B. Jiang et al. / Tetrahedron: Asymmetry 17 (2006) 942–951
947
4.3. Bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phenyl
phosphine oxide (9a)
1105, 1020, 770 cmꢀ1
.
1H NMR: d 8.16–8.08 (m, 1H),
7.99–7.91 (m, 2H), 7.50–7.38 (m, 5H), 7.28–7.19 (m, 2H),
7.12–7.07 (m, 1H), 6.99–6.94 (m, 1H), 6.83–6.78 (m, 1H),
3.78–3.68 (m, 2H), 3.48 (s, 3H), 3.12 (s, 3H), 3.00–2.95
(dd, 1H, J = 3.6, 9.3 Hz), 2.65–2.58 (m, 1H), 2.46–2.40 (t,
1H, J = 8.4 Hz), 1.85–1.78 (m, 1H), 1.62–1.53 (m, 1H),
1.43–1.29 (m, 2H). 13C NMR: d 159.4 (d, C, J = 4.0 Hz),
153.4 (d, C, J = 4.6 Hz), 134.6–133.2 (d, C, J = 107 Hz),
134.2–134.1 (d, CH, J = 5.7 Hz), 133.9 (CH), 132.79–
132.77 (d, CH, J = 1.7 Hz), 132.23–132.20 (d, CH,
J = 2.3 Hz), 132.1 (CH), 131.9 (CH), 131.00–130.96 (d,
CH, J = 2.7 Hz), 130.5–129.1 (d, C, J = 110 Hz), 127.9
(CH), 127.7 (CH), 123.4–121.9 (d, C, J = 105 Hz), 122.4–
122.2 (d, CH, J = 13.7 Hz), 121.6–121.5 (d, CH,
J = 9.1 Hz), 120.9–120.8 (d, CH, J = 11.6 Hz), 110.35–
110.26 (d, CH, J = 6.8 Hz), 74.5 (CH2), 60.6 (CH), 58.6
(CH3), 55.9 (CH2), 54.6 (CH3), 28.9 (CH2), 23.3 (CH2).
31P NMR: d +25.3. EIMS: 390 ([MꢀMeO]+, 20%);
HRMS: 390.1661 ([MꢀMeO]+, 13%), calcd for
C24H25NO2P+.
Into the solution of (S)-2-methoxyl-methyl-pyrrolidine
(0.5 mL, 4.0 mmol) in THF (4 mL) was added dropwise
2.5 M n-BuLi (1.6 mL, 4.0 mmol) at ꢀ78 ꢁC. After warm-
ing to rt in 3 h, 7a (0.676 g, 2.0 mmol) was added into
the resulting lithium amide 8 solution in one portion under
an argon flow. The mixture was diluted with ether
(100 mL) after stirring for 20 h and washed with saturated
NH4Cl (2 · 50 mL) and brine (2 · 50 mL). The ether layer
was dried over MgSO4. After filtration and concentration
to dryness, the residue was purified by flash chromatogra-
phy on silica gel (petroleum ether/EtOAc/acetone = 10:1:4)
to give a foaming solid. Recrystallization from hexane gave
a light brown solid (0.63 g, 62% yield). Mp: 160.5–
20
160.7 ꢁC. ½aꢁD ¼ þ43 (c 1.00, CHCl3). IR: 2981, 2873,
2808, 1584, 1568, 1470, 1440, 1280, 1195, 1107, 950, 771,
709 cmꢀ1 1H NMR: 7.60–6.92 (m, 13H), 3.95–3.86 (m,
.
2H), 3.70–3.65 (m, 2H), 3.13 (s, 3H), 3.07 (dd, 1H,
J = 3.4, 9.4 Hz), 3.00 (s, 3H), 2.85–2.61 (m, 4H), 2.28
(t, 1H, J = 8.7 Hz), 2.03–1.49 (m, 8H). 13C NMR:
154.4–154.3 (d, C, J = 3.8 Hz), 153.7 (d, C, J = 3.9 Hz),
135.5–134.1 (d, C, J = 107 Hz), 134.7, 134.6, 134.5, 134.3,
132.6, 132.4, 132.37, 132.34, 132.27, 132.24, 130.6–129.1
(d, C, J = 106 Hz), 130.51, 130.47, 130.1–128.7 (d, C,
J = 105 Hz), 127.5, 127.4, 122.6, 122.51, 122.49, 122.32,
122.29, 122.2, 121.8, 121.6, 74.80 (CH2), 74.75 (CH2),
60.8 (CH), 60.2 (CH), 58.6 (CH3), 57.1 (CH2), 55.9
(CH2), 29.3 (CH2), 28.9 (CH2), 23.8 (CH2), 23.6 (CH2).
31P NMR: +30.2. EIMS: 503 ([MꢀH]+), 473 ([MꢀOMe]+,
13%); HRMS: M+ calcd for C30H37N2O3P+, found
504.2501. Anal. Calcd for C30H37N2O3P: C, 71.41; H,
7.39; N, 5.55. Found: C, 71.21; H, 7.47; N, 5.52.
4.6. (Rp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl]
(2-methoxyl-phenyl)phenyl phosphine oxide 10b
Following the procedure described for 9a and using 1 equiv
20
of 8, 21% yield. Yellow oil. ½aꢁD ¼ ꢀ5 (c 1.00, CHCl3). IR:
2938, 1712, 1590, 1478, 1437, 1277, 1167, 1135, 1109, 802,
1
760, 710 cmꢀ1. H NMR: d 8.12–8.05 (m, 1H), 7.81–7.74
(m, 2H), 7.52–7.23 (m, 7H), 7.15–7.09 (m, 1H), 6.99–6.93
(m, 1H), 6.87–6.83 (dd, H, J = 5.4, 7.8 Hz), 3.88–3.85 (m,
1H), 3.57 (s, 3H), 3.53–3.45 (m, 1H), 3.16 (s, 3H), 3.13–
3.09 (dd, 1H, J = 3.6, 9.3 Hz), 2.78–2.68 (m, 2H), 1.83–
1.77 (m, 1H), 1.55–1.23 (m, 3H). 13C NMR: d 159.90–
159.86 (d, C, J = 3.5 Hz), 153.53–153.47 (d, C,
J = 4.7 Hz), 134.8–133.4 (d, C, J = 109 Hz), 127.4–126.0
(d, C, J = 108 Hz), 122.5–121.1 (d, C, J = 105 Hz),
134.75–134.66 (d, CH, J = 6.4 Hz), 134.52 (CH), 133.48–
133.45 (d, CH, J = 2.3 Hz), 132.60–132.57 (d, CH, J =
2.1 Hz), 131.9 (CH), 131.7 (CH), 130.6–130.5 (d, CH,
J = 2.9 Hz), 127.3 (CH), 127.2 (CH), 122.0–121.9 (d, CH,
J = 3.8 Hz), 121.8–121.7 (d, CH, J = 7.5 Hz), 121.1–120.9
(d, CH, J = 10.5 Hz), 110.9–110.8 (d, CH, J = 6.2 Hz),
74.6 (CH2), 60.8 (CH), 58.7 (CH3), 55.4 (CH2), 54.8
(CH3), 28.9 (CH2), 23.6 (CH2). 31P NMR: d +27.3. ESIMS:
444 ([M+Na]+, 25%), 422 ([M+H]+, 100%); HRMS:
[M+Na]+ calcd for C25H28O3NPNa+ 444.1699, found
444.1684.
4.4. tert-Butyl bis[2-(S)-(2-methoxylmethylpyrrolidinyl)-
phenyl]phosphine oxide 9b
Following the procedure described for 9a, 73% yield. Mp:
20
147–149 ꢁC. ½aꢁD ¼ þ143 (c 1.02, CHCl3). IR: 2966,
1
1715, 1586, 1472, 1438, 1113, 949, 768, 749 cmꢀ1. H NMR:
d 7.97 (t, 1H, J = 8.4 Hz), 7.55–7.47 (m, 2H), 7.33–7.18
(m, 3H), 6.75–6.69 (m, 2H), 4.43–4.36 (m, 1H), 4.12–4.05
(m, 1H), 3.96–3.90 (m, 1H), 3.53–3.44 (m, 2H), 3.30 (s,
3H), 3.18 (t, 1H, J = 8.5 Hz), 3.07–2.99 (m, 1H), 2.95
(s, 3H), 2.59–2.50 (m, 2H), 2.27–2.18 (m, 1H), 2.09–1.88
(m, 3H), 1.80–1.64 (m, 4H), 1.50–1.40 (m, 2H), 1.31–1.26
(d, 9H, J = 14.1 Hz). 13C NMR: d 155.71 (d, J = 2.2 Hz),
154.84 (d, J = 2.5 Hz), 134.43, 134.27, 133.63, 132.39,
132.37, 132.34, 132.11, 131.99, 131.24, 131.21, 126.82,
125.62, 125.21, 125.12, 123.59, 123.43, 119.76, 119.58,
119.48, 119.38, 75.59, 75.28, 61.90, 59.09, 58.96, 58.61,
58.15, 36.44, 35.47, 29.78, 29.49, 26.56, 23.56, 22.97. 31P
NMR: d +43.6. EIMS: 484 (M+, 1%); HRMS: [M+H]+
calcd for C28H42N2O3P+ 485.2928, found 485.2937.
4.7. Bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phenyl
phosphine 6a
Into the solution of 9a (0.40 g, 0.8 mmol) and Et3N
(0.9 mL, 3.2 mmol) in dry m-xylene (6 mL) with ice-water
cooling, HSiCl3 (0.65 mL, 3.2 mmol) was added with cau-
tion. The mixture was heated to 140 ꢁC for 8 h. After cool-
ing to 0 ꢁC and diluting with ether (50 mL), the mixture
was treated with 2 M NaOH with caution to dissolve all
the solid and extracted with ether. The ether layer was
dried over MgSO4. After filtration and concentration to
dryness, the residue was purified by flash chromatography
on silica gel (petroleum ether/EtOAc = 20:1) to give a light
yellow solid (0.29 g, 74% yield). Mp 114.0–114.5 ꢁC.
4.5. (Sp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl]
(2-methoxyl-phenyl)phenyl phosphine oxide 10a
Following the procedure described for 9a and using 1 equiv
20
of 8, 28% yield. Mp: 119–120 ꢁC. ½aꢁD ¼ þ146 (c 1.05,
CHCl3). IR: 2985, 1587, 1475, 1437, 1276, 1242, 1173,