1
4,4,7,7-Tetraethyl-2-oxo-2-(1-phenylpentyloxy)-1,3,2-dioxaphosphepane (10a ).
2
H ꢀꢀꢀ
NMR (90 MHz) ꢀ 0.50-0.97 (15H, complex), 1.07-2.00 (18H, complex), 5.09 (1H, dt, J=6.4 and 6.4 ꢀꢀ
31
Hz), 7.11 (5H, complex); P NMR (109 MHz) ꢀ -5.41.
1,3,4,5-Tetra-O-benzoyl-myo-inositol 6-(4,4,7,7-tetramethylbutylene phosphate). rt, 3 h
1
then reflux, 1 h for phosphitylation: mp 194-195 ˚C (from AcOEt); H NMR (270 MHz) ꢀ 0.86 (3H, s),
0.91 (3H, s), 0.94 (3H, s), 1.05 (3H, s), 1.63 and 1.74 (ABq, J=14.3 Hz), 4.66 (1H, br), 5.44-5.57 ꢀꢀ
31
(3H, complex), 5.80 (1H, t, J=9.5 Hz), 6.27 (1H, t, J=9.5 Hz), 7.26-8.27 (20H, complex); P NMR
(109 MHz) ꢀ -4.99; Anal. Calcd for C H O P: C, 64.12; H, 5.51. Found: C, 64.08; H, 5.51.
34 43 12
3-N-( p-Methoxybenzyl)-2'-O-methyluridine 5'-(4,4,7,7-tetramethylbutylene phosphate).
1
3.3 Equiv. of pyridine based on the alcohol was additionally used to promote the reaction (rt, 3 h). H ꢀ
NMR (270 MHz) ꢀ 1.39 (3H, d, J=1.5 Hz), 1.40 (3H, s), 1.53 (6H, s), 2.02 (4H, m), 3.60 (3H, s), 3.72 ꢀ
(1H, dd, J=5.2 and 2.1 Hz), 3.76 (3H, s), 4.06 (1H, dt, J=7.3 and 2.1 Hz), 4.18 (1H, dd, J=7.3 and 5.2 ꢀ
Hz), 4.26 and 4.37 (2H, dddx2, J=12.5, 6.4, and 2.1 Hz), 4.97 and 5.09 (ABq, J=13.7 Hz), 5.74 (1H, ꢀꢀꢀ
d, J=7.9 Hz), 5.93 (1H, d, J=2.1 Hz), 6.81 (2H, d, J=8.8 Hz), 7.42 (2H, d, J=8.8 Hz), 7.71 (1H, d, ꢀꢀ
31
J=7.9 Hz); P NMR (109 MHz) ꢀ -4.59; Anal. Calcd for C H N O P: C, 54.93; H, 6.56; N, 4.93.
26 37 2 10
Found: C, 54.98; H, 6.63; N, 5.06.
1
1,12-Octadecanediol 1-(4,4,7,7-tetramethylbutylene phosphate). 0 ˚C, 6.5 h: H NMR (270 ꢀꢀ
MHz) ꢀ 0.88 (3H, t, J=4.6 Hz), 1.41 (6H, s), 1.53 (6H, s), 1.27-1.67 (30H, complex), 1.95 (4H, m), ꢀꢀ
31
3.58 (1H, br), 4.02 (2H, q J=6.7 Hz); P NMR (109 MHz) ꢀ -5.31; Anal. Calcd for C H O P: C,
26 53 5
65.51; H, 11.21. Found: C, 65.62; H, 11.25.
Hydrolysis experiment (typical). A solution of phosphoramidite (5a) (91.7 mg, 0.37 mmol), PPrOH
(45.9 mg, 0.34 mmol), and tetrazole (28.3 mg, 0.40 mmol) in CH Cl (1 mL) was stirred at ambient
2 2
temperature for 2 h and water (18 mg, 1.00 mmol) was added. The mixture was vigorously stirred for 1 h
and cooled to -78 ˚C. After addition of mCPBA (87.2 mg, 0.51 mmol), the mixture was stirred at ambient
temperature for 30 min and AcOEt was added. The organic solution was washed with 10% Na SO
2
3
solution, sat. NaHCO solution, and brine, dried and evaporated. The residue was subjected to PTLC
3
(AcOEt/CH Cl , 1:4) to give 9a (48.9 mg, 44%), 16a (13.1 mg, 18%), and PPrOH (13.1 mg, 29%). In a
2 2
similar manner, 5b and 5c were treated.
Synthesis of hydrophosphonate 16 (typical). A mixture of phosphoramidite 5a (121 mg, 0.49 ꢀꢀ
mmol), tetrazole (134 mg, 0.49 mmol), water (44 mg, 2.46 mmol), and CH Cl (5 mL) was stirred for 1 h ꢀ
2 2
at rt, and volatile materials were evaporated. The residue was extracted with ether (84 mg) and the soluble
fraction was subjected to a bulb to bulb distillation to afford 16a (31 mg, 33%).
2-Hydro-4,4,7,7-tetramethyl-1,3,2-dioxaphosphepane (16a): R 0.3 (AcOEt/CH Cl , 1:4); bp
2 2
f
1
110 ˚C (bath temp.)/0.4 mmHg; H NMR (90 MHz) ꢀ 1.30 (6H, s), 1.43 (6H, s), 1.89 (4H, br), 6.59
31
-1
(1H, d, J=705.6 Hz); P NMR (109 MHz) ꢀ 1.58; IR (neat) 2430 cm ; Anal. Calcd for
C8H17O3P•3/4H2O: C, 46.71; H, 9.06. Found: C, 46.43; H, 8.72.
2-Hydro-4,4,6,6-tetramethyl-1,3,2-dioxaphosphane (16b). R 0.2 (AcOEt/Hexane, 2:1); bp
f
1
110 ˚C (bath temp.)/0.5 mmHg; H NMR (90 MHz) ꢀ 1.48 (6H, s), 1.52 (6H, s), 1.65 (2H, br), 1.91 ꢀꢀ