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Synlett 2002(8): 1277-1280
DOI: 10.1055/s-2002-32966
LETTER
© Georg Thieme Verlag Stuttgart · New York

First Chemoenzymatic Synthesis of Optically Active Uracil and Chromen-4-one Substituted Homoallylic Alcohols: An Entry into Chiral Pool

Satwinder Singh, Subodh Kumar, Swapandeep Singh Chimni*
Department of Chemistry, Guru Nanak Dev University, Amritsar 143 005, India
Fax: +91(183)258820; e-Mail: sschimni@angelfire.com;
Further Information

Publication History

Received 11 May 2002
Publication Date:
25 July 2002 (online)

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Abstract

Optically active uracil and chromen-4-one substituted homoallylic alcohols were obtained from the corresponding racemic alcohols by Pseudomonas cepacia lipase catalyzed transesterification in high enantiomeric ratio (E) under mild reaction conditions.

Key words

kinetic resolution - homoallylic alcohol - enzymes - indium - allylations

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General procedure for allylation: Indium metal (0.506 mg, 4.4 mmol) and allyl bromide (970 mg, 0.75 ml, 8 mmol) were added to a stirred solution of aldehydes 1a-c (4 mmol) in 20 mL 50% aq THF. The reaction was allowed to proceed till the aldehyde was consumed (12-16 h) (TLC). Finally, a saturated aqueous solution of NH4Cl was added and the solution was extracted with CH2Cl2. The combined organic layers were dried and concentrated to give 2a-c, which were purified by column chromatography.

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Physical and spectral data for the representative cases are given here. (RS)-2a: Yellow liquid (76%); IR (Neat): 3410, 2980, 1620 cm-1; MS (m/z): 210 (M+); 1H NMR (CDCl3): δ 2.32-2.64 (m, 2 H, CH2), 3.33 (s, 3 H, CH3), 3.42 (s, 3 H, CH3), 4.62 (dd, 1 H, J = 5.1 and 7.2 Hz, CH), 5.10-5.18 (m, 2 H, CH2), 5.76-5.90 (m, 1 H, CH), 7.21 (m, 1 H, Ur-6H);13C NMR (CDCl3): δ 27.71 (CH3), 37.03 (CH3), 40.78 (CH2), 67.49 (CH), 114.67 (Ur-C5), 118.55 (CH2), 134.10 (CH), 139.35 (Ur-C6), 151.38 (C=O), 162.87 (C=O). (RS)-2b: Pale yellow liquid (80%); IR (Neat): 3447, 2958, 1560
cm-1; MS (m/z): 210 (M+); 1H NMR (CDCl3): δ 2.39-2.66 (m, 3 H, CH2 and OH), 3.98 (s, 3 H, OCH3), 4.01 (s, 3 H, OCH3), 4.83 (dd, 1 H, J = 7.6 and 5.1 Hz, CH), 5.12-5.19 (m, 2 H, CH2), 5.74-5.82 (m, 1 H, CH), 8.24 (s, 1 H, Pym-6H); 13C NMR/DEPT (CDCl3): δ 41.15 (-ve, CH2), 53.82 (+ve, OCH3), 54.61 (+ve, OCH3), 66.67 ((+ve, CH), 118.28 (-ve, =CH2), 133.73 (+ve, =CH), 144.78 (ab, Pym-C5), 155.70 (+ve, Pym-C6), 164.42 (ab, Pym-C), 168.03 (ab, Pym-C). (R)-3a: Pale liquid; [α]D 27: +66.53 (c 0.52, CH2Cl2) for 98% ee. IR (Neat) : 2910, 1720, 1650 cm-1; MS (m/z): 252 (M+); 1H NMR (CDCl3): δ 2.02 (s, 3 H, OAc), 2.49-2.69 (m, 2 H,CH2), 3.28 (s, 3 H, CH3), 3.35 (s, 3 H, CH3), 4.98-5.06 (m, 2 H,CH2), 5.55-5.73 (m, 2 H, 2 × CH)), 7.12 (m, 1 H, C6H); 13C NMR (CDCl3): δ 21.00 (CH3), 27.75 (CH3), 37.07 (N-CH3), 37.51 (CH2), 69.37 (CH), 111.40 (C-5), 118.33 (CH2), 132.78 (CH), 140.82 (C-6), 151.30 (C=O), 161.71(C=O), 169.83 (C=O). (R)-3b: Yellow liquid; [α]D 27: +49.42 (c 1.05, CH2Cl2) for 95% ee; IR (Neat): 2920, 1730 and 1590 cm-1; MS (m/z): 252 (M+); 1H NMR (CDCl3): δ 2.08 (s, 3 H, OAc), 2.57-2.62 (m, 2 H, CH2), 3.99 (s, 3 H, OCH3), 4.01 (s, 3 H, OCH3), 5.03-5.09 (m, 2 H,CH2), 5.64-5.78 (m, 1 H, CH), 5.97 (t, 1 H, J = 4.33 Hz, CH), 8.19 (s, 1 H, Pym-6H); 13C NMR (CDCl3): δ 20.97 (CH3), 38.58 (CH2), 54.04 (OCH3), 5.76 (OCH3), 68.16 (CH), 113.78 (Pym-C5), 118.36 (CH2), 132.70 (CH), 156.19 (Pym-C6), 164.79 (Pym-C), 168.10 (Pym-C), 169.92 (C=O).

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The acetates of (S)- alcohols and racemic alcohols were prepared by stirring with excess (5 equiv) of acetyl chloride and finally washing with 20% Na2CO3 solution.