Selective Synthesis of Benzyl Enol Ethers of β-Dicarbonyl Compounds in Basic Condition and the Application towards Synthesis of Naphthoquinones

Abstract

Selective synthesis of benzyl enol ether of -tetronic acids and -dicarbonyl compounds in basic condition was examined. Benzylation of -methyl--tetronic acid with benzyl tosylate in the presence of potassium carbonate gave the corresponding benzyl enol ether exclusively. The reaction of -tetronic acid and cyclic 1,3-diketones gave the O-benzyl adducts preferentially than the C,O-dibenzylated ones. Diels-Alder reaction of furan derived the benzyl enol ether of -methyl--tetronic acid and benzyne furnished the functionalized napthoquinone derivatives. Enol ethers of -tetronic acids (4-O-alkyl -tetronates) 1 are versatile building blocks in natural product synthesis and medicinal chemistry (Figure 1). 1 Synthesis of these compounds is normally achieved by treating -tetronic acids 2 and alcohols in the presence of acid catalyst. 2 Mitsunobu reaction condition 3 and alkylation in basic condition 4 are another candidates and can be applicable to acid-sensitive substrates.The drawback of these conditions is the selectivity of C-/ O-alkylation, in which C-alkylated 3 (or C,O-dialkylated 4) -dicarbonyl compounds can be generated in this reaction system. For example, CsF-mediated O-selective alkylation of tetronic acid was achieved in high selectivity with alkyl halides with low reactivity such as ethyl iodide, however, low selectivity was observed when more reactive alkyl halide such as benzyl bromide was utilized. 4b As a part of our projects of synthetic studies of natural products including naphthoquinones such as teretifoliones B (5), 5 we have planned construction of oxygen- † This article is dedicated to Professor Victor Snieckus on the occasion of his 77th birthday.