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DOI: 10.1055/s-0030-1257890
Tetrahydropyran Synthesis by Intramolecular Conjugate Addition to Enones: Synthesis of the Clavosolide Tetrahydropyran Ring
Publication History
Publication Date:
22 July 2010 (online)
Abstract
The synthesis of a tetrahydropyran intermediate for clavosolide A is reported, employing a combination of cross-metathesis and intramolecular oxa-Michael addition. The intramolecular oxa-Michael addition to α,β-unsaturated esters requires the use of strong bases and can result in either modest yields or stereoisomeric mixtures, and can be highly variable according to the substrate structure. In contrast, the corresponding ketones cyclise under very mild conditions to give the 2,6-cis-isomers directly. The use of appropriately substituted ketones allows efficient conversion into esters.
Key words
Michael addition - tandem reaction - cyclisation
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References
Data for the trans-isomer of tetrahydropyran 2: [α]D ²5 +90.6 (c 0.28, CH2Cl2). IR (neat): 3054, 2952, 2926, 2855, 1714, 1434, 1315, 1200, 1177, 1098, 898 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 0.99 (3 H, d, J = 6.9 Hz), 1.20-1.32 (2 H, m), 1.47 (1 H, d, J = 3.0 Hz), 1.75-1.91 (2 H, m), 1.99 (1 H, ddd, J = 12.5, 4.3, 2.6 Hz), 2.44 (1 H, dd, J = 14.5, 4.4 Hz), 2.65 (1 H, dd, J = 14.5, 11.0 Hz), 3.48-3.62 (3 H, m), 3.66 (3 H, s), 3.85-3.89 (1 H, m), 4.43 (1 H, ddd, J = 10.8, 5.1, 4.9 Hz), 4.48 (1 H, d, J = 11.8 Hz), 4.54 (1 H, d, J = 11.8 Hz), 7.26-7.36 (5 H, m). ¹³C NMR (75 MHz, CDCl3): δ = 172.0, 138.5, 128.4, 127.7, 127.5, 73.9, 73.1, 69.7, 66.9, 66.7, 51.7, 41.0, 40.4, 36.0, 33.4, 13.1. MS (EI): m/z = 345 (M + Na), 323 (M + H), 214. HRMS (EI): m/z calcd for C18H27O5 (M + H): 323.1858; found: 323.1859.
17The enantiomer was prepared by White et al. (ref. 5b).