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Synlett 2003(6): 0870-0872
DOI: 10.1055/s-2003-38751
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Zinc-Mediated Synthesis of α-C-Glycosides from 1,2-Anhydroglycosides

Song Xue*, Kai-Zhen Han, Lin He, Qing-Xiang Guo
Department of Chemistry, University of Science and Technology of China, Hefei, 230026, P.R.China
e-Mail: xuesong@ustc.edu.cn;
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Publikationsverlauf

Received 24 February 2003
Publikationsdatum:
17. April 2003 (online)

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Abstract

α-C-Glycosides have been prepared by the addition of organozinc reagents to glycal epoxides. Dialkyl and diaryl zinc reagents in the presence of CF3COOH provide the corresponding α-glycosides in 53-82% yields. Organozinc chlorides RZnCl formed by the reaction RLi with zinc chloride can also be successfully applied to this coupling reaction with high α-selectivity.

Key words

α-C-glycosides - epoxide - organozinc reagents - stereoselectivity - trifluoroacetic acid

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General Procedure for Preparation of α- C -Glycosides. To a solution of tri-O-benzyl-d-glucal (42 mg, 0.1 mmol) and 1.5 mL of CH2Cl2 at 0 °C was added a solution of dimethyldioxirane (0.15 mmol) in actone dropwise. After stirring for 30 min, the reaction mixture was concentrated in vacuum. The resulting white solid was taken up in CH2Cl2 (1.0 mL). To another solution of ZnR2 (0.2 mmol, 2 equiv) in 1 mL of CH2Cl2 at 0 °C was added CF3COOH (15 µL, 0.2 mmol, 2 equiv) very slowly via syringe under N2. After stirring for 30 min, to this solution was added the solution of epoxide dropwise via syringe. The mixture was stirred for 3-5 h from 0 °C to r.t. The reaction was quenched with sat. aq NH4Cl and extracted with CH2Cl2 (3 ¥ 10 mL). The combined organic solution was washed with brine, dried (MgSO4), and concentrated. Then, the product was isolated by silica gel column chromatography. Acetylated 3a: Mp 55-56 °C. 1H NMR (400 MHz, CDCl3): δ = 7.33-7.27 (m, 13 H), 7.16 (m, 2 H), 5.05 (dd, J = 8.8, 5.5 Hz, 1 H), 4.77 (d, J = 11.5 Hz, 1 H), 4.74 (d, J = 9.5 Hz, 1 H), 4.71 (d, J = 11.2 Hz, 1 H), 4.63 (d, J = 12.2 Hz, 1 H), 4.52 (d, J = 10.3 Hz, 1 H), 4.50 (d, J = 10.9 Hz, 1 H), 4.02 (m, 1 H), 3.82 (m, 1 H), 3.71-3.65 (m, 4 H), 1.99 (s, 3 H), 1.70 (m, 1 H), 1.48 (m, 1 H), 0.94 (t, J = 7.4 Hz, 3 H). 13C NMR (400 MHz, CDCl3): δ = 170.1, 138.4, 138.2, 138.0, 128.4, 128.3, 128.0, 127.8, 127.7, 127.6, 80.2, 77.7, 74.7, 74.6, 73.7, 73.5, 73.1, 71.6, 69.0, 20.9, 19.1, 9.6. HRMS (FAB+) calcd for C31H36O6: 505.2590 [MH+]. Found: 505.2585. Acetylated 3e: Mp 62-63 °C. 1H NMR (400 MHz, CDCl3): δ = 7.33-7.26 (m, 13 H), 7.15 (m, 2 H), 5.05 (dd, J = 8.6, 5.3 Hz, 1 H), 4.76 (d, J = 11.5 Hz, 1 H), 4.74 (d, J = 10.4 Hz, 1 H), 4.71 (d, J = 9.8 Hz, 1 H), 4.61 (d, J = 12.1 Hz, 1 H), 4.52 (d, J = 12.0 Hz, 1 H), 4.49 (d, J = 10.8 Hz, 1 H), 4.11 (m, 1 H), 3.82 (m, 1 H), 3.72-3.65 (m, 4 H), 3.51 (t, J = 6.6 Hz, 2 H), 1.99 (s, 3 H), 1.80-1.77 (m, 3 H), 1.55 (m, 1 H), 1.43-1.40 (m, 2 H). 13C NMR (400 MHz, CDCl3): δ = 170.1, 138.4, 138.1, 137.9, 129.7, 128.4, 128.3, 127.9, 127.8, 127.7, 127.6, 80.0, 77.5, 74.7, 74.6, 73.5, 72.9, 71.9, 68.9, 44.8, 32.2, 25.4, 22.6, 20.9. HRMS (FAB+) calcd for C33H39O6Cl: 567.2513 [MH+]. Found: 567.2500. Acetylated 3f: Mp 77-78 °C. 1H NMR (400 MHz, CDCl3): δ = 7.27-7.10 (m, 13 H), 7.10 (m, 2 H), 4.98 (dd, J = 8.7, 5.4 Hz, 1 H), 4.71 (d, J = 11.8 Hz, 1 H), 4.67 (d, J = 10.7 Hz, 1 H), 4.65 (d, J = 11.1 Hz, 1 H), 4.55 (d, J = 12.1 Hz, 1 H), 4.46 (d, J = 11.9 Hz, 1 H), 4.44 (d, J = 10.9 Hz, 1 H), 4.09-3.94 (m, 3 H), 3.74 (m, 1 H), 3.66-3.59 (m, 4 H), 1.96 (s, 3 H), 1.93 (s, 3 H), 1.71-1.51 (m, 4 H), 1.47-1.26 (m, 2 H). 13C NMR (400 MHz, CDCl3): δ = 171.2, 170.1, 138.4, 138.2, 138.1, 128.5, 128.4, 128.1, 127.9, 127.8, 127.7, 127.6, 80.1, 77.6, 74.8, 74.7, 73.6, 73.1, 72.1, 72.0, 69.0, 64.3, 29.8, 28.4, 25.7, 21.8, 21.0. HRMS (FAB+) calcd for C35H42O8: 591.2958 [MH+]. Found: 591.2952. Acetylated 3h: Mp 70-71 °C. 1H NMR (300 MHz, CDCl3): δ = 7.38 (m, 2 H), 7.29-7.19 (m, 16 H), 7.08 (m, 2 H), 5.13 (d, J = 5.7 Hz, 1 H), 4.91 (dd, J = 9.9, 5.7 Hz, 1 H), 4.81-4.71 (m, 3 H), 4.58 (d, J = 12.0 Hz, 1 H), 4.48 (d, J = 10.8 Hz, 1 H), 4.46 (d, J = 12.3 Hz, 1 H), 3.98 (m, 2 H), 3.71-3.63 (m, 3 H), 1.96 (s, 3 H). 13C NMR (300 MHz, CDCl3): δ = 170.2, 138.7, 138.2, 138.1, 132.1, 128.6, 128.5, 128.2, 128.1, 127.9, 127.8, 122.3, 89.6, 83.2, 81.4, 77.9, 75.5, 75.4, 74.2, 73.7, 72.8, 68.8, 66.3, 21.1. IR (KBr): ν = 2909, 2228, 1741, 1454, 1238, 1099, 1041 cm-1. HRMS (FAB+) calcd for C37H36O6: 599.2409 [MNa+]. Found: 599.2408.

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For ZnCl2 mediated acetylide anion additions to glycal epoxides with α-selectivity, see ref. [11a]

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For comparison, the reaction of n-butylmagnesium chloride with epoxide 2 in THF from -78 °C to 0 °C gave a 45:55 mixture of α- and β-C-glycoside.