Water-Soluble Phosphinothiols
A R T I C L E S
solution was washed with water and brine. The combined organic
extracts were dried over anhydrous MgSO4(s) and filtered, and the
solvent was removed under reduced pressure. The residue was purified
by flash chromatography (silica gel, 20% v/v MeOH in CH2Cl2) to
3.13 (m, 4H), 2.98-2.94 (m, 4H), 2.95 (s, 3H), 2.67 (s, 12H), 2.20-
0.50 (m, 9H) ppm; 13C NMR (CDCl3, 125 MHz) δ 143.20, 133.51 (d,
J ) 10.4 Hz), 129.88 (d, J ) 10.8 Hz), 123.51 (d, J ) 57.8 Hz), 65.76,
64.58 (d, J ) 37.4 Hz), 52.19, 37.71, 31.11 ppm; 31P NMR (CDCl3,
161 MHz) δ 17.82 ppm; MS (ESI) m/z 501.2811 (MNa+ [C22H42B3N2O3-
PSNa+] ) 501.2831).
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give phosphine oxide 20 as a colorless oil in 75% yield. H NMR
(CDCl3, 400 MHz) δ 8.03 (d, J ) 1.2 ppm, 1H), 7.64-7.59 (m, 4H),
7.35-7.33 (m, 4H), 2.83 (t, J ) 7.5 Hz, 4H), 2.54 (t, J ) 8.2 Hz, 4H),
2.29 (s, 12H) ppm; 13C NMR (CDCl3, 125 MHz) δ 145.72, 131.08 (d,
J ) 11.5 Hz), 129.41 (J ) 12.4 Hz), 128.71, 61.11, 45.64, 34.56 ppm;
31P NMR (CDCl3, 161 MHz) δ 21.75 ppm; MS (ESI) m/z 345.2090
(MNa+ [C20H29N2OPNa+] ) 345.2096).
Phosphine-Borane Complex 24. Potassium thioacetate (404 mg,
3.54 mmol) was added to a solution of phosphine-borane complex 23
(1.41 g, 2.95 mmol) in anhydrous DMF (29 mL) under Ar(g). The
resulting solution was stirred overnight at room temperature, after which
the solvent was removed under reduced pressure. The residue was
dissolved in ethyl acetate (20 mL), and the resulting solution was
washed with water and brine. The combined organic extracts were dried
over anhydrous MgSO4(s), filtered, and concentrated under reduced
pressure. The residue was purified by flash chromatography (silica gel,
2% v/v ethyl acetate and 28% hexanes in CH2Cl2) to give phosphine-
Phosphine-Borane Complex 21. A solution of phosphine oxide
20 (3.18 g, 9.24 mmol) in anhydrous CH2Cl2 (25 mL) was added
dropwise slowly to a solution of DIBAL (1 M in CH2Cl2, 46.2 mL, 46
mmol) under Ar(g) in a flame-dried three-neck round-bottom flask.
The resulting solution was stirred for 20 min, and then cooled to 0 °C
with an ice bath. The solution was then diluted with CH2Cl2 (20 mL),
and a sparge needle of Ar(g) was allowed to blow through the solution
for 5 min. A solution of 2 N NaOH (20 mL) was added dropwise slowly
to the reaction mixture (Caution! Gas evolution!) followed by a
saturated solution of Rochelle’s salt (20 mL) to dissipate the emulsion
that forms. The resulting biphasic solution was transferred to a
separatory funnel, and the organic layer was separated, dried over
anhydrous MgSO4(s), filtered, and concentrated under reduced pressure
to ∼75 mL. The resulting solution was cooled to 0 °C with an ice bath
under Ar(g), and borane‚dimethyl sulfide complex (10 M, 2.96 mL,
29.6 mmol) was added dropwise. The resulting reaction mixture was
allowed to warm slowly to room temperature overnight. The solvent
was removed under reduced pressure, and the crude oil was purified
by flash chromatography (silica gel, CH2Cl2) to give phosphine-borane
complex 21 as a white solid in 82% yield. 1H NMR (CDCl3, 400 MHz)
δ 7.62-7.57 (m, 4H), 7.31-7.29 (m, 4H), 6.30 (d, J ) 378.8 Hz, 1H),
3.13-3.09 (m, 4H), 2.95-2.91 (m, 4H), 2.67 (s, 12H), 2.30-0.70 (m,
9H) ppm; 13C NMR (CDCl3, 125 MHz) δ 142.42, 133.54 (d, J ) 10.7
Hz), 129.79 (d, J ) 10.0 Hz), 124.66 (d, J ) 58.7 Hz), 65.83, 52.12,
31.53 ppm; 31P NMR (CDCl3, 161 MHz) δ 0.00 ppm; MS (ESI) m/z
343.2474 (MH+ - 2BH3 [C20H32BN2PH+] ) 343.2474).
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borane complex 24 as a white solid in 60% yield. H NMR (CDCl3,
400 MHz) δ 7.65-7.60 (m, 4H), 7.33-7.30 (m, 4H), 3.68 (d, J ) 7.0
Hz, 2H), 3.14-3.10 (m, 4H), 2.97-2.93 (m, 4H), 2.67 (s, 12H), 2.27
(s, 3H), 2.20-0.60 (m, 9H) ppm; 13C NMR (CDCl3, 125 MHz) δ
193.32, 142.50, 133.00 (d, J ) 10.5 Hz), 129.55 (d, J ) 12.3 Hz),
126.03 (d, J ) 56.2 Hz), 65.75, 54.09, 30.98, 30.27, 23.88 (d, J )
35.6 Hz) ppm; 31P NMR (CDCl3, 161 MHz) δ 18.69 ppm; MS (ESI)
m/z 481.2929 (MNa+ [C23H42B3N2OPSNa+] ) 481.2932).
Phosphinothioester 25. Phosphine-borane complex 24 (250 mg,
0.55 mmol) was dissolved in toluene (5 mL) under Ar(g). DABCO
(190 mg, 1.69 mmol) was added, and the resulting solution was heated
to 40 °C for 4 h. The solvent was removed under reduced pressure,
and the residue was purified by flash chromatography (silica gel, 20%
v/v MeOH in CH2Cl2) to give phosphinothioester 25 as a colorless oil
in 86% yield. 1H NMR (CDCl3, 400 MHz) δ 7.36-7.33 (m, 4H), 7.20-
7.18 (m, 4H), 3.47 (d, J ) 3.5 Hz, 2H), 2.79-2.75 (m, 4H), 2.55-
2.51 (m, 4H), 2.29 (s, 15H) ppm; 13C NMR (CDCl3, 125 MHz) δ
194.89, 141.76, 134.25 (d, J ) 12.9 Hz), 132.95 (d, J ) 19.5 Hz),
129.03 (d, J ) 6.1 Hz), 61.36, 45.61, 34.29, 30.46, 26.13 (d, J ) 21.1
Hz) ppm; 31P NMR (CDCl3, 161 MHz) δ -16.84 ppm; MS (ESI) m/z
417.2135 (MH+ [C23H33N2OPSH+] ) 417.2129).
Phosphine-Borane Complex 22. Phosphine-borane complex 21
(2.32 g, 6.27 mmol) was dissolved in 1:1 THF/CH2Cl2 (60 mL).
Formaldehyde (37% v/v in H2O; 3.83 mL) was added to this solution,
followed by potassium hydroxide (358 mg, 6.39 mmol). The resulting
biphasic solution was stirred overnight at room temperature, after which
the organic solvent was removed under reduced pressure. The residue
was dissolved in ethyl acetate (30 mL), and the organic layer was dried
over anhydrous MgSO4(s), filtered, and concentrated under reduced
pressure. The residue was purified by flash chromatography (silica gel,
5% v/v ethyl acetate in CH2Cl2) to give phosphine-borane complex
22 as a white solid in 80% yield. 1H NMR (CDCl3, 400 MHz) δ 7.69-
7.64 (m, 4H), 7.34-7.32 (m, 4H), 4.42 (d, J ) 6.5 Hz, 2H), 3.15-
3.11 (m, 4H), 2.97-2.93 (m, 4H), 2.67 (s, 12H), 2.20-0.50 (m, 9H)
ppm; 13C NMR (CDCl3, 125 MHz) δ 142.46, 133.38 (d, J ) 8.7 Hz),
129.72 (d, J ) 10.6 Hz), 125.16 (d, J ) 56.1 Hz), 65.90, 60.60 (d, J
) 42.1 Hz), 52.18, 31.11 ppm; 31P NMR (CDCl3, 161 MHz) δ 16.92
ppm; MS (ESI) m/z 423.3047 (MNa+ [C21H40B3N2OPNa+] ) 423.3055).
Phosphine-Borane Complex 23. Triethylamine (650 µL, 4.67
mmol) was added to a solution of phosphine-borane complex 22 (1.25
g, 3.11 mmol) in CH2Cl2 (30 mL), and this solution was cooled to
0 °C with an ice bath. Methanesulfonyl chloride (337 µL, 4.36 mmol)
was added dropwise, and the resulting solution was allowed to warm
slowly to room temperature overnight. The solution was washed with
0.1 N HCl and brine, and the combined organic extracts were dried
over anhydrous MgSO4(s), filtered, and concentrated under reduced
pressure. The residue was purified by flash chromatography (silica gel,
2% v/v ethyl acetate in CH2Cl2) to give phosphine-borane complex
23 as a white solid in 95% yield. 1H NMR (CDCl3, 400 MHz) δ 7.69-
7.64 (m, 4H), 7.37-7.27 (m, 4H), 4.87 (d, J ) 2.0 Hz, 2H), 3.17-
Phosphinothiol 17. Phosphinothioester 25 (323 mg, 0.78 mmol) was
dissolved in degassed MeOH (8 mL), and NaOH (31 mg) was added
to this solution under Ar(g). The resulting solution was stirred at room
temperature for 1.5 h. The solvent was removed under reduced pressure,
and the residue was acidified with 4 N HCl in dioxane and filtered to
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give phophosphinothiol 17 as a white solid in quantitative yield. H
NMR (DMSO-d6, 400 MHz) δ 11.05 (bs, 1H), 7.40 (t, J ) 7.3 Hz,
4H), 7.30 (t, J ) 8.2 Hz, 4H), 4.25 (bs, 2H), 3.26-3.22 (m, 4H), 3.20-
3.18 (m, 2H), 3.05-3.01 (m, 4H), 2.77 (s, 12H), 1.20 (t, J ) 7.0 Hz,
1H) ppm; 13C NMR (DMSO-d6, 125 MHz) δ 138.12, 135.50, 132.93,
128.97, 56.83, 41.87, 45.22, 29.47 ppm; 31P NMR (DMSO-d6, 161
MHz) δ -10.60 ppm; MS (ESI) m/z 375.2039 (MH+ [C21H31N2PSH+]
) 375.2024).
Phosphinothioester 26. N-Acetyl glycine (95.3 mg, 0.81 mmol) was
dissolved in anhydrous DMF (6 mL) under Ar(g). Hydroxybenzotriazole
(105 mg, 0.78 mmol) was then added to the solution, followed by N,N′-
diisopropylcarbodiimide (DIC, 121 µL, 0.78 mmol). After the reaction
mixture was allowed to stir for 20 min, a solution of phosphinothiol
17 (293 mg, 0.78 mmol) was added, followed by DIEA (564 µL, 3.24
mmol). The resulting solution was stirred for 4 h at room temperature
under Ar(g). The solvent was removed under reduced pressure, and
the resulting crude oil was purified by flash chromatography (silica
gel, 20% v/v MeOH in CH2Cl2) to give phosphinothioester 26 as a
colorless oil in 75% yield. 1H NMR (CDCl3, 400 Hz) δ 7.35-7.31 (m,
4H), 7.20-7.18 (m, 4H), 6.04 (s, 1H), 4.16 (d, J ) 5.4 Hz, 2H), 3.49
(d, J ) 3.9 Hz, 2H), 2.81-2.77 (m, 4H), 2.59-2.55 (m, 4H), 2.32 (s,
12H), 2.03 (s, 3H) ppm; 13C NMR (CDCl3, 125 MHz) δ 196.45, 170.38,
141.79, 133.99, 132.99, 129.11, 61.29, 49.25, 45.58, 34.18, 25.60, 23.14
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J. AM. CHEM. SOC. VOL. 129, NO. 37, 2007 11429