A Route to Functionalized Tertiary Phosphane Oxides
FULL PAPER
organic extracts were dried (MgSO4) and filtered, and the filtrate
was concentrated under reduced pressure. The residue was purified
(8 mL). The ether layer was separated and aqueous layer was ex-
tracted with Et2O (2 ϫ 10 mL). The combined ether extracts were
by chromatography (ethyl acetate/hexanes, 80:20) to give the prod- dried (MgSO4) and concentrated under reduced pressure to give a
uct 16 (309 mg, 72%) as colourless needles, m.p. 118Ϫ119 °C. Ϫ
white solid, which was purified by flash chromatography (MeOH/
[α]2D3 ϭ ϩ104 (c ϭ 4.41, CHCl3), from dichloromethane/hexanes.
EtOAc, 1:9) to give 28 as an oil (198 mg, 88%). 1H NMR
Ϫ 1H NMR (300 MHz): δ ϭ 1.21 (d, J ϭ 15.5 Hz, 9 H, Me3C), 3.72 (400 MHz): δ ϭ 1.14 (d, J ϭ 14.65 Hz, 9 H, Me3C), 2.18Ϫ2.26 (m,
(dd, J ϭ 11.6, 13.05 Hz, 1 H, CH2), 4.07 (dd, J ϭ 15.3, 13.05 Hz,
1 H, 1Ј-H), 3.87Ϫ3.98 (m, 2 H, 2Ј-H), 2.40Ϫ2.50 (m, 1 H, 1Ј-H),
1 H, CH2), 7.39Ϫ7.57 (m, 6 H, ArH), 7.75Ϫ7.83 (m, 2 H, ArH), 7.49Ϫ7.58 (m, 3 H, ArH), 7.68Ϫ7.74 (m, 2 H, ArH). Ϫ 13C NMR
8.05Ϫ8.06 (m, 2 H, ArH). Ϫ 13C NMR (75.5 MHz): δ ϭ 24.8, 34.7 (100 MHz): δ ϭ 23.93 (s, Me), 25.58 (d, J ϭ 64.3 Hz, C1), 32.75
(d, J ϭ 70.0 Hz), 38.5 (d, J ϭ 47.1 Hz), 128.5 (d, J ϭ 11.3 Hz), (d, J ϭ 68.0 Hz, Me3C), 57.19 (d, J ϭ 3.7 Hz, C2), 128.32 (d, J ϭ
128.8, 129.3 (d, J ϭ 90.9 Hz), 129.9, 132.3 (d, J ϭ 2.8 Hz), 132.6
10.9 Hz, o-C), 129.40 (d, J ϭ 88.2 Hz, ipso-C), 131.70 (d, J ϭ
(d, J ϭ 8.3 Hz), 133.9, 137.5, 194.1 (d, J ϭ 6 Hz). Ϫ 31P NMR 7.4 Hz, m-C). Ϫ 31P NMR (161 MHz): δ ϭ 51.5. Ϫ IR (film)
(121 MHz): δ ϭ 43.8. Ϫ MS (CI); m/z (%): 301 (100) [MHϩ]. Ϫ ν˜max ϭ 4050, 3360, 3058, 2962, 2904, 2870, 1658, 1642, 1590, 1548,
C18H21O2P (300.3): calcd. C 71.99, H 7.05; found C 72.02, H 7.12.
Ϫ Small amounts of other uncharacterized products were also
formed.
1476, 1438, 1396, 1368, 1210, 1144, 1106, 1072, 1042, 998, 942,
818, 784, 752, 700, 632 cmϪ1. Ϫ MS (EI); m/z (%): 227 (16) [M ϩ
Hϩ], 196 [MHϩ ϪCH2OH], 165 [MHϩ Ϫ Me3C], 91 [C7H7ϩ]; (CI);
227 (100) [M ϩ 1], 196 [MHϩ Ϫ CH2OH]. Ϫ C12H19O2P (226.3):
calcd. C 63.70, H 8.46; found C 63.91, H 8.46. Ϫ Alternatively,
ozone (1 mL/min) was bubbled through a solution of 6 (125 mg,
0.563 mmol) in CH2Cl2/MeOH (1:5, 12 mL) at Ϫ78 °C until the
solution became pale blue in colour (ca. 30 min). The solution was
warmed to 0 °C and sodium tetrahydroborate (100 mg) was added.
The resulting mixture was stirred at 0 °C for 45 min, diluted with
Et2O (20 mL) and treated with water (5 mL). The ether layer was
separated and the aqueous layer was extracted with Et2O (2 ϫ
5 mL). The combined ether extracts were processed as described
above to give 28 as an oil (73.2 mg, 58%). Ϫ Compound 28
(45.2 mg, 0.2 mmol) and triethylamine (31 µL, 0.22 mmol) in
CH2Cl2 (5 mL) was treated with tosyl chloride (41.9 mg,
0.22 mmol) at 0 °C under nitrogen. The resulting mixture was
stirred at room temperature under nitrogen for 12 h. It was then
diluted with CH2Cl2 (5 mL), washed with water (3 ϫ 4 mL), and
dried (MgSO4) and concentrated under reduced pressure to give a
yellow oil. Chromatography (EtOAc/hexanes, 5:95) gave the tosyl-
ate as a white microcrystalline solid (48.2 mg, 63%), m.p. 144Ϫ145
°C. Ϫ 1H NMR (400 MHz): δ ϭ 1.09 (d, J ϭ 15.1 Hz, 9 H, Me3C),
2.53Ϫ2.60 (m, 2 H, 2Ј-H), 4.06Ϫ4.14 (m, 1 H, 1Ј-H), 4.28Ϫ4.36
(m, 1 H, 1Ј-H), 7.27 (d, J ϭ 7.81 Hz, 2 H, m-ArH), 7.46Ϫ7.50 (m,
2 H, ArH), 7.53Ϫ7.57 (m, 1 H, ArH), 7.64Ϫ7.69 (m, 2 H, ArH),
7.65 (d, J ϭ 8.3 Hz, 2 H, o-ArH). Ϫ 13C NMR (100 MHz): δ ϭ
21.92 (s, MePh), 23.33 (s, Me3C), 24.38 (d, J ϭ 60.7 Hz, C1Ј), 33.29
(d, J ϭ 69.9 Hz, Me3C), 65.52 (C2Ј), 128.23 (s), 128.81 (d, J ϭ
11.1 Hz, o-C), 129.60 (s), 130.20 (p-C), 131.96 (d, J ϭ 7.3 Hz, m-
C), 132.32 (s), 132.76 (s), 145.31 (s). Ϫ 31P NMR (161 MHz): δ ϭ
44.6. Ϫ IR (KBr): ν˜max ϭ 3426, 2966, 1654, 1598, 1476, 1438, 1358,
1214, 1190, 1176, 1110, 1046, 1012, 958, 816, 744, 700, 664, 630
cmϪ1. Ϫ MS (EI); m/z (%): 380 (2) [Mϩ], 323 [Mϩ Ϫ Me3C], 209
[Mϩ Ϫ OTs], 91 [C7H7ϩ]. Ϫ C19H25O4PS (380.4): calcd. C 59.99, H
6.62; found C 60.22, H 6.66. Ϫ A solution of DBU (17 µL,
0.2 mmol) and the tosylate (38.0 mg, 0.2 mmol) in CH2Cl2 (2 mL)
was stirred at room temperature under nitrogen for 1 h. It was then
concentrated under reduced pressure. Chromatography (EtOH/
EtOAc, 5:95) of the residue afforded the vinylphosphane oxide 29
as an oil (19.8 mg, 48%). Ϫ 1H NMR (400 MHz): δ ϭ 1.12 (d, J ϭ
14.65 Hz, 9 H, Me3C), 6.34 (ddd, 1 H, J ϭ 1.95, 12.7, 36.65 Hz,
2-H), 6.47 (ddd, J ϭ 1.95, 18.55, 19.5 Hz, 2-H), 6.73 (ddd, J ϭ 12.7,
18.55, 27.8 Hz, 1 H, 1-H), 7.43Ϫ7.53 (m, 3 H, ArH), 7.71Ϫ7.76 (m,
2 H, ArH). Ϫ 13C NMR (100 MHz): δ ϭ 24.06 (s, Me3C), 32.46
(d, J ϭ 71.7 Hz, Me3C), 127.02 (d, J ϭ 88.2 Hz, C2Ј), 128.12 (d,
J ϭ 11.0 Hz, o-C), 130.66 (d, J ϭ 91.9 Hz, ipso-C), 131.44 (C1Ј),
131.70 (d, J ϭ 7.3 Hz, m-C), 136.09 (s, p-C). Ϫ 31P NMR
(161 MHz): δ ϭ 36.5. Ϫ IR (film): ν˜max ϭ 3056, 2960, 2902, 2868,
1716, 1644, 1600, 1476, 1462, 1436, 1392, 1366, 1258, 1214, 1168,
1110, 1072, 988, 940, 838, 816, 778, 734, 708, 638 cmϪ1. Ϫ MS
Preparation of Ditertiary Bis(phosphane oxides)
Exploratory Approaches from Dihaloethanes and 1: Treatment of a
mixture of 1 (364 mg, 2.00 mmol) and 1,2-dibromoethane (188 mg,
1.00 mmol) in THF (10 mL) at Ϫ78 °C with LDA (1.35 mL,
2.00 mmol) followed by quenching after 1 h with saturated aqueous
NH4Cl and the usual workup gave a yellow residue, chromato-
graphy (EtOAc/hexanes, 30:70) of which gave 23 (407 mg, 78%) as
needles, m.p. 82Ϫ83 °C (ref.[35] 81Ϫ83 °C) from EtOAc/hexanes. Ϫ
Similarly, from 1 (364 mg, 2.00 mmol), 1,2-diiodoethane (282 mg,
1.00 mmol) and LDA (1.35 mL, 2.00 mmol) was obtained a yellow
residue, chromatography (EtOAc/hexanes, 30:70) of which gave 26
as needles (320 mg, 52%) from EtOAc/hexanes. Ϫ 1H NMR
(400 MHz): δ ϭ 1.29 (d, J ϭ 19.5 Hz, 9 H, Me3C), 7.49Ϫ7.75 (m,
2 H, ArH), 7.57Ϫ7.61 (m, 1 H, ArH), 7.86Ϫ7.91 (m, 2 H, ArH).
Ϫ
31P NMR (161 MHz): δ ϭ 75.6. Ϫ MS (CI); m/z (%): 309 (42)
[Mϩ]. Ϫ C10H14IOP (308.1): calcd. C 38.98, H 4.58; found C 39.26,
H 4.61.
From (؎)-tert-Butyl(phenyl)vinylphosphane Oxide 29: To a solution
of phosphane oxide 6 (442 mg, 2.0 mmol) in tBuOH/water (1:1,
30 mL) was added K3Fe(CN)6 (1.98 g, 6.0 mmol), K2CO3 (83 mg,
6.0 mmol), and OsO4 (2 drops, 100 mg in 2 mL of tBuOH) at 0 °C.
The reaction mixture was stirred first at 0 °C for 6 h and then at
room temperature for 12 h. Sodium sulfite was then added to the
yellow solution until the colour changed to brown. The mixture
was then stirred for a further 1 h. The solvent was removed under
reduced pressure and the residue was extracted with Et2O (3 ϫ
15 mL). The organic extracts was dried (MgSO4) and concentrated
under reduced pressure to give a colourless oil, which was purified
by flash chromatography (EtOH/CH2Cl2, 16:84) to give (Ϯ)-tert-
butyl-(2,3-dihydroxypropyl)phenylphosphane oxide as an insepar-
able mixture of diastereomers (55:45) as a colourless oil (465 mg,
1
90%). Ϫ H NMR (400 MHz): δ (both isomers) ϭ 7.45Ϫ7.58 (m,
3 H, ArH), 7.66Ϫ7.72 (m, 2 H, ArH); δ (major) ϭ 1.12 (d, J ϭ
15.1 Hz, 9 H, Me3C), 2.13 (ddd, J ϭ 2.4, 5.4, 15.1 Hz, 1 H, 1Ј-H),
2.28Ϫ2.41 (m, 1 H, 1Ј-H), 3.45Ϫ3.62 (m, 2 H, 3Ј-H), 4.05Ϫ4.13
(m, 1 H, 2Ј-H); δ (minor) ϭ 1.11 (d, J ϭ 15.1 Hz, 9 H, Me3C),
2.28Ϫ2.41 (m, 2 H, 1Ј-H), 3.45Ϫ3.62 (m, 2 H, 3Ј-H), 3.89Ϫ3.96
(m, 1 H, 2Ј-H). Ϫ MS (CI); m/z (%): 257 (100) [Mϩ ϩ 1], 239 [Mϩ
Ϫ OH]. Ϫ C13H21O3P (256.3): calcd. C 60.93, H 8.26; found C
61.12, H 8.30. Ϫ A solution of the dihydroxy phosphane oxide
(256 mg, 1 mmol) in tBuOH/water (1:1, 16 mL) was treated with
NaIO4 (426 mg, 2 mmol) at room temperature. The mixture was
stirred at room temperature overnight after which it was cooled to
0 °C and treated with solid sodium tetrahydroborate (30 mg). The
resulting mixture was stirred at 0 °C for 45 min. It was then diluted
with Et2O (25 mL) and quenched by the dropwise addition of water
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