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Synlett 2005(13): 1999-2002  
DOI: 10.1055/s-2005-871937
LETTER
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Desymmetrization of 2-Substituted 1,3-Propanediols via Catalytic Enantioselective Ring-Cleavage Reaction of Cyclic Acetal Derivatives

Toshiro Harada*, Koudai Shiraishi
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Fax: +81(75)7247580; e-Mail: harada@chem.kit.ac.jp;
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Publication History

Received 1 June 2005
Publication Date:
12 July 2005 (online)

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Abstract

Non-enzymatic desymmetrization of 2-substituted 1,3-propanediols leading to the enantiomerically enriched 3-benzyloxy-1-propanols was achieved by using oxazaborolidinone-catalyzed enantioselective ring-cleavage reaction of the cyclic acetal derivatives with dimethylsilyl ketene S,O-acetal as a key reaction.

Key words

asymmetric - catalysis - cleavage - diols - Lewis acids

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Acetal 4a was prepared from 2-phenyl-1,3-propanediol and 1-naphthaldehyde (1.1 equiv) under the conventional conditions (p-TsOH, toluene reflux). A pure trans-isomer isolated by recrystallization from EtOAc and hexane (74% yield) was used in ring-cleavage reaction.

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For the use of diethyl ether as an additive, see ref. 8 and 9d.

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The overall enantioselectivity of 6, for example, is calculated by [(syn-6 + anti-6) - (ent-syn-6 + ent-anti-6)}/{(syn-6 + anti-6) + (ent-syn-6 + ent-anti-6)].

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Representative Procedure for Catalytic Ring-Cleavage Reaction (Table 1, Entry 6). To a solution of N-tosyl-3-(2-naphthyl)-l-alanine (57.5 mg, 0.15 mmol) in CH2Cl2 (1.6 mL) under argon atmosphere at r.t. was added dibromo-4-chlorophenylborane (23 µL, 0.15 mmol). After being stirred for 30 min, the mixture was concentrated in vacuo. To a solution of the resulting OXB 3 in CH2Cl2 (1.5 mL) at -50 °C were added dimethylsilyl ketene acetal 5d (428 mg, 2.25 mmol), Et2O (117 µL), and a toluene (1.5 mL) solution of acetal 4a (218 mg, 0.75 mmol). After being stirred for 18 h at -50 °C, the mixture was quenched by the addition of aq NaHCO3 and filtered. The filtrate was extracted three times with Et2O. The organic layers were dried (MgSO4) and concentrated in vacuo. The residue was treated with aq 70% HOAc (0.5 mL) in THF (0.5 mL) at r.t. for 1 h. The mixture was diluted with H2O, extracted three times with Et2O, and washed with aq NaHCO3. The organic layers were dried (MgSO4) and concentrated in vacuo. Purification of the residue by flash chromatography (SiO2, 5-20% EtOAc in hexane) gave 262 mg (83%) of 7a 8 (syn:anti = 15:1, 93% ee and 17% ee for syn- and anti-isomers, respectively). 1H NMR (500 MHz, CDCl3): δ = 1.53 (9 H, s), 2.41 (1 H, br), 2.90 (1 H, dd, J = 2.7, 15.4 Hz), 3.12 (1 H, dd, J = 8.3, 15.4 Hz) 3.19 (1 H, m), 3.68-3.80 (2 H, m), 3.88 (1 H, dd, J = 5.7, 11.0 Hz), 4.09 (1 H, dd, J = 7.6, 11.0 Hz), 5.61 (1 H, dd, J = 2.7, 8.3 Hz), 7.09-7.30 (5 H, m), 7.42-7.59 (4 H, m), 7.81 (1 H, d, J = 8.1 Hz), 7.89 (1 H, br d, J = 8.0 Hz), 8.15 (1 H, br d, J = 8.2 Hz) [a minor anti-isomer resonated at δ = 1.55 (9 H, s), 3.95 (1 H, dd, J = 5.0, 11.2 Hz)]. 13C NMR (125.8 MHz, CDCl3): δ = 29.8, 47.9, 48.5, 52.0, 65.3, 66.2, 71.7, 122.7, 123.9, 125.4, 125.7, 126.3, 126.8, 128.2, 128.38, 128.39, 129.0, 130.4, 133.8, 135.7, 139.9, 198.4. HPLC: ee determination (HPLC, Chiralpak AD-H, 1.0 mL/min, 3% 2-PrOH in hexane, (anti- 7a) τ1 = 31.3 min, (ent-syn-7a) τ2 = 34.3 min, (syn-7a) τ3 = 38.8 min, (ent-anti-7a) τ4 = 46.8 min).

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[α]D 25 -22.9 (c 1.06, CHCl3) {lit.6d [α]D +24.8 (c 1.00, CHCl3)}.