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

Hirama, Naomichi; Sakamoto, Ryu; Maruoka, Keiji

doi:10.1002/ajoc.201900299

Cited by 6 publications

(2 citation statements)

References 65 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Desymmetric Partial Reduction of Malonic Esters

Liu

Huang

2022

J. Am. Chem. Soc.

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Desymmetrization of easily available disubstituted malonic esters is a rewarding strategy to access structurally diverse quaternary stereocenters. Particularly, asymmetric reduction of malonic esters would generate a functional group with a lower oxidation state than the remaining ester, thus allowing for more chemoselective derivatization. Here, we report a new set of conditions for the zinccatalyzed desymmetric hydrosilylation of malonic esters that afford aldehydes as the major product. Compared with alcohol-selective desymmetrization, the partial reduction uses a higher concentration of silanes and new pipecolinol-derived tetradentate ligands, proposedly to switch the pathway of zinc hemiacetal intermediates from elimination to silylation. As a result, high aldehyde-to-alcohol ratios and enantioselectivity of aldehydes are obtained from malonic esters with a large collection of substituents. Together with the abundant reactivity of aldehydes, the partial reduction has enabled an expeditious synthesis of bioactive compounds and natural metabolites containing a quaternary stereocenter.

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Section: Introductionmentioning

confidence: 99%

Desymmetric Partial Reduction of Malonic Esters

Liu

Huang

2022

J. Am. Chem. Soc.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Kim,

Son,

Lim

et al. 2024

J. Org. Chem.

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A photooxygenation−epoxidation cascade sequence converting alkenes to epoxy alcohols was developed and evaluated in batch and continuous-flow systems. In the batch system, the undesired interactions between the photooxygenation and epoxidation catalysts resulted in suboptimal yields, whereas the fine control of reaction parameters in the flow system allowed the allyl hydroperoxides produced through photooxygenation of alkenes to be rapidly converted to epoxy alcohols in yields of up to 93%. The developed procedure allows one to avoid an important synthetic bottleneck, works well where traditional batch synthesis fails, and can be scaled up to meet the needs of industrial production, thus presenting a valuable addition to the toolbox of practicing organic chemists.

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New Synthetic Approaches for the Construction of Enantioenriched Molecules Bearing Quaternary Stereocenters

Sun,

Liu,

Shi

et al. 2024

Adv Synth Catal

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Optically active molecule architectures stand as an important class of organic compounds and occupy a key role in academic and industrial communities. Particularly, the molecules bearing quaternary carbon are of vital importance because of its favorable conformation and valuable three‐dimensional molecules, which frequently play a key role in a broad spectrum of functional materials, pharmaceutical relevant natural molecules, and agrochemicals. Over the past few decades, a large amount of synthetic strategies for the enantioselective construction of compounds with chiral quaternary carbon centers have been the focus of a number of research initiatives. In this review, the state‐of‐the‐art toward the synthesis of enantioenriched molecules bearing quaternary stereocenters are summarized, which could be segmented into four categories: 1) Construction of optically active quaternary carbon centers by addition to prochiral sp2 carbon; 2) Construction of optically active all‐carbon quaternary stereocenters via substitution at non‐chiral tetra‐substituted carbon; 3) Construction of optically active all‐carbon quaternary stereocenters via kinetic resolution; 4) Construction of optically active all‐carbon quaternary stereocenters via desymmetrization reactions.

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

Cited by 6 publications

References 65 publications

Desymmetric Partial Reduction of Malonic Esters

Desymmetric Partial Reduction of Malonic Esters

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

New Synthetic Approaches for the Construction of Enantioenriched Molecules Bearing Quaternary Stereocenters

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