3- Methoxyfuran, reaction with dienophiles

The introduction of a nitro or trifluoromethyl group at the C-3 position on the pyridine ring in 3-(2-pyridylsulfinyl)acrylates has been shown to enhance the reactivity and diastereoselectivity of the dienophile in the Diels-Alder reaction with furan and its derivatives [171]. Such a modification of the dienophile renders the addition of diethylaluminium chloride unnecessary in order to achieve the desired asymmetric cycloaddition. The cycloadduct (207), prepared with high stereoselectivity from the asymmetric Diels-Alder reaction between (5)-menthyl 3-(3-trifluoromethylpyrid-2-ylsulfinyl)acrylate (194) and 2-methoxyfuran (208), was converted in seven steps to the glyoxalase I inhibitor (209) [171] (Scheme 5.67). 

Copper(I) and copper(II) salts have been shown to catalyze the reaction of furan with -acetoxyacrylonitrile (CH2=C (OAc)CN). Alkoxy and silyloxy groups activate the furan nucleus to cycloaddition reactions, e.g., 3-methoxyfuran readily undergoes [4 + 2] cycloaddition with electron-deficient dienophiles with regio- and stereo-control to give endo-adducts (Scheme 97). 

Furan also undergoes cycloadditions with allenes," " with benzyne" and with simpler dienophiles, like acrylonitrile and acrylate various Lewis acidic catalysts can assist" in some cases, zinc iodide is one such, hafnium tetrachloride another, and improved endo exo ratios are obtained in an ionic liquid as reaction solvent. Maleate and fumarate esters react if the addition is conducted under high pressure. This device can also be used to increase markedly the reactivity of 2-methoxyfuran and 2-acetoxyfuran towards dienophiles. At higher reaction temperatures alkynes and even electron-rich alkenes will add to furan. 3- or 5-Halo-furans react faster in these cycloadditions. ... 

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