Fast and Efficient Preparation of an α-Fucosyl Building Block by Reductive 1,2-Benzylidene Ring-Opening Reaction

Abstract

1,2-Benzylidene ring opening on fucose was promoted in the presence of different reducing agents and Lewis acids, providing a fast access to fucosyl building blocks.

Key words

carbohydrates - fucose - building block - protecting group - benzylidene

References and Notes

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17

3,4-Di- O -benzoyl-1,2- O -benzylidene-α- l -fuco-pyranose (6)
To a stirred solution of fucosyl bromide 5 (16.9 g, 31.3 mmol, 1.00 equiv) in abs. MeCN (106 mL) was added dry KI (7.46 g, 44.9 mmol, 1.43 equiv) and NaBH₄ (1.13 g, 29.9 mmol, 0.96 equiv). The mixture was stirred for 2.5 h. Then more NaBH₄ (1.13 g, 29.9 mmol, 0.96 equiv) was added. After a total reaction time of 5 h, the solvent was removed. The residue was dissolved in EtOAc, washed with ice water, cold sat. NaHCO₃ solution, and twice with brine. The mixture was dried (Na₂SO₄), concentrated, and the residue purified by column chromatography (SiO₂; pentane-EtOAc, 5:1) to afford 10.2 g (71%) of 6 as a colorless foam.
Analytical Data of the exo -Product
IR (KBr): 2985, 1727, 1602, 1452, 1280 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.31 (d, J = 6.2 Hz, 3 H), 4.51 (dd, J = 6.9, 5.2 Hz, 1 H), 4.53 (m, 1 H), 5.51 (dd, J = 6.8, 3.5 Hz, 1 H), 5.64 (dd, J = 3.4, 1.6 Hz, 1 H), 5.91 (d, J = 5.1 Hz,
1 H), 6.04 (s, 1 H), 7.31-7.65 (m, 11 H), 7.93 (m, 2 H), 8.03 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 16.4, 67.8, 69.5, 71.9, 72.9, 98.8, 101.9, 126.3, 128.2, 128.6, 129.4, 129.6, 129.7, 133.2, 133.4, 137.7, 165.6, 165.7. ESI-HRMS: m/z calcd for C₂₇H₂₄O₇Na: 483.14142; found: 483.14160.

18

3,4-Di- O -benzoyl-2- O -benzyl-α/β-l-fucopyranose (7)
To a stirred solution of benzylidene fucose 6 (161 mg, 0.35 mmol, 1.0 equiv) in abs. THF (2 mL) BH₃×THF (0.53 mL, 0.53 mmol, 1.5 equiv) was added at r.t., then Bu₂BOTf
(52 µL, 0.053 mmol, 0.15 equiv). The mixture was stirred for 1-2 h. Water was added and the reaction mixture was extracted with EtOAc. The organic phase was dried (Na₂SO₄), concentrated, and the residue purified by column chromatography (SiO₂; pentane-EtOAc, 3:1 to 2:1) to afford 72 mg (45%) of 7 and 70 mg (43%) of 8 as a colorless foam. The two products were easily separable (7 is much more polar than 8).
Analytical Data of the Anomeric Mixture (1:1) of 7
IR (film): 3434, 2936, 1726, 1602, 1453, 1283 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.19 (d, J = 6.1 Hz, 3 H), 1.27 (d, J = 6.1 Hz, 3 H), 3.38 (br s, 1 H), 3.84 (m, 2 H), 3.98 (q, J = 6.1 Hz, 1 H), 4.11 (dd, J = 7.4, 3.3 Hz, 1 H), 4.55 (q, J = 6.1 Hz, 1 H), 4.72 (d, J = 7.4 Hz, 1 H), 4.86 (d, J = 7.4 Hz, 1 H), 4.90 (m, 1 H), 5.39 (dd, J = 7.4, 3.3 Hz, 1 H), 5.43 (m, 1 H), 5.58 (m, 1 H), 5.64 (m, 1 H), 5.75 (dd, J = 7.4, 3.3 Hz, 1 H), 7.11-7.37 (m, 14 H), 7.40-7.55 (m, 6 H), 7.60 (m, 2 H), 7.81 (m, 4 H), 7.99 (m, 4 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 16.1, 16.3, 65.1, 69.5, 70.5, 71.5, 72.3, 73.1, 73.7, 74.6, 77.4, 91.7, 97.5, 127.6, 128.0, 128.1, 128.2, 128.2, 128.3, 128.4, 128.5, 129.6, 129.7, 129.8, 129.9, 133.0, 133.0, 133.2, 133.3, 137.3, 137.8, 165.6, 165.9, 165.9. ESI-HRMS: m/z calcd for C₂₇H₂₆O₇Na: 485.15707; found: 485.15705.

20

Analytical Data of the α-Anomer
[α]_D ^²0 -148.4 (c 1.90, CDCl₃). IR (film): 2943, 2867, 1733, 1672, 1464, 1278 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.24 (d, J = 6.1 Hz, 3 H), 4.29 (dd, J = 7.8, 3.4 Hz, 1 H), 4.55 (m, 1 H), 4.61 (d, J = 7.8 Hz, 1 H), 4.69 (d, J = 7.8 Hz, 1 H), 4.75-5.81 (m, 2 H), 6.68 (d, J = 3.4 Hz, 1 H), 7.23-7.33 (m, 7 H), 7.43-7.49 (m, 3 H), 7.62 (m, 1 H), 7.80 (m,
2 H), 7.94 (m, 2 H), 8.66 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 16.2, 67.8, 70.3, 71.7, 72.3, 72.6, 91.2, 94.5, 127.8, 127.9, 127.9, 128.0, 128.2, 128.3, 128.5, 129.4, 129.5, 129.6, 129.7, 133.0, 133.3, 137.4, 161.4, 165.5, 165.7. ESI-HRMS: m/z calcd for C₂₉H₂₆Cl₃NO₇Na: 628.06725; found: 628.06734.