reac-
d
23
Ipc) in 84% isolate yield, as an oily mass. [a]
D
33
tion. The procedure followed was from the literature. To an
+
1
3
oven-dried 10 mL round-bottomed ask, a solution of ligand 3c
(
3
3
(
39.0 mg, 0.12 mmol) and Cu(OAc) $H O (20.0 mg, 0.10 mmol)
2 2
ꢀ
in the CH Cl solvent (1 mL) was stirred for 6 h at 22 C. A clear,
2
2
–
CH , cyclohexane); 1.53 (dd, 2H, –CH , cyclohexane); 1.82 (m,
2 2
deep blue solution resulted. The CH
2 2
Cl was removed under
2
H, –CH, cyclohexane); 1.83 (m, 2H, –CH, cyclohexane); 2.00 (s,
–N).
N -((1S,2S,3S,5R)-2,6,6-Trimethylbicyclo[3.1.1]heptan-3-yl)-
reduced pressure, and then propanol (1 mL) and nitromethane
10 mmol) were added and stirred for 30 min. The aldehyde
–
2H, 2NH); 2.56 (2H, cyclohexane–2H); 2.67 (tt, 4H, –2CH
2
(
(
2
1
1 mmol) was added and the reaction mixture was stirred at
2
N -((2S,3S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)ethane-1,2-
ꢀ
2 C until the reaction was complete (upon disappearance of
+
1
diamine (2c). MS m/z 332 (M ); IR: 2970, 2780, 1470, 1035; H
NMR: d 0.96 (s, 6H, –2CH ); 0.99 (2s, 12H, –4CH ); 1.41 (dd, 2H,
CH, cyclohexane); 1.42 (dd, 2H, –CH, cyclohexane); 1.24 (dd,
aldehyde by TLC). Aer evaporation of the solvent, the residue
was puried by column chromatography on silica gel (10–15%
EtOAc–hexane) to afford the nitroaldol product.
3
3
–
2
H, –CH , cyclohexane); 1.53 (dd, 2H, –CH , cyclohexane); 1.82
2
2
(
(
m, 2H, –CH, cyclohexane); 1.83 (m, 2H, –CH, cyclohexane); 2.01
s, –2H, 2NH); 2.56 (2H, cyclohexane–2H); 2.67 (t, 4H, –2CH
2
–N). Acknowledgements
1
2
N ,N -Bis((1S,2R,3S,6R)-3,7,7-trimethylbicyclo[4.1.0]heptan-
+
Financial support from the United States Army Research Office,
Grant no. (DAAH-94-G-O3L3), is gratefully acknowledged.
2
1
1
1
-yl)ethane-1,2-diamine (3c). MS m/z 332 (M ); IR: 2920, 1440,
1
300, 780; H NMR: d 0.96 (s, 6H, –2CH
3
); 0.99 (2s, 12H, –4CH
3
);
.41 (t, 2H, –2CH, cyclohexane); 1.64 (t, 2H, –2CH, cyclohexane);
.27 (dd, 2H, –CH , cyclohexane); 1.52 (dd, 2H, –CH , cyclo-
2
2
References
hexane); 1.83 (m, H, –CH, cyclohexane); 1.84 (m, H, –CH,
cyclohexane); 2.01 (s, –2H, 2NH); 2.55 (2H, cyclohexane–2H);
2
1 (a) A. Pasini and F. Zunino, Angew. Chem., Int. Ed. Engl., 1987,
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York, 1983, vol. 4.
2
.67 (t, 4H, –2CH –N).
1
2
N ,N -Bis((1R,3R,4R,6S)-4,7,7-trimethylbicyclo[4.1.0]heptan-
+
3
1
1
1
-yl)ethane-1,2-diamine (4c). MS m/z 332 (M ); IR: 2940, 1460,
1
050, 735; H NMR: d 0.96 (s, 6H, –2CH
3
); 0.99 (2s, 12H, –4CH
3
);
.41 (t, 4H, –4CH, cyclohexane); 1.64 (t, 2H, –2CH, cyclohexane);
.24 (dd, 2H, –CH , cyclohexane); 1.49 (dd, 2H, –CH , cyclo-
2
2
hexane); 1.36 (dd, 2H, –CH , cyclohexane); 1.61 (dd, 2H, –CH ,
cyclohexane); 1.84 (m, 2H, –2CH, cyclohexane); 1.84 (m, H, –CH,
cyclohexane); 2.00 (s, –2H, 2NH); 2.56 (2H, cyclohexane–2H);
2
2
2
.67 (t, 4H, –2CH
2
–N).
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1
N -(((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)methyl)-
2
N -(((2R)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)methyl)ethane-
1
NMR: d 0.99 (2s, 12H, –4CH ); 1.41 (dd, 2H, –2CH, cyclohexane);
1
+
1
,2-diamine (5c). MS m/z 332 (M ); IR: 2930, 1515, 1275, 740; H
3
.42 (dd, 2H, –2CH, cyclohexane); 1.24 (dd, 2H, –2CH , cyclo-
2
hexane); 1.49 (dd, 2H, –2CH , cyclohexane); 1.35 (dd, 2H,
2
–
2CH
2
, cyclohexane); 1.45 (dd, 2H, –2CH
, cyclohexane); 1.52 (m, 2H, –2CH
.66 (m, 2H, –2CH, cyclohexane); 2.38 (d, 2H, –CH
2
, cyclohexane); 1.27
, cyclohexane);
–N–cyclo-
–N–cyclohexane); 2.67 (t, 4H, –2CH
(m, 2H, –2CH
2
2
1
2
hexane); 2.63 (d, 2H, –CH
N); 2.00 (s, –2H, 2NH).
2
2
–
7 H. Kubota, M. Nakajima and K. Koga, Tetrahedron Lett., 1993,
34, 8135–8138.
14268 | RSC Adv., 2014, 4, 14264–14269
This journal is © The Royal Society of Chemistry 2014