CDCl3) δ 8.13 – 8.04 (m, 4H, ArH), 7.66 – 7.38 (m, 6H, ArH),
1H, H-4), 2.40 (s, 3H, CH3); 13C NMR (126 MHz, CDCl3) δ
165.97 (C=O), 165.07 (C=O), 145.64 (ArC), 134.20 (ArC),
133.83 (ArC), 133.57 (ArC), 130.20 (ArC x 2), 130.03 (ArC x 2),
129.89 (ArC x 2), 129.32 (ArC), 128.78 (ArC x 2), 128.61 (ArC
x 2), 128.25 (ArC), 127.96 (ArC x 2), 120.60 (dd, JC - F = 270.7,
253.1 Hz, C-2), 98.83 (dd, JC - F = 41.5, 25.1 Hz, C-1), 82.42 (C-
4), 69.88 (dd, JC - F = 25.9, 15.6 Hz, C-3), 62.59 (C-5), 21.81
(CH3); 19F NMR (471 MHz, CDCl3) δ δ -108.55 (ddd, J = 255.0,
ACCEPTED MANUSCRIPT
6.13 – 6.04 (m, 2H, H-1, H-3), 4.78 – 4.74 (m, 1H, H-5a), 4.66 –
4.59 (m, 2H, H-5b, H-4); 13C NMR (126 MHz, CDCl3) δ 166.07
(C=O), 164.97 (C=O), 134.26 (ArC), 133.45 (ArC), 130.27 (ArC
x 2), 129.96 (ArC x 2), 129.45 (ArC), 128.83 (ArC x 2), 128.55
(ArC x 2), 128.19 (ArC), 122.02 (dd, JC - F = 274.8, 250.8 Hz, C-
2), 90.85 (dd, JC - F = 37.3, 27.2 Hz, C-1), 80.01 (d, JC - F = 7.5 Hz,
C-4), 69.91 (dd, JC - F = 26.1, 15.9 Hz, C-3), 63.36 (C-5); 19F
NMR (471 MHz, CDCl3) δ -117.32 (dd, J = 230.3, 6.7 Hz), -
120.97 (ddd, J = 230.5, 15.2, 8.4 Hz); HRMS (ESI+) calcd. For
1
16.5, 5.9 Hz), -123.38 (d, J = 254.5 Hz); For beta-anomer: H
NMR (500 MHz, CDCl3) δ 8.06 – 8.02 (m, 2H, ArH), 7.99 – 7.94
(m, 2H, ArH), 7.71 (d, J = 8.3 Hz, 2H, ArH), 7.65 – 7.54 (m, 2H,
ArH), 7.43 (dt, J = 20.1, 7.8 Hz, 4H, ArH), 7.17 (d, J = 8.1 Hz,
2H, ArH), 6.06 (d, J = 6.4 Hz, 1H, H-1), 5.89 – 5.77 (m, 1H, H-
3), 4.52 (ddd, J = 7.6, 5.1, 3.7 Hz, 1H, H-4), 4.40 (dd, J = 12.4,
3.4 Hz, 1H, H-5a), 4.20 (dd, J = 12.4, 5.2 Hz, 1H, H-5b), 2.30 (s,
3H, CH3); 13C NMR (126 MHz, CDCl3) δ 165.72 (C=O), 164.91
(C=O), 145.69 (ArC), 134.26 (ArC), 133.83 (ArC), 133.48
(ArC), 130.24 (ArC x 2), 129.92 (ArC x 2), 129.89 (ArC x 2),
129.28 (ArC), 128.78 (ArC x 2), 128.58 (ArC x 2), 128.25 (ArC),
128.07 (ArC x 2), 120.60 (dd, JC - F = 270.7, 253.1 Hz, C-2),
98.83 (dd, JC - F = 41.5, 25.1 Hz, C-1), 79.50 (d, JC - F = 7.7 Hz, C-
4), 69.88 (dd, JC - F = 25.9, 15.6 Hz, C-3), 63.60 (C-5), 21.69
(CH3); 19F NMR (471 MHz, CDCl3) δ -121.54 (dd, J = 240.3, 6.9
Hz), -124.40 (ddd, J = 240.3, 15.3, 6.6 Hz); HRMS (ESI+) calcd.
For C26H23F2O8S+ 533.1076, found 533.1070.
+
C19H16ClF2O5 397.0649 (base peak), found 397.0637 (base
peak).
4.2.9. ((2R,3R)-3-(benzoyloxy)-4,4-difluoro-5-iodotetrahydro-
furan-2-yl)methyl benzoate (10b)
To a solution of 9 10a (742 mg, 1.96 mmol, 1.00 equiv.) in DCM
(20 mL) at RT was added PPh3 (513 mg, 1.96 mmol, 1.00
equiv.), iodine (496 mg, 1.96 mmol, 1.00 equiv.), and imidazole
(133 mg, 1.96 mmol, 1.00 equiv.). The mixture was then stirred
at RT for
3
h, concentrated, and purified by flash
o
chromatography on silica gel (10:1, 60 - 90 C petroleum ether –
10b, c, d.
EtOAc) to give 10b
(colorless oil, 717.00 mg, 1.47 mmol,
75%, alpha : beta = 1 : 0.33). Rf 0.63 (5:1, 60 - 90 oC petroleum
ether – EtOAc); HPLC tR 4.33 min; NMR data was resolved
1
separately for each anomer: For alpha-anomer: H NMR (500
4.2.11. ((2R,3R)-3-(benzoyloxy)-4,4-difluoro-5-((phenylsulfonyl)-
oxy)tetrahydrofuran-2-yl)methyl benzoate (10d)
MHz, CDCl3) δ 8.16 (d, J = 8.0 Hz, 2H, ArH), 8.05 (d, J = 8.0
Hz, 2H, ArH), 7.68 – 7.37 (m, 6H, ArH), 6.92 (d, J = 11.1 Hz,
1H, H-1), 5.57 (dd, J = 17.1, 4.7 Hz, 1H, H-3), 4.83 – 4.64 (m,
3H, H-5a, H-5b, H-4); 13C NMR (126 MHz, CDCl3) δ 166.03
(C=O), 165.17 (C=O), 134.22 (ArC), 133.57 (ArC), 130.38 (ArC
x 2), 129.94 (ArC x 2), 129.34 (ArC), 128.84 (ArC x 2), 128.63
(ArC x 2), 128.32 (ArC), 121.47 (dd, JC - F = 270.7, 253.8 Hz, C-
2), 83.17 (C-4), 71.90 (dd, JC - F = 38.2, 17.7 Hz, C-3), 67.33 –
64.33 (m, C-1), 61.88 (C-5); 19F NMR (471 MHz, CDCl3) δ -
100.55 (ddd, J = 236.8, 16.9, 10.9 Hz), -105.05 (d, J = 236.4 Hz);
10a
To a solution of 9
(800 mg, 2.11 mmol, 1.00 equiv.) solution
in DCM (20 mL) at RT was added TEA (0.44 mL, 3.17 mmol,
1.5 equiv.) and benzenesulfonyl chloride (0.32 mL, 2.54 mmol,
1.20 equiv.). The mixture was then stirred at RT for 3 h,
concentrated, and purified by flash chromatography on silica gel
(10:1, 60 - 90 oC petroleum ether – EtOAc) to give 10d (colorless
oil, 910 mg, 1.76 mmol, 83%, alpha : beta = 1 : 5.6). Rf 0.63
1
o
For beta-anomer: H NMR (500 MHz, CDCl3) δ 8.08 (d, J = 7.9
(2:1, 60 - 90 C petroleum ether – EtOAc); HPLC tR 4.00 min;
Hz, 2H, ArH), 8.05 (d, J = 8.0 Hz, 2H, ArH), 7.68 – 7.37 (m, 6H,
ArH), 6.73 (d, J = 11.1 Hz, 2.0 Hz, 1H, H-1), 6.24 – 6.14 (m, 1H,
H-3), 4.83 – 4.64 (m, 3H, H-5a, H-5b, H-4); 13C NMR (126
MHz, CDCl3) δ 166.06 (C=O), 164.91 (C=O), 134.25 (ArC),
133.46 (ArC), 130.27 (ArC x 2), 130.06 (ArC x 2), 129.44 (ArC),
128.80 (ArC x 2), 128.53 (ArC x 2), 128.21 (ArC), 121.47 (dd,
JC - F = 270.7, 253.8 Hz, C-2), 81.14 (d, JC - F = 6.7 Hz, C-4),
70.16 (dd, JC - F = 28.1, 16.4 Hz, C-3), 62.17 (C-5), 61.57 (C-1);
19F NMR (471 MHz, CDCl3) δ -106.12 (dd, J = 226.5, 6.3 Hz), -
121.20 (dt, J = 227.2, 11.7 Hz); HRMS (ESI+) calcd. For
NMR data was resolved separately for each anomer: For alpha-
anomer: H NMR (400 MHz, CDCl3) δ 8.07 – 7.93 (m, 4H,
1
ArH), 7.83 (d, J = 8.4 Hz, 2H, ArH), 7.68 – 7.37 (m, 9H, ArH),
6.11 (d, J = 5.6 Hz, 1H, H-1), 5.45 (dd, J = 16.4, 4.2 Hz, 1H, H-
3), 4.58 (dd, J = 12.5, 3.4 Hz, 1H, H-5a), 4.48 (dd, J = 6.6, 4.2
Hz, 1H, H-4), 4.41 (m, H-5b); 13C NMR (126 MHz, CDCl3) δ
165.95 (C=O), 165.06 (C=O), 137.23 (ArC), 134.42 (ArC),
134.24 (ArC), 133.59 (ArC), 130.19 (ArC x 2), 129.90 (ArC x 2),
129.43 (ArC x 2), 129.28 (ArC), 128.82 (ArC x 2), 128.60 (ArC
x 2), 128.22 (ArC), 127.91 (ArC x 2), 122.62 (dd, JC - F = 270.8,
253.5 Hz, C-2), 99.64 (m, C-1), 82.55 (d, JC - F = 2.7 Hz, C-4),
71.00 (m, C-3), 62.56 (C-5). 19F NMR (471 MHz, CDCl3) δ -
108.51 (ddd, J = 255.2, 16.6, 6.2 Hz), -123.34 (d, J = 255.0 Hz);
+
C19H16IF2O5 489.0005, found 488.9994.
4.2.10. ((2R,3R)-3-(benzoyloxy)-4,4-difluoro-5-(tosyloxy)-
tetrahydrofuran-2-yl)methyl benzoate (10c)
1
For beta-anomer: H NMR (400 MHz, CDCl3) δ 8.07 – 7.93 (m,
4H, ArH), 7.83 (d, J = 8.4 Hz, 2H, ArH), 7.68 – 7.37 (m, 9H,
ArH), 6.08 (d, J = 6.4 Hz, 1H, H-1), 5.84 (dt, J = 14.6, 7.1 Hz,
1H, H-3), 4.52 (dd, J = 6.6, 4.2 Hz, 1H, H-4), 4.37 (dd, J = 12.3,
3.4 Hz, 1H, H-5a), 4.21 (dd, J = 12.4, 4.9 Hz, 1H, H-5b); 13C
NMR (126 MHz, CDCl3) δ 165.75 (C=O), 164.91 (C=O), 136.84
(ArC),134.41 (ArC), 134.28 (ArC), 133.52 (ArC), 130.25 (ArC x
2), 129.94 (ArC x 2), 129.31 (ArC x 2), 129.28 (ArC), 128.79
(ArC x 2), 128.60 (ArC x 2), 128.05 (ArC), 128.03 (ArC x 2),
122.62 (dd, JC - F = 270.8, 253.5 Hz, C-2), 99.00 (dd, JC - F = 41.6,
10a
To a solution of 9
(800 mg, 2.11 mmol, 1.00 equiv.) solution
in DCM (20 mL) at RT was added TEA (0.44 mL, 3.17 mmol,
1.5 equiv.) and TsCl (484 mg, 2.54 mmol, 1.20 equiv.). The
mixture was then stirred at RT for 3 h, concentrated, and purified
by flash chromatography on silica gel (10:1, 60 - 90 oC petroleum
ether – EtOAc) to give 10c (colorless oil, 1036 mg, 1.95 mmol,
92%, alpha : beta = 1 : 9.1). Rf 0.67 (2:1, 60 - 90 C petroleum
ether – EtOAc); HPLC tR 4.12 min; NMR data was resolved
separately for each anomer: For alpha-anomer: H NMR (500
MHz, CDCl3) δ 8.02 – 7.99 (m, 4H, ArH), 7.84 (d, J = 8.4 Hz,
2H, ArH), 7.65 – 7.54 (m, 2H, ArH), 7.43 (dt, J = 20.1, 7.8 Hz,
4H, ArH), 7.29 (d, J = 8.0 Hz, 2H, ArH), 6.10 – 6.07 (m, 1H, H-
1), 5.46 (dd, J = 16.3, 4.2 Hz, 1H, H-3), 4.59 (dd, J = 12.4, 3.6
Hz, 1H, H-5a), 4.55 – 4.49 (m, 1H, H-5b), 4.44 (q, J = 4.1 Hz,
o
1
25.3 Hz, C-1), 79.57 (d, JC - F = 7.7 Hz, C-4), 69.87 (dd, JC - F
=
25.9, 15.6 Hz, C-3), 63.44 (C-5); 19F NMR (471 MHz, CDCl3) δ -
121.36 (dd, J = 240.5, 7.1 Hz), -124.28 (ddd, J = 240.6, 15.6, 6.6
Hz); HRMS (ESI+) calcd. For C25H21F2O8S+ 519.0920, found
519.0917.
6