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Synlett 2003(14): 2182-2184  
DOI: 10.1055/s-2003-42060
LETTER
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Synthesis of 4,5-Disubstituted 3-Hydroxy δ-Lactones: Prelactone B and Prelactone V

Dieter Enders*, Mareile Haas
Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule Aachen, Professor-Pirlet-Str. 1, 52074 Aachen, Germany
Fax: +49(241)8092127; e-Mail: Enders@RWTH-Aachen.de;
Further Information

Publication History

Received 13 August 2003
Publication Date:
07 October 2003 (online)

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Abstract

An efficient asymmetric synthesis of δ-lactones such as prelactone B has been developed. As key steps, the SAMP/RAMP-hydrazone methodology for the synthesis of 2-methylenated 1,3-diols and a homogenous hydrogenation were used.

Key words

asymmetric synthesis - prelactone B - hydrazones - hydrogenation - Crabtree’s catalyst

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General Procedure for 4,6-Disubstituted 2,2-Dimethyl-1,3-dioxan-5-ones: t-BuLi (5 mmol, 15% in pentane) was added dropwise to a solution of RAMP-hydrazone (5 mmol) in anhyd THF (25 mL) at -78 °C. After stirring for 2 h the mixture was cooled to -100 °C and the electrophile (6 mmol) was added slowly. The mixture was allowed to warm up to r.t. over 15 h. The reaction mixture was quenched with a buffer solution (pH = 7, 5 mL) and diluted with Et2O (30 mL). The aq layer was extracted with Et2O. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. For alkylation at α′-position the procedure was repeated. The product hydrazone was dissolved in Et2O (50 mL) and a sat. aq solution of oxalic acid was added at r.t. The bi-phase system was stirred vigorously at r.t. until the reaction was completed (TLC control). The layers were separated and the aq phase was extracted with Et2O. The combined organic layers were washed with brine and dried over MgSO4. The solvent was removed under reduced pressure. Purification was carried out by flash chromatography (SiO2; pentane-Et2O, 2:1).

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Prelactone B (1a): Mp 90 °C; [α]D 25 +37.8 (c 1.10, MeOH). IR: 3473, 2970, 2929, 2882, 1717, 1468, 1383, 1310, 1273, 1230, 1192,3, 1103, 1064, 1004, 847, 819, 705, 620, 579
cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.93 (d, J = 6.9 Hz, 3 H, 6-CH3), 1.07 (d, 3 H, J = 6.6 Hz, 4-CH3), 1.10 (d, 3 H, J = 7.1 Hz, 6-CH3), 1.75 (ddq, J = 10.2 Hz, 8.2, 6.6, 1 H, H-4), 1.99 (dsept, J = 2.2 Hz, 7.0, 1 H, H-5), 2.49 (dd, J = 7.9 Hz, 17.3, 1 H, H-2a), 2.93 (dd, J = 6.0 Hz, 17.3, 1 H, H-2b), 3.77 (m, 2 H, H-3, H-5). 13C NMR (100 MHz, CDCl3): δ = 13.76, 14.24, 20,18, 29.09, 39.13, 39.20, 69.93, 86.33, 171.61. MS (EI, 70 eV): m/z (%) = 130 (30), 129 (100), 112 (6), 111 (90), 100 (10), 87 (78), 84 (15), 83 (14), 82 (8), 73 (20), 72 (8), 71 (25), 69 (9), 59 (40), 58 (84), 57 (23), 55 (22). Anal. Calcd. for C9H16O3: C, 62.77; H, 9.36. Found: C, 63.00; H, 9.57.

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(R,R,R,)-Tetrahydro-4-hydroxy-5,6-methyl-2H-pyran-2-one (prelactone V, 1b): Mp 46 °C; [α]D 25 +38.9 (c 1.17, MeOH). IR: 3435, 2980, 2932, 1730, 1383, 1267, 1095, 1046, 979 cm-1. 1H NMR (400 MHz, C5D5N): δ = 1.09 (d,
J = 7.0 Hz, 3 H, 5-CH3), 1.28 (d, J = 6.1 Hz, 3 H, 4-CH3), 1.75 (ddq, J = 10.2 Hz, 7.2, 6.8, 1 H, H-4), 2.82 (dd, J = 7.2 Hz, 16.6, 1 H, H-2a), 3.13 (dd, J = 5.6 Hz, 16.6, 1 H, H-2b), 3.93 (dtr, J = 5.7 Hz, 7.2, 2 H, H-3), 4.00 (q, J = 6.2 Hz, 10.1, 2 H, H-3). 13C NMR (100 MHz, C5D5N): δ = 14.12, 19.49, 39.90, 44.06, 69.23, 78.65, 170.91. MS (CI): m/z (%) = 146 (10), 145 (73), 117 (90), 109 (13), 102 (9), 89 (100), 85 (56), 83 (17), 81 (7) 71 (11). Anal. Calcd. for C7H12O3:
C, 58.32; H, 8.39. Found: C, 58.15; H, 8.10.