Iodoetherification of Isosorbide-Derived Glycals
(2R,3R,3aS,6R,6aR)-6-(Benzyloxy)-2-[(3S,3aR,6R,6aR)-6-(benz-
(C-6a), 90.2 (C-3a), 108.0 (C-2), 127.7 (CHAr), 127.8 (CHAr), 128.3
yloxy)-hexahydrofuro[3,2-b]furan-3-yloxy]-3-iodo-hexahydrofuro- (CHAr), 137.7 (CAr) ppm. HRMS (ESI+) calcd. for C17H23IO4Na:
[3,2-b]furan (3ak): The title compound was prepared according to
the above general procedure from glycal 4a (218 mg, 1.00 mmol),
5-O-benzyl isosorbide 7k (500 mg, 2.1 mmol) and NIS (472 mg,
2.1 mmol) in CH2Cl2 (10 mL) affording the corresponding β-iodo
ether 3ak as a white solid (350 mg, 0.60 mmol, 60%), m.p. 129–
441.05333, found 441.05276 [M + Na]+.
(2R,3R,3aS,6R,6aR)-2,6-Bis(benzyloxy)-3-iodo-hexahydrofuro-
[3,2-b]furan [Benzyl 3,6-Anhydro-2-iodo-5-O-(benzyloxy)-β-D-gluco-
furanoside] (3an): The title compound was prepared according to
the above general procedure from glycal 4a (218 mg, 1.00 mmol),
benzyl alcohol 7n (220 μL, 2.1 mmol) and NIS (472 mg, 2.1 mmol)
in CH2Cl2 (10 mL) affording the corresponding β-iodo ether 3an
as a yellow oil (398 mg, 0.88 mmol, 88%). [α]2D0 = –39.3 (c = 0.99,
130 °C. [α]2D0 = +48.8 (c = 1.01, CHCl ). IR (ATR diamond): ν =
˜
3
3080, 3060, 3020, 2970, 2950, 2870, 1110, 1060, 1010, 750 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 3.59 (app. t, J = 8.3 Hz, 1 H, 5Јa-
H), 3.84 (dd, J = 8.7, 6.6 Hz, 1 H, 5Јb-H), 3.90–4.11 (m, 5 H, 5-H,
6-H, 2Јa-H, 6Ј-H), 4.14 (s, 1 H, 3-H), 4.26–4.33 (m, 2 H, 2Јb-H, 3Ј-
H), 4.49 (d, J = 4.4 Hz, 1 H, 3aЈ-H), 4.52–4.57 (m, 2 H, Ha and
HaЈ of CH2Ph), 4.63 (app. d, J = 4.5 Hz, 1 H, 6aЈ-H), 4.72–4.78 (m,
2 H, Hb and HbЈ of CH2Ph), 4.91 (app. d, J = 4.4 Hz, 1 H, 3a-H),
4.99 (app. t, J = 4.4 Hz, 1 H, 6a-H), 5.66 (s, 1 H, 2-H), 7.29–7.36
(m, 10 H, HAr) ppm. 13C NMR (75 MHz, CDCl3): δ = 29.5 (C-3),
69.8 (C-5), 69.8 (C-5Ј), 71.9 (CH2Ph), 72.2 (CH2Ph), 73.5 (C-2Ј),
78.1 (C-6), 78.9 (C-6Ј), 80.0 (C-6aЈ), 81.6 (C-6a), 82.9 (C-3Ј), 86.0
(C-3aЈ), 90.1 (C-3a), 112.6 (C-2), 127.7 (CHAr), 127.8 (CHAr), 128.3
(CHAr), 128.3 (CHAr), 137.0 (CAr), 137.6 (CAr) ppm. HRMS (ESI+)
calcd. for C26H29IO7Na: 603.08502, found 603.08538 [M + Na]+.
CHCl ). IR (ATR diamond): ν = 3080, 3060, 3030, 2960, 2900,
˜
3
2870, 1450, 1100, 1050, 1010, 940, 740 cm–1. H NMR (300 MHz,
1
CDCl3): δ = 3.97–3.99 (m, 2 H, 5-H), 4.06–4.13 (m, 1 H, 6-H), 4.22
(s, 1 H, 3-H), 4.70 (ABq, JA,B = 11.5 Hz, ΔA,B = 72.1 Hz, 2 H,
CH2Ph), 4.72 (ABq, JA,B = 11.6 Hz, ΔA,B = 105.1 Hz, 2 H,
CH2Ph), 4.97 (app. d, J = 4.5 Hz, 1 H, 3a-H), 5.05 (app. t, J =
4.6 Hz, 1 H, 6a-H), 5.60 (s, 1 H, 2-H), 7.29–7.42 (m, 10 H, HAr
)
ppm. 13C NMR (75 MHz, CDCl3): δ = 30.0 (C-3), 69.6 (CH2Ph),
70.0 (C-5), 72.1 (CH2Ph), 78.3 (C-6), 81.5 (C-6a), 90.5 (C-3a), 111.3
(C-2), 127.8 (CHAr), 127.9 (CHAr), 127.9 (CHAr), 128.2 (CHAr),
128.4 (CHAr), 128.5 (CHAr), 136.8 (CAr), 137.6 (CAr) ppm. HRMS
(ESI+) calcd. for C20H21IO4Na: 475.03768, found 475.03734 [M +
Na]+.
(2R,3R,3aS,6R,6aR)-6-(Benzyloxy)-2-[(3S,3aR,6R,6aR)-6-(do-
decyloxy)-hexahydrofuro[3,2-b]furan-3-yloxy]-3-iodo-hexahydrofuro- (2S,3R,3aS,6R,6aR)-6-(Benzyloxy)-3-iodo-2-phenoxy-hexahydro-
[3,2-b]furan (3al): The title compound was prepared according to
the above general procedure from glycal 4a (218 mg, 1.00 mmol),
5-O-docedyl isosorbide 7l (660 mg, 2.1 mmol) and NIS (472 mg,
2.1 mmol) in CH2Cl2 (10 mL) affording the corresponding β-iodo
ether 3al as a yellow oil (436 mg, 0.66 mmol, 66%). [α]2D0 = +32.2
furo[3,2-b]furan [Phenyl 3,6-Anhydro-2-iodo-5-O-(benzyloxy)-β-D-
glucofuranoside] (3ao): The title compound was prepared according
to the above general procedure from glycal 4a (218 mg, 1.00 mmol),
phenol 7o (200 mg, 2.1 mmol) and NIS (472 mg, 2.1 mmol) in
CH2Cl2 (10 mL) affording the corresponding β-iodo ether 3ao as a
(c = 1.00, CHCl ). IR (ATR diamond): ν = 3080, 3060, 3030, 2930,
white solid (240 mg, 0.54 mmol, 54%), m.p. 112–113 °C. [α]2D0
=
˜
3
2860, 1450, 1370, 1320, 1200, 1110, 1070, 1050, 1020, 740 cm–1. 1H
–3.6 (c = 1.00, CHCl ). IR (ATR diamond): ν = 3080, 3070, 3030,
˜
3
NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 6.7 Hz, 3 H, CH3), 1.25 2960, 2900, 2860, 1600, 1500, 1220, 1150, 1090, 1010, 750 cm–1. 1H
(br. s, 18 H, CH2), 1.59 (s, 2 H, CH2), 3.39–3.47 (m, 1 H, Ha of
CH2O), 3.53–3.59 (m, 1 H, 5Јa-H), 3.62–3.69 (m, 1 H, Hb of
CH2O), 3.89–4.09 (m, 6 H, 5-H, 6-H, 2Јa-H, 5Јb-H, 6Ј-H), 4.14 (s,
1 H, 3-H), 4.22 (dd, J = 10.3, 1.9 Hz, 1 H, 2Јb-H), 4.31–4.33 (m, 1
H, 3Ј-H), 4.51–4.55 (m, 1 H, 3aЈ-H), 4.60 (app. t, J = 4.3 Hz, 1 H,
6aЈ-H), 4.63 (ABq, JA,B = 11.6 Hz, ΔA,B = 58.6 Hz, 2 H, CH2Ph),
NMR (300 MHz, CDCl3): δ = 4.01–4.16 (m, 3 H, 5-H and 6-H),
4.42 (s, 1 H, 3-H), 4.61 (ABq, JA,B = 11.6 Hz, ΔA,B = 68.2 Hz, 2
H, CH2Ph), 5.02 (app. d, J = 4.3 Hz, 1 H, 3a-H), 5.11 (app. t, J =
4.1 Hz, 1 H, 6a-H), 6.13 (s, 1 H, 2-H), 7.01–7.13 (m, 3 H, HAr),
7.19–7.33 (m, 7 H, HAr) ppm. 13C NMR (75 MHz, CDCl3): δ =
29.5 (C-3), 70.1 (C-5), 71.9 (CH2Ph), 78.1 (C-6), 82.3 (C-6a), 90.0
4.91 (app. d, J = 4.4 Hz, 1 H, 3a-H), 4.98 (app. t, J = 4.4 Hz, 1 H, (C-3a), 111.0 (C-2), 117.1 (CHAr), 122.4 (CHAr), 127.7 (CHAr),
6a-H), 5.66 (s, 1 H, 2-H), 7.30–7.37 (m, 5 H, HAr) ppm. 13C NMR 127.7 (CHAr), 128.3 (CHAr), 129.4 (CHAr), 137.5 (CAr), 156.4 (CAr
)
(75 MHz, CDCl3): δ = 14.1 (CH3), 22.7 (CH2), 25.9 (CH2), 29.3 ppm. HRMS (ESI+) calcd. for C19H19IO4Na: 461.02203, found
(CH2), 29.4 (CH2), 29.5 (C-3), 29.6 (CH2), 29.6 (CH2), 29.6 (CH2), 461.02157 [M + Na]+.
29.6 (CH2), 29.7 (CH2), 31.9 (CH2), 69.7 (C-5Ј), 70.0 (C-5), 71.0
(CH2O), 72.1 (CH2Ph), 73.6 (C-2Ј), 78.2 (C-6), 80.0 (C-6aЈ), 80.2
(C-6Ј), 81.8 (C-6a), 83.1 (C-3Ј), 86.2 (C-3aЈ), 90.3 (C-3a), 112.7 (C-
2), 127.9 (CHAr), 127.9 (CHAr), 128.5 (CHAr), 137.4 (CAr) ppm.
HRMS (ESI+) calcd. for C31H47IO7Na: 681.22587, found
681.22504 [M + Na]+.
(2S,3R,3aS,6R,6aR)-6-(Benzyloxy)-3-iodo-hexahydrofuro[3,2-b]-
furan-2-yl Acetate [3,6-Anhydro-5-O-(benzyloxy)-2-deoxy-2-iodo-β-
D-arabinohexofuranose Acetate] (3ap): The title compound was pre-
pared according to the above general procedure from glycal 4a
(218 mg, 1.00 mmol), acetic acid 7p (288 μL, 5.00 mmol) and NIS
(472 mg, 2.10 mmol) in CH2Cl2 (10 mL) affording the correspond-
ing β-iodo ether 3ap as a yellow oil (349 mg, 0.86 mmol, 86%).
(2S,3R,3aS,6R,6aR)-6-(Benzyloxy)-2-(tert-butoxy)-3-iodo-hexa-
hydrofuro[3,2-b]furan [tert-Butyl 3,6-Anhydro-2-iodo-5-O-(benz-
yloxy)-β-D-glucofuranoside] (3am): The title compound was pre-
pared according to the above general procedure from glycal 4a
(218 mg, 1.00 mmol), tert-butanol 7m (200 μL, 2.1 mmol) and NIS
(472 mg, 2.1 mmol) in CH2Cl2 (10 mL) affording the corresponding
β-iodo ether 3am as a yellow oil (246 mg, 0.59 mmol, 59%). [α]2D0
[α]2D0 = +47.6 (c = 1.01, CHCl ). IR (ATR diamond): ν = 3090,
˜
3
3060, 3030, 2990, 2900, 2860, 1750, 1450, 1370, 1230, 1210, 1100,
1
1040, 1000, 980, 930 cm–1. H NMR (300 MHz, CDCl3): δ = 2.06
(s, 3 H, CH3), 3.93–4.16 (m, 3 H, 5-H and 6-H), 4.26 (s, 1 H, 3-
H), 4.65 (ABq, JA,B = 11.7 Hz, ΔA,B = 65.4 Hz, 2 H, CH2Ph), 4.94
(app. d, J = 4.1 Hz, 1 H, 3a-H), 5.05 (app. t, J = 4.3 Hz, 1 H, 6a-
H), 6.59 (s, 1 H, 2-H), 7.30–7.37 (m, 5 H, HAr) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.0 (CH3), 28.0 (C-3), 70.3 (C-5), 72.2
(CH2Ph), 77.7 (C-6), 82.3 (C-6a), 89.5 (C-3a), 105.9 (C-2), 127.9
(CHAr), 127.9 (CHAr), 128.4 (CHAr), 137.2 (CAr), 169.4 (C=O)
ppm. HRMS (ESI+) calcd. for C15H17IO5Na: 427.00129, found
427.00111 [M + Na]+.
= +15.8 (c = 1.00, CHCl ). IR (ATR diamond): ν = 3090, 3060,
˜
3
3030, 2970, 2930, 2890, 2860, 1370, 1100, 1060, 1000, 750 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 1.28 (s, 9 H, CH3), 3.96–4.06 (m, 2
H, 5a-H and 6-H), 4.08 (s, 1 H, 3-H), 4.13–4.18 (m, 1 H, 5b-H),
4.65 (ABq, JA,B = 11.5 Hz, ΔA,BB = 74.2 Hz, 2 H, CH2Ph), 4.89–
4.94 (m, 2 H, 3a-H and 6a-H), 5.75 (s, 1 H, 2-H), 7.28–7.38 (m, 5
H, HAr) ppm. 13C NMR (75 MHz, CDCl3): δ = 28.6 (CH3), 31.9 (3R,3aR,5R,6R,6aS)-6-Iodo-5-methoxy-hexahydrofuro[3,2-b]furan-
(C-3), 69.7 (C-5), 71.8 (CH2Ph), 75.6 [C(CH3)3], 78.5 (C-6), 80.7 3-yl Acetate [Methyl 3,6-Anhydro-2-deoxy-2-iodo-β-
D-arabinohexo-
Eur. J. Org. Chem. 2013, 1937–1949
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1945