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Synlett 2006(20): 3521-3524  
DOI: 10.1055/s-2006-956488
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© Georg Thieme Verlag Stuttgart · New York

Organocatalytic Asymmetric Synthesis of 1,2,3-prim,sec,sec-Triols

Gui-Ling Zhao, Pawel Dziedzic, Ismail Ibrahem, Armando Córdova*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden
Fax: +46(8)154908; e-Mail: acordova@organ.su.se;
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Publication History

Received 30 August 2006
Publication Date:
08 December 2006 (online)

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Abstract

A tandem organocatalytic asymmetric synthesis of 1,2,3-triols using a,b-unsaturated aldehydes as the substrates and hydrogen peroxide as the oxidant is presented. The reaction can also be applied to the asymmetric synthesis of 3-chloro-1,2-propandiols.

Key words

triols - epoxidation - asymmetric catalysis - epoxide opening - tandem reactions

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To a stirred solution of 3 (16 mg, 20 mol%) in CHCl3 (2 mL) was added trans-cinnamaldehyde (1a, 66 mg, 0.5 mmol) and H2O2 (0.6 mmol, 50% aq solution). The reaction was vigorously stirred at 4 °C for 7 h. Then the reaction mixture was diluted with EtOH (2 mL) and cooled to 0 °C followed by addition of NaBH4 (38 mg, 1.0 mmol). The mixture was then stirred for 10 min, quenched with H2SO4 (0.5 N, 8 mL) and EtOAc (8 mL). Next, the reaction mixture was stirred at r.t. for 1 h. The mixture was separated and the water layer was extracted with EtOAc (6 × 5 mL). The organic layer was collected, dried over Na2SO4 and the solvent was removed. The residue was purified by silica gel chromatography (EtOAc) to give the product 2a (53 mg, 63%).
(2R,3S)-1-Phenyl-propane-1,2,3-triol (2a): [a]D 25 +30.3 (c 1.0, CHCl3); [a]D 25 +25.3 (c 1.0, H2O), lit. [4a] [a]D 23 +19.6 (c 6.3, H2O). 1H NMR (400 MHz, D2O): d (major diastereomer) = 3.64 (dd, J = 7.2, 11.6 Hz, 1 H), 3.82 (dd, J = 3.2, 11.6 Hz, 1 H), 3.94 (ddd, J = 3.2, 7.2, 7.2 Hz, 1 H), 4.67 (d, J = 7.2 Hz, 1 H), 7.41-7.49 (m, 5 H); d (minor diastereomer) = 3.43 (dd, J = 7.2, 12.0 Hz, 1 H), 3.54 (dd, J = 4.0, 12.0 Hz, 1 H), 3.89 (ddd, J = 4.0, 6.4, 7.2 Hz, 1 H), 4.70 (d, J = 6.4 Hz, 1 H), 7.41-7.49 (m, 5 H). 13C NMR (100 MHz, D2O): d (major isomer) = 62.8. 74.1, 74.8, 127.4, 128.4, 128.8, 140.6; d (minor isomer) = 62.7. 74.4, 75.7, 126.9, 128.4, 128.9, 140.7. The ee was determined after acetylation by HPLC on Daicel Chiralpak OJ with iso-hexane-i-PrOH (85:15) as the eluent; major diastereomer - minor isomer: t R = 20.923 min; major isomer: t R = 28.299 min; minor diastereomer - minor isomer: t R = 36.090 min; major isomer: t R = 49.281 min. HRMS (ESI): m/z calcd for C9H12O3Na [M + Na]+: 191.0679; found: 191.0687.

13

To a stirred solution of 3 (16 mg, 20 mol%) in CHCl3 (2 mL) was added trans-cinnamaldehyde (1a, 66 mg, 0.5 mmol) and H2O2 (0.6 mmol, 50% aq solution). The reaction was vigorously stirred at 4 °C for 7 h. Then the reaction mixture was diluted with EtOH (2 mL) and cooled to 0 °C followed by addition of NaBH4 (38 mg, 1.0 mmol) and the mixture was stirred for 10 min. Next, NaOH (0.5 N, 10 mL) and
t-BuOH (2 mL) were added and the reaction temperature increased to 70 °C. After 24 h of stirring at this temperature, the mixture was separated and the water layer was extracted with EtOAc (6 × 5 mL). Then the organic layer was collected, dried over Na2SO4 and the solvent was removed. The crude residue was purified by silica gel chromatography using a gradient system (pentane-EtOAc = 1:1) to give the 2-epoxy alcohol (45 mg) and then EtOAc to give the triol 2a (39 mg, 39%).

14

To a stirred solution of 3 (16 mg, 20 mol%) in CHCl3 (2 mL) was added trans-cinnamaldehyde (1a, 66 mg, 0.5 mmol) and H2O2 (0.6 mmol, 50% aq solution). The reaction was vigorously stirred at 4 °C for 7 h. Then the reaction mixture was diluted with EtOH (2 mL) and cooled to 0 °C followed by addition of NaBH4 (38 mg, 1.0 mmol) After 10 min of stirring, EtOAc (8 mL) and HCl (2 N, 4 mL) were added. The mixture was extracted and the water layer was extracted with EtOAc (3 × 5 mL). The organic layers were collected, dried over Na2SO4 and the solvent was removed. The residue was purified by silica gel chromatography (pentane-EtOAc = 1:1) to give 4b (68%). Compound 4b: [a]D 25 +25.7 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): d = 3.78 (dd, J = 6.4, 12.8 Hz, 1 H), 3.85 (dd, J = 3.2, 12.8 Hz, 1 H), 4.01-4.04 (m, 1 H), 4.84 (d, J = 7.6 Hz, 1 H), 7.36 (s, 4 H). 13C NMR (100 MHz, CDCl3): d = 61.3. 63.3, 75.3, 129.1, 129.6, 134.9, 136.6. The ee was determined by HPLC on Agilent Chiralpak AD column with hexane-i-PrOH (90:10) as the eluent; minor isomer: t R = 22.750 min; major isomer: t R = 28.463 min. HRMS (ESI): m/z calcd for C9H10Cl2O2Na [M + Na]+: 242.9950; found: 242.9952.