Furanose Synthesis via Regioselective Dihydroxylation of 1-Silyloxy-1,3-dienes: Application to the Furanose Unit of 4-epi-Hygromycin A

Abstract

Asymmetric dihydroxylation of a 1-silyloxy-1,3-diene is shown to occur regioselectively on the non-oxygenated alkene. Second dihydroxylation is complicated by over-oxidation to the dione and epimerisation of reaction products. However, subsequent manipulations including selective oxidation of a primary alcohol allow synthesis of a protected furanose corresponding to that present in C4-epi-hygromycin.

Key words

alkenes - dihydroxylation - osmium - regioselective - oxidations

References

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7

‘Super AD-mix’ refers to commercial AD-mix supplemented with 1 mol% K₂OsO₂(OH)₄, 5 mol% ligand and 1 equiv MeSO₂NH₂. The absolute configuration of 9 is assigned based upon the Sharpless mnemonic. [1] The ee of (Z)-9 was determined using HPLC (Chiralcel OD, 1 mL per min, 5% IPA/hexane, detection at 210 nm, retention times: 11.8 min (minor enantiomer), 27.8 min (major enantiomer). We have been unable to determine the ee of (E)-9.

9

R_f values (20% Et₂O-petroleum Et₂O): 11, 0.85; 10a, 0.21; 10b, 0.14. Characteristic data for dione 11 include carbonyl stretches in the IR spectrum at 1716 and 1675 cm^-1, and ¹³C NMR resonances at δ = 201 and 200 ppm.

13

We have demonstrated that deketalisation of the benzyl ether of 12 regenerates 10a, suggesting that epimerisation has not occurred here. We cannot rule out epimerisation at C4 in the deprotection of 15. However, molecular mechanics (MMFF) indicate that the 16 is 7.7 kcal/mol less stable than its C4-epimer, suggesting that epimerisation is unlikely.
Data for 16: white amorphous solid; mp 79-81 °C; [α]_D ²⁰
-37.5 (c 0.1, CH₂Cl₂). IR (film): ν_max = 2949, 2928, 2857, 1718, 1587, 1490, 1254, 1254 cm^-1. ¹H NMR (250 MHz, CDCl₃) δ = 7.35-7.01 (5 H, m, Ph), 5.82 (1 H, d, J = 3.1 Hz, 2-H), 4.72 (1 H, d, J = 4.4 Hz, 5-H), 4.42 (1 H, dd, J = 2.6 and 4.4 Hz, 4-H), 4.16 (1 H, app. t, J = 3.0 Hz, 3-H), 2.28
(3 H, s, 6-CH₃), 0.95 [9 H, s, SiC(CH₃)₃], 0.86 [9 H, s, SiC(CH₃)₃], 0.15 [3 H, s, Si(CH₃)₂], 0.13 [3 H, s, ROSi(CH₃)₂], 0.10 [3 H, s, Si(CH₃)₂], 0.05 [3 H, s, Si(CH₃)₂]. ¹³C NMR (62.5 MHz, CDCl₃): δ = 209.0 (C), 157.3 (C), 129.5 (CH), 122.2 (CH), 116.3 (CH), 102.2 (CH), 85.7 (CH), 79.2 (CH), 77.9 (CH), 28.6 (CH₃), 25.7 (CH₃), 25.6 (CH₃), 18.2 (C), 17.8 (C), -4.4 (C), -4.7 (C), -5.1 (C), -5.2 (C). MS (CI): m/z = 484 (100) [M + NH₄]⁺, 390 (5), 201 (31), 132 (24). Anal. Calcd for C₂₄H₄₂Si₂O₅ [M+NH₄]⁺ requires 484.2915. Found: 484.2919.