Page 13 of 21
The Journal of Organic Chemistry
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MHz): δ = ꢀ0.4 (SiMe
3
), 4.9 (SiCH
C1′), 87.3 (5′ꢀOꢀCIV), 88.1 (C4′), 95.1 (C≡CꢀTMS), 100.0 (C≡CꢀTMS), 100.5 (C5), 113.6 (CmꢀPhOMe), 127.3 (CpꢀPh), 128.3
oꢀPh), 128.4 (CmꢀPh), 129.0 (CiꢀTol), 130.3 (CoꢀPhOMe), 130.4 (CmꢀTol), 130.9 (CoꢀTol), 135.9 (CiꢀPhOMe), 142.9 (C6), 145.0 (Ciꢀ
2 2 3 3
), 6.8 (SiCH CH ), 22.0 (pꢀCH ), 42.4 (C2′), 55.6 (OMe), 63.6 (C5′), 72.9 (C3′), 86.8
(
(
C
+
+
Ph), 147.5 (CpꢀTol), 148.6 (C2), 159.1 (CpꢀPhOMe), 160.9 (C4), 168.2 (C(O)ꢀTol); MS (ESI , MeOH) m/z: 881.6 [M+Na] ,
0
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97.6 [M+K] . HRMS (ESI ): m/z calcd for C49
′ꢀOꢀ(4,4′ꢀDimethoxytrityl)ꢀ3ꢀNꢀ(4ꢀmethylbenzoyl)ꢀ5ꢀethynylꢀ2′ꢀdeoxyuridine (10). To a stirred solution of 9b (1.90
NF.H O (2.00 g, 13.27 mmol,
eq.). The reaction mixture was stirred at rt for 1.5 h and then carefully quenched with aq. NH Cl. The organic phase was
extracted with Et O (3 x), dried over MgSO , filtered and reduced in vacuo. The residue was purified by flash
chromatography on silica gel eluted with toluene/Et
yellow foam (1.23 g, 83 %). C40 (672.72). R
.25–2.43 (m, 1H, H2′ ), 2.44 (s, 3H, pꢀCH ), 2.44–2.55 (m, 1H, H2′
Hz, 1H, H5′ ), 3.41 (dd, J=10.8 Hz, J=3.4 Hz, 1H, H5′
H3′), 6.24 (dd, J=7.2, 6.0 Hz, 1H, H1′), 6.89 (d, J=8.6 Hz, 4H, HmꢀPhOMe), 7.20–7.31 (m, 3H, HmꢀPh, HpꢀPh), 7.33 (d,
58 2 8 2
H N NaO Si : 881.3624 [M+Na] ; found 881.3601.
2
1
5
g, 2.21 mmol) in THF (22 mL), previously cooled down to 0 °C, was portionwise added Et
4
2
6
4
2
4
2
O (93:7 → 1:1, v/v) to provide the desired compound 10 as a light
1
H
36
N
2
O
8
f
= 0.22 (toluene/Et
2
O = 7:2). HꢀNMR (CD
2
Cl
2
, 200 MHz): δ =
2
3
2
A
3
B
), 2.97 (s, 1H, C≡CH), 3.32 (dd, J=10.8 Hz, J=3.0
2
3
A
B
), 3.80 (s, 3H, OMe), 4.03–4.12 (m, 1H, H4′), 4.52–4.62 (m, 1H,
3
3
3
3
3
4
3
J=8.1 Hz, 2H, HmꢀTol), 7.39 (d, J=8.6 Hz, 4H, HoꢀPhOMe), 7.48 (dd, J=8.2 Hz, J=1.4 Hz, 2H, HoꢀPh), 7.81 (d, J=8.1 Hz,
1
3
2 2 3
2H, HoꢀTol), 8.21 (s, 1H, H6); CꢀNMR (CD Cl , 50 MHz): δ = 22.0 (pꢀCH ), 41.9 (C2′), 55.6 (OMe), 63.8 (C5′), 72.4
(C3′), 74.4 (C≡CH), 82.4 (C≡CH), 86.6 (C1′), 87.1 (C4′), 87.5 (5′ꢀOꢀCIV), 99.3 (C5), 113.7 (CmꢀPhOMe), 127.3 (CpꢀPh),
128.3 (CoꢀPh), 128.5 (CmꢀPh), 128.8 (CiꢀTol), 130.4 (CmꢀTol), 130.4 (CoꢀPhOMe), 130.9 (CoꢀTol), 135.7 (CiꢀPhOMe), 136.0 (CiꢀPhOMe),
+
144.0 (C6), 145.0 (CiꢀPh), 147.7 (CpꢀTol), 148.6 (C2), 159.2 (CpꢀPhOMe), 161.0 (C4), 168.1 (C(O)ꢀTol); MS (ESI , MeOH)
+
+
+
+
36 2 8
m/z: 695.5 [M+Na] 711.5 [M+K] . HRMS (ESI ): m/z calcd for C40H N NaO : 695.2364 [M+Na] ; found 695.2357.
5′ꢀOꢀ(4,4′ꢀDimethoxytrityl)ꢀ3ꢀNꢀ(4ꢀmethylbenzoyl)ꢀ5ꢀ(5ꢀ(3ꢀMethoxyꢀ4ꢀoxoꢀchromenꢀ2ꢀyl)thienꢀ2ꢀyl)ethynylꢀ2’ꢀ
deoxyuridine (11). To a stirred solution of 10 (300 mg, 0.45 mmol) and 6 (206 mg, 0.58 mmol, 1.3 eq) in THF (10 mL)
2 3 2
under argon, were sequentially added triethylamine (311 µL, 2.23 mmol, 5 eq), and CuI (6 mg, 7 mol%)/PdCl (PPh ) (22
mg, 7 mol%) all together. The reaction mixture was warmed to 55 °C for 2 h. The volatiles were removed in vacuo and
the residue was purified by flash chromatography on silica gel eluted with toluene/EA (93:7 → 3:2, v/v) to provide the
1
desired compound 11 as a yellow foam (276 mg, 67 %). C54
H
44
N
2
O11S (929.0). R
f
= 0.38 (toluene/EA = 7:3). HꢀNMR
2
3
(CDCl , 200 MHz): δ = 2.39–2.49 (m, 1H, H2′ ), 2.43 (s, 3H, pꢀCH
3
A
3
), 2.58 (ddd, J=13.6 Hz, J=5.8, 2.9 Hz, 1H, H2′
B
),
3.37–3.51 (m, 2H, H5′), 3.73 (s, 3H, OMe), 3.74 (s, 3H, OMe), 3.97 (s, 3H, 3′′ꢀOMe), 4.10–4.19 (m, 1H, H4′), 4.59–4.71
3
3
3
(m, 1H, H3′), 6.35 (dd, J=5.0, 4.0 Hz, 1H, H1′), 6.82 (d, J=8.8 Hz, 2H, HmꢀPhOMe), 6.84 (d, J=8.8 Hz, 2H, HmꢀPhOMe),
3
3
6
.87 (d, J=4.0 Hz, 1H, H3ꢀthioph.), 7.15–7.35 (m, 6H, H6′′, HmꢀTol, HmꢀPh, HpꢀPh), 7.37 (d, J=8.8 Hz, 4H, HoꢀPhOMe), 7.42–
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