Synthesis of α‐Quaternary Aldehydes via a Stereoselective Semi‐Pinacol Rearrangement of Optically Active Epoxy Alcohols

Abstract

This article describes a Lewis-acid-promoted semipinacol rearrangement of chiral epoxy alcohols to provide chiral β-hydroxy aldehydes with a quaternary center at the α-position that are otherwise difficult to access in modern organic synthesis. The aldehydes thus obtained are highly useful synthetic intermediates, which is demonstrated by the synthesis of a serotonin antagonist.[a] N.

Desymmetric Partial Reduction of Malonic Esters

“…Our recent discovery of a dinuclear zinc catalyst has enabled the selective hydrosilylation of a single carbonyl in malonic esters to a primary alcohol . While the asymmetric reduction creates ample capacity of derivatization by generating an alcohol that is much lower in oxidation state than the remaining ester, enabling a partial reduction to the α-quaternary aldehyde is equally attractive and would fill an important gap of reactivity. Particularly, the electrophilicity of aldehyde can further unravel the potential of the desymmetric hydrosilylation, as it allows for the reactions of the chiral aldehydes with a plethora of nucleophiles to generate useful motifs like unsaturated bonds and additional stereocenters.…”

Cascade Sequence of Photooxygenation–Epoxidation for the Flow Synthesis of Epoxy Alcohols

“…Epoxy alcohols are valuable building blocks for organic synthesis. − For instance, their semipinacol rearrangements are useful alternatives to aldol and related reactions for synthesizing β-hydroxycarbonyl compounds. − To date, considerable effort has been directed toward improving the synthetic routes to epoxy alcohols, as exemplified by the eco-friendly method reported by Adam and Nestler. − According to this method, the hydroperoxides, generated via the photooxygenation of alkenes using green, nontoxic, and inexpensive O 2 gas, are converted to epoxy alcohols through secondary epoxidation in the absence of additional oxidants. However, further research on the combination of the first (photooxygenation) and second (epoxidation) steps is required to reduce the reaction time and improve product yields.…”