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Synlett 2004(8): 1367-1370  
DOI: 10.1055/s-2004-825620
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Alternative Route to Protected Aldols: Cobalt-Catalyzed Hydroformyl­ation of Epoxides and in situ Protection of β-Hydroxyaldehydes by HC(OMe)3

Koji Nakanoa, Masaya Katayamaa, Shinjiro Ishiharab, Tamejiro Hiyamab, Kyoko Nozaki*a
a Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Fax: +81(3)58417261; e-Mail: nozaki@chembio.t.u-tokyo.ac.jp;
b Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan
Further Information

Publication History

Received 27 February 2004
Publication Date:
04 June 2004 (online)

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Abstract

A wide range of epoxides were efficiently converted to protected aldols by hydroformylation-acetalization using Co2(CO)8 as a catalyst in trimethyl orthoformate. The formylation of terminal epoxides was regioselective for the terminal position, and (S)-1-benzyloxy-2,3-epoxypropane was transformed into (R)-1-benzyl­oxy-4,4-dimethoxybutan-2-ol with retention of the configuration.

Key words

acetals - hydroformylations - epoxides - cobalt - aldols

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A typical procedure is as follows: A mixture of cyclohexene oxide (0.50 mL, 5.0 mmol), Co2 (CO)8 (43 mg, 0.125 mmol) and 5 (98 mg, 0.25 mmol) in trimethyl orthoformate (10 mL) was placed in a 20 mL Schlenk tube and degassed by freeze-thaw cycles. Then, the solution was transferred into a 50 mL autoclave. After carbon monoxide (40 atm) and hydrogen (40 atm) were pressurized, the resulting mixture was stirred at 90 °C for 21 h. The reaction mixture was cooled down to the ambient temperature, and the carbon monoxide and hydrogen pressure were slowly released. The volatile materials were evaporated and the resulting crude residue was treated with MeOH (10 mL) under refluxing overnight. The solvent was removed off by evaporation, and then the residue was purified by silica gel chromatography (hexane-EtOAc = 10:1) to give 3 in 70% yield. 1H NMR (CDCl3): δ = 4.28 (d, J = 6.9 Hz, 1 H), 4.12 (s, 1 H), 3.53-3.46 (m, 1 H), 3.45 (s, 3 H), 3.35 (s, 3 H), 2.04-1.97 (m, 1 H), 1.79-1.61 (m, 4 H), 1.25-1.12 (m, 3 H), 1.05-0.96 (m, 1 H). 13C NMR (CDCl3): δ = 108.97, 71.22, 55.26, 52.32, 45.78, 34.24, 26.37, 24.99, 24.39. Anal. Calcd for C9H18O3: C, 62.04; H, 10.41. Found: C, 61.86; H, 10.35.

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The configuration was assigned by comparing the 1H NMR signals of the diol given by reduction of 3 (60% yield) with those reported. [11]

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Spectral data for new compounds. Compound 7a: 1H NMR (CDCl3): δ = 4.26 (d, J = 8.3 Hz, 1 H), 3.99-3.94 (m, 1 H), 3.42 (s, 3 H), 3.32 (s, 3 H), 2.68 (br s, 1 H), 2.10-2.03 (m, 1 H), 2.01-1.92 (m, 1 H), 1.88-1.81 (m, 1 H), 1.77-1.65 (m, 1 H), 1.63-1.53 (m, 1 H), 1.41-1.33 (m, 1 H). 13C NMR (CDCl3): δ = 108.02, 75.59, 54.83, 51.56, 49.26, 33.49, 25.56, 21.27. Anal. Calcd for C8H16O3: C, 59.97; H, 10.07. Found: C, 60.11; H, 9.85. Compound 7b: 1H NMR (CDCl3): δ = 4.33 (d, J = 5.5 Hz, 1 H), 3.89-3.82 (m, 1 H), 3.44 (s, 3 H), 3.37 (s, 3 H), 2.95 (d, J = 5.1 Hz, 1 H), 1.76-1.71 (m, 1 H), 1.59-1.50 (m, 1 H), 1.45-1.27 (m, 7 H), 0.97-0.90 (m, 6 H). 13C NMR (CDCl3): δ = 108.32, 70.51, 56.16, 53.88, 44.91, 35.78, 27.05, 21.46, 19.75, 14.44, 14.13. Anal. Calcd for C11H24O3: C, 64.67; H, 11.84. Found: C, 64.63; H, 11.94. Compound linear-7c: 1H NMR (CDCl3): δ = 4.29 (d, J = 6.0 Hz, 1 H), 3.70-3.64 (m, 1 H), 3.61-3.56 (m, 1 H), 3.45 (s, 3 H), 3.37 (s, 3 H), 2.85 (dd, J = 7.8, 4.1 Hz, 1 H), 1.87-1.81 (m, 1 H), 1.42-1.20 (m, 10 H), 0.88 (t, J = 6.9 Hz, 3 H). 13C NMR (CDCl3): δ = 108.89, 62.62, 55.85, 53.48, 42.73, 31.72, 29.56, 27.06, 26.61, 22.60, 14.05. Anal. Calcd for C11H24O3: C, 64.67; H, 11.84. Found: C, 64.56; H, 11.92. Compound linear-7d: 1H NMR (CDCl3): δ = 4.61 (t, J = 5.5 Hz, 1 H), 4.05-3.99 (m, 1 H), 3.55 (qd, J H-Cl = 11 Hz,
J H-H = 6.0 Hz, 2 H), 3.39 (s, 3 H), 3.38 (s, 3 H), 3.07 (br s, 1 H), 1.93-1.84 (m, 2 H). 13C NMR (CDCl3): δ = 103.16, 68.33, 53.87, 53.43, 49.34, 36.72. Anal. Calcd for C6H13O3Cl: C, 42.74; H, 7.77. Found: C, 42.56; H, 7.88. Compound linear-7e: 1H NMR (CDCl3): δ = 7.37-7.27 (m, 5 H), 4.60 (t, J = 5.5 Hz, 1 H), 4.56 (s, 2 H), 4.02-3.95 (m, 1 H), 3.49-3.46 (m, 1 H), 3.43-3.40 (m, 1 H), 3.36 (s, 3 H), 3.36 (s, 3 H), 2.87 (s, 1 H), 1.81-1.78 (m, 2 H). 13C NMR (CDCl3): δ = 138.00, 128.41, 127.70, 103.17, 74.09, 73.32, 67.33, 53.51, 53.32, 36.23. Anal. Calcd for C13H20O4: C, 64.98; H, 8.39. Found: C, 64.80; H, 8.35. [α]D 26 for linear-(R)-7e = 1.7° (c 3.0, CHCl3).

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No racemization was confirmed by HPLC analysis (DAICEL CHIRALCEL OD-H, Hexane-i-PrOH = 95:5). The absolute configuration was determined based on the optical rotation of 2-hydroxy-1,4-butanediol which was prepared from linear-(R)-7e in 4 steps.