R. Rayala et al. / Tetrahedron xxx (2016) 1e9
7
3
5a69 had: 1H NMR (CDCl3)
d
4.25 (q, JH,H¼7.2 Hz, 2H, CH2),
(MeOH) lmax 253, 280 nm, lmin 239, 271 nm; 1H NMR (CDCl3)
d
7.84
2.09e1.88 (m, 2H, H3, H30), 1.42e1.30 (m, 4H, H4, H40, H5, H50),
(s, 1H, H6), 7.81 (d, J¼2.1 Hz, 0.2H, Ph), 7.66 (d, J¼2.2 Hz, 0.8H, Ph),
7.49e7.23 (m, 17H, Ph), 6.78 (d, J¼8.7 Hz, 0.8H, Ph), 6.75 (d,
J¼8.7 Hz, 0.2H, Ph), 6.44 (d, J¼13.9 Hz, 0.8H, H10), 6.27 (br s, 0.2H,
H10), 5.09 (‘d’, J¼13.6 Hz, 1H, benzylic), 4.92e4.80 (m, 1H, benzylic),
4.73e4.65 (m, 1H, benzylic), 4.62e4.41 (m, 3H, benzylic), 4.18e4.09
(m, 2H, H30, H40), 3.92 (s, 0.6H, CH3), 3.91 (s, 2.4H, CH3), 3.82e3.72
(m, 1H, H50), 3.61e3.53 (m, 1H, H500); 19F NMR (CDCl3)
3
3
1.28 (t, JH,H¼7.1 Hz, 3H, CH3), 0.85 (t, JH,H¼7.2 Hz, 3H, H6, H60,
H600); 13C NMR (CDCl3)
d
164.4 (t, JF,C¼33.2 Hz, C1), 116.4 (t,
2
1JF,C¼249.8 Hz, C2), 63.0 (CH2), 34.5 (t, JF,C¼23.2 Hz, C3), 23.5 (t,
2
3JF,C¼4.3 Hz, C4), 22.2 (C5), 13.9 (CH3), 13.7 (C6); 19F NMR (CDCl3)
3
d
ꢀ105.92 ppm (t, JFeH¼16.8 Hz); GCeMS (tR¼7.5 min) 151 (Mþ-
Et, 1.1), 87 (100).
3
5b69 had: 1H NMR (CDCl3)
d
4.25 (q, JH,H¼7.2 Hz, 2H, CH2),
d
ꢀ133.52 ppm (br s, 0.8F), e131.57 ppm (br s, 0.2F); 13C NMR
2.03e1.91 (m, 2H), 1.45e1.18 (m, 11H), 0.81 (‘t’, 3JH,H¼6.8 Hz, 3H, H6,
(CDCl3) for major isomer: d 158.4, 157.2, 149.4, 138.1, 137.79, 137.76,
H60, H600); 13C NMR (CDCl3)
d
164.5 (t, JF,C¼33.0 Hz, C1), 116.4 (t,
137.3, 136.8, 135.9, 134.1, 134.0, 129.3, 128.6, 128.5, 128.4, 128.3,
128.2, 128.1, 128.0, 127.9, 120.24, 120.23, 112.2, 112.0, 108.7 (d,
2
1JF,C¼249.7 Hz, C2), 62.7 (CH2), 34.5 (t, 2JF,C¼23.2 Hz, C3), 31.4, 28.7,
22.4, 21.4 (t, 3JF,C¼4.3 Hz, C4), 13.9; 19F NMR (CDCl3)
d
ꢀ105.89 ppm
JC2 eF¼239.1 Hz, C20), 96.9, 90.4 (d, JC1 eF¼47.3 Hz, C10), 80.3 (C40),
1
2
0
0
(t, JFeH¼17.0 Hz); GCeMS (tR¼7.4 min) 179 (Mþ-Et, 60.8), 144
79.7 (d, 2JC3 eF¼17.7 Hz, C30), 73.5 (CH2), 73.1 (CH2), 67.0 (C50), 56.4
3
0
(100).
(OCH3), 45.7 (CH2). HRMS (ESI) m/z 755.1182 [MþNa]þ, calcd for
C
37H3479BrFN2NaO6Sþ 755.1197.
4.5. 3-N-Benzyl-30,50-di-O-benzyl-5-iodo-20-S-(4-
methoxyphenyl)-20-thiouridine (7) and 3-N-benzyl-30,50-di-O-
benzyl-20-fluoro-20-S-(4-methoxyphenyl)-20-thiouridine (8)
4.7. 50-O-Acetyl-20,30-dideoxy-20,30-didehydro-20-[(4-
methoxyphenyl)sulfonyl]uridine (13), 1-[5-acetyl-4-hydroxy-
2-((4-methoxyphenyl)sulfonyl)-1,3-pentadien-1-yl]uracil (14)
and [4-[(4-methoxyphenyl)sulfonyl]furan-2-yl]methyl acetate
(11)
NIS (95 mg, 0.42 mmol) was added to a stirred solution of 6
(128 mg, 0.2 mmol) and Py.9HF (138 mL, 0.6 mmol) in anhydrous
CH2Cl2 (3 mL) at ꢀ78 ꢁC in a polypropylene vessel and the resulting
brown solution was brought to w5 ꢁC overnight (16 h). Stirring was
continued at ambient temperature for 7 h (total reaction time:
23 h). The reaction was quenched by addition of ice-cold water
(10 mL), diluted with CH2Cl2 (5 mL), neutralized with drop-wise
addition of conc. NH4OH. Organic layer was separated and aque-
ous layer was back extracted (2ꢃCH2Cl2). Combined organic layer
was washed with 1N HCl (10 mL), brine (10 mL), dried (MgSO4), and
filtered. Volatiles were evaporated in vacuo and the brown residue
was column chromatographed (5% / 20% EtOAc in hexanes) to
give 7 (44 mg, 29%) as a colourless oil and 851 (20-R/SeS, w1:1;
16 mg, 12%) as a pale-yellow oil.
TDAE (0.24 mL, 1.04 mmol) was added to a stirred solution of 10
(100 mg, 0.207 mmol) in anhydrous DMF (2 mL) at ꢀ78 ꢁC under
argon. The reaction mixture was brought to ambient temperature
over 1 h 15 min and a 10% HCl solution (2 mL) was then added. The
crude was extracted with EtOAC (3ꢃ) and the combined organic
phase was dried over anhydrous Na2SO4. Volatiles were evaporated
in vacuo and the residue was column chromatographed (PE 100%/
EtOAc/PE 2/1/EtOAc 100%) to give 11 (29.5 mg, 46%), 14 (17.5 mg,
20%), and 13 (30 mg, 34%), all as colourless oils.
13 had: 1H NMR (CDCl3)
d 9.23 (br, 1H, NH), 7.79e7.75 (m, 2H,
Ph), 7.24 (d, J¼8.4 Hz, 1H, H6), 7.18 (t, J¼1.6 Hz, 1H, H30), 7.03e6.99
(m, 3H, Ph, H10), 5.55 (dd, J¼2, 8.4 Hz, 1H, H5), 5.12e5.09 (m, 1H,
H40), 4.41 (dd, J¼4, 12.4 Hz, 1H, H50), 4.29 (dd, J¼3.6, 12.4 Hz, 1H,
H500), 3.87 (s, 3H, OCH3), 2.09 (s, 3H, Ac); 13C NMR (50 MHZ,
7 had: UV (MeOH) lmax 253, 283 nm, lmin 246, 273 nm; 1H NMR
(CDCl3) d 7.66e7.63 (m, 2H, Ph), 7.56 (s, 1H, H6), 7.44e7.31 (m, 13H,
Ph), 7.12e7.10 (m, 2H, Ph), 6.51 (d, J¼8.9 Hz, 1H, H10), 6.33e6.30 (m,
2H, Ph), 5.15 (‘d’, J¼13.4 Hz, 1H, benzylic), 5.02 (‘d’, J¼13.3 Hz, 1H,
benzylic), 4.68e4.52 (m, 4H, benzylic), 4.33e4.25 (m, 2H, H40, H30),
3.76e3.67 (m, 2H, H20, H50), 3.66 (s, 3H, OCH3), 3.51 (dd, J¼2.0,
CDCl3)
d
170.1 (C]O), 164.9 (CPh), 162.9 (C4), 150.3 (C2), 142.1
(C6), 141.9 (C20), 139.5 (C30), 130.8 (CHPh), 129.1 (CPh), 115.2 (CHPh),
103.2 (C5), 87.5 (C10), 82.8 (C40), 63.9 (C50), 56.1 (OCH3), 20.8 (Ac).
HRMS (ESI) m/z 423.0856 [MþH]þ, calcd for C18H19N2O8Sþ
423.0857.
10.5 Hz, 1H, H500); 13C NMR (CDCl3)
d 159.8, 159.1, 150.8, 142.2 (C6),
137.22, 137.16, 136.2, 135.2, 130.4, 128.8, 128.6, 128.4, 128.2, 128.1,
128.06, 127.8, 127.7, 123.0, 114.7, 90.2 (C10), 82.1 (C30), 80.7 (C40),
73.8 (CH2), 72.3 (CH2), 70.5 (C5), 68.9 (C50), 56.4 (C20), 55.5 (OCH3),
46.0 (CH2). HRMS (ESI) m/z 785.1119 [MþNa]þ, calcd for
14 had: 1H NMR (CDCl3)
d
9.00 (br s, 1H, NH), 7.76 (d, J¼8.8 Hz,
2H, Ph), 7.58 (s, 1H, H10), 6.97e6.99 (m, 3H, Ph, H6), 5.69 (br, 1H,
OH), 5.62 (dd, J¼1.2, 8.0 Hz, 1H, H5), 4.93e4.79 (m, 1H, H30), 4.27
(dd, J¼4.4, 12.4 Hz, 1H, H50), 4.21 (dd, J¼4.8, 12.4 Hz, 1H, H500), 3.86
C
37H35IN2NaO6Sþ 785.1133.
Analogous treatment of 6 (128 mg, 0.2 mmol) with NIS (95 mg,
(s, 3H, OCH3), 1.95 (s, 3H, Ac); 13C NMR (CDCl3)
d 170.4 (C]O), 164.2
0.42 mmol) and DAST (160
m
L, 1.2 mmol) followed by aqueous
(CPh), 162.6 (C4), 160.3 (C10), 150.3 (C2), 140.2 (broad, C6), 131.5
(CPh), 129.9 (CHPh), 116.9 (broad, C20), 114.9 (CHPh), 103.7 (C5), 88.7
(broad, C30), 63.4 (C50), 55.6 (OCH3), 20.5 (CHA3c). HRMS (ESI) m/z
423.0864 [MþH]þ, calcd for C18H19N2O8Sþ 423.0857; 440.1119
[MþNH4]þ, calcd for C18H22N3O8Sþ 440.1122.
workup (satd Na2S2O3, satd NaHCO3, brine, MgSO4) and column
chromatography gave 851 (20-R/SeS, w1:1; 58 mg, 44%) as a pale-
yellow oil.
4.6. 3-N-Benzyl-30,50-di-O-benzyl-5-bromo-20-fluoro-20-S-(4-
11 had: 1H NMR (CDCl3)
d
7.93 (d, J¼0.8 Hz, 1H, H1), 7.85e7.89
methoxyphenyl)-20-thiouridine (9)
(m, 2H, Ph), 6.96e7.00 (m, 2H, Ph), 6.56 (s, 1H, H3), 4.97 (s, 2H, H5,
H50), 3.85 (s, 3H, OCH3), 2.05 (s, 3H, Ac); 13C NMR (CDCl3)
d 170.3
Py.9HF (62
mL, 0.27 mmol) was added to a chilled solution of
(C]O), 163.8 (CPh), 152.4 (C4), 145.7 (C1), 132.9 (C2), 131.1 (CPh),
129.8 (CHPh), 114.7 (CHPh), 108.7 (C3), 57.4 (C5), 55.8 (OCH3), 20.8
(CHA3c); HRMS (ESI) m/z 328.0852 [MþNH4]þ, calcd for C14H18NO6Sþ
328.0849.
DBH (19 mg, 0.066 mmol) in dry CH2Cl2 (1 mL) at ꢀ78 ꢁC. The
resulting pale solution was stirred at ꢀ78 ꢁC for 10 min and a so-
lution of substrate 8 (40 mg, 0.06 mmol) in dry CH2Cl2 (2 mL) was
added via syringe. The resultant orange solution was stirred at
ꢀ78 ꢁC for 2 h and was brought to ꢀ30 ꢁC over 45 min. The reaction
mixture was diluted with CH2Cl2 (5 mL), washed with NaHCO3/H2O
(5 mL), H2O (5 mL), brine (5 mL), dried (MgSO4). Volatiles were
evaporated in vacuo and the yellow residue was column chroma-
tographed (15% EtOAc in hexanes) to give 9 as mixture of di-
astereomers (20-R/SeS, w4:1) (pale-yellow oil, 22 mg, 50%): UV
4.8. [4-[(4-Methoxyphenyl)sulfonyl]furan-2-yl]methyl ace-
tate (11) and uracil (12)
In a glove box, SED (31 mg, 0.1 mmol) was added to a solution of
10 (50 mg, 0.1 mmol) in anhydrous DMF (4 mL) and the resulting
mixture was stirred at ambient temperature for 15 min. Then the