An Aromatic Amide-Derived Phosphane Library
FULL PAPER
N,N-Diisopropyl 4-n-butyl-2-dicyclohexylphosphinobenzamide (18b):
Compound 18b was isolated in 87% yield from 17a and n-butylboronic
acid after 8 h at 808C according to general procedure B. White amor-
phous solid; m.p. 110–1138C; Rf =0.28 (10% EtOAc in hexane);
1H NMR (400 MHz, CDCl3, 2 38C): d= 7.26 (s, 1H), 7.10 (d, J=8.0 Hz,
1H), 7.03 (dd, J=8.0, 3.2Hz, 1H), 3.58 (septet, J=6.8 Hz, 1H), 3.46
(septet, J=6.8 Hz, 1H), 2.62 (t, J=7.2Hz, 2H), 2.15–1.51 (m, 14H), 1.58
(d, J=6.8 Hz, 3H), 1.53 (d, J=6.8 Hz, 3H), 1.49–0.90 (m, 12H), 1.19 (d,
J=7.2Hz, 3H), 1.01 (d, J=6.8 Hz, 3H), 0.92ppm (t, J=7.2Hz, 3H);
13C NMR (100 MHz, CDCl3, 2 38C): d=170.6 (d, JP-C =3.0 Hz), 144.8 (d,
N,N-Diisopropyl 2-dicyclohexylphosphino-4-(3’-nitrophenyl)benzamide
(19q): Compound 19q was prepared in 82% from 17a and 3-nitrophenyl-
boronic acid after 15 h at 808C according to general procedure B by
using 10 mol% Pd(OAc)2. Amorphous white solid; m.p. 91–938C; Rf =
A
0.18 (9.1% EtOAc in hexane); 1H NMR (300 MHz, CDCl3, 2 38C): d=
8.40 (s, 1H), 8.23 (dt, J=7.2, 0.9 Hz, 1H), 7.88 (d, J=7.5 Hz, 1H), 7.68
(s, 1H), 7.65 (dd, J=7.8, 7.8 Hz, 1H), 7.56 (d, J=7.8 Hz, 1H), 7.27 (dd,
J=8.1, 3.0 Hz, 1H), 3.63–3.49 (m, 2H), 1.94–0.84 ppm (m, 34H);
13C NMR (75 MHz, CDCl3, 2 83C): d=169.9 (d,
JP-C =3.9 Hz), 148.9,
147.5 (d, JP-C =35.0 Hz), 142.7, 137.5, 134.1 (d, JP-C =25.1 Hz), 133.3, 131.4
(d, JP-C =3.8 Hz), 130.0, 127.8, 126.3 (d, JP-C =8.0 Hz), 122.4, 122.3, 51.1,
J
J
P-C =35.5 Hz), 141.2, 132.6, 132.1 (d, JP-C =21.4 Hz), 128.8, 125.1 (d,
P-C =7.9 Hz), 50.6, 45.5, 35.5 (d, JP-C =19.0 Hz), 35.4, 33.5, 32.9 (d, JP-C
P-C =18.8 Hz), 30.1 (d, JP-C
=
46.0, 35.9 (d,
J
P-C =15.2Hz), 33.1 (d,
J
P-C =12.2 Hz), 30.8 (d, JP-C
=
=
=
12.0 Hz), 30.5 (d, JP-C =15.4 Hz), 30.2(d,
J
=
14.0 Hz), 30.6, 30.4 (d, JP-C =3.6 Hz), 29.6 (d, JP-C =5.3 Hz), 28.1 (d, JP-C
3.1 Hz), 28.0 (d, JP-C =3.8 Hz), 27.4 (d, JP-C =10.0 Hz), 27.2 (d, JP-C
15.0 Hz), 29.0 (d, JP-C =3.8 Hz), 27.7, 27.7, 27.1 (d, JP-C =4.7 Hz), 27.0 (d,
J
P-C =5.8 Hz), 26.6, 26.3, 22.1, 21.0 (d, JP-C =3.6 Hz), 20.7, 20.6, 20.2,
7.3 Hz), 26.9 (d, JP-C =2.4 Hz), 26.6, 21.4 (d, JP-C =4.4 Hz), 21.1, 21.0,
20.5 ppm; 31P NMR (121 MHz, CDCl3, 2 38C): d=À7.35 ppm; IR (film):
n˜ =2926, 1630, 1531, 1441, 1342 cmÀ1; MS (CI): m/z (%): 523 (100)
[M+H]+; elemental analysis calcd (%) for C31H43N2O3P (522.7): C 71.24,
H 8.29, N 5.36; found: C 71.08, H 8.28, N 5.28.
13.9 ppm; 31P NMR (161 MHz, CDCl3, 2 38C): d= À9.90 ppm; IR (film):
n˜ =2926, 1632, 1439, 1338 cmÀ1; HRMS (CI): m/z: calcd for C29H49NOP:
458.3552; found: 458.3549 [M+H]+.
N,N-Diisopropyl 2-dicyclohexylphosphino-4-phenylbenzamide (18c).
Compound 18c was prepared in 78% yield from 17a and phenylboronic
N,N-Diisopropyl 2-dicyclohexylphosphinobenzamide (21): N,N-Diisopro-
pylbenzamide (454.0 mg, 2.2 mmol) and THF (4 mL) were added to a
flame dried flask with a stirring bar under a nitrogen atmosphere. nBuLi
(1.6m in hexanes, 1.66 mL, 2.65 mmol) was added dropwise to the resul-
tant solution which had been cooled in a dry ice-acetone bath (À788C).
After stirring the solution at À788C for 20 min, chlorodicyclohexylphos-
phane (0.59 mL, 2.65 mmol) was added to the mixture, followed by stir-
ring at À788C for 2h and at room temperature for 1 h. The reaction mix-
ture was filtered through a pad of silica gel topped with a layer of Celite,
and eluted with EtOAc. The filtrate was concentrated under reduced
pressure to give the crude product, which was purified by flash column
chromatography (silica gel, 10% EtOAc/hexane) to afford 21 (635.2mg,
72%). White solid; m.p. 168–169 8C (CH2Cl2/hexane); Rf =0.49 (9.1%
EtOAc in hexane); 1H NMR (300 MHz, CDCl3, 2 38C): d=7.48 (br s,
1H), 7.29 (t, J=3.4 Hz, 2H), 7.13 (br s, 1H), 3.59–3.43 (m, 2H), 2.20–
0.90 ppm (m, 34H); 13C NMR (75 MHz, CDCl3, 2 38C): d=170.4 (d,
acid after 8 h at 808C according to general procedure
B by using
10 mol% Pd(OAc)2. A higher yield of 18c was obtained by using the fol-
ACHTREUNG
lowing modified conditions. A 10 mL pressurized process vial containing
a magnetic stirring bar was charged with phenylboronic acid (45.7 mg,
3.810À1 mmol), 17a (109.0 mg, 2.510À1 mmol), [Pd2
(dba)3] (4.6 mg,
R
5.010À3 mmol) and KF·2H2O (70.6 mg, 7.510À1 mmol). The loaded
vial was sealed with a cap containing a silicon septum and then evacuated
through a needle under vacuum and backfilled with nitrogen (this se-
quence was repeated for three times). Degassed dry toluene (2mL) was
added through the septum by a syringe, and the resultant mixture was
stirred at room temperature for 2min followed by stirring at 110 8C for
7 h. Then, the reaction mixture was allowed to cool to room temperature,
diluted with EtOAc (5 mL), and filtered through a thin pad of Celite and
silica gel while eluting with EtOAc. The filtrate was concentrated under
reduced pressure and the residue was purified by flash column chroma-
tography (silica gel, 10% EtOAc/hexane) to afford 18c (103.6 mg, 87%).
White crystalline solid; m.p. 157–1598C (EtOAc/hexane); Rf =0.44
J
J
P-C =3.9 Hz), 147.5 (d, JP-C =34.5 Hz), 132.9 (d, JP-C =3,3 Hz), 132.5 (d,
P-C =2.0 Hz), 128.8, 127.2 (d, JP-C =3.9 Hz), 125.5 (d, JP-C =7.9 Hz), 50.9,
1
(9.1% EtOAc in hexane); H NMR (300 MHz, CDCl3, 2 38C): d=7.69 (s,
45.9, 35.8 (d,
14.2Hz), 30.6 (d,
5.3 Hz), 28.1 (d, JP-C =4.4 Hz), 28.0, 27.5 (d, JP-C =4.2Hz), 27.3 (d, JP-C
J
P-C =15.1 Hz), 33.1 (d,
J
P-C =11.7 Hz), 30.8 (d, JP-C
=
=
=
1H), 7.59–7.35 (m, 6H), 7.21 (dd, J=7.8, 3.0 Hz, 1H), 3.71–3.47 (m, 2H),
J
P-C =14.5 Hz), 30.4 (d, JP-C =9.5 Hz), 29.4 (d, JP-C
2.30–1.00 ppm (m, 34H); 13C NMR (75 MHz, CDCl3, 2 38C): d= 169.7
(d, JP-C =4.0 Hz), 145.7 (d, JP-C =35.0 Hz), 140.3, 139.2, 132.6 (d, JP-C
26.7 Hz), 130.7 (d, JP-C =4.4 Hz), 128.4 (2), 127.1, 127.0, 126.7 (2),
=
5.5 Hz), 26.9, 26.7, 21.4 (d, JP-C =4.1 Hz), 21.0 (2), 20.6 ppm; 31P NMR
(121 MHz, CDCl3, 2 38C): d=À7.97 ppm; IR (KBr): n˜ =2919, 1627 cmÀ1
;
125.2 (d, JP-C =8.3 Hz), 50.3, 45.2, 35.2 (d, JP-C =15.5 Hz), 32.5 (d, JP-C
11.7 Hz), 30.2( P-C =14.3 Hz), 30.0 (d, P-C =8.6 Hz), 29.7 (d, JP-C
2.5 Hz), 28.8 (d, JP-C =5.6 Hz), 27.4 (d, JP-C =2.9 Hz), 27.3 (d, JP-C
3.2Hz), 26.8 (d,
=
=
=
MS (CI): m/z (%): 402(100) [ M+H]+; elemental analysis calcd (%) for
C25H40NOP (401.6): C 74.77, H 10.40, N 3.49; found: C 74.64, H 10.20, N
3.40.
J
J
J
P-C =9.9 Hz), 26.7 (d, JP-C =10.9 Hz), 26.2, 26.0, 20.7 (d,
J
P-C =4.1 Hz), 20.4, 20.3, 19.9 ppm; 31P NMR (121 MHz, CDCl3, 2 38C):
N,N-Diisopropyl 2-dicyclohexylphosphino-5-(3’-nitrophenyl)benzamide
(24): Compound 24 was prepared in 70% yield from 15a and 3-nitrophe-
nylboronic acid after 8 h at 1008C according to general procedure B by
d= À7.45 ppm; IR (KBr): n˜ =2925, 1631 cmÀ1; MS (CI): m/z (%): 478
(100) [M+H]+; elemental analysis calcd (%) for C31H44NOP (477.7): C
77.95, H 9.28, N 2.93; found: C 78.00, H 9.31, N 2.76.
using 10 mol% Pd(OAc)2. White crystalline solid; m.p. 210–2128C
G
(CH2Cl2/hexane); Rf =0.35 (9.1% EtOAc in hexane); 1H NMR
(500 MHz, CDCl3, 2 38C): d=8.46 (t, J=2.0 Hz, 1H), 8.21 (dt, J=8.5,
1.0 Hz, 1H), 7.93 (t, J=1.5 Hz, 1H), 7.62(t, J=8.0 Hz, 2H), 7.56 (dd, J=
8.0, 2.0 Hz, 1H), 7.36 (t, J=2.5 Hz, 1H), 3.62 (septet, J=7.0 Hz, 1H),
3.52(septet, J=7.0 Hz, 1H), 2.25–1.00 ppm (m, 34); 13C NMR (125 MHz,
CDCl3, 2 38C): d=170.0 (d, JP-C =3.6 Hz), 149.0, 148.4 (d, JP-C =35.3 Hz),
142.2, 139.3, 133.9 (br, 2), 133.2 (d, JP-C =4.2 Hz), 130.1, 126.0, 124.0 (d,
N,N-Diisopropyl 2-dicyclohexylphosphino-4-(2’,6’-dimethylphenyl)benz-
ACHTREUNG
AHCTREUNG
crystalline solid; m.p. 181–1828C (EtOAc/hexane); Rf =0.31 (10%
EtOAc in hexane); 1H NMR (300 MHz, CDCl3, 2 38C): d=7.31 (t, J=
1.8 Hz, 1H), 7.23–7.09 (m, 5H), 3.69 (septet, J=6.8 Hz, 1H), 3.51
(septet, J=6.8 Hz, 1H), 2.04 (s, 3H), 2.02 (s, 3H), 1.95–1.00 ppm (m,
34H); 13C NMR (75 MHz, CDCl3, 2 83C): d=170.5 (d, JP-C =3.5 Hz),
146.0 (d, JP-C =35.0 Hz), 141.6, 139.8, 136.4 (d, JP-C =46.2Hz), 133.5 (d,
J
J
J
P-C =8.8 Hz), 122.6, 122.2, 51.0, 45.9, 35.8 (d, JP-C =14.8 Hz), 32.9 (d,
P-C =11.4 Hz), 30.7 (d, JP-C =13.1 Hz), 30.4 (d, JP-C =18.5 Hz), 30.2(d,
P-C =21.6 Hz), 29.3, 27.9, 27.9, 27.2 (d, JP-C =8.4 Hz), 27.2 (d, JP-C
=
10.7 Hz), 26.7, 26.5, 21.2, 21.1, 20.9, 20.3 ppm; 31P NMR (202 MHz,
CDCl3, 2 83C): d=À8.26 ppm; IR (film): n˜ =2927, 1626, 1532, 1447,
1348 cmÀ1; MS (ESI): m/z (%): 545 (100) [M+Na]+; elemental analysis
calcd (%) for C31H43N2O3P (522.7): C 71.24, H 8.29, N 5.36; found: C
71.24, H 8.13, N 5.30.
J
J
P-C =3.6 Hz), 129.5 (d, JP-C =1.3 Hz, 2), 127.6, 127.4 (3), 125.6 (d,
P-C =8.8 Hz), 51.0, 45.9, 35.9 (d, JP-C =15.5 Hz), 33.5 (d, JP-C =11.9 Hz),
31.2(d,
JP-C =15.2Hz), 30.6 (d, JP-C =12.8 Hz), 30.4 (d, JP-C =7.7 Hz), 29.4
(d, JP-C =3.5 Hz), 28.1 (d, JP-C =10.9 Hz), 28.0 (d, JP-C =4.2Hz), 27.4 (d,
J
P-C =3.2Hz), 27.3 (d,
JP-C =2.6 Hz), 26.9, 26.8, 21.6 (d, JP-C =4.2Hz),
Microwave-assisted synthesis and 31P NMR characterization of Cy-Aphos
18c, 19a-q, and 20: A 10 mL pressurized process vial containing a mag-
netic stirring bar was charged with arylboronic acid (3.010À2 mmol),
21.3, 21.2, 21.1, 21.0, 20.7 ppm; 31P NMR (121 MHz, CDCl3, 2 38C): d=
À8.27 ppm; IR (KBr): n˜ =2925, 1631, 1440, 1336 cmÀ1; MS (TOF): m/z
(%): 506 (100) [M+H]+; elemental analysis calcd (%) for C33H48NOP
(505.7): C 78.37, H 9.57, N 2.77; found: C 78.30, H 9.58, N 3.24.
[Pd
2(dba)3] (4.6 mg, 5.010À3 mmol), 17a (8.8 mg, 2.010À2 mmol), and
A
Chem. Eur. J. 2008, 14, 5538 – 5554
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5551