Nickel-Catalyzed Enantioselective Synthesis of Pre-Differentiated Homoallylic syn- or anti-1,2-Diols from Aldehydes and Dienol Ethers.

Thomas Q Davies,Alois Fürstner,Maxime Dousset,John J Murphy

doi:10.1021/jacs.1c07042

Thomas Q Davies, Alois Fürstner + Show 2 more

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https://doi.org/10.1021/jacs.1c07042

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Abstract

Nickel catalysis allied with cyclodiphosphazane or VAPOL-derived phosphoramidite ligands provides selective access to monoprotected vicinal diols by reductive coupling of dienol ethers and aldehydes. The observed regioselectivity is unprecedented, in that the diene reacts at the least nucleophilic and most hindered C atom that is attached to the oxygen substituent rather than at the terminal position. Notably, both syn and anti diastereomers of the products can be accessed depending on the configuration of the diene partner with usually excellent diastereo- and enantioselectivity.

Highlights

Nickel catalysis allied with cyclodiphosphazane or VAPOL-derived phosphoramidite ligands provides selective access to monoprotected vicinal diols by reductive coupling of dienol ethers and aldehydes
The lack of catalyst control surfaced during a recent total synthesis campaign, where we tried to take advantage of nickel-catalyzed isoprenylations of sugar-derived aldehydes; the inability to overwrite the stereochemical bias of some substrates with the aid of chiral nickel complexes marked an inherent limitation of this approach.[14,15]
Our studies began with the coupling of silyloxydiene 7 with hydrocinnamaldehyde using Ni(cod)[2] as a catalyst and triethylborane as reductant

Summary

Introduction

Nickel catalysis allied with cyclodiphosphazane or VAPOL-derived phosphoramidite ligands provides selective access to monoprotected vicinal diols by reductive coupling of dienol ethers and aldehydes. Switching to the cyclodiphosphazane ligand L4 proved key,[37,38] with the diol product obtained with excellent regioselectivity, diastereoselectivity, and quantitative yield (NMR), though in virtually racemic form.

Results

Conclusion