3
400.13 MHz) δ = 9.55 (s, 1H, NH), 7.55 (d, JHH = 8.1 Hz, 1H,
CH3); MS ESI+ m/z = 656 (100%) [M + H]+; HRMS-ESI+ (m/z):
3
4
NCH), 7.31–7.20 (m, 5H, CH), 5.57 (dd, JHH = 8.1 Hz, JHH
1.7 Hz, 1H, CH), 5.41 (t, JHH = JPH = 3.2 Hz, 1H, OCHN),
=
[M + H]+ calcd for C26H32N3O7IP: 656.1023; found 656.1017.
3
3
2
4.49 and 4.45 (2 d, 2H, JHH = −11.9 Hz, PhCH2), 4.35 (dd,
2JPH = 14.3 Hz, JHH = 3.2 Hz, 1H, PCH), 4.24–4.05 (m, 4H, 2
3
General procedure for the deiodination reaction – synthesis of
10a–c
OCH2), 3.92–3.50 (m, 4H, CH2CH2), 1.28 and 1.27 (2 t, 3JHH
=
4.1 Hz, 6H, 2 CH3); 13C NMR (CDCl3, 100.61 MHz) δ = 162.6
(s, CvO), 149.3 (s, CvO), 139.0 (s, NCH), 136.6 (s, C), 126.8
(s, CH), 126.6 (s, CH), 127.5 (s, CH), 100.2 (s, CH), 82.8 (s,
OCHN), 72.2 (s, PhCH2), 69.3 (s, OCH2), 67.4 (s, OCH2), 63.2,
Iodophosphonate 9a–c (1 eq, concentration 0.024 mol L−1 in
toluene – 1 volume) was dissolved in a two-necked round-
bottom flask with a condenser and under nitrogen. AIBN (0.8
eq) and nBu3SnH (1.8 eq) were added to the solution and the
mixture was heated for 5 h at 70 °C. After cooling at room temp-
erature, saturated NH4Cl solution was added (1 volume) and the
resulting phases separated. The aqueous layer was extracted 3
times by AcOEt (1 volume) and the organic layers were dried
over MgSO4, filtered and concentrated under vacuum. The crude
mixture was purified by chromatography on silica gel.
2
1
62.9 (2 d, JCP = 6.6 Hz, OCH2), 18.1 (d, JCP = 145.6 Hz,
PCH), 15.3 (d, JCP = 5.9 Hz, CH3); MS-ESI+ m/z = 553.0
3
(100%) [M + H]+; HRMS-ESI+ (m/z): [M + H]+ calcd for
C19H27IN2O7P: 553.0601; found 553.0607.
( )-(1R,2R)-Diethyl 2-[2-(benzyloxy)ethoxy]-2-(5-methyl-2,4-
dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-1-iodoethylphosphonate
(9b). Ester 6 (1.02 g, 3.20 mmol, 1 eq.) was reacted according
to the general procedure. The crude reaction mixture was
purified by chromatography on silica gel (25 g, gradient 100%
CH2Cl2 to 100% AcOEt) affording 9b as a clear oil (0.81 g,
45%). 31P NMR (CDCl3, 161.97 MHz) δ = 16.6; 1H NMR
(CDCl3, 400.13 MHz) δ = 8.03 (s, 1H, NH), 7.36 (s, 1H,vCH–
( )-Diethyl 2-[2-(benzyloxy)ethoxy]-2-(2,4-dioxo-3,4-dihydro-
2H-pyrimidin-1-yl)ethylphosphonate (10a). Iodophosphonate 9a
(0.61 g, 1.10 mmol, 1 eq.) was reacted according to the general
procedure. The crude reaction mixture was purified by chromato-
graphy on silica gel (gradient 100% AcOEt–50%–50% AcOEt–
(AcOEt–EtOH 9 : 1)) affording 10a as a colorless oil (0.398 g,
85%). 31P NMR (CDCl3, 161.97 MHz) δ = 22.9; 1H NMR
(CDCl3, 400.13 MHz) δ = 8.78 (s, 1H, NH), 7.34 (d, 3JHH = 8.1
3
3
N), 7.30–7.20 (m, 5H, CH), 5.42 (t, JHH = JPH = 3.3 Hz, 1H,
2
OCHN), 4.48 and 4.46 (2 d, 2H, JHH = −11.8 Hz, PhCH2),
3
4.31 (dd, 2JPH = −14.1 Hz, 3JHH = 3.3 Hz, 1H, PCH), 4.18–4.09
(m, 4H, POCH2), 3.84–3.50 (m, 4H, 2 CH2), 1.28 and 1.27 (2 t,
3JHH = 7.3 Hz, 6H, CH3); 13C NMR (CDCl3, 100.61 MHz) δ =
163.7 (s, CvO), 150.2 (s, CvO), 139.0 (s, CHN), 137.7 (s,
PhC), 128.5 (s, CH), 127.9 (s, CH), 127.7 (s, CH), 109.8 (s,
CMe), 83.6 (s, OCHN), 73.3 (s, CH2Ph), 70.1 (s, OCH2), 68.5
Hz, 1H, NCH), 7.31–7.18 (m, 5H, CH), 5.95 (ddd, JPH = 7.80
3
3
3
Hz, JHH = 6.6 Hz, JHH = 6.1 Hz, 1H, OCHN), 5.64 (dd, JHH
4
= 8.1 Hz, JHH = 2.2 Hz, 1H, CHC(O)), 4.45 (s, 2H, PhCH2),
4.07–3.99 (m, 4H, 2 OCH2), 3.73–3.47 (m, 4H, CH2CH2), 2.30
3
2
3
(ddd, JPH = −18.3 Hz, JHH = −15.4 Hz, JHH = 6.1 Hz, 1H,
3
2
3
PCH2), 2.23 (ddd, JPH = −18.9 Hz, JHH = −15.4 Hz, JHH
=
3
2
2
6.6 Hz, 1H, PCH2), 1.22 and 1.23 (2 t, JHH = 7.0 Hz, 6H, 2
CH3), 13C NMR (CDCl3, 100.61 MHz) δ = 162.9 (s, CvO),
150.4 (s, CvO), 139.2 (s, NCH), 137.7 (s, C), 128.5 (s, CH),
127.8 (s, CH), 127.7 (s, CH), 102.9 (s, CH), 81.6 (s, OCHN),
73.3 (s, CH2), 68.9 (s, CH2), 68.6 (s, CH2), 62.4, 62.1 (2 d, 2JCP
(s, OCH2), 64.2 (d, JCP = 5.9 Hz, OCH2), 63.9 (d, JCP = 6.6
Hz, OCH2), 18.9 (d, 1JCP = 145.6 Hz, PCH), 16.4 (d, JCP = 5.9
3
Hz, CH3), 12.5 (s, CH3); MS-ESI+ m/z = 567.2 (100%) [M +
H]+; HRMS-ESI+ (m/z): [M + H]+ calcd for C20H29N2O7IP:
567.0757; found 567.0757.
1
= 6.6 Hz, OCH2), 32.4 (d, JCP = 142.0 Hz, PCH2), 16.4 (d,
3JCP = 6.6 Hz, 2 CH3); MS ESI+ m/z = 427.2 (100%) [M + H]+,
m/z = 853.5 (92%) [2M + H]+; HRMS-ESI+ (m/z): [M + H]+
calcd for C19H28N2O7P: 427.1634; found 427.1633.
( )-(1R,2R)-Diethyl 2-[2-(benzyloxy)ethoxy]-2-[2-(4-benzoyl-
amino-2-oxo-2H-pyrimidin-1-yl)]-1-iodoethylphosphonate (9c).
Ester 6 (0.94 g, 3.00 mmol, 1 eq.) was reacted according to the
general procedure. The crude reaction mixture was purified by
chromatography on silica gel (40 g, gradient 100% CH2Cl2 to
100% AcOEt) affording 9c as a yellow solid (0.62 g, 32%). 31P
NMR (CDCl3, 161.97 MHz) δ = 17.1; 1H NMR (CDCl3,
( )-Diethyl 2-(2-(benzyloxy)ethoxy)-2-(5-methyl-2,4-dioxo-3,4-
dihydro-2H-pyrimidin-1-yl)ethylphosphonate (10b). Iodophos-
phonate 9b (0.64 g, 1.10 mmol, 1 eq.) was reacted according to
the general procedure. The crude reaction mixture was purified
by chromatography on silica gel (gradient 100% AcOEt–50%–
50% AcOEt–(AcOEt–EtOH 9 : 1)) affording 10b as a colorless
oil (0.416 g, 84%). 31P NMR (CDCl3, 161.97 MHz) δ = 23.2;
1H NMR (CDCl3, 400.13 MHz) δ = 8.92 (s, 1H, NH),
3
400.13 MHz) δ = 8.99 (s, 1H, NH), 8.03 (d, JHH = 7.5 Hz, 1H,
NCH), 7.87–7.83 (m, 2H, CH), 7.56–7.40 (m, 4H, CH and CH),
3
7.32–7.19 (m, 5H, CH), 5.45 (t, JHH
=
3JPH = 2.6 Hz, 1H,
2
3
OCHN), 4.62 (dd, JPH = −14.6 Hz, JHH = 2.6 Hz, 1H, PCH),
4.48 and 4.45 (2 d, JHH = −10.0 Hz, 2H, PhCH2), 4.20–4.08
2
3
7.30–7.14 (m, 6H, CH and PhCH), 5.96 (ddd, JPH = 7.6 Hz,
2
3
3
(m, 4H, 2 POCH2), 3.88 (ddd, JHH = −9.9 Hz, JHH = 4.3 Hz,
3JHH = 2.0 Hz, 1H, OCH2), 3.75–3.62 (m, 2H, OCH2), 3.54
(ddd, 3JHH = 6.7 Hz, 2JHH = 4.3 Hz, 3JHH = 2.0 Hz, 1H, OCH2),
3JHH = 6.7 Hz, JHH = 6.2 Hz, 1H, OCHN), 4.44 (s, 2H, CH2),
4.07–3.99 (m, 4H, OCH2), 3.70–3.47 (m, 4H, CH2CH2), 2.30
2
2
3
(ddd, JPH = −20.3 Hz, JHH = −16.8 Hz, JHH = 6.7 Hz, 1H,
1.26 (t, JHH = 7.0 Hz, 6H, 2 CH3); 13C NMR (CDCl3,
PCH2), 2.23 (ddd, JPH = −19.7 Hz, JHH = −16.8 Hz, JHH =
3
2
2
3
3
100.61 MHz) δ = 162.8 (s, CvO), 145.1 (s, CH), 137.7 (s, C),
133.1, 128.9, 128.5, 127.8, 127.6, 127.5 (6 s, CH), 95.8 (s, CH),
84.5 (s, OCHN), 73.2 (s, PhCH2), 70.5 (s, OCH2), 68.4 (s,
6.2 Hz, 1H, PCH2), 1.79 (s, 3H, CH3), 1.21 and 1.23 (2 t, JHH
= 7.2 Hz, 6H, 2 CH3); 13C NMR (CDCl3, 100.61 MHz) δ =
163.7 (s, CvO), 150.6 (s, CvO), 137.8 (s, C), 134.7 (s, CH),
128.4 (s, CH), 127.8 (s, CH), 127.6 (s, CH), 111.5 (s, C), 81.0
(s, OCHN), 73.3 (s, PhCH2), 68.7 (s, 2 CH2), 62.3 (d, 2JCP = 5.9
2
2
OCH2), 64.1 (d, JCP = 6.3 Hz, OCH2), 63.8 (d, JCP = 6.8 Hz,
OCH2), 19.8 (d, 1JCP = 145.6 Hz, PCH), 16.4 (d, 3JCP = 6.1 Hz,
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3448–3454 | 3451