Full Papers
doi.org/10.1002/ejoc.202100042
128.3(6), 128.4, 128.5, 128.6, 128.7, 129.0, 129.8, 129.9, 130.0(0),
130.0(5), 130.0(8), 130.5, 133.6, 133.7, 133.8, 133.9, 134.0. LRMS: m/z
601.8 [M+H]+; HRMS: calcd for C28H22BrFO9Na 623.0329 found
623.0314 [M+Na]+.
128.2, 128.3, 128.4, 128.5(0), 128.5(3), 128.5(8), 129.7, 129.9(6),
1
2
3
1
129.9(9), 130.1, 130.2, 164.1, 164.5, 165.1(2), 165.1(9), 165.3. The H
and 13C NMR spectra were in accord with the literature.[32] LRMS: m/
z 802.6 [M+Na]+.
4
5
6
7
8
2,3,4,6-Tetra-O-acetyl-5-C-bromo-
β-D-glucopyranosyl fluoride – 5
General procedure for tributyltin hydride reduction
The substrate (1 eq.) was dissolved in anhydrous toluene (40 mM)
and stirred under Ar(g). Bu3SnH (1.0 M in hexanes, 1.5 eq.) and Et3B
(1.0 M in hexanes, 0.1 eq.) were added and the solution was stirred
at r.t. until complete consumption of starting material was
confirmed by TLC. The product mixture was concentrated under
reduced pressure before the resulting crude residue was dissolved
in acetonitrile and washed with hexane (3x). The acetonitrile phase
was then concentrated, and an aliquot was subjected to analysis by
1H NMR spectroscopy.
The glucosyl fluoride 12 (215 mg, 0.61 mmol) was brominated
according to the general procedure (2 h) to afford 21 mg (8%) of
the 5-C-bromide 5 as a colourless oil, after purification by flash
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
chromatography (8:1 PhMe:EtOAc). ½a� 23 =À 58.1 (c. 0.26, acetone)
D
1
lit.[20] À 109. H NMR (500 MHz, CDCl3): δ 2.02 (CH3), 2.09 (CH3), 2.11
(CH3), 2.13 (CH3), 4.40 (d, 1H, J6a,6b =12.2 Hz, H-6b), 4.55 (d, 1H, H-
6a), 5.27 (ddd, 1H, J1,2 =7.6 Hz, J2,3 =9.7 Hz, J2,F =14.3 Hz, H-2), 5.29
(d, 1H, J3,4 =9.8 Hz, H-4), 5.53 (dd, 1H, H-3), 5.67 (dd, 1H, J1,F
51.8 Hz, H-1). 13C NMR (125 MHz, CDCl3): δ 20.4(4) (CH3), 20.4(7)
(CH3), 20.4(8) (CH3), 20.5 (CH3), 65.6 (C-6), 68.0 (C-4), 70.4 (d, J2,F
=
=
Methyl (2,3,4-Tri-O-benzoyl-1-deoxy-1-fluoro–
α-L-idopyran)uronate – 16
24.3 Hz, C-2), 70.5 (d, J3,F = 10.4 Hz, C-3), 94.7 (d, J5,F =7.5 Hz, C-5),
106.7 (d, J1,F =220.0 Hz, C-1), 168.9, 169.1, 169.6, 169.7. 19F NMR
1
(470 MHz, CDCl3): δ À 149.8 (dd, J1,F =52.0 Hz, J2,F =14.0 Hz). The H
The mixture of 5-C-bromides 4 and 10 (120 mg, 0.21 mmol) was
reduced according to the general procedure (1 h) to afford an
inseparable mixture of the L-idosyl fluoride 16 and the D-glucosyl
and 13C NMR spectra were in accord with the literature.[20] LRMS:
451.0 [M+Na]+. HRMS: calcd for C14H18BrFO9Na [M+Na]+ 451.0016
found 451.0011 [M+Na]+.
fluoride
9 in a ratio of 2.9:1 (96 mg, 89%, combined), as
1
determined by H NMR spectroscopy, as a white foam. The product
was purified by flash chromatography (80:1 PhMe:EtOAc). Key data
2,3,4,6-Tetra-O-benzoyl-5-C-bromo-
β-D-glucopyranosyl fluoride – 6
1
for 16: H NMR (500 MHz, CDCl3): δ 3.78 (s, 3H, À CH3), 5.26 (d, 1H,
J
4,5 =1.9 Hz, H-5), 5.31 (m, 1H, H-2), 5.61 (m, 1H, H-4), 5.73 (m, 1H, H-
3), 5.99 (ap. d, J1,F =46.9 Hz, H-1). 13C NMR (125 MHz, CDCl3): δ 52.8
The glucosyl fluoride 15 (210 mg, 0.35 mmol) was brominated
according to the general procedure (5 h) to afford 140 mg (61%
isolated, 81% based on recovered starting material) of the bromide
6 as a white foam after purification by flash chromatography
(stepwise gradient 1:1:0.05 hexane:PhMe:EtOAc!1:1:0.1 hexa-
ne:PhMe:EtOAc!EtOAc). Rf 0.38 (1:1:0.05 hexane:PhMe:EtOAc);
(CH3), 64.6 (d, J2,F =38.2 Hz, C-2), 65.3 (C-3), 66.4 (C-4), 67.7 (d, J5,F
=
2.6 Hz, C-5), 104.7 (d, J1,F =227.8 Hz, C-1). 19F NMR (470 MHz, CDCl3):
δ À 136.5 (dd, J1,F =46.1 Hz, J2,F =3.9 Hz). LRMS: m/z 1066.6 [2 M+
Na]+.
½a� 23 = +19.6 (c. 0.19, CHCl3) lit.[31] +23.5; 1H NMR (500 MHz,
D
2,3,4,6-Tetra-O-acetyl-α-L-idopyranosyl fluoride – 17
CDCl3): δ 4.67 (d, 1H, B part of AB system, J6a,6b =12.3 Hz, H-6b), 5.01
(d, 1H, A part of AB system, H-6a), 5.77 (ddd, 1H, J1,2 =7.3 Hz, J2,3
9.3 Hz, J2,F =13.1 Hz, H-2), 5.95 (d, 1H, J3,4 =9.9 Hz, H-4), 5.99 (dd, 1H,
1,F =51.9 Hz, H-1), 6.20 (dd, 1H, H-3), 7.27–7.32 (m, 2H), 7.35–7.47
=
The 5-C-bromide 5 (18 mg, 0.042 mmol) was reduced according to
the general procedure (1 h) to afford an inseparable mixture of the
L-idosyl fluoride 17 and the D-glucosyl fluoride 12 in a ratio of
1:1.4 (11 mg, 75%, combined), as determined by 1H NMR
spectroscopy, as a white foam. The product was purified by flash
chromatography (5:1 PhMe:EtOAc). Key data for 17: 1H NMR
(500 MHz, CDCl3): δ 4.55–4.58 (m, 1H, H-5), 4.89–4.92 (m, 2H, H-2, H-
4), 5.02–5.05 (m, 1H, H-3), 5.57 (ap. d, 1H, J1,F =49.1 Hz, H-1). 13C
NMR (125 MHz, CDCl3): δ 64.8 (d, J2,F =38.0 Hz, C-2), 65.3 (C-4), 65.5
(C-3), 65.9 (d, J5,F =2.7 Hz, C-5), 104.5 (d, J1,F =225.4 Hz, C-1). 19F
NMR (470 MHz, CDCl3): δ À 133.7 (dd, J1,F =48.7 Hz, J2,F =6.1 Hz).
LRMS: m/z 373.3 [M+Na]+.
J
(m, 5H), 7.48–7.64 (m, 5H), 7.80–7.85 (m, 2H), 7.94–7.98 (m, 2H),
8.00–8.05 (m, 2H), 8.10–8.15 (m, 2H). 13C NMR (125 MHz, CDCl3): δ
66.3 (C-6), 69.1 (C-4), 70.8 (d, J3,F =9.8 Hz, C-3), 71.0 (d, J2,F =25.0 Hz,
C-2), 95.5 (d, J5,F =6.7 Hz, C-5), 106.9 (d, J1,F =224.8 Hz, C-1), 128.0,
128.3(2), 128.3(7), 128.4, 128.5(2), 128.5(7), 128.5(8), 128.9, 129.8,
130.0(1), 130.0(5), 130.1, 133.4, 133.5, 133.7, 133.9, 164.4, 164.8,
165.1, 165.3. 19F NMR (470 MHz, CDCl3): δ À 147.5 (dd, J1,F =51.9 Hz,
1
J
2,F =13.1 Hz). The H and 13C NMR spectra were in accord with the
literature.[31] LRMS: m/z 699.0 [M+Na]+.
1,2,3,4,6-Penta-O-benzoyl-5-C-bromo-β-D-glucopyranose – 7
2,3,4,6-Tetra-O-benzoyl-α-L-idopyranosyl fluoride – 18
The perbenzoate 13 (200 mg, 0.29 mmol) was brominated accord-
ing to the general procedure (6 h) to afford 123 mg (51%) of the
bromide 7 as a white foam after purification by flash chromatog-
raphy (stepwise gradient 1:1:0.05 hexane:PhMe:EtOAc!1:1:0.1
hexane:PhMe:EtOAc!EtOAc). The product was observed to
The 5-C-bromide 6 (30 mg, 0.04 mmol) was reduced according to
the general procedure (4 h) to give a mixture of the L-idosyl
fluoride 18 and the D-glucosyl fluoride 15 (25 mg, 94%, combined)
in a ratio of 2.0:1, as determined by 1H NMR spectroscopy. The
product was purified by flash chromatography (stepwise gradient
8:1:0.1 hexane:EtOAc:PhMe!2:1 PhMe:EtOAc!EtOAc) and was
subsequently crystallised from Et2O/hexane. Data for 18: Rf 0.20
°
decompose at r.t. and was therefore stored under Ar(g) at À 20 C. Rf
0.30 (1:1:0.05 hexane:MePh:EtOAc); ½a� 23 =À 13.8 (c. 0.50, CHCl3)
D
1
lit. [32] À 12.0; H NMR (500 MHz, CDCl3): δ 4.70 (d, 1H, B part of AB
(10:1:0.1 hexane:EtOAc:PhMe; m.p. ( C): 140.0–140.5; ½a� 24 =À 2.7
°
D
system, J6a,6b =12.2 Hz, H-6b), 4.95 (d, 1H, A part of AB system, H-
1
(c. 0.1, CHCl3); H NMR (500 MHz, CDCl3): δ 4.57 (dd, B part of ABX,
6a), 5.96 (d, 1H, J3,4 =9.7 Hz, H-4), 5.99 (dd, 1H, J1,2 =8.5 Hz, J2,3
=
1H, J6a,6b =11.7 Hz, J5,6b =5.2 Hz, H-6b), 4.74 (dd, A part of ABX spin
system, 1H, J5,6a =5.1 Hz, H-6a), 5.02 (ddd, 1H, J4,5 =1.4 Hz, H-5),
5.31–5.34 (m, 1H, H-2), 5.44–5.48 (m, 1H, H-4), 5.68–5.72 (m, 1H, H-
3), 5.90 (ap. d, 1H, J1,F =47.6 Hz), 7.17 (m, 2H), 7.38–7.45 (m, 4H),
9.7 Hz, H-2), 6.35 (dd, 1H, H-3), 6.79 (d, 1H, H-1), 7.27–7.62 (m, 15H,
ArÀ H), 7.81–7.85 (m, 2H, ArÀ H), 7.93–7.99 (m, 4H, ArÀ H), 8.02–8.06
(m, 2H, ArÀ H), 8.08–8.11 (m, 2H, ArÀ H). 13C NMR (125 MHz, CDCl3): δ
66.6 (C-6), 69.5 (C-4), 69.9 (C-2), 71.3 (C-3), 92.4 (C-1), 96.6 (C-5),
Eur. J. Org. Chem. 2021, 1575–1584
1583
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