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Synlett 2002(9): 1508-1510
DOI: 10.1055/s-2002-33516
LETTER
© Georg Thieme Verlag Stuttgart · New York

Introduction of a Hydroxylmethyl Group Onto the Ring of 4-Cyclopentene-1,3-diol Monoacetate

Michitaka Matsuumi, Michiko Ito, Yuichi Kobayashi*
Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan
Fax: +81(45) 9245789; e-Mail: ykobayas@bio.titech.ac.jp;
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Publication History

Received 17 June 2002
Publication Date:
17 September 2002 (online)

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Abstract

Reaction of 4-cyclopentene-1,3-diol monoacetate and ClMgCH2SiMe2(i-PrO) (2a) with CuI as a catalyst afforded the 1,4-isomer 3a, while reaction with the reagent derived from 2a and CuCN in a ratio of 1:1 produced the 1,2-isomer 4a. These products were transformed into useful intermediates through Tamao oxidation of the CH2SiMe2(i-PrO) group into the CH2OH group.

Key words

allylation - carbovir - copper reagent - cyclopentenyl acetate - Grignard reagent

1

Although both enantiomers are available, the present reaction was carried out using the racemic monoacetate.

2

Only one enantiomer is shown for convenience.

5

Kobayashi, Y.; Matsuumi, M. Tetrahedron Lett. 2002, in press.

7

Synthesis of 1,4-Isomer 3a (Table 1, Entry 3): To a slurry of CuI (10 mg, 0.053 mmol) in THF (1.5 mL) was added ClMgCH2SiMe2(OPr-i) (1.47 mL, 0.95 M in THF, 1.40 mmol) slowly at 0 °C. After 20 min of stirring at 0 °C, a solution of 1 (50 mg, 0.35 mmol) in THF (0.5 mL) was added dropwise. The reaction was continued at the same temperature for 2.5 h, and quenched by addition of sat. NH4Cl and 28% NH4OH. The resulting mixture was extracted with EtOAc to afford a mixture of 3a and 4a in a ratio of 88:12 ratio by 1H NMR spectroscopy, and silica gel chromatography (hexane/EtOAc) furnished 3a (61 mg) in 81% yield: IR (neat): 3337, 1129, 1027 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.125 (s, 3 H), 0.130 (s, 3 H), 0.62 (dd, J = 15, 9 Hz, 1 H), 0.79 (dd, J = 15, 7 Hz, 1 H), 1.14 (d, J = 6 Hz, 6 H), 1.45 (br s, 1 H), 1.74 (ddd, J = 14, 7, 6 Hz, 1 H), 2.01 (ddd, J = 14, 7, 2.5 Hz, 1 H), 2.94-3.09 (m, 1 H), 3.91-4.05 (m, 1 H), 4.85 (br s, 1 H), 5.77 (dt, J = 5.5, 2.5 Hz, 1 H), 5.95 (dd, J = 5.5, 2 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = -0.5, -0.3, 24.2, 26.0, 39.2, 43.9, 65.0, 77.4, 131.2, 142.9.
Synthesis of 1,2-Isomer 4a (Table 1, a Larger Scale Reaction of Entry 6): To a slurry of CuCN (881 mg, 9.84 mmol) in THF (10 mL) was added ClMgCH2SiMe2(OPr-i) (6.70 mL, 1.32 M in THF, 8.84 mmol) slowly at -18 °C
(ice/NaCl). After 20 min of stirring at -18 °C, a solution of 1 (251 mg, 1.77 mmol) in THF (2 mL) was added dropwise. The reaction mixture was stirred at 0 °C and gradually warmed to r.t. After 22 h, the reaction was quenched by addition of sat. NH4Cl and 28% NH4OH, and the resulting mixture was extracted with EtOAc several times to afford a mixture of 4a and 3a. The crude product was purified by silica gel chromatography (hexane/EtOAc) to give 1,2-isomer 4a (333 mg) in 88% yield: IR (neat): 3393, 3055, 1252, 1027 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.16 (s, 3 H), 0.18 (s, 3 H), 0.67 (dd, J = 15, 11 Hz, 1 H), 0.76 (dd, J = 15, 5 Hz, 1 H), 1.18 (d, J = 6 Hz, 6 H), 2.30 (ddq, J = 16, 7, 2 Hz, 1 H), 2.58-2.72 (m, 2 H), 3.80 (br s, 1 H), 3.94-4.10 (m, 2 H), 5.46-5.52 (m, 1 H), 5.54-5.60 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = -1.0, -0.9, 22.4, 25.7, 25.8, 40.1, 49.2, 65.8, 81.2, 126.9, 136.3.

8

Although the first step (Mitsunobu inversion) produced a mixture of 8 and its isomer in 94:6 ratio in 82% yield, the minor isomer was separated after the second step by chromatography.

11

An attempted allylation of 1 by using Equation 1 with CH2=CHCH2MgCl and CuCN was unsuccessful.