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Synlett 2009(14): 2287-2290  
DOI: 10.1055/s-0029-1217809
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Step Regioselective Functionalization of myo-Inositol by Dissolution Strategy

Satoe Yamauchi, Minoru Hayashi, Yutaka Watanabe*
Department of Materials Science and Biotechnology, Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577, Japan
Fax: +81(89)9279921; e-Mail: wyutaka@dpc.ehime-u.ac.jp;
Further Information

Publication History

Received 4 June 2009
Publication Date:
07 August 2009 (online)

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Abstract

Functionalizations of hydroxy groups of myo-inositol were usually nonselective due to its poor solubility. By dissolving myo-inositol in DMSO or LiCl-N,N-dimethylacetamide, we have achieved regioselective acylation, silylation, sulfonylation, phosphinylation to give the corresponding 1,3-di-O-substituted products in good yields.

Key words

acylation - regioselectivity - substitutions - inositol - DMA

    References and Notes

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21

When a solution of dinaphthoate in EtOAc was washed with H2O, the dinaphthoate could be recovered completely in the organic layer. However, the presence of DMA in the solution resulted in the loss of about 10% of the dinaphthoate into the aqueous layer.

23

myo-Inositol was dried prior to the reaction. Commercial myo-inositol was first dried by heating at 200 ˚C for 12 h under reduced pressure (0.5 mmHg) and secondly, the inositol was treated three times with pyridine (1 g Ins/5 mL Py) under atmospheric pressure to remove azeotropically a trace of H2O. The resulting inositol was finally heated at 120 ˚C for 12 h under reduced pressure (0.5 mmHg). Anhydrous DMA and DMSO were obtained by treating with powdered CaH2 and BaO overnight, respectively, and subsequent distillation (1 and 20 mmHg). LiCl is so hygroscopic that it was weighed in a reaction vessel and dried by application of heat at about 300-400 ˚C under reduced pressure (0.5 mmHg).
Typical Procedure for the Synthesis of 1,3-Di- O -benzoyl- myo -inositol (2a): To a reaction flask containing LiCl (400 mg, 9.44 mmol) were added inositol (100 mg, 0.55 mmol) and DMA (5 mL), and the mixture was heated at about 120 ˚C until the mixture became a clear solution (about 3 min). After addition of Et3N (391 mg, 3.89 mmol), the resulting solution was kept at -10 ˚C, and then benzoyl chloride (234 mg, 1.67 mmol) was added. The mixture was stirred at the same temperature for 4 h, and pyridine (2 mL) and TMSCl (1 mL, 7.82 mmol) were carefully added. The mixture was stirred at 0 ˚C for 5 h, and diluted with H2O and EtOAc. After partition to two layers, the aqueous layer was extracted with EtOAc (3 ×), and the organic layers combined with the initial organic one were washed successively with H2O (2 ×), 0.5 N HCl solution, H2O, sat. NaHCO3 solution, H2O, and then brine. The organic layer was dried over Na2SO4, filtered and evaporated. The residue was dissolved in a small volume of CHCl3 (1 mL), and MeOH (5 mL) and CF3CO2H (74 mg, 0.64 mmol) were added. The solution was stirred for 4 h at r.t., and the volatile materials were all distilled off under reduced pressure (1.0 mmHg). The residue was subjected to a column chromatography on silica gel (MeOH-CHCl3, 1:10) to give crystalline 1,3-di-O-benzoate (205 mg, 95% yield): R f 0.5 (MeOH-CHCl3, 1:5); mp 174.5-175.0 ˚C (EtOAc-hexane). ¹H NMR (400 MHz, CD3OD): δ = 3.44 (1 H, t, J = 9.8 Hz, InsH5), 4.08 (2 H, t, J = 9.8 Hz, InsH4,6), 4.43 (1 H, t, J = 2.6 Hz, InsH2), 5.01 (2 H, dd, J = 9.8, 2.6 Hz, InsH1,3), 7.47 (4 H, t, J = 8.0 Hz, H m ), 7.60 (2 H, t, J = 8.0 Hz, H p ), 8.00 (4 H, d, J = 8.0 Hz, H o ). ¹³C NMR (100 MHz, CD3OD): δ = 69.29, 71.89, 75.90, 76.52 (6 × C, InsC), 129.42 (4 × C, Car3), 130.88 (4 × C, Car2), 131.50 (2 × C, Car1), 134.26 (2 × C, Car4), 167.69 (2 × C, CO). MS (FAB+, m-nitrobenzyl alcohol): m/z = 389 [M + H]+. Anal. Calcd for C20H20O8˙1/2H2O: C, 60.45; H, 5.33. Found: C, 60.09; H, 5.13.
1,3-Di- O -(1-naphthoyl)- myo -inositol (2b): As described above, a solution of inositol (100 mg, 0.55 mmol) and LiCl (400 mg, 9.44 mmol) in DMA (5 mL) was prepared. After addition of Et3N (391 mg, 3.89 mmol), the resulting solution was kept at -10 ˚C, and then 1-naphthoyl chloride (317 mg, 1.67 mmol) was added. The mixture was stirred at the same temperature for 20 h. H2O (about 0.1 mL) was added and the mixture was stirred for 10 min, and then partitioned to EtOAc and H2O layers. The aqueous solution was extracted with EtOAc (3 ×). The combined extract was washed with H2O (3 ×) and brine, dried over Na2SO4, filtered, and then evaporated. The residue was recrystallized from EtOAc-hexane to give crystals of 2b (193 mg, 71%). The remaining dinaphthoate (32 mg, 12%) was isolated from the mother liquor by a flash column chromatography on silica gel (MeOH-CHCl3, 1:14): R f 0.4 (MeOH-CHCl3, 1:10); mp 195.5-196.0 ˚C (EtOAc-hexane). ¹H NMR (270 MHz, CD3OD): δ = 3.61 (1 H, t, J = 9.6 Hz, InsH5), 4.23 (2 H, t, J = 9.6 Hz, InsH4,6), 4.73 (1 H, t, J = 2.4 Hz, InsH2), 5.26 (2 H, dd, J = 9.6, 2.4 Hz, InsH1,3), 7.61 (6 H, complex, aromatic H3,6,7), 7.96 (2 H, d, J = 8.0 Hz, aromatic H5), 8.11 (2 H, d, J = 8.4 Hz, aromatic H4), 8.41 (2 H, d, J = 7.2 Hz, aromatic H2), 9.00 (2 H, d, J = 8.4 Hz, aromatic H8). ¹³C NMR (100 MHz, CDCl3): δ = 69.58 (C, InsC2), 72.26 (2 × C, InsC4,6), 76.30 (2 × C, InsC1,3), 77.04 (C, InsC5), 125.9, 127.2, 127.6, 128.8, 128.9, 129.9, 131.9, 132.9, 134.8, 135.5 (10 × C, aromatic), 169.0 (C=O). MS (FAB+, m-nitrobenzyl alcohol): m/z = 689 [M + H]+. Anal. Calcd for C28H24O8: C, 68.85; H, 4.95. Found: C, 68.56; H, 4.91.
The other compounds were identified similarly by spectros-copic data (¹H NMR and ¹³C NMR, FAB-MS) and elemental analysis.