Cycloadditions of P-Nitroso Phosphine Oxides
(11) (0.220 g, 0.763 mmol) was refluxed in concentrated HCl
(5 mL) for 18 h. The mixture was diluted with water (20 mL),
extracted with methylene chloride (4 × 20 mL), dried over
magnesium sulfate, and concentrated in vacuo. The resulting
solid was recrystallized (1:1, methylene chloride/hexanes) to
yield 12 as a white solid (0.161 g, 81%): mp 129-130 °C; Rf
0.19 (EtOAc); 1H NMR (CDCl3, 300 MHz) δ 10.9 (s, 1H), 7.40-
7.16 (m, 10H), 1.49 (d, 6H, J ) 15.7 Hz); 13C NMR (CDCl3, 75
MHz) δ 141.4-126.3 (m, aromatic), 40.5 (d, 1C, J ) 93.4 Hz),
22.7; 31P NMR (CDCl3, 121 MHz) δ 50.0; IR (CDCl3) 3160-
2489 (br OH) cm-1; LRMS (ESI) m/z 261 (M + H)+. Anal. Calcd
for C15H17O2P: C, 69.22; H, 6.58. Found: C, 68.75; H, 6.66.
LRMS (ESI) m/z 326 (M + H)+. Anal. Calcd for C19H20NO2P:
C, 70.14; H, 6.20; N, 4.31. Found: C, 68.28; H, 7.00; N, 3.44.
3-[P h en yl-(1-p h en ylet h yl)p h osp h in oyl]-2-oxa -3-a za -
bicyclo[2.2.2]oct-5-en e (17a a n d 17b). A solution of 14a
(0.138 g, 0.531 mmol) dissolved in anhydrous methylene
chloride (5 mL) was added dropwise to a cooled (0 °C), stirred
solution of tetra n-butylammonium periodate (0.253 g, 0.584
mmol) and 1,3-cyclohexadiene (0.085 g, 1.06 mmol) in anhy-
drous methylene chloride (10 mL) under an argon atmosphere
and stirred for 2 h. The reaction was warmed to room
temperature and stirred an additional 6 h and concentrated
in vacuo. Phosphorus NMR of the crude reaction mixture
indicated that diastereomers 17a and 17b were formed in a
3.5:1 ratio. The two diastereomers were separated by flash
chromatography (3:1, EtOAc/pentane) to yield compounds 17a
and 17b (0.115 g, 64%) as clear viscous oils. Da ta for 17a : Rf
0.34 (3:1 EtOAc/pentane); 1H NMR (CDCl3, 300 MHz) δ 7.73-
7.67 (m, 2H), 7.45-7.13 (m, 8H), 5.93-5.83 (m, 2H), 4.43-
4.40 (m, 1H), 3.99 (br s, 1H), 3.61-3.53 (sextet, 1H, J ) 7.5
Hz), 2.10-2.02 (m, 1H), 1.87-1.79 (m, 1H), 1.24 (dd, 3H, J PMe
) 18.1 Hz, J HMe ) 7.6 Hz), 1.23-1.11 (m, 2H); 13C NMR
(CDCl3, 75 MHz) δ 138.4-127.0 (m, aromatic and alkene), 70.1,
47.7 (d, 1C, J ) 3.5 Hz), 38.0 (d, 1C, J ) 89.0 Hz), 24.4, 22.9
(d, 1C, J ) 9.7 Hz), 14.7; 31P NMR (CDCl3, 121 MHz) δ 41.6;
IR (CDCl3) 1197, 1110, 1060 cm-1; LRMS (ESI) m/z 340 (M +
H)+. Anal. Calcd for C20H22NO2P: C, 70.78; H, 6.53; N, 4.13.
Found: C, 69.78; H, 6.77; N, 3.94. Da ta for 17b: Rf 0.18 (3:1
EtOAc/pentane); 1H NMR (CDCl3, 300 MHz) δ 7.59-7.56 (m,
2H), 7.48-7.43 (m, 1H), 7.35-7.29 (m, 2H), 7.09-7.07 (m, 3H),
6.94-6.92 (m, 2H), 6.51-6.40 (m, 2H), 4.61-4.60 (m, 1H),
3.80-3.78 (m, 1H), 3.64-3.49 (m, 1H), 2.21-2.12 (m, 1H), 1.46
(dd, 3H, J PMe ) 17.0 Hz, J HMe ) 7.4 Hz), 1.42-1.32 (m, 2H);
13C NMR (CDCl3, 75 MHz) δ 133.7-127.0 (m, aromatic and
alkene), 70.3, 49.0 (d, 1C, J ) 2.4 Hz), 40.5 (d, 1C, J ) 86.8
Hz), 24.3, 23.1 (d, 1C, J ) 11.6 Hz), 14.0; 31P NMR (CDCl3,
121 MHz) δ 41.4; IR (CDCl3) 1197, 1110, 1060 cm-1; LRMS
(ESI) m/z 340 (M + H)+.
(1-Met h yl-1-p h en ylet h yl)(p h en yl)p h osp h in ic An h y-
d r id e (13). Phosphinic acid (12) was stirred with oxalyl
chloride (0.571 g, 4.50 mmol) in anhydrous methylene chloride
(5 mL) for 2 days. The reaction mixture was concentrated in
vacuo and purified by silica gel chromatography (EtOAc) to
1
afford 13 as a white solid: Rf 0.66 (EtOAc); H NMR (CDCl3,
300 MHz) δ 7.49-7.17 (m, 20H), 1.63-1.53 (m, 12H); 31P NMR
(CDCl3, 122 MHz) δ 46.3.
N -[P h e n y l-(1-p h e n y le t h y l)p h o s p h in o y l]h y d r o x y -
la m in e (14a ). N,O-Bis(trimethylsilyl)hydroxylamine (2.26 g,
12.8 mmol) was added dropwise to a stirred solution of phenyl-
(1-phenylethyl)phosphinic chloride (15)4 (2.60 g, 9.82 mmol)
in anhydrous methylene chloride (20 mL) under an atmosphere
of argon and stirred for 2 h at 0 °C. The reaction was warmed
to room temperature for 16 h during which time a white solid
precipitated. The solid was filtered, washed with diethyl ether,
and dried in vacuo. Crude 1H NMR indicated that the white
solid was the O-(TMS)hydroxylamine and it was used without
further purification. The O-(TMS)hydroxylamine (2.02 g) was
dissolved in a solution of anhydrous methylene chloride (20
mL) containing anhydrous methanol (1.50 mL) and stirred at
room temperature for 3 days to afford a mixture of diastere-
omers 14a and 14b. Recrystallization of the diastereomeric
mixture from methylene chloride produced 14a (1.12 g, 64%):
1
Rf 0.47 (EtOAc); H NMR (CDCl3, 300 MHz) δ 7.68-7.51 (m,
2H), 7.48-7.39 (m, 1H), 7.36-7.27 (m, 2H), 7.20-6.99 (m, 5H),
3.34-3.21 (m, 1H), 1.31 (dd, 3H, J PH ) 16.6 Hz, J HH ) 7.3
Hz); 31P NMR (CDCl3, 121 MHz) δ 41.1.
(E)-Hep ta -4,6-d ien -1-ol (22). (E)-Hepta-4,6-dienoic acid
ethyl ester (14.32 g, 92.9 mmol) was dissolved in anhydrous
diethyl ether (750 mL) under a stream of argon and cooled to
0 °C in an ice bath. After stirring for 0.5 h, a solution of lithium
aluminum hydride (1.80 g, 47.4 mmol) in anhydrous diethyl
ether (200 mL) was added dropwise via a syringe pump over
45 min. The reaction was stirred at 0 °C until complete as
determined by TLC. While maintaining the reaction at 0 °C a
5% sodium hydroxide solution was carefully added until the
evolution of hydrogen gas ceased. During this period a white
solid precipitated. The mixture was stirred an additional 20
min and the solid was vacuum filtered and washed with
diethyl ether (3 × 150 mL). The filtrates were combined,
concentrated in vacuo and purified by silica gel chromatogra-
phy (3:1 pentane/EtOAc) to give 22 (8.96 g, 86%) as a colorless
liquid: Rf 0.49 (3:1 pentane/EtOAc); 1H NMR (CDCl3, 300
MHz) δ 6.35-6.22 (m, 1H), 6.10-6.01 (m, 1H), 5.73-5.64 (m,
1H), 5.07 (d, 1H, J ) 16.9 Hz), 4.95 (d, 1H, J ) 10.2 Hz), 3.59
(m, 2H), 2.92 (br s, 1H) 2.15 (q, 2H, J ) 7.5 Hz) 1.69-1.59 (m,
2H); 13C NMR (CDCl3, 75 MHz) δ 137.5, 134.7, 131.8, 115.4,
62.4, 32.4, 29.1; IR (CDCl3) 3622, 1006 cm-1; LRMS (ESI) m/z
113 (M + H)+.
3-[P h en yl-(1-p h en ylet h yl)p h osp h in oyl]-2-oxa -3-a za -
bicyclo[2.2.1]oct-5-en e (16a a n d 16b). A solution of 14a
(0.172 g, 0.660 mmol) in anhydrous methylene chloride (5 mL)
was added dropwise to a cooled (0 °C), stirred solution of tetra
n-butylammonium periodate (0.314 g, 0.726 mmol) and 1,3-
cyclopentadiene (0.087 g, 1.32 mmol) in anhydrous methylene
chloride (10 mL) under an argon atmosphere and stirred for 2
h. The reaction was warmed to room temperature and stirred
an additional 6 h and concentrated in vacuo. Phosphorus NMR
of the crude reaction mixture indicated that diastereomers 16a
and 16b were formed in a 3.1:1 ratio. The two diastereomers
were separated by flash chromatography (3:1, EtOAc/pentane)
to yield compounds 16a and 16b (0.140 g, 65%) as clear viscous
oils. Da ta for 16a : Rf 0.34 (3:1 EtOAc/pentane); 1H NMR
(CDCl3, 300 MHz) δ 7.70-7.55 (m, 2H), 7.48-7.43 (m, 1H),
7.39-7.30 (m, 2H), 7.19-7.08 (m, 5H), 6.12-6.11 (m, 2H), 5.11
(br s, 1H), 4.29 (br s, 1H), 3.65-3.43 (m, 1H), 2.14-1.96 (m,
2H), 1.39 (dd, 3H, J PMe ) 17.3 Hz, J HMe ) 7.5 Hz), 1.23-1.11
(m, 2H); 13C NMR (CDCl3, 75 MHz) δ 138.4-127.2 (m,
aromatic and alkene), 83.2, 64.2 (d, 1C, J ) 4.3 Hz), 48.9 (d,
1C, J ) 2.3 Hz), 41.3 (d, 1C, J ) 87.1 Hz), 16.3; 31P NMR
(CDCl3, 121 MHz) δ 42.5; IR (CDCl3) 1198, 1009 cm-1; LRMS
(ESI) m/z 326 (M + H)+. Anal. Calcd for C19H20NO2P: C, 70.14;
H, 6.20; N, 4.31. Found: C, 70.44; H, 6.57; N, 3.38. Da ta for
16b: Rf 0.24 (3:1 EtOAc/pentane); 1H NMR (CDCl3, 300 MHz)
δ 7.86-7.56 (m, 2H), 7.49-7.24 (m, 3H), 7.19-7.08 (m, 5H),
6.21-6.20 (m, 2H), 5.01 (br s, 1H0, 4.01 (br s, 1H), 3.51-3.37
(m, 1H), 1.91-1.89 (m, 1H), 1.46 (dd, 3H, J PMe ) 20.7 Hz, J HMe
) 7.5 Hz); 13C NMR (CDCl3, 75 MHz) δ 133.7-127.0 (m,
aromatic and alkene), 70.3, 49.0 (d, 1C, J ) 2.4 Hz), 40.5 (d,
1C, J ) 86.8 Hz), 24.3, 23.1 (d, 1C, J ) 11.6 Hz), 14.0; 31P
Tolu en e-4-su lfon ic Acid (E)-H ep t a -4,6-d ien yl E st er
(23). p-Toluenesulfonyl chloride (18.18 g, 95.4 mmol) was
added via a solid addition funnel to a cooled (0 °C, ice bath)
solution of (E)-hepta-4,6-dien-1-ol (7.13 g, 63.6 mmol) and 1,4-
diazabicylo[2.2.2]octane (14.26 g, 127 mmol) in anhydrous
methylene chloride (75 mL). The reaction was slowly warmed
to room temperature and stirred for 4 days during which time
a white solid precipitated. The solid was filtered and washed
with methylene chloride (3 × 25 mL). The filtrates were
combined and concentrated in vacuo to afford an oil. The crude
product was purified by flash chromatography (20:1 to 10:1
pentane/EtOAc) to yield 23 (11.73 g, 69%) as a clear viscous
NMR (CDCl3, 121 MHz) δ 41.4; IR (CDCl3) 1198, 1009 cm-1
;
oil: Rf 0.58 (8:1 pentane/EtOAc); H NMR (CDCl3, 300 MHz)
1
J . Org. Chem, Vol. 67, No. 17, 2002 6179