Ring Expansion of Isopropenyldihydrofuran Derivatives.

Abstract

In our previous paper we reported a ring expansion of 5-isopropenyl-4,5-dihydrofuran-2,3-dicarboxylic acid (A) giving 6-methyl-4,7-dihydroxepin-2,3-dicarboxylic anhydride (B) [1], as shown in Scheme 1. It is thought that this ring expansion might be caused by the ring strain due to the 5-5 fused ring system in 5-isopropenyl-4,5-dihydrofuran-2,3-dicarboxylic anhydride (C), which might be formed through anhydride formation.In this paper, we describe a similar ring expansion in the lactone formation of some 2-(hydroxymethyl)-5-isopropenyl-4,5-dihydrofuran-3-carboxylic acids (1) giving corresponding 3-methyl-5,In accordance with the reported procedure [3], the starting material, diethyl 5-isopropenyl-4,5-dihydrofuran-2,3-dicarboxylate (4) was prepared through condensation of diethyl oxaloacetate with (E)-1,4-dibromo-2-methyl-2-butene. As describe in our previous paper [3], Grignard methylation of diester 4 with excess methylmagnesium bromide gave a half ester, ethyl 2-(1-hydroxy-1-methylethyl)-5-isopropenyl-4,5-dihydrofuran-3-carboxyl-ate (1c). This showed that the carbonyl might be inert for any nucleophile. Reduction of diester 4 with lithium borohydride gave another half ester, ethyl 2-(hydroxymethyl)-5-isopropenyl-4,5-dihydrofuran-3-carb-oxylate (1a'). For an approach to the third half ester, ethyl 2-(1-hydroxyethyl)-5-isopropenyl-4,5-dihydrofuran-3-carboxylate (1b'), 1a' was oxidized under Swern condition to ethyl 2-formyl-5-isopropenyl-4,5-dihydro-furan-3-carboxylate (5), and then 5 was subjected to Grignard methylation. However, the Grignard methylation of 5 with methylmagnesium bromide caused decomposition of the furan ring in any condition.

Total Synthesis of Oxepin and Dihydrooxepin Containing Natural Products

“…The developed strategy was later further expanded to the synthesis of radulanin E ( 91 ) via a three-step sequence (temporary protection, Vilsmeier formulation and selective oxidation). 23…”