B.-J. Uang et al. / Tetrahedron 60 (2004) 10479–10486
10483
i
potassium. Ti(O Pr) and TMSCN were purchased from
Aldrich.
1.16–1.40 (m, 4H), 1.67–1.95 (m, 12H), 2.30–2.38 (m, 2H),
3.70–3.76 (m, 4H), 5.20 (d, JZ6 Hz, 2H), 6.89 (d, JZ9 Hz,
4
1
H); C NMR (100 MHz, CDCl ): d 173.7 (C), 77.4 (CH),
3
2
3
4
.3. Procedure for the synthesis of 3a and 3b
58.4 (C), 53.4 (CH), 49.5 (CH), 45.5 (CH), 41.0 (CH ), 32.4
2
(CH ), 29.0 (CH ), 26.3 (CH ), 24.9 (CH ), 21.0 (CH ), 20.9
(CH
2
2
2
2
3
C
); HRMS (M ) calcd for C26
Ketopinic acid chloride (1) (20.1 g, 100 mmol) in CH Cl
2
3
H
42
O
4
N
2
446.3145, found
2
(
(
50 mL) was added to a stirred solution of triethylamine
7.2 g, 100 mmol) and racemic trans-1,2-diamino-cyclo-
446.3136.
0
hydroxy-bicyclo[2.2.1]heptylcarboxyl]cyclohexyl-dia-
hexane (2) (5.7 g, 50 mmol) in CH Cl (50 mL) at 0 8C over
2
4.4.2. (1S,2S)-1,2-N,N -Bis[(1S,2R,4R)-7,7,-dimethyl-2-
2
a 1 h period. The reaction was then allowed to come to room
temperature and then stirred for an additional 1 h period.
The reaction was then quenched by pouring into water
2
6
mine (4b). Mp 224.8–225.4 8C; [a] ZK17.8 (c 1.0,
D
K1
1
CHCl ); IR (KBr) 3367, 3319, 1626 cm
;
(400 MHz, CDCl ): d 0.99 (s, 6H), 1.21 (s, 6H), 1.09–1.40
H NMR
3
(
was washed with brine, dried with Na SO , followed by
200 mL) and extracted with CH Cl2. The organic phase
2
3
(m, 6H), 1.60–1.93 (m, 14H), 2.04 (d, JZ12 Hz, 2H), 3.72
(brs, 2H), 3.96 (dt, JZ3, 3 Hz, 2H), 5.14 (d, JZ1.5 Hz, 2H),
2
4
evaporation and chromatographic separation (EtOAc/
hexaneZ1/2) to give 3a (9.9 g) and 3b (9.8 g) (90%).
1
6.71 (brs, 2H); C NMR (100 MHz, CDCl ): d 175.8 (C),
3
3
7
(CH
(CH
8.0 (C), 56.7 (C), 53.3 (CH), 49.8 (CH), 45.6 (CH), 40.8
0
bicyclo[2.2.1]heptylcarboxyl]cyclohexyldiamine (3a).
4
.3.1. (1R,2R)-1,2-N,N -Bis[(1S,4R)-7,7,-dimethyl-2-oxo-
2
3
), 32.5 (CH
), 20.8 (CH
2
), 30.2 (CH
C
); HRMS (M ) calcd for C26
), 27.4 (CH ), 24.6 (CH ), 21.8
2 2 2
H
O
4
N
3
42
2
2
6
Mp 153.5–154.3 8C; [a] ZC51.5 (c 1.25, CHCl ); IR
446.3145, found 446.3115.
4.5. Procedure for the synthesis of 8a and 8b
Ketopinic acid chloride (1) (20.1 g, 100 mmol) in CH Cl
(200 mL) was added to a stirred solution of triethylamine
(7.2 g, 100 mmol) and the appropriate diamine (7a or 7b)
(50 mmol) in CH Cl (50 mL) at 0 8C over a 1 h period. The
reaction was then allowed to warm to room temperature and
then stirred for an additional 1 h period. The reaction was
then quenched by pouring into water (100 mL) and
extracted with dichloromethane (2!200 mL). The organic
phase was washed with brine (2!200 mL), dried (Na SO )
and concentrated. The residue was purified by passing
through a silica column eluting with EtOAc/hexane (1/3 for
8a and 1/2 for 8b) to provide 8a (93%) or 8b (95%) as a
white solid.
D
3
K1
1
(KBr) 3324, 1733, 1659 cm
CDCl ): d 0.96 (s, 6H), 1.18 (s, 6H), 1.20–1.39 (m, 4H),
;
H NMR (400 MHz,
3
1
2
2
2
.47–1.54 (m, 2H), 1.65–1.70 (brs, 4H), 1.90 (d, JZ20 Hz,
H), 2.01–2.10 (m, 6H), 2.40–2.49 (m, 4H), 3.76–3.81 (m,
2
2
1
3
H), 7.43 (d, JZ8 Hz, 2H); C NMR (100 MHz, CDCl ): d
3
15.9 (C), 169.0 (C), 64.7 (C), 52.3 (CH), 49.7 (C), 43.6
(
CH ), 43.2 (CH), 32.6 (CH ), 27.9 (CH ), 27.4 (CH ), 24.5
2 2 2 2
2
2
C
CH ), 20.7 (CH ), 20.4 (CH ); HRMS (M ) calcd for
(
C H O N 442.2832, found 442.2846.
2
3
3
2
6 38 4 2
0
bicyclo[2.2.1]heptylcarboxyl]cyclohexyldiamine (3b).
4
.3.2. (1S,2S)-1,2-N,N -Bis[(1S,4R)-7,7,-dimethyl-2-oxo-
2
4
2
D
6
Mp 117.3–117.9 8C; [a] ZC55.5 (c 1.5, CHCl ); IR
3
K1
1
(
(
(
KBr) 3406, 3343, 3309, 1750, 1640 cm ;
400 MHz, CDCl ): d 0.92 (s, 6H), 1.18 (s, 6H), 1.20–1.41
m, 4H), 1.53–1.69 (m, 6H), 1.89 (d, JZ20 Hz, 2H), 2.01 (t,
H NMR
3
JZ4 Hz, 2H), 2.02–2.15 (m, 4H), 2.38–2.46 (m, 4H), 3.75
1
brs, 2H), 7.63 (brs, 2H); C NMR (100 MHz, CDCl ): d
3
0
bicyclo[2.2.1]heptylcarboxyl]diphenylethylenediamine
(
4.5.1. (1R,2R)-1,2-N,N -Bis[(1S,4R)-7,7,-dimethyl-2-oxo-
3
2
16.0 (C), 169.4 (C), 64.7 (C), 52.3 (CH), 49.9 (C), 43.7
CH ), 43.2 (CH), 32.1 (CH ), 28.3 (CH ), 27.5 (CH ), 24.3
2
4
(
(
(8a). Mp 243.5–244.3 8C; [a] ZC39.9 (c 1.46, CHCl );
2
2
2
2
D
3
C
CH ), 20.7 (CH ), 20.5 (CH ); HRMS (M ) calcd for
K1
1
2
3
3
IR (KBr) 3346, 1740, 1664, 1649 cm
;
H NMR
C H O N 442.2832, found 442.2817.
2
(400 MHz, CDCl ): d 0.83 (s, 6H), 1.11 (s, 6H), 1.34–1.35
3
6
38
4
2
(m, 2H), 1.48–1.55 (m, 2H), 1.92–2.08 (m, 6H), 2.36–2.51
4
.4. Procedure for the synthesis of 4a and 4b
(m, 4H), 5.41 (dd, JZ2.0, 6.0 Hz, 2H), 7.05–7.08 (m, 4H),
1
3
7.12–7.19 (m, 6H), 8.41 (d, JZ6.8 Hz, 2H); C NMR
To a solution of 3a or 3b (4 mmol) in THF (5 mL) at
K78 8C was added 1 M L-selectride in THF (18.0 mL)
dropwise. The reaction mixture was stirred at K78 8C for
(100 MHz, CDCl ): d 216.9 (C), 168.8 (C), 138.8 (C), 127.9
3
w
(2CH), 127.1 (3CH), 64.3 (C), 57.2 (CH), 49.9 (C), 43.5
(CH ), 43.1 (CH), 28.3 (CH ), 27.5 (CH ), 20.6 (CH ), 20.1
(CH ); HRMS (M ) calcd for C H O N : 541.2988(MC
2
2
2
3
C
1
and quenched by the successive addition of H O (4.0 mL),
h followed by 2 h at room temperature, then cooled to 0 8C
3
34 41 4 2
1), found 541.3066.
2
EtOH (12 mL), 3 M aq. NaOH (16 mL), followed by the
dropwise addition of 30% aq. H O (12 mL) over a 30 min
period. The aqueous phase was saturated with K CO and
0
cyclo[2.2.1]heptylcarboxyl]phenyldiamine (8b). Mp
136.3–136.8 8C; [a] ZC29.0 (c 1.0, CHCl ); IR (KBr)
D 3
K1 1
3282, 2968, 1730, 1683, 1603 cm ; H NMR (300 MHz,
2
2
4.5.2.
1,2-N,N -Bis[(1S,4R)-7,7,-dimethyl-2-oxo-bi-
2
3
2
6
extracted with CH Cl . The organic phase was dried with
2
2
Na SO , and filtered. Evaporation of solvent followed by
2
4
crystallization (EtOAc/hexaneZ1/5) from the organic
phase gave 4a (95%) or 4b (96%).
CDCl ): d 1.07 (s, 6H), 1.28 (s, 6H), 1.40–1.49 (m, 2H),
3
1.74–1.83 (m, 2H), 1.96 (s, 1H), 2.02 (s, 1H), 2.07–2.18 (m,
4H), 2.50–2.65 (m, 4H), 7.12–7.15 (m, 2H), 7.69–7.72 (m,
2H), 9.43 (m, 2H); C NMR (75 MHz, CDCl ): d 185.0 (C),
0
hydroxy-bicyclo[2.2.1]heptylcarboxyl]cyclohexyl-dia-
13
4
.4.1. (1R,2R)-1,2-N,N -Bis[(1S,2R,4R)-7,7,-dimethyl-2-
3
168.2 (C), 129.9 (C), 125.6 (CH), 124.8 (CH), 65.2 (C), 50.4
(C), 43.7 (CH ), 43.4 (CH), 28.8 (CH ), 27.7 (CH ), 20.9
2
6
mine (4a). Mp 208.2–208.3 8C; [a] ZK55.3 (c 1.0,
D
2
2
2
K1
1
CHCl ); IR (KBr) 3328, 1629 cm ; H NMR (400 MHz,
C
(CH ), 20.5 (CH ); HRMS (M ) calcd for C H N O :
3 3 26 32 2 4
3
CDCl ): d 0.85 (s, 6H), 0.90–1.02 (m, 4H), 1.14 (s, 6H),
3
436.2362, found 436.2358.