Diels–Alder adducts of 2-acetoxyfuran as a route to 2,3-functionalized 4-hydroxycyclohexanones. Application of X-ray diffraction to the problem of regio- and stereochemistry

Abstract

The Diels–Alder adducts of 2-acetoxyfuran and maleic anhydride and 2-acetoxyfuran and chloromethylmaleic anhydride have been obtained and their dihydro derivatives manipulated in high yield to various 2,3-functionalized 4-hydroxycyclohexanones. In all cases the hemiketal acetate bridge of the oxabicyclo[2.2.1] derivatives was cleaved smoothly using sodium methoxide in methanol at 0 °C; however, in the case of the chloromethyl compounds the reaction proceeds further to give an almost quantitative yield of the corresponding fused cyclopropane derivatives. These sequences, starting from the readily accessible but seldom used 2-acetoxyfuran, are therefore extremely advantageous to gain rapid and efficient access to a number of 2,3-functionalized 4-hydroxycyclohexanones. In the case of the adduct involving chloromethylmaleic anhydride, stereochemistry and regiochemistry were established by X-ray diffraction on the dihydro derivative.

Using ring-opening reactions of oxabicyclic compounds as a strategy in organic synthesis

“…The oxabicyclic compounds required for this sequence can be assembled using 2-oxygenated furans. Gravel and Brisse synthesized the oxabicyclic substrate 150 by the Diels-Alder reaction between 2-acetoxyfuran and chloromethyl maleic anhydride [150]. Ring-opening was induced by treatment with methanolic hydrogen chloride to give hydroxycyclohexanone 151, Eq.…”

Five-membered heteroaromatic rings as intermediates in organic synthesis

“…Protecting-group chemistry has also benefited from a potentially valuable procedure wherein primary amines are converted, upon exposure to hexane-2,5dione, to 2,5-dimethylpyrroles, e.g., 35. Such deriva-…”

“…Cyclohexanone derivatives, potentially useful synthetic intermediates, can be arrived at by way of Diels-Alder additions using 2-acetoxyfuran. 35 Initial treatment with maleic anhydride leads to 41, which upon hydrogenation, selective reduction with NaBH4, and methoxide cleavage affords 42. Acetylation to 43 conclusively demonstrated the regiospecific nature of the hydride reduction. Furan has been employed in a Diels-Alder sense as a means of constructing the previously unknown, theoretically interesting dibenzo[2.2]paracyclophane 46. Base-induced formation of acetylene 44 followed by [4 + 2] cycloaddition leads to 45, which is deoxygenated by a low-valent titanium species generated in situ.36a…”