C. Nꢀjera, J. M. Saꢀ et al.
70 eV on a Shimadzu QP-5000 and high-resolution mass spectra were ob-
tained on a Finnigan VG Platform. HRMS (EI) were recorded on a Fin-
nigan MAT 95S. Microanalyses were performed on a Perkin–Elmer 2400
and a Carlo Erba EA1108. Analytical TLC was performed on Schleicher
and Schuell F1400/LS silica gel plates and the spots were visualised
under UV light (l=254 nm). For flash chromatography we employed
Merck silica gel 60 (0.040–0.063 mm). The retention time of the major
enantiomer is highlighted in italics
1.0 mLminÀ1, tr =17.9 and 37.4 min; Rf = 0.20 (n-hexane/ethyl acetate
3:2); IR (neat): n˜
= ;
2363, 1530, 1350, 1271, 1032 cmÀ1 1H NMR
(300 MHz, CDCl3): d=1.28, 1.40 (2ꢄt, J=7.1 Hz, 6H, 2ꢄCH3), 4.02–
4.15, 4.18–4.30 (2ꢄm, 4H, 2ꢄCH2), 6.17 (d, J=9.0 Hz, 1H, CHCN), 7.76,
8.32 ppm (2ꢄd, J=8.7 Hz, 4H, ArH); 13C NMR (75 MHz, CDCl3): d=
15.9 (m, 2ꢄCH3), 65.1 (d, J=4.4 Hz, CHCN), 65.2 (d, J=6.3 Hz, 2ꢄ
CH2), 115.2 (d, J=6.6 Hz, CN), 124.4, 128.3, 138.6, 149.0 ppm (ArC); MS
(EI): m/z: 314 (4) [M]+, 258 (100), 161 (28), 125 (26), 114 (44); HRMS:
m/z: calcd for C12H15O6N2P: 314.0668; found: 314.0669.
General procedure for the preparation of compounds 3: Dimethylalumi-
nium chloride (1m solution in hexanes, 0.025 mmol, 25 mL) was added
under argon to a solution of enantiopure (S)-BINOLAM 2 (0.025 mmol,
11.4 mg), in dry toluene (1 mL), and the resulting suspension stirred at
room temperature for 1 h. Then, freshly distilled aldehyde (0.25 mmol)
and diethyl cyanophosphonate (0.75 mmol, 125 mL) were added in one
portion. The reaction was monitored by GC and 1H NMR spectroscopy
and, when it was judged complete, 2m aqueous solution of hydrochloric
acid (2 mL) and ethyl acetate (2 mL) were added. The resulting mixture
was stirred vigorously for 10 min. The emulsion was filtered and the
aqueous phase treated with a 1m buffer solution of NH3/NH4Cl until the
pH was basic; then ethyl acetate was added (2ꢄ10 mL) and the organic
layer was separated, dried (MgSO4) and eventually evaporated, thereby
recovering pure ligand 2 (11 mg, 95%). The organic phase from the
acidic work up was dried (MgSO4) and evaporated to dryness. The resi-
due was purified by flash chromatography thereby yielding pure cyanohy-
drin O-phosphates 3 (yields shown in Table 2). Spectroscopic and physi-
cal data for 3a–n follows:
(R)-2-(Diethylphosphoryloxy)-2-(3-phenoxyphenyl)acetonitrile (3e): Col-
ourless oil; [a]2D5 =+8.9 (c=2, CHCl3); 97% ee from HPLC analysis
Daicel Chiralpak AS, l=254 nm, n-hexane/2-propanol 90:10,
1.0 mLminÀ1, tr =15 and 19.7 min; Rf
3:2); IR (neat): n˜ = 2361, 1268, 1024 cmÀ1
=
0.44 (n-hexane/ethyl acetate
;
1H NMR (300 MHz, CDCl3):
d=1.28, 1.36 (2ꢄdt, J=7.1, 1.0 Hz, 6H, 2ꢄCH3), 3.96–4.09, 4.13–4.26
(2ꢄm, 4H, 2ꢄCH2), 6.01 (d, J=8.9 Hz, 1H, CHCN), 7.00–7.09 (m, 3H,
ArH), 7.13–7.17 (m, 2H, ArH), 7.34 (t, J=2 Hz, 1H, ArH), 7.36–
7.42 ppm (m, 3H, ArH); 13C NMR (75 MHz, CDCl3): d=15.9, 16.2 (2ꢄd,
J=7.5 Hz, 2ꢄCH3), 64.5, 64.9 (2ꢄd, J=5.7 Hz, 2ꢄCH2), 66.0 (d, J=
4.4 Hz, CHCN), 115.9 (d, J=5.5 Hz, CN), 117.1, 119.3, 120.3, 121.6,
124.1, 129.9, 130.6 (ArC), 134.1 (d, J=5.5 Hz, ArC), 156.2, 158.2 ppm
(ArC); MS (EI): m/z: 361 (84) [M]+, 305 (100), 225 (51), 207 (29), 197
(39), 181 (67), 114 (72); HRMS: m/z: calcd for C18H20O5NP: 361.1079;
found: 361.1079.
(R)-2-(2-Chlorophenyl)-2-(diethylphosphoryloxy)acetonitrile (3 f): Col-
ourless oil; [a]2D5 =+23.8 (c=2, CHCl3); 97% ee from HPLC analysis
Daicel Chiralpak AD, l=254 nm, n-hexane/2-propanol 95:5,
1.0 mLminÀ1, tr =10.1 and 12.5 min; Rf = 0.35 (n-hexane/ethyl acetate
(S)-2-(Diethylphosphoryloxy)-2-phenylacetonitrile (3a): Colourless oil;
[a]2D5 =À20.12 (c=2, CHCl3); 98% ee from HPLC analysis, Daicel Chiral-
pak AD, l = 254 nm, n-hexane/2-propanol 95:5, 1.0 mLminÀ1, tr =16.8
and 19.9 min; Rf = 0.57 (n-hexane/ethyl acetate 3:2); IR (neat): n˜ =2240,
3:2); IR (neat): n˜ = 2358, 1274, 1027 cmÀ1 1H NMR (300 MHz, CDCl3):
;
d=1.29, 1.37 (2ꢄdt, J=7.1, 1.1 Hz, 6H, CH3), 4.05–4.15, 4.17–4.28 (2ꢄm,
4H, 2ꢄCH2), 6.36 (d, J=8.7 Hz, 1H, CHCN), 7.36–7.47 (m, 3H, ArH),
7.68–7.72 ppm (m, 1H, ArH); 13C NMR (75 MHz, CDCl3): d = 15.8, 16.0
(2ꢄd, J=4.4 Hz, 2ꢄCH3), 63.5 (d, J=4.4 Hz, CHCN), 64.6, 65.0 (2ꢄd,
J=5.5 Hz, 2ꢄCH2), 115.4 (d, J=4.4 Hz, CN), 127.7, 128.9 (ArC), 130.1
(d, J=4.4 Hz, ArC), 130.3, 131.7, 132.8 ppm (ArC); MS (EI): m/z: 268
(59) [MÀCl]+, 240 (18), 212 (31), 185 (100), 150 (57), 122 (19), 114 (18);
HRMS calcd for C12H15O4NP: 268.0738; found: 268.0739 [MÀCl]+.
1270, 1024 cmÀ1 1H NMR (300 MHz, CDCl3): d=1.18–1.23 (dt, J=7.1,
;
0.9 Hz, 3H, CH3), 1.34–1.39 (dt, J=7.1, 0.9 Hz, 3H, CH3), 3.94–4.05,
4.13–4.25 (2ꢄm, 4H, 2ꢄCH2), 6.05 (d, J=8.9 Hz, 1H, CHCN), 7.44–7.46
(m, 3H, ArH), 7.53–7.56 ppm (m, 2H, ArH); 13C NMR (75 MHz,
CDCl3): d=15.7–15.9 (m, 2ꢄCH3), 64.5–64.7 (m, 2ꢄCH2), 66.4 (d, J=
4.4 Hz, CHCN), 116.1 (d, J=6.6 Hz, CN), 127.4, 129.1, 130.5, 132.4 ppm
(ArC); MS (EI): m/z: 269 (4) [M]+, 213 (70), 133 (42), 116 (100), 115
(69), 105 (48), 89 (33); HRMS: m/z: calcd for C12H16O4NP: 269.0817;
found: 269.0820.
(R)-2-(Diethylphosphoryloxy)-2-(6-methoxy-2-naphthyl)acetonitrile (3g):
Colourless oil; [a]2D5 =+12.2 (c=2, CHCl3); 94% ee from HPLC analysis
Daicel Chiralpak AD, l=254 nm, n-hexane/2-propanol 90:10,
1.0 mLminÀ1, tr =16.4 and 24.0 min; Rf = 0.21 (n-hexane/ethyl acetate
(S)-2-(4-Chlorophenyl)-2-(diethylphosphoryloxy)acetonitrile (3b): Col-
ourless oil; [a]2D5 =À14.60 (c=2, CHCl3); 96% ee from HPLC analysis
Daicel Chiralpak AD,
l
=
254 nm, n-hexane/2-propanol 90:10,
3:2); IR (neat): n˜ = 2357, 1271, 1029 cmÀ1 1H NMR (300 MHz, CDCl3):
;
1.0 mLminÀ1, tr =12.0 and 14.7 min; Rf = 0.43 (n-hexane/ethyl acetate
3:2); IR (neat): n˜ =2354, 1273, 1032 cmÀ1; 1H NMR (300 MHz, CDCl3): d
= 1.24, 1.38 (2ꢄt, J=7.1 Hz, 6H, 2ꢄCH3), 3.98–4.07, 4.14–4.26 (2ꢄm,
4H, 2ꢄCH2), 6.03 (d, J=8.9 Hz, 1H, CHCN), 7.43 (d, J=8.5 Hz, 2H,
ArH), 7.50 ppm (d, J=8.5 Hz, 2H, ArH); 13C NMR (75 MHz, CDCl3):
d=15.9 (m, 2ꢄCH3), 64.8 (d, J=6 Hz, 2ꢄCH2), 65.7 (d, J=4.4 Hz,
CHCN), 115.7 (d, J=6.6 Hz, CN), 128.8, 129.5, 130.9, 136.8 ppm (ArC);
MS (EI): m/z: 303 (15) [M]+, 247 (88), 150 (98), 149 (100), 139 (42), 114
(32); HRMS: m/z: calcd for C12H15O4NPCl: 303.0427; found: 303.0432.
d=1.19, 1.39 (2ꢄt, J=7.1 Hz, 6H, 2ꢄCH3CH2), 3.93 (s, 3H, CH3O),
3.95–4.02, 4.18–4.26 (2ꢄm, 4H, 2ꢄCH2), 6.18 (d, J=8.8 Hz, 1H, CHCN),
7.16 (brs, 1H, ArH), 7.21 (m, 1H, ArH), 7.58 (d, J=8.5, 1H, ArH), 7.80
(t, J=9.5 Hz, 2H, ArH), 7.96 ppm (s, 1H, Ar-H); 13C NMR (75 MHz,
CDCl3): d=15.8 (m, 2ꢄCH3), 55.3 (s, CH3O), 64.4, 64.6 (2ꢄd, J=5.5 Hz,
2ꢄCH2), 66.8 (d, J=5.5 Hz, CHCN), 116.2 (d, J=6.6 Hz, CN), 105.7,
119.9, 124.6, 127.2, 127.3, 127.5, 128.2, 129.9, 135.4, 158.9 ppm (ArC); MS
(EI): m/z: 349 (0.1) [M]+, 321 (10), 265 (10), 212 (17), 196 (91), 195
(100), 180 (10), 166 (14), 153 (27), 125 (17), 91 (28); HRMS: m/z: calcd
for C17H20NPO5: 349.3200; found: 349.3995.
(R)-2-(Diethylphosphoryloxy)-2-(4-methoxyphenyl)acetonitrile
(3c):
Data of the colourless oily crude product (see text): 98% ee from HPLC
analysis Daicel Chiralpak AD, l=254 nm, n-hexane/2-propanol 90:10,
1.0 mLminÀ1, tr =12.0 and 14.7 min; Rf = 0.30 (n-hexane/ethyl acetate
(R)-2-(Diethylphosphoryloxy)-2-(3-pyridyl)acetonitrile (3h): Pale yellow
oil; 4% ee from HPLC analysis Daicel Chiralpak AD, l=254 nm, n-
hexane/2-propanol 90:10, 1.0 mLminÀ1, tr =28.7 and 29.9 min; Rf = 0.55
3:2); IR (neat): n˜ = 2243, 1258, 1028 cmÀ1
;
1H NMR (300 MHz, CDCl3):
(ethyl acetate); IR (neat): n˜ = ;
2254, 1286, 1016 cmÀ1 1H NMR
d = 1.22, 1.38 (2ꢄt, J=7.1 Hz, 6H, 2ꢄCH3CH2O), 3.84 (s, 3H, CH3O),
3.83–4.04, 4.15–4.25 (2ꢄm, 4H, 2ꢄCH2O), 5.99 (d, J=8.6 Hz, 1H,
CHCN), 6.95 (d, J=8.6 Hz, 2H, ArH), 7.48 ppm (d, J=8.6 Hz, 2H,
ArH); 13C NMR (75 MHz, CDCl3): d=15.9 (d, J=7.3 Hz, 2ꢄCH3CH2),
55.40 (d, J=3.3 Hz, CH3O), 64.7 (d, J=5.5 Hz, 2ꢄCH2O), 66.3 (d, J=
4.4 Hz, CHCN), 114.5 (ArC), 116.3 (d, J=6.6 Hz, CN), 124.5 (d, J=
5.5 Hz, ArC), 161.3 ppm (ArC); MS (IE): m/z: 299 (8) [M]+, 162 (12),
147 (39), 46 (97), 145 (100), 135 (17); HRMS: m/z: calcd for
C13H18O5NP: 299.0923; found: 299.0928.
(300 MHz, CDCl3): d = 1.30, 1.37 (2ꢄm, 6H, 2ꢄCH3), 4.15, 4.23 (2ꢄm,
4H, 2ꢄCH2), 6.13 (d, J=9.2 Hz, 1H, CHCN), 7.37 (m, 1H, ArH), 7.60
(d, J=8.0 Hz, 1H, ArH), 7.82 (t, J=7.6 Hz, 1H, ArH), 8.65 ppm (brs,
1H, ArH); 13C NMR (75 MHz, CDCl3): d=15.9, 16.1 (2ꢄd, J=4.4 Hz,
2ꢄCH3), 64.9 (m, 2ꢄCH2), 67.2 (d, J=5.5 Hz, CHCN), 115.6 (d, J=
4.4 Hz, CN), 121.4, 124.8, 137.7, 149.9, 151.5 ppm (ArC); MS (EI): m/z:
270 (16) [M]+, 214 (37), 133 (60), 118 (100), 117 (69), 108 (42), 98 (48);
HRMS: m/z: calcd for C11H15O4N2P: 270.0769; found: 270.0773.
(E,2R)-2-(Diethylphosphoryloxy)pent-3-enenitrile (3i): Colourless oil;
[a]2D5 =À17.48 (c=2, CHCl3); 88% ee from HPLC analysis Daicel Chiral-
pak AD, l=210 nm, n-hexane/2-propanol 95:5, 1.0 mLminÀ1, tr =9.6 and
12.3 min; Rf = 0.36 (n-hexane/ethyl acetate 3:2); IR (neat): n˜ = 2247,
(R)-2-(Diethylphosphoryloxy)-2-(4-nitrophenyl)acetonitrile (3d): Pale
yellow oil; [a]2D5 =À0.9 (c=2, CHCl3); 26% ee from HPLC analysis
Daicel Chiralpak AD, l=254 nm, n-hexane/2-propanol 90:10,
3858
ꢂ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 3849 – 3862