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

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.

kinetic resolution - homoallylic alcohol - enzymes - indium - allylations

References

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21

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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23

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).

24

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.

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