T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 2435–2440
2439
4.2.3.
3-Isopropyl-2-methoxyphenyldiphenylphosphine
and 1H (maj)), 1.92–2.11 (m, 1H), 2.34 (br-s, 1H (min)),
2.57–2.81 (br-m, 1H and 1H (min)), 2.88 (br-s, 1H
(min)), 3.00–3.28 (br-m, 2H), 3.11 (s, 3H), 3.28–3.59
(br-m, 1H), 4.46 (br-s, 1H (min)), 6.96 (br-s, 1H), 7.12
(br-s, 1H), 7.32–7.91 (br-m, 11H); 13C NMR (CDCl3)
l: 23.6, 24.0, 24.7, 27.6, 28.6 (min), 30.2 (maj), 52.2
(min), 55.0 (maj), 58.7, 62.2 (min), 63.6 (maj), 75.6,
124.9–136.4 (m, Ar), 150.2–152.2 (m, Ar); 31P NMR
(CDCl3) l: 26.08 (maj), 27.80 (min); FAB-MS m/z (rel.
intensity): 434 (M++1, 100); HRMS (FAB-MS) m/z
calcd for C27H32NO2P+H 434.2249, found 434.2240.
1
oxide 5c. Yield 92%; mp 111–114°C; H NMR (CDCl3)
l: 1.23 (d, J=6.9 Hz, 6H), 3.29 (sept, J=6.9 Hz, 1H),
3.53 (s, 3H), 7.07–7.18 (m, 2H), 7.41–7.56 (m, 7H),
7.66–7.78 (m, 4H); 31P NMR (CDCl3) l: 28.02; FAB-
MS m/z (rel. intensity): 351 (M++1, 100); HRMS (FAB-
MS) m/z calcd for C22H23O2P+H 351.1514, found
351.1497.
4.2.4. 2-Methoxy-3-phenylphenyldiphenylphosphine oxide
1
5d. Yield 83%; mp 119–121°C; H NMR (CDCl3) l:
2.76 (s, 3H), 7.13–7.62 (m, 14H), 7.73–7.85 (m, 4H); 31P
NMR (CDCl3) l: 27.92; FAB-MS m/z (rel. intensity):
385 (M++1, 100); HRMS (FAB-MS) m/z calcd for
C25H21O2P+H 385.1357, found 385.1356.
4.3.4. (R)-1-[2%-(Diphenylphosphinyl)-6%-phenylphenyl]-2-
(methoxymethyl)pyrrolidine 6d. Yield 22%; mp 57–59°C;
[h]2D5=−165 (c 0.11, CHCl3); 1H NMR (CDCl3) l:
1.03–1.17 (m, 1H) 1.17–1.42 (m, 2H) 1.47–1.64 (m, 1H),
1.96–2.44 (br-m, 1H), 2.66 (dd, J=3.6 and 8.9 Hz, 1H),
2.82 (q, J=7.5 Hz, 1H), 2.95 (s, 3H), 3.00–3.25 (br-m,
1H), 3.78 (br, 1H), 7.00–7.18 (m, 2H), 7.25–7.55 (m,
12H), 7.65–7.75 (m, 2H), 7.75–7.85 (m. 2H); 13C NMR
(CDCl3) l: 23.4, 29.2, 56.5, 58.6, 59.9, 75.0, 123.0–142.9
(m, Ar), 150.7 (d, Jcp=4.4 Hz); 31P NMR (CDCl3) l:
27.39; FAB-MS m/z (rel. intensity): 468 (M++1, 100);
HRMS (FAB-MS) m/z calcd for C30H30NO2P+H
468.2092, found 468.2091.
4.3. Typical procedure for the preparation of
aminophosphine oxides 6
To a solution of (R)-2-(methoxymethyl)pyrrolidine
(1.03 mmol) in THF (1 mL) was added slowly n-BuLi
in hexane (0.71 mL, 1.1 mmol, 1.56 M) at −80°C for 10
min, and the resulting mixture stirred at rt for 2 h. The
mixture was cooled to 0°C and phosphine oxide 5 (1.0
mmol) was added. The mixture was allowed to warm to
rt and stirred at rt for 20 h. The mixture was diluted
with ether and quenched with satd aqueous NH4Cl.
The organic layer was washed with brine, dried over
MgSO4, and concentrated under reduced pressure. The
residue was purified by silica gel chromatography.
4.4. Typical procedure for the preparation of
aminophosphine ligands 4
To a mixture of phosphine oxide 6 (0.3 mmol) and
triethylamine (0.34 mL, 1.2 mmol) in m-xylene (2 mL)
was added trichlorosilane (0.24 mL, 1.2 mmol) at 0°C
under an Ar atmosphere. The reaction mixture was
stirred under reflux for 6 h then cooled to rt, diluted
with ether and quenched with 2 M aqueous NaOH
solution. The organic layer was washed with brine,
dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by silica gel chro-
matography (elution with n-hexane/EtOAc=6/1).
4.3.1. (R)-1-[2%-(Diphenylphosphinyl)-6%-methylphenyl]-2-
(methoxymethyl)pyrrolidine 6a. Yield 52%; mp 84–86°C;
[h]2D5=−115 (c 0.20, CHCl3); 1H NMR (CDCl3) l:
1.48–1.72 (m, 3H), 1.87–2.03 (m, 1H), 2.31 (s, 3H),
2.35–3.80 (m, 5H), 3.09 (s, 3H), 6.89–7.05 (m, 2H),
7.29–7.36 (m, 1H), 7.37–7.54 (m, 6H), 7.56–7.87 (m,
4H); 13C NMR (CDCl3) l: 19.7 (d, Jcp=1.1 Hz), 24.1,
29.3, 55.0, 58.6, 61.9, 75.3, 109.8 (d, Jcp=1.7 Hz),
120.9, 124.6–139.5 (m, Ar), 150.9, 155.9 (d, Jcp=6.0
Hz); 31P NMR (CDCl3) l: 26.22; FAB-MS m/z (rel.
intensity): 406 (M++1, 100); HRMS (FAB-MS) m/z
calcd for C25H28NO2P+H 406.1936, found 406.1918.
4.4.1. (R)-1-[2%-(Diphenylphosphino)-6%-methylphenyl]-2-
(methoxymethyl)pyrrolidine 4a. Yield 92%; [h]2D5=−56.0
1
(c 0.11, CHCl3); H NMR (CD2Cl2) l: 1.67–1.86 (m,
3H), 2.05 (br-s, 1H), 2.26 (s, 3H), 2.64 (br-s, 1H), 2.83
(q, J=7.7 Hz, 1H), 3.03 (d, J=5.3 Hz, 1H), 3.08–3.30
(m, 1H), 3.10 (s, 3H), 3.59 (br-s, 1H), 6.70 (br-s, 1H),
6.99 (t, J=7.5 Hz, 1H), 7.17 (d, J=7.4 Hz, 1H),
7.20–7.36 (m, 10H); 13C NMR (CD2Cl2) l: 19.0 (d,
Jcp=1.5 Hz), 24.9, 30.3, 52.9, 58.8, 61.7, 77.1, 126.2,
128.6–128.7 (m, Ar), 131.9, 133.4, 134.1, 134.4, 134.7,
137.7, 139.2, 139.7, 142.2, 150.6 (d, Jcp=14.6 Hz); 31P
NMR (CDCl3) l: −15.55; FAB-MS m/z (rel. intensity):
390 (M++1, 50); HRMS (FAB-MS) m/z calcd for
C25H28NOP+H 390.1987, found 390.2018.
4.3.2. (R)-1-[2%-(Diphenylphosphinyl)-6%-methoxylphenyl]-
2-(methoxymethyl)pyrrolidine 6b. Yield 60%; mp 138–
1
140°C; [h]2D5=−66.4 (c 0.11, CHCl3); H NMR (CDCl3)
l: 1.41–1.58 (m, 3H), 1.87–2.04 (m, 1H), 2.22 (br-s,
1H), 2.49–2.80 (br-m, 2H), 3.00 (dd, J=4.2 and 9.2 Hz,
1H), 3.13 (s, 3H), 3.73 (br-s, 1H), 3.81 (s, 3H), 6.76
(ddd, J=1.8, 7.3 and 13.4 Hz, 1H), 7.03–7.17 (m, 2H),
7.38–7.34 (m, 6H), 7.69–7.85 (m, 4H); 13C NMR
(CDCl3) l: 24.2, 29.6, 53.0, 55.2, 58.7, 61.8, 75.4, 116.1
(d, Jcp=2.1 Hz), 125.9–136.4 (m, Ar), 142.5, 159.1 (d,
Jcp=11.4 Hz); 31P NMR (CDCl3) l: 25.34; FAB-MS
m/z (rel. intensity): 422 (M++1, 100); HRMS (FAB-
MS) m/z calcd for C25H28NO3P+H 422.1885, found
422.1856.
4.4.2. (R)-1-[2%-(Diphenylphosphino)-6%-methoxyphenyl]-
2-(methoxymethyl)pyrrolidine 4b. Yield 82%; mp 87–
1
89°C; [h]2D5=−40.0 (c 0.10, CHCl3); H NMR (CDCl3)
l: 1.56–1.73 (m, 3H), 1.96–2.13 (m, 1H), 2.41 (br-s,
1H), 2.75 (q, J=7.2 Hz, 1H), 3.03 (t, J=9.2 Hz, 1H),
3.16–3.24 (m, 1H), 3.18 (s, 3H), 3.63–3.74 (m, 1H), 3.79
(s, 3H), 6.39 (ddd, J=1.2, 2.8 and 7.6 Hz, 1H), 6.88 (d,
J=7.9 Hz, 1H), 7.06 (t, J=7.9 Hz, 1H), 7.22–7.37 (m,
4.3.3. (R)-1-[2%-(Diphenylphosphinyl)-6%-isopropylphenyl]-
2-(methoxymethyl)pyrrolidine 6c. Yield 17%; [h]2D5=
1
−93.6 (c 0.14, CHCl3); H NMR (CDCl3) l: 0.93–1.36
(br, 1H (maj)), 1.20 (d, J=6.8 Hz, 6H), 1.63 (br-s, 2H