IBX Oxidations for the Synthesis of Substituted 2H-Pyrans

Abstract

Facile oxidation of highly substituted 3,5-hexadien-1-ols using 3-iodoxybenzoic acid (IBX) in DMSO has resulted in a one-pot preparation of 2,3,4,6-tetrasubstituted 2H-pyrans.Cycloisomerizations of the 1-oxatriene moiety, produced in the oxidation, spontaneously occur via a disrotatory oxa-electrocyclization. The 2H-pyran products of Table 1 features three differentiated carbonyl substituents. In Celebration of Professor Yasuyuki Kita on His 77th BirthdayThe pyran heterocycle is a common structural motif found within pharmaceuticals, agrichemicals, and biologically active natural products. Several reviews have summarized a variety of techniques for the preparation of substituted pyrans. 1 Methods for the synthesis of tetrahydropyrans have been extensivelyexplored, and we have previously described a general strategy using asymmetric S E ' allylation reactions for enantiocontrolled syntheses of substituted tetrahydropyrans 2,3 Similarly, the formation of dihydropyrans has attracted much attention because these structural motifs also appear within naturally-occurring macrolactones of biological interest. 4 While syntheses of tetrahydropyrans and dihydropyrans are often focused on issues of stereochemistry and efficient strategies for regiocontrolled substitutions, the increased unsaturation of 2H-pyrans results in the characterization of notably less stable species. Successful methods toward substituted derivatives of this reactive family of pyrans are generally limited in scope.In this communication, we report an efficient preparation of 2H-pyrans stemming from 3-iodoxybenzoic acid (IBX) oxidations of highly substituted 3,5-hexadien-1-ols with in situ electrocyclization. The formation of 2H-pyrans via the oxa-electrocyclization reaction has been reported by several investigators in the course of studies for natural product synthesis, 5 and a recent review has compiled key strategies for