Furans, alkyl-, ring-opening

Fischer indole synthesis, 91-95 Formamidine disulfide, salts of, 281, 282 Formazans, oxidation of, 37 Furans, alkyl-, ring-opening of, 63... 

Ring opening is common in the alkali metal and liquid ammonia reduction of furans unless an anion stabilizing group is present, so most work has been done with derivatives of furancarboxylic acids. Treatment of furan-2-carboxylic acid with lithium and ammonia at -78 °C followed by rapid addition of ammonium chloride affords 2,5-dihydrofuran-2-carboxylic acid (80%). Reductive alkylation similarly gives 2-alkyl-2,5-dihydrofuran-2-carboxylic acids. This method has been used in a synthesis of rosefuran, the intermediate dihydrofuran (66) being converted into the product (67) by oxidative decarboxylation with... 

Arenes and heteroarenes which are particularly easy to metalate are tricarbo-nyl( 76-arene)chromium complexes [380, 381], ferrocenes [13, 382, 383], thiophenes [157, 158, 181, 370, 384], furans [370, 385], and most azoles [386-389]. Meta-lated oxazoles, indoles, or furans can, however, be unstable and undergo ring-opening reactions [179, 181, 388]. Pyridines and other six-membered, nitrogen-containing heterocycles can also be lithiated [59, 370, 390-398] or magnesiated [399], but because nucleophilic organometallic compounds readily add to electron-deficient heteroarenes, dimerization can occur, and alkylations of such metalated heteroarenes often require careful optimization of the reaction conditions [368, 400, 401] (Schemes 5.42 and 5.69). 

Furan undergoes 1,4-addition with ethoxycarbonylnitrene to give 197 (Z = 0) which rearranges to the pyrrolinone 198. The corresponding reaction with pyrrole gives a mixture of 199 and 200. Ethoxycarbonylnitrene attacks thiophene and its simple alkyl derivatives at the -position subsequent ring opening and reclosure with loss of sulfur leads to pyrroles. 

The majority of the bicyclic cyclopropanes so obtained undergo facile acid-catalyzed ring open-ing/isomerization to the corresponding (Z,Z)-6-oxohexa-2,4-dienoates this transformation already occurs when the workup by column chromatography is performed on silica gel rather than on alumina. Treatment of the bicyclic systems (as well as the E,Z- and Z,Z-dienes) with iodine in dichloromethane results in isomerization to (is,is)-l,4-diacylbuta-l,3-dienes in high yield.The ring-opened products in carbenoid reactions of furans are not likely to result from isomerization of the alkyl-2-oxabicyclo[3.1.0]hex-3-ene-e c/o-6-carboxylates. For mechanistic proposals, see refs 300 and 301. 

Furan and the simple alkyl-furans are relatively stable to aqueous mineral acids, though furan is instantly decomposed by concentrated sulfuric acid or by Lewis acids, such as aluminium chloride. Furan reacts only slowly with hydrogen chloride, either as the concentrated aqueous acid or in a non-hydroxylic organic solvent. Hot, dilute aqueous mineral acids cause hydrolytic ring opening. 

Considerable attention has been paid to the photochemistry of cyclobutanones and in particular to their ring-expansion in alcohol solvents to 2-alkoxytetrahydro-furans. The ring-expansion reaction is believed to involve the generation of an a-oxa-carbene, and evidence for this has now been adduced from spectroscopic observations made during the irradiation of 2,2,4,4-tetramethylcyclobutanone. However, the earlier suggestion that this intermediate is formed by opening of the cyclobutanone to a 1,4-alkyl-acyl biradical, which then closes to the five-membered ringcarbene. 

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