A Flexible Synthesis of Polypropionates via Diastereodivergent Reductive Ring‐Opening of Trisubstituted Secondary Glycidols

Abstract Polypropionates, characterized by their alternating sequence of stereocenters bearing methyl‐ and hydroxy‐groups, are structurally diverse natural products of utmost importance. [1] Herein, we introduce a novel concept approach towards polypropionate synthesis featuring a diastereodivergent reductive epoxide‐opening as a key step. Readily available and stereochemically uniform trisubstituted sec‐glycidols serve as branching points for the highly selective synthesis of all isomers of polypropionate building blocks with three or more consecutive stereocenters. Stereodiversification is accomplished by an unprecedented mechanism‐control over the stereochemically complementary modification of the epoxide's tertiary C‐atom with excellent control of regio‐ and stereoselectivity. Since our method is not only suited for the preparation of specific targets but also for compound libraries, it will have a great impact on polypropionate synthesis.