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Synlett 2010(10): 1497-1500  
DOI: 10.1055/s-0029-1220071
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Short and Efficient Route from myo- to neo-Inositol

Pablo Wessig*, Kristian Möllnitz, Sebastian Hübner
Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
Fax: +49(331)9775065; e-Mail: wessig@uni-potsdam.de;
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Publication History

Received 8 March 2010
Publication Date:
26 May 2010 (online)

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A Short and Efficient Route from myo- to neo-InositolSynlett 2011; 2011(03): 434-434
DOI: 10.1055/s-0030-1259522

Abstract

An efficient route from myo- to neo-inositol is described. The key steps of the sequence are oxidation of the hydroxy group at C-5 to the corresponding ketone, followed by a highly (dr = 7.8:1) stereoselective reduction. The route includes nine steps with an overall yield of 51% and is therefore superior to all hitherto reported methods for the preparation of neo-inositol.

Key words

inositols - cyclitols - carbocycles - stereoselective synthesis - regioselectivity

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27

Ketone 9 was obtained as an oil, which was partly decomposed upon flash column chromatography on silica gel.

28

Alcohol 4 (20.18 g, 43.63 mmol) was dissolved in anhyd CH2Cl2 (500 mL) and Dess-Martin periodinane (20.59 g, 48.55 mmol, 1.1 equiv) was added. The resulting mixture was stirred at r.t. until complete conversion of 4 was monitored by TLC. The organic layer was washed several times with an aq solution of Na2S2O3/NaHCO3, dried, and evaporated. Ketone 9 was obtained as an oil (19.85 g, 43.10 mmol, 99%) and can be used without further purification; R f  = 0.7 (hexanes-EtOAc, 2:1). ¹H NMR (500 MHz, CDCl3): δ = 3.95-3.97 (m, 2 H), 4.51 (d, ² J = 11.6 Hz, 2 H), 4.52-4.54 (m, 2 H), 4.64 (d, ² J = 4.8 Hz, 1 H), 4.67 (d, ² J = 11.6 Hz, 2 H), 4.73 (s, 2 H), 4.76 (t, ³ J = 1.3 Hz, 1 H), 5.52 (d, ³ J = 4.8 Hz, 1 H), 7.24-7.41 (m, 15 H). ¹³C NMR (125 MHz, CDCl3): δ = 69.8 (CH), 71.1 (CH2), 72.2 (CH), 72.3 (CH2), 81.6 (CH), 85.5 (CH2), 127.8 (CH), 127.9 (CH), 127.9 (CH), 128.3 (CH), 128.4 (CH), 136.8 (C), 137.3 (C), 202.7 (C). HRMS: m/z [M + H]+ calcd for C28H28O6 + H: 461.1964; found: 461.1986.

29

Ketone 9 (19.84 g, 43.08 mmol) was dissolved in anhyd MeOH (800 mL) and NaBH4 (1.98 g, 52.39 mmol, 1.2 equiv) was added. The reaction mixture was stirred about 20 min until gas and heat evolution ceased. This mixture was directly used in the next step. To obtain spectroscopic data a small sample (2 mL) was taken from the mixture, and the solvent was evaporated. The resulting residue was treated with 0.1 M aq HCl solution and extracted thrice with Et2O. The combined organic layers were dried and evaporated giving a pale yellow oil (49 mg, 0.10 mmol, 98%) with a ratio of 8 (neo) to 4 (myo) of 7.8:1 (determined by ¹H NMR); R f (8) = 0.46 (hexanes-EtOAc, 2:1); R f (4) = 0.44 (hexanes-EtOAc, 2:1). ¹H NMR (8): δ = 2.74 (br s, 1 H), 3.91-3.96 (m, 2 H), 4.30-4.32 (m, 1 H), 4.34-4.37 (m, 2 H), 4.43-4.47 (m, 1 H), 4.52 (s, 2 H), 4.59 (d, ² J = 11.9 Hz, 2 H), 4.63 (d, ² J = 4.5 Hz, 1 H), 4.67 (d, ² J = 11.9 Hz, 2 H), 5.52 (d, ² J = 4.5 Hz, 1 H), 7.25-7.39 (m, 15 H). ¹H NMR (4): matches with literature.²4

30

The reaction mixture of the previous step, containing 8 + 4, was treated with concd HCl (60 mL) and refluxed for 3 h. The solvents were evaporated, and the resulting residue was treated with H2O and extracted thrice with CH2Cl2. The combined organic layers were dried, evaporated, and the resulting residue purified by flash chromatography (silica, CHCl3 → CHCl3-EtOAc, 1:2) giving 10 as colorless crystals (14.96 g, 33.21 mmol, 77%); mp 97-98 ˚C; R f  = 0.26 (CHCl3-EtOAc, 1:2).