Diastereoselective Hartwig–Buchwald Reaction
FULL PAPER
1
3
J=8.5 Hz, 2H, Ph H-3*), 6.82 (dd, J=7.7, 1.8 Hz, 1H, Pc HAr), 6.52 (dd,
J=7.8, 1.8 Hz, 1H, Pc HAr), 6.35 (dd, J=7.8, 1.7 Hz, 1H, Pc HAr), 6.23
10H, Cy H-2,3,4), 1.00 (d, J=6.3Hz, 3H, Me); C NMR (major diaster-
eomer, (R ,R) (S ,S), 100 MHz, CDCl ): d=146.0, 141.1, 138.8, 138.8 (Pc
p
p
3
(
(
d, 1H, J=7.5 Hz, Pc H-7), 6.03(dd, J=7.5, 1.3Hz, 1H, Pc H Ar), 5.86
dd, J=7.7, 1.7 Hz, 1H, Pc HAr), 5.42 (s, 1H, Pc H-5), 4.20 (q, J=6.8 Hz,
C-4, C-6, C-11, C-14), 134.9, 133.1, 132.4, 131.1, 127.6 (Pc C-8, C-12, C-
131, C-15, C-16), 123.8 (Pc C-3), 120.3 (Pc C-7*), 117.3 (Pc C-5*), 52.7
(C-1), 43.8 (Cy C-1), 35.3, 33.1, 32.9, 30.2, 29.4, 26.7, 26.7 (Pc C-1, C-2, C-
1
H, H-1), 3.87 (s, 3H, OMe), 3.55 (s, 1H, NH), 3.2–2.5 (m, 8H, PcCH
2
),
.44 (d, J=6.8 Hz, 3H, Me); C NMR (major diastereomer, 125 MHz,
): d=158.7 (Ph C-4), 146.6, 141.3, 138.7, 138.6, 138.0 (Pc C-4, C-6,
C-11, C-14, Ph C-1), 134.8 (t), 132.8 (t), 132.4 (t), 131.4 (t), 127.9 (t),
27.7 (Ph C-2*), 123.7 (Pc C-3), 121.4 (t), 117.1 (t), 113.9 (Ph C-3*), 55.4
OMe), 53.3 (C-1), 35.3, 35.3, 33.3, 32.4 (Pc C-1, C-2, C-9, C-10), 23.8
1
3
1
1
9, C-10, Cy C-2, C-3, C-4), 17.1 (Me); H NMR (minor diastereomer,
CDCl
3
(R ,S) or (S ,R), 400 MHz, CDCl ): d=6.99 (dd, J=8.4, 1.9 Hz, 1H, Pc
p
p
3
HAr), 6.59 (dd, J=7.6, 2.4 Hz, 1H, Pc HAr), 6.4–6.3(m, 2H, Pc H Ar), 6.24
(d, J=7.6 Hz, 1H, Pc H-8), 6.03(m, 1H, Pc H Ar), 5.30 (s, 1H, Pc H-5),
1
(
(
3.38 (brs, 1H, NH), 3.3–2.6 (m, 10H, Pc CH , H-1, Cy H-1), 2.1–1.0 (m,
2
1
13
Me); H NMR (minor diastereomer, 500 MHz, CDCl
3
): d=7.17 (d, J=
10H, Cy H-2,3,4), 1.28 (d, J=6.7 Hz, 3H, Me); C NMR (minor diaster-
1
8
8
.6 Hz, 2H, Ph H-2* ), 6.96 (dd, J=7.7, 1.7 Hz, 1H, Pc HAr), 6.79 (d, J=
.6 Hz, 2H, Ph H-3* ), 6.56 (dd, J=7.8, 1.9 Hz, 1H, Pc HAr), 6.45 (dd,
eomer, (R ,S) or (S ,R), 100 MHz, CDCl ): d=146.3, 141.1, 138.8, 138.7
p
p
3
1
(Pc C-4, C-6, C-11, C-14), 135.1, 133.2, 132.4, 131.0, 127.1 (Pc C-8, C-12,
C-131, C-15, C-16), 123.2 (Pc C-3), 120.2 (Pc C-7*), 117.0 (Pc C-5*), 52.5
J=7.7, 1.8 Hz, 1H, Pc HAr), 6.38 (dd, J=7.6, 1.8 Hz, 1H, Pc HAr), 6.26
d, J=7.5 Hz, 1H, Pc H-7), 6.01 (dd, J=7.5, 1.1 Hz, 1H, Pc HAr), 5.14 (s,
(
1
(
C-1), 41.9 (Cy C-1), 35.4, 33.0, 32.9, 30.0, 27.4, 26.5, 26.3 (Pc C-1, C-2, C-
H, Pc H-5), 4.36 (q, J=6.8 Hz, 1H, H-1), 3.74 (s, 3H, OMe), 3.55 (s,
H, NH), 3.2–2.5 (m, 8H, PcCH ), 1.65 (d, J=6.8 Hz, 1H, Me);
C NMR (minor diastereomer, 125 MHz, CDCl ): d=158.3(Ph C-4),
45.5, 141.0, 139.0, 138.7, 137.1 (Pc C-4, C-6, C-11, C-14, Ph C-1), 134.9
9
, C-10, Cy C-2, C-3, C-4), 17.8 (Me); FTIR (both diastereomers, neat):
1
2
À1
n˜ = 3405, 2922, 2851, 1886, 1593, 1505, 1425, 1137, 892, 796 cm ; EI-
1
3
+
+
3
MS: m/z (both diastereomers, %): 333 (7) [M ], 229 (15) [M ÀC
8 8
H
],
1
(
3
3
+
+
1
46 (6) [M ÀC
8
H
8
ÀCy] 104 (100) [C
8 8
H ]; HRMS: m/z: calcd for
t), 133.3 (t), 132.6 (t), 130.9 (t), 127.1 (t), 126.7 (Ph C-2*), 123.2 (Pc C-
), 121.1 (t), 117.6 (t), 113.9 (Ph C-3*), 55.2 (OMe), 52.0 (C-1), 35.3, 33.1,
24
C H31N: 333.2459; found: 333.2456.
(
4-[2.2]Paracyclophanyl)morpholine: The product was synthesised ac-
cording to GP 1. It was purified by column chromatography (silica gel
0, cyclohexane for the separation of [2.2]paracyclophane followed by di-
chloromethane) yielding a colourless oil (56 mg, 0.19 mmol, 38%). R
2.7, 29.7 (Pc C-1, C-2, C-9, C-10), 25.7 (Me); FTIR (both diastereomers,
À1
neat): n˜ = 3412, 2927, 1570, 1511, 1245, 832 cm ; EI-MS: m/z (both dia-
6
+
+
stereomers, %): 357 (34) [M ], 342 (11) [MÀMe ], 135 (100)
f
=
+
+
+
[
MÀPcNH ], 119 (43) [C
8 8 2 8 8
H NH ], 104 (83) [C H ]; HRMS: m/z:
1
0
.05 (cyclohexane); R
f
= 0.6 (dichloromethane); H NMR (250 MHz,
calcd for C25H27NO: 357.2093; found: 357.2089.
CDCl
3
): d=6.69 (dd, J=7.9, 1.7 Hz, 1H, Pc HAr), 6.54 (dd, J=7.9,
(
1-(4-Fluorophenyl)ethyl)-(4-[2.2]paracyclophanyl)amine: The product
1
1
1
1
.8 Hz, 1H, Pc HAr), 6.50–6.40 (m, 2H, Pc HAr), 6.35 (dd, J=7.8, 1.8 Hz,
was synthesised according to GP 1 or GP 2. It was purified by column
chromatography (silica gel 60, cyclohexane/dichloromethane 2:1) yielding
H, Pc HAr), 6.30 (dd, J=7.7, 1.7 Hz, 1H, Pc HAr), 5.73(d, J=1.6 Hz,
H, Pc H-5), 4.02 (ddd, J=11.1, 6.3, 3.2 Hz, 1H, CHHO), 3.98 (ddd, J=
1.4, 6.2, 3.1 Hz, 2H, CHHO), 3.94 (ddd, J=11.0, 6.1, 3.1 Hz, 1H,
a colourless oil (GP 2, 76 mg, 0.22 mmol, 88%). R
f
=0.12 (both diaster-
eomers, cyclohexane/dichloromethane 2:1); H NMR (major diastereom-
er, 400 MHz, CDCl ): d=7.65–7.55 (m, 2H, Ph H-2*), 7.20–7.10 (m, 2H,
Ph H-2*), 6.79 (dd, J=7.8, 1.8 Hz, 1H, Pc HAr), 6.54 (dd, J=7.8, 1.9 Hz,
1
CHHO), 3.44–3.21 (m, 2H, Pc CH
2
), 3.12–2.66 (m, 10H, Pc CH
): d=150.4 (Pc C-4), 141.0, 139.8, 138.9 (Pc
C-6, C-11, C-14), 136.3 (t), 133.2 (t), 132.8 (t), 132.2 (Pc C-3), 131.2 (t),
2 2
, CH N);
3
13
C NMR (100 MHz, CDCl
3
1
1
1
1
6
1
H, Pc HAr), 6.38 (dd, J=7.7, 1.8 Hz, 1H, Pc HAr), 6.25 (d, J=7.6 Hz,
H, Pc H-7), 6.06 (dd, J=7.8, 1.8 Hz, 1H, Pc HAr), 5.79 (dd, J=7.8,
.8 Hz, 1H, Pc HAr), 5.37 (d, J=1.3Hz, 1H, Pc H-5), 4.20 (q, J=6.7 Hz,
1
3
1
2
2 2
28.7 (t), 127.4 (t), 121.2 (t), 67.5 (CH O), 52.3( CH N), 35.3, 35.2, 34.9,
4.1 (Pc C-1, C-2, C-9, C-10); FTIR (neat): n˜ = 3381, 2926, 2850, 1588,
À1
491, 1415, 1371, 1231, 1119, 988, 898, 716, 659 cm ; EI-MS: m/z (%):
H, C-1), 4.23 (brs, 1H, NH), 3.3–2.7 (m, 8H, Pc CH
2
), 1.46 (d, J=
.7 Hz, 3H, Me); C NMR (major diastereomer, 100 MHz, CDCl ): d=
61.9 (d, J=245 Hz, C-F), 146.6 (q), 141.7 (d, J=3Hz, Ph C-1), 141.3
q), 138.7 (q), 138.6 (q), 134.8 (t), 133.3 (t), 132.8 (t), 131.3 (t), 128.1 (d,
J=8 Hz, 2 C, Ph C-2), 127.9 (t), 123.8 (Pc C-3), 121.8 (t), 117.2 (t), 115.4
d, J=21 Hz, 2H, Ph C-3), 53.7 (C-1), 35.3, 35.3, 33.4, 32.3 (Pc C-1, C-2,
+
+
+
+
93(4) [ M ], 189 (3) [M ÀC
8 8 8 8 2 6
H ], 104 [C H ], 44 (100) [C H N ];
1
3
3
HRMS: m/z: calcd for C20
H
23NO: 293.1780; found: 293.1776.
Methyl-(4-[2.2]paracyclophanyl)amine: The product was synthesised ac-
cording to GP 1 with methylammonium chloride as amine precursor and
an additional equivalent of base. It was purified by column chromatogra-
phy (silica gel 60, cyclohexane/ethyl acetate 5:1) yielding a colourless oil
(
(
1
9
C-9, C-10), 24.3(Me); F NMR (major diastereomer, 376 MHz, CDCl
3
):
):
1
(83mg, 35 mmol, 70%). R =0.65 (cyclohexane/ethyl acetate 5:1);
d=À115–(À116) (m); H NMR (minor diastereomer, 400 MHz, CDCl
3
f
1
H NMR (250 MHz, CDCl
.58 (dd, J=7.8, 1.9 Hz, 1H, Pc HAr), 6.41 (dd, J=7.8, 1.9 Hz, 1H, Pc
Ar), 6.36 (dd, J=7.8, 1.9 Hz, 1H, Pc HAr), 6.29 (dd, J=7.8, 1.9 Hz, 1H,
Pc HAr), 6.29 (d, J=7.6 Hz, 1H, Pc H-7), 6.11 (dd, J=7.6, 1.7 Hz, 1H, Pc
Ar), 5.32 (d, J=1.6 Hz, 1H, Pc H-5), 3.64 (brs, 1H, NH), 3.13–2.60 (m,
3
): d=6.89 (dd, J=7.8, 1.9 Hz, 1H, Pc HAr),
d=7.25–7.20 (m, 2H, Ph H-2*), 7.00–6.90 (m, 3H, Ph H-2*, Pc HAr), 6.57
6
H
(
6
6
4
CH
1
1
dd, J=7.8, 1.9 Hz, 1H, Pc HAr), 6.46 (dd, J=7.8, 1.8 Hz, 1H, Pc HAr),
.37 (dd, J=7.7, 1.8 Hz, 1H, Pc HAr), 6.28 (d, J=7.6 Hz, 1H, Pc H-7),
.04 (dd, J=7.7, 1.8 Hz, 1H, Pc HAr), 5.08 (d, J=1.3Hz, 1H, Pc H-5),
.40 (q, J=6.7 Hz, 1H, H-1), 4.23 (brs, 1H, NH), 3.3–2.7 (m, 8H, Pc
H
1
3
1
3
2 3
8H, Pc CH ), 2.76 (s, 3H, Me); C NMR (100 MHz, CDCl ): d=147.5
2
), 1.66 (d, J=6.7 Hz, 3H, Me); C NMR (minor diastereomer,
): d=161.6 (d, J=244 Hz, C-F), 145.2 (q), 141.0 (q),
40.6 (d, J=3 Hz, Ph C-1), 139.0 (q), 138.6 (q), 135.0 (t), 132.7 (t), 132.4
(
Pc C-4), 141.3, 139.4, 139.1 (Pc C-6, C-11, C-14), 134.6 (t), 133.5 (t),
00 MHz, CDCl
3
1
3
2
9
33.0 (t), 130.7 (t), 127.1 (t), 123.7 (Pc C-3), 120.9 (t), 116.0 (t), 35.3, 33.0,
2.8, 30.3, (Pc C-1, C-2, C-9, C-10,), 27.0 (Me); FTIR: n˜ = 3394, 2926,
803, 1596, 1570, 1510, 1441, 1413, 1330, 1295, 1264, 1169, 1089, 1062,
(
t), 130.8 (t), 127.1 (d, J=8 Hz, 2 C, Ph C-2), 127.1 (t), 123.3 (Pc C-3),
1
3
21.3(t), 117.5 (t), 115.3(d, J=21 Hz, 2H, Ph C-3), 52.0 (C-1), 35.3, 35.3,
À1
+
1
9
72, 854, 796, 722, 666 cm ; EI-MS: m/z (%): 237 (28) [M ], 133 (76)
3.0, 32.7 (Pc C-1, C-2, C-9, C-10), 25.8 (Me); F NMR (minor diaster-
+
+
+
eomer, 376 MHz, CDCl
ers, neat): n˜ = 3421, 2927, 1570, 1508, 1427, 1222, 837, 718 cm ; EI-MS:
3
): d=À116–(À117) (m); FTIR (both diastereom-
[M ÀC
for C17
17
C H19N: C 86.03, H 8.07, N 5.90; found: C 85.68, H 7.71, N 5.87.
8
H
8
], 104 (13) [C
8 8 2 5
H ], 43(100) [C H N ]; HRMS: m/z: calcd
À1
H19N: 237.1517, found: 237.1514; elemental analysis calcd (%) for
+
+
m/z (both diastereomers, %): 345 (56) [M ], 330 (13) [MÀMe ], 421
+
+
+
(
64) [MÀC
8
H
8
], 123(100) [ MÀPcNH ], 104 (59) [C
8
H
8
]; HRMS: m/
Butyl-(4-[2.2]paracyclophanyl)amine: The product was synthesised ac-
cording to GP 1. It was purified by column chromatography (cyclohex-
z: calcd for C24
H
24NF: 345.1893; found: 345.1891.
(
1-(Cyclohexyl)ethyl)-(4-[2.2]paracyclophanyl)amine: The product was
ane) yielding a colourless oil (103mg, 37 mmol, 74%).
R
f
=0.03(silica
1
synthesised according to GP 1 or GP 2. It was purified by column chro-
matography (silica gel 60, cyclohexane/dichloromethane 2:1) yielding a
gel 60, cyclohexane); H NMR (250 MHz, CDCl ): d=6.92 (dd, J=7.8,
3
1.8 Hz, 1H, Pc HAr), 6.59 (dd, J=7.8, 1.9 Hz, 1H, Pc HAr), 6.42 (dd, J=
8.0, 2.0 Hz, 1H, Pc HAr), 6.38 (dd, J=7.9, 1.9 Hz, 1H, Pc HAr), 6.29 (d,
J=7.6 Hz, 1H, Pc H-7), 6.10 (dd, J=7.6, 1.6 Hz, 1H, Pc HAr), 5.34 (d,
colourless oil (GP 1, 136 mg, 0.41 mmol, 82%). R
f
=0.41 (both diaster-
eomers, cyclohexane/dichloromethane 2:1); H NMR (major diastereo-
mer, (R ,R) (S ,S), 400 MHz, CDCl ): d=7.01 (dd, J=7.4, 1.5 Hz, 1H, Pc
Ar), 6.59 (dd, J=7.8, 1.9 Hz, 1H, Pc HAr), 6.4–6.3(m, 2H, Pc H Ar), 6.24
d, J=7.6 Hz, 1H, Pc H-8), 6.03(m, 1H, Pc H Ar), 5.33 (s, 1H, Pc H-5),
.38 (brs, 1H, NH), 3.3–2.6 (m, 10H, Pc CH , H-1, Cy H-1), 2.1–1.0 (m,
1
J=1.2 Hz, 1H, Pc H-5), 3.64 (brs, 1H, NH), 3.70–2.60 (m, 10H, Pc CH
+ Bu H-1, H-1’), 1.80–1.40 (m, 4H, Bu H-2, H-2’, H-3, H-3’), 1.05 (t, J=
2
p
p
3
H
(
3
1
3
7.2 Hz, 3H, Me); C NMR (100 MHz, CDCl
3
): d=146.9 (Pc C-4), 141.2,
2
138.8, 138.7 (Pc C-6, C-11, C-14), 134.7 (t), 133.3 (t), 132.3 (t), 130.8 (t),
Chem. Eur. J. 2005, 11, 7387 – 7394
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7393