L. Fadini, A. Togni / Tetrahedron: Asymmetry 19 (2008) 2555–2562
2561
965 (8, [M–Cl]+, 845 (100, [M–Cl–Fecp]+; Monoisotopic mass, calc:
1001.1252; found: 1001.1254. EA: Anal. Calcd for C54H55F6P4ClFe2-
Ni + CH2Cl2 (1147.75): C, 55.74; H, 4.78. Found: C, 55.71; H,
5.09.
umn chromatography. The isolated product was characterized by
1H and 13C NMR, EA, and GC–MS.
4.2.1. (+)-[2-(R)-Methyl-3-(morpholinium)propanenitrile][(S)-
1,10-binaphthyl-2,20-diylphosphate], 2a
A solution of (S)-(+)-1,10-binaphthyl-2,20-diyl hydrogen phos-
phate (80.4 mg, 0.231 mmol) and 2-methyl-3-(morpholin-4-
yl)propanenitrile (37 mg, 0.231 mmol, 64% ee from the catalysis)
in MeOH (1 mL) was stirred at room temperature for 15 min (all
the products were dissolved). Et2O was added, and a white solid
precipitated. The suspension was cooled at ꢀ20 °C and was stirred
for 4 h. The solid was filtered off and washed with Et2O
(3 ꢂ 20 mL). After drying (HV): 95 mg (80.9% yield). X-ray-quality
crystals were obtained by recrystallization from EtOH/Et2O. 1H
NMR (250.13 MHz, D2O): d 0.79 (d br, 3H, CHMe), 2.62 (m br, 7H,
CH2CH + CHMe + (CH2)2N), 3.36 (s br, 4H, (CH2)2O), 5.82 (s br, 2H,
arom.), 6.28 (s br, 2H, arom.), 6.49 (s br, 2H, arom.), 7.15 (s br,
2H, arom.), 7.35 (s br, 2H, arom.), 7.61 (s br, 2H, arom.). 31P{1H}
4.1.4. [Ni((R,S)-Pigiphos)(THF)](ClO4)2 1b
Ni(ClO4)2ꢁ6H2O (183 mg, 0.5 mmol) and (R,S)-Pigiphos (398 mg,
0.44 mg) were dissolved in THF (10 mL). The mixture was stirred
for 1 h at room temperature yielding a dark red solution. The sol-
vent was removed under reduced pressure (HV), and the solid
was washed twice with hexane (in a glove box). The product was
dissolved in THF (20 mL) and purified by filtration of the suspen-
sion. Evaporation of the solvent yielded 454 mg (84.7%) of a dark
red hydroscopic solid. 1H NMR (300.13 MHz, THF-d8): d 0.8–2.7
(m, 11H, CH2(Cy) or CH(Cy)), 1.89 (m, 4H, CH2), 2.27 (m, 6H,
2 ꢂ CHCH3), 2.71, 2.76 (m, 2H, 2 ꢂ CHMe), 3.72 (m, 4H, OCH2),
3.80 (s, 5H, 5 ꢂ CH(cp)), 4.16 (s, 1H, CH(cp)), 4.37 (s, 5H,
5 ꢂ CH(cp)), 4.79 (m, 1H, CH(cp)), 4.85 (m, 1H, CH(cp)), 4.92 (m,
1H, CH(cp)), 5.21 (m, 1H, CH(cp)), 5.47 (m, 1H, CH(cp)), 6.72 (m,
2H, CH(Ph)), 7.17 (m, 2H, CH(Ph)), 7.43 (m, 4H, CH(Ph)), 7.62 (m,
4H, CH(Ph)), 7.73 (m, 4H, CH(Ph)), 8.10 (m, 2H, CH(Ph)). 31P{1H}
NMR (121.49 MHz, THF-d8): d 6.31 (dd, J = 84.7, J = 247.8, PAPh2),
10.39 (dd, J = 65.7, J = 247.5, PBPh2), 74.26 (dd, J = 83.9, J = 67.5,
PCy). 13C{DEPT} NMR (75.47 MHz, THF-d8): d 12.36 (CH3CH), 22.8
(CH(Cy)), 25.3 (CH2), 25.8, 29.3, 31.0 (CH2(Cy)), 36.4 (PCHCH3),
65.1, 65.2 (CH(cp)), 66.1 (OCH2), 68.9, 69.8 (2 ꢂ CH(cp0)), 69.5,
72.0 (CH(cp)), 126.0–134.0 (20 ꢂ CH(Ph)).
NMR (101.25 MHz, CDCl3): d 6.54 (PO4ꢀ). [
a]D = +335.2 (c 1,
CH2Cl2) rot. = +0.889°. MS (ESI+Q1MS): m/z 155.3 (40, [M]+), 87.3
(10, [M–CH2CH(CH3)CN]+. EA: Anal. Calcd for C28H27N2O5P
(52.51): C, 66.93; H, 5.42; N, 5.57. Found: C, 66.74; H, 5.44; N, 5.45.
4.2.2. (ꢀ)-[2-(R)-Methyl-3-(morpholinium)propanenitrile][(R)-
1,10-binaphthyl-2,20-diylphosphate], 2b
A solution of (R)-(ꢀ)-1,10–binaphthyl-2,20-diyl hydrogen phos-
phate (67.4 mg, 0.19 mmol) and 2-methyl-3-(morpholin-4-yl)pro-
panenitrile (31 mg, 0.19 mmol, 64% ee from the catalysis) in
MeOH (2 mL) was stirred at room temperature for 1 h (all the prod-
ucts were dissolved). Next, Et2O was added and a small amount of
a white solid precipitated. The suspension was cooled to ꢀ20 °C for
4 h, and then the white solid was filtered off and washed with Et2O
(3 ꢂ 20 mL). After drying (HV): 14 mg (14.6% yield). X-ray quality
crystals were obtained by recrystallization from EtOH/Et2O. 1H
NMR (250.13 MHz, CD2Cl2): d 1.35 (d, 3H, CHMe), 2.99 (m br, 6H,
CH2CH + (CH2)2N), 3.40 (m br, 1H, CHCH3), 3.79 (s br, 4H,
(CH2)2O), 7.33–7.53 (m, 8H, arom.), 7.98 (m, 4H, arom.). 31P{1H}
4.1.5. [Ni((R,S)-Pigiphos)(NCCH3)](ClO4)2 1c
At first, Ni(ClO4)2ꢁ6H2O (120.7 mg, 0.33 mmol) and (R,S)-Pigi-
phos (300 mg, 0.33 mmol) were dissolved in CH3CN/Et2O (20 mL,
1:1). The mixture was stirred for 1 h at room temperature. The
resulting red-violet solution was filtered through a 0.45 lm Milli-
pore, the solvent removed under reduced pressure (HV), and the
solid washed with hexane. After drying: 304 mg (76.3%) of a red
powder. 1H NMR (300.13 MHz, CDCl3): d 0.5–2.8 (m, 11H, CH2(Cy)
or CH(Cy)), 1.91 (m, 6H, 2 ꢂ CHCH3), 1.99 (s, CH3CN), 3.42 (m, 1H,
CHMe), 3.75 (m, 1H, CHMe), 3.90 (s, 5H, 5 ꢂ CH(cp)), 4.19 (s, 5 H,
5 ꢂ CH(cp)), 4.35 (s, 1H, CH(cp)), 4.72 (s, 1H, CH(cp)), 4.77 (s, 1H,
CH(cp)), 4.86 (s, 1H, CH(cp)), 5.01 (s, 1H, CH(cp)), 5.08 (m, 1H,
CH(cp)), 6.92 (m, 2H, CH(Ph)), 7.44 (m, 2H, CH(Ph)), 7.5–7.9 (m,
12H, CH(Ph)), 8.0 (m, 4H, CH(Ph)). 31P{1H} NMR (121.49 MHz,
CDCl3): d 9.6 (dd, J = 69.1, J = 188.8, PAPh2), 18.6 (dd, J = 65,
J = 189, PBPh2), 84.75 (d br, J = 64, PCy). 13C{DEPT} NMR
(75.47 MHz, CDCl3): d 14.26 (CH3CH), 14.36 (CH3CH), 24.0–28.0
(CH2(Cy)), 38.1, 38.2 (PCHCH3), 70.6 (CH(cp)), 71.3, 71.7
(2 ꢂ CH(cp0)), 72.3, 72.6, 73.0, 74.9, 76.1 (CH(cp)), 129.5, 129.6,
131.9, 132.4, 132.9, 133.2, 133.5, 133.7, 134.9, 135.3 (20 ꢂ CH(Ph)).
IR (KBr): 2856.7 (br, CH), 2293.0, 2261.5 (s, CN), 1460.9 (s), 1377.0
(s), 1088.2 (s), 973.5 (s).
NMR (101.25 MHz, CDCl3): d 5.27 (PO4ꢀ). [
a]D = -337.3 (c 1, CH2Cl2)
rot. ꢀ0.657°. EA: Anal. Calcd for C28H27N2O5P (502.51): C, 66.93; H,
5.42; N, 5.57. Found: C, 66.87; H, 5.58; N, 5.33.
The salt (14 mg, 0.026 mmol) was hydrolyzed with 0.1 M NaOH.
The mixture was stirred at room temperature for 1 h. Extraction
with Et2O (3 ꢂ 10 mL) yielded 4 mg (97%) of the pure (R)-enantio-
mer of 2-methyl-3-(morpholin-4-yl)propanenitrile (product con-
firmed by GC–MS and 1H NMR); retention time in GC4 (b-dex,
92 °C iso): 139.2 min (major product).
4.2.3. (ꢀ)-[3-(R)-(Phenylammonium)butanenitrile][(R)-1,10-
binaphthyl-2,20-diylphosphate], 3
A solution of (R)-(ꢀ)-1,10-binaphthyl-2,20-diyl hydrogen phos-
phate (63.04 mg, 0.181 mmol) and 3-(phenylamino)butanenitrile
(29 mg, 0.181 mmol, 18% ee from the catalysis) in MeOH (1 mL)
was stirred at room temperature for 15 min (all the products were
dissolved). Et2O was added, and a white solid precipitated. The sus-
pension was cooled to ꢀ20 °C for 24 h, and the white solid was fil-
tered off and washed with Et2O (3 ꢂ 20 mL). After drying (HV):
46 mg (50% yield; expected from 18% ee: 59%). Crystals suitable
for X-ray diffraction were obtained after recrystallization with
EtOH/Et2O. 1H NMR (250.13 MHz, D2O): d 1.47 (d, 3H, J = 7, CHMe),
2.74 (dd, 1H, J = 8, J = 16, CHH0), 2.90 (dd, 1H, J = 4, J = 16, CHH0),
3.71 (m br, 1H, CHCH3), 4.5 (s br, 1H, NH), 7.2–7.6 (m, 8H, arom.),
7.98 (m, 4H, arom.). 31P{1H} NMR (121.49 MHz, CDCl3): d 4.53
4.2. General hydroamination procedure
In the glove box or in a Teflon valve flask (Young), 0.02–
0.1 mmol (5 mol %) of Ni(ClO4)2ꢁ6H2O and 0.02–0.1 mmol
(5 mol %) of the ligand (R,S)-Pigiphos were dissolved in THF
(3 mL). The resulting red-purple solution was stirred at room tem-
perature for 20 min, and then 0.4–2.0 mmol of olefin was added.
The solution was stirred for an additional 30 min. In some cases,
precipitation of the [Ni(PPP)(Olefin)]2+ was observed. After the
addition of 0.2–1.0 mmol of the amine, the solution was stirred
overnight at room temperature. After 24 h, hexane was added to
precipitate the catalyst, and the product was purified by flash col-
(PO4ꢀ). [
a]
D = ꢀ204.2 (c 1, CH2Cl2) rot. ꢀ0.326°.
The salt (24 mg, 0.047 mmol) was hydrolyzed with 0.1 M NaOH.
Extraction with Et2O (3 ꢂ 10 mL) yielded 8 mg (95%) of the pure
(R)-enantiomer of 3-(phenylamino)butanenitrile (product con-