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Synthetic Approaches to Hydroazulenes and Guaianes through [4 + 3] Cycloadditions of Oxyallyl Intermediates
Author(s) -
Föhlisch Baldur,
Flogaus Robert,
Henle Gerhard H.,
Sendelbach Stefan,
Henkel Sonja
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200500777
Subject(s) - chemistry , aldol reaction , ketone , diketone , aldol condensation , medicinal chemistry , organic chemistry , enone , acetal , thioester , hydrogenolysis , sodium hydroxide , decarboxylation , catalysis , enzyme
Building blocks for syntheses of guaiane and secoguaiane sesquiterpenoids were prepared by the title reaction. 4‐(3‐Methylfuran‐2‐yl)butan‐2‐one ( 1 ) was obtained in five steps from methyl 3‐methylfuran‐2‐carboxylate ( 4 ), and treatment of 1 with pentachloroacetone and sodium 2,2,3,3‐tetrafluoropropoxide in 2,2,3,3‐tetrafluoropropan‐1‐ol produced a [4 + 3] cycloadduct that was dechlorinated without prior isolation to give the oxabicyclic diketone 2 in a low yield. A better route to diketone 2 was via the oxabicycle 10b , prepared in a high yield from 2‐(but‐3‐en‐1‐yl)‐3‐methylfuran ( 9 ) and pentachloroacetone, followed by dechlorination. Treatment of 2 with dilute methanolic potassium hydroxide resulted in the cleavage of the oxa bridge, with formation of 3,8‐dimethylazulen‐4‐ol ( 11 ). Catalytic hydrogenation of 2 afforded the saturated oxabicyclic diketone 14 , intramolecular aldol condensation of which gave the tricycle 15 . The oxa bridge of the oxatricyclic enone 15 was cleaved by hydrogenolysis in the presence of palladium/carbon catalyst to give the 6‐hydroxydecahydroazulen‐4‐one 16 . Treatment of isobutyl trichloromethyl ketone ( 20 ) with furan 9 and sodium trifluoroethoxide in trifluoroethanol eventually gave the 2‐chlorooxabicycle 22 . This solvolysis product was dechlorinated to furnish the oxabicyclic trifluoroethoxy ketone 24 as a single product that was subjected to the sequence of transformations used for 10b . X‐ray structure analysis of the resulting saturated diketone 26 established the endo configuration of the isopropyl group. Finally, aldol cyclization of 26 furnished the guaiane derivative 27 . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)