A Facile and Practical Synthesis of Nicolaou’s Key Intermediates, 2-Methyl- and 2,6-Dimethyltetrahydropyrans, toward the Total Synthesis of Ladder-Shaped Polyethers

This paper is dedicated to the memory of Choji Ueno.

Abstract

A facile and robust method to prepare 2-methyl- and 2,6-dimethyltetrahydropyrans, most useful Nicolaou intermediates for the synthesis of ladder-shaped polyethers, is disclosed. The established highly practical recipe, adopting chemo- and stereoselective catalytic oxidations and one-pot reactions with few chromatographic purifications, would significantly facilitate the large-scale supply of pivotal monocyclic building blocks, which is a rate-determining process of gigantic tetrahydropyran-containing natural products synthesis.

Key words

total synthesis - ladder-shaped polyethers - trans/syn/trans-fused-ring system - one pot - selective oxidation

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