D. L o¨ tscher et al. / Tetrahedron: Asymmetry 11 (2000) 4341–4357
4355
3
Hz, 1H, HꢀC(10)); 2.71 (ddd, 1H, HꢀC(9b)); 2.40 (sept, J=3.2 Hz, 1H, HꢀC(8)); 1.42 (s, 3H,
3
13
HꢀC(12)); 1.32 (d, J
=9.5 Hz, 1H, HꢀC(9a)); 0.68 (s, 3H, HꢀC(13)). C NMR (75 MHz,
9
a,9b
CDCl ): l 156.6 (C, 1C); 156.5 (C, 1C), 154.0 (C, 1C); 142.5 (C, 1C); 139.8; 137.8 (CH, 1C);
3
1
1
3
3
34.0 (CH, 1C); 129.1 (CH, 1C); 128.9 (CH, 1C), 127.2 (CH, 1C), 119.9 (CH, 1C); 119.3 (CH,
C), 118.4 (CH, 1C), 46.8 (CH, 1C), 40.6 (CH, 1C); 39.8 (C or CH ; 1C); 37.0 (C or CH , 1C);
2
2
−
6
2.2 (C or CH , 1C), 26.4 (CH , 1C); 21.6 (CH , 1C). UV–vis (CHCl , 8.94×10 M): u
04.0; 253.5 (29000). EI-MS: 326 (100, M ), 311 (50, M−CH ); 297 (36, M−C H ); 283 (93,
(m)
2
3
3
3
max
+
+
3
+
2
5
+
+
+
M−C H ); 246 (10); 231 (2), 205 (7); 154 (15, C H N ); 128 (35); 77 (20, C H ); 51 (9).
3
7
11
8
6
5
Elemental analysis: calculated for C H N : C 84.63, H 6.79, N 8.58%; found C 83.16, H 6.89,
2
3
22
2
N 8.19.
4
.3.5. Bipyridine 12a
To a 25 ml Schlenk flask 15 ml of dry THF (distilled over Na/benzophenone) and 0.29 ml
2.083 mmol, 1.7 equiv.) of dry diisopropylamine (distilled over KOH) were added. This mixture
(
was then cooled down to −40°C and 1.3 ml of n-BuLi (1.6 M in hexane, 1.96 mmol, 1.6 equiv.)
was added via a syringe. The weakly yellow colored solution was allowed to warm up to 0°C
using an ice bath. After having stirred this solution for 30 min, it was cooled down again to
−
40°C and ligand 12 (400 mg, 1.225 mmol, 1 equiv.) dissolved in 5 ml of dry THF was added
using a syringe pump within 1 h. After addition of one drop of this ligand solution, the reaction
mixture became immediately blue. After this addition, the resulting dark blue solution was
stirred at −40°C for 2 h. Then a solution of ethyliodide in 5 ml of dry THF was added using
a syringe pump during 1 h. This resulting reaction mixture was allowed to warm up to room
temperature overnight, and was quenched with 1 ml of water. THF was removed under reduced
pressure and the residue was taken up with 50 ml of CH Cl . More water was added and the
2
2
water phase was extracted with four 20 ml portions of CH Cl . The combined organic phases
2
2
were dried over MgSO , filtered, and evaporated to yield a brown solid, which was then purified
4
by column chromatography (SiO , hexane/ether/triethylamine=10:1:0.1). A pale yellow solid
2
1
3
could be isolated (yield 84%). H NMR (300 MHz, CDCl ): l 8.37 (d, J =8.0 Hz, 1H,
3
3%4%
3
3
4
HꢀC(3%)); 8.31 (d, J =8.0 Hz, 1H, HꢀC(3)); 8.13 (dd, J =8.0 Hz, J
=2.1 Hz, 2H,
3
,4
8%,9%
8%,10%
3
3
4
HꢀC(8%,12%)); 7.85 (dd, J=7.4 Hz, 2H, HꢀC(4%)); 7.72 (dd, J=7.8 Hz, J=0.8 Hz, 1H,
3
3
HꢀC(5%)); 7.48 (dd, J=7.4 Hz, 2H, HꢀC(9%,11%)); 7.42 (dd, J=7.9 Hz, 1H, HꢀC(10%)); 7.37 (d,
3
3
J=8.0 Hz, 1H, HꢀC(4)); 3.22 (m, 1H, HꢀC(9a)); 2.83 (dd, J=6.0 and 5.6 Hz, 1H, HꢀC(10));
3
2
.71 (ddd, 1H, HꢀC(9b)); 2.51 (m, 1H, 14b); 2.40 (sept, J=3.2 Hz, 1H, HꢀC(8)); 1.55 (m, 1H,
3
3
HꢀC(14a); 1.42 (s, 3H, HꢀC(12)); 1.32 (d, J
=9.5 Hz, 1H, HꢀC(9a)); 1.23 (t, J=7.45 Hz,
9a,9b
1
3
3
1
1
1
1
H, HꢀC(15); 0.68 (s, 3H, HꢀC(13)). C NMR (75 MHz, CDCl ): l 159.5 (C, 1C); 156.27 (C,
3
C), 154.0 (C, 1C); 139.5 (C, 1C); 137.6 (CH, 1C); 134.0 (CH, 1C); 128.9 (CH, 1C); 128.7 (CH,
C), 126.9 (CH, 1C), 119.8 (CH, 1C); 119.4 (CH, 1C), 118.4 (CH, 1C), 46.9 (CH, 1C), 45.7 (CH2
C); 42.8 (CH, 1C); 41.1 (C or CH ; 1C); 28.41 (C or CH , 1C), 26.4 (CH , 1C); 25.65 (CH ,
2
2
3
2
C); 20.98 (CH , 1C). Elemental analysis: calculated for C H N : C 84.70, H, 7.39, N 7.90;
found C 84.24, H 7.66, N 7.93. MS-FAB: 355.3 m/z (100, M +H), 325.2 (18, M−C H ), 297.2
3
25 26
2
+
2
5
(
12), 283.2 (18), 147.1 (15).
4
1
.3.6. Typical procedure for the synthesis of mono- and bis-substituted bipyridines 10a–c and
1a–m ( for details see Refs. 14 and 15)
A Schlenk flask was charged with 15 ml of dry THF and diisopropylamine and cooled down
to −40°C. Then n-BuLi (1.6 M in hexane) was added. This mixture was stirred for 30 min at
°C, and cooled again to −40°C. The corresponding bipyridine was dissolved in 5 ml of dry
0