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A Novel Synthesis of 2‐Alkoxy‐3‐hydroxytropones and 2,7‐Dihydroxytropones from Dialkoxy‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐ones
Author(s) -
Zinser Hartmut,
Henkel Sonja,
Föhlisch Baldur
Publication year - 2004
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.200300600
Subject(s) - chemistry , sodium methoxide , acetal , hemiacetal , bicyclic molecule , aldehyde , methanol , enol ether , alkoxy group , acetic acid , medicinal chemistry , organic chemistry , alkylation , ether , methyl iodide , aldol reaction , substituent , alkyl , catalysis
Trichloro‐substituted 8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐ones 6 and 7 are solvolysed by methanolic sodium methoxide to form the bicyclo[3.2.1] α,α‐dimethoxy ketones 13 and 14 , with preservation of one chloro substituent. In the case of 6a , prolonged reaction time with an excess of methanolic sodium methoxide provides a trimethoxy‐substituted oxanorbornene aldehyde 19 through ring contraction. Treatment of the mixture of 13 and 14 with zinc and aqueous acetic acid affords dechlorinated α‐oxo acetals 15 and 16 . Starting with the [4+3] cycloadducts derived from 2‐methylfuran and tetrachloroacetones ( 6b and 7b ), the same procedure, but with use of ethanol or trifluoroethanol, results in the corresponding ethoxy‐ and trifluoroethoxy acetals. These compounds can be converted into the oxabicyclic compounds 15 , which undergo cleavage of the ether bridge on heating with KOH in methanol, thus providing 2‐alkoxy‐3‐hydroxytropones 20 , which can be dealkylated to give the 2,7‐dihydroxytropones (7‐hydroxytropolones) 29 . The lithium enolate generated from the α‐oxo acetal 15a can be exo ‐alkylated with methyl iodide. Michael addition with 2‐nitro‐1‐butene followed by a Nef reaction furnishes the bicyclic dioxo acetal 5 . Treatment of 5 with basic methanol results in an epoxyazulenone derivative 26 , and a hydroxytropone 20f , which is in equilibrium with the cyclic hemiacetal form 28 . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)