Modified Cinchona Alkaloid-Zinc
Complex Catalysts: Enantioselective Monoacetylation of
Glycerol Derivatives with Acetic Anhydride

Shigeki Sano; Takeshi Tsumura; Noriaki Tanimoto; Takashi Honjo; Michiyasu Nakao; Yoshimitsu Nagao

doi:10.1055/s-0029-1218562

LETTER

Modified Cinchona Alkaloid-Zinc Complex Catalysts: Enantioselective Monoacetylation of Glycerol Derivatives with Acetic Anhydride

Shigeki Sano*, Takeshi Tsumura, Noriaki Tanimoto, Takashi Honjo, Michiyasu Nakao, Yoshimitsu Nagao
Graduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Fax: +81(88)6339503; e-Mail: ssano@ph.tokushima-u.ac.jp;

Abstract

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Abstract

Enantioselective monoacetylation of σ-symmetric glycerol derivatives with acetic anhydride catalyzed by modified cinchona alkaloid-zinc complexes was achieved in up to 86% ee at 5 mol% catalyst loading.

Key words

cinchona alkaloid - zinc complex - asymmetric synthesis - glycerol - acetylation

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Referenzen

References and Notes

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General Experimental Procedure for a Modified Cinchona Alkaloid-Zinc Complex Catalyzed Desymmetrization of Glycerol Derivatives
To a solution of modified cinchona alkaloid 1 (6.0 mg, 0.01 mmol) in Et₂O (4 mL) was added Et₂Zn (1.0 M in n-hexane, 10 µL, 0.01 mmol) at r.t. The mixture was stirred at r.t. for 10 min, and diol 9a (51.3 mg, 0.2 mmol) and Ac₂O (28 µL, 0.3 mmol) were then added to the solution at 0 ˚C. After stirring at 0 ˚C for 20 h, the reaction mixture was treated with sat. aq NaHCO₃ (5 mL) followed by extraction with CHCl₃ (75 mL). The extract was dried over anhyd MgSO₄, filtered, and concentrated in vacuo. The oily residue was purified by silica gel column chromatography (EtOAc-n-hexane, 1:1) to afford 9aa (46.3 mg, 78% yield, 86% ee) as a colorless oil.
The ee (%) of (S)-9aa (Scheme [²] ) was determined on a Chiralpak IA, n-hexane-EtOH (3:1), flow rate: 1 mL/min, detection: 254 nm]. The retention times were 9.4 min [minor product, (R)-9aa] and 12.2 min [major product, (S)-9aa], respectively. The absolute configuration of (S)-9aa was explicitly determined by its chemical conversion to acetonide (S)-15 {[α]_D ^²0 -3.1 (c 1.01, EtOH), lit.^¹6 (R)-15 [α]_D +5.8 (c 1.00, EtOH)}.

Scheme 2

Spectroscopic Data of 9aa-ea (Table 4)
Compound 9aa (R = Me): colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 1.28 (3 H, s), 2.10 (3 H, s), 2.15 (1 H, s), 3.56-3.59 (2 H, m), 3.79 (6 H, s), 4.17 (1 H, d, J = 11.7 Hz), 4.24 (1 H, d, J = 11.7 Hz), 4.48 (2 H, s), 6.38 (1 H, t, J = 2.2 Hz), 6.49 (2 H, d, J = 2.2 Hz). ^¹³C NMR (75 MHz, CDCl₃): δ = 17.5, 20.9, 55.3, 64.6, 65.4, 65.7, 76.8, 99.4, 105.2, 141.1, 160.9, 171.1. IR (neat): 3471, 2939, 2843, 1738, 1599, 1464, 1244, 1205, 1155, 1053 cm^-¹. ESI-MS: m/z calcd for C₁₅H₂₂NaO₆: 321.1314; found: 321.1324 [M⁺ + Na].
Compound 9ba (R = Et): colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 0.96 (3 H, t, J = 7.7 Hz), 1.60-1.72 (2 H, m), 2.10 (3 H, s), 2.21 (1 H, s), 3.57 (1 H, d, J = 12.0 Hz), 3.62 (1 H, d, J = 12.0 Hz), 3.79 (6 H, s), 4.20 (1 H, d, J = 11.7 Hz), 4.25 (1 H, d, J = 11.7 Hz), 4.45 (2 H, s), 6.37 (1 H, t, J = 2.2 Hz), 6.51 (2 H, d, J = 2.2 Hz). ^¹³C NMR (75 MHz, CDCl₃): δ = 7.0, 20.9, 22.6, 55.3, 62.8, 63.6, 63.9, 78.6, 99.4, 105.2, 141.0, 160.9, 171.2. IR (neat): 3481, 2968, 1741, 1599, 1462, 1238, 1205, 1155, 1063 cm^-¹. ESI-MS: m/z calcd for C₁₆H₂₄NaO₆: 335.1471; found: 335.1471 [M⁺ + Na].
Compound 9ca (R = i-Pr): colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 1.01 (3 H, d, J = 3.2 Hz), 1.03 (3 H, d, J = 3.2 Hz), 2.07-2.10 (4 H, m), 2.17-2.25 (1 H, m), 3.73-3.76 (2 H, m), 3.79 (6 H, s), 4.34 (1 H, d, J = 12.2 Hz), 4.36 (1 H, d, J = 12.2 Hz), 4.52 (1 H, d, J = 11.5 Hz), 4.54 (1 H, d, J = 11.5 Hz), 6.38 (1 H, t, J = 2.2 Hz), 6.52 (2 H, d, J = 2.2 Hz). ^¹³C NMR (75 MHz, CDCl₃): δ = 17.06, 17.13, 21.0, 30.1, 55.3, 62.6, 64.5, 64.6, 79.7, 99.3, 105.0, 141.4, 160.9, 171.0. IR (neat): 3483, 2964, 1741, 1599, 1238, 1205, 1155, 1055 cm^-¹. ESI-MS: m/z calcd for C₁₇H₂₆NaO₆: 349.1627; found: 349.1597 [M⁺ + Na].
Compound 9da (R = CH₂=CHCH₂): colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 2.10 (3 H, s), 2.21 (1 H, br s), 2.44 (2 H, d, J = 7.3 Hz), 3.60 (1 H, d, J = 12.0 Hz), 3.64 (1 H, d, J = 12.0 Hz), 3.78 (6 H, s), 4.21 (1 H, d, J = 12.0 Hz), 4.26 (1 H, d, J = 12.0 Hz), 4.52 (2 H, s), 5.14-5.20 (2 H, m), 5.81-5.92 (1 H, m), 6.38 (1 H, t, J = 2.2 Hz), 6.50 (2 H, d, J = 2.2 Hz). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.9, 35.2, 55.3, 63.2, 63.9, 64.3, 78.3, 99.4, 105.3, 118.9, 132.2, 140.9, 160.8, 171.1. IR (neat): 3483, 2939, 1741, 1599, 1464, 1238, 1205, 1155, 1055 cm^-¹. ESI-MS: m/z calcd for C₁₇H₂₄NaO₆: 347.1471; found: 347.1494 [M⁺ + Na].
Compound 9ea (R = Ph): colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 2.06 (3 H, s), 2.22 (1 H, br s), 3.79 (6 H, s), 3.88-3.99 (2 H, m), 4.30 (1 H, d, J = 11.5 Hz), 4.35 (1 H, d, J = 11.5 Hz), 4.64 (2 H, s), 6.38 (1 H, t, J = 2.2 Hz), 6.50 (2 H, d, J = 2.2 Hz), 7.32-7.36 (1 H, m), 7.38-7.45 (4 H, m). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.9, 55.3, 65.0, 65.3, 65.5, 80.5, 99.4, 105.2, 126.7, 128.3, 128.7, 138.5, 140.7, 160.9, 170.9. IR (neat): 3481, 2939, 1741, 1599, 1462, 1238, 1205, 1155, 1053 cm^-¹. ESI-MS: m/z calcd for C₂₀H₂₄NaO₆: 383.1471; found: 383.1466 [M⁺ + Na].

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