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Welcome to Stuart L, a new contributor to the cascade

We’re delighted to welcome a new contributor to the Chemistry Cascade – Stuart Leckie.

Stuart is a synthetic organic chemist whose main interest is in catalytic asymmetric transformations, although currently he has been side-tracked by a desire to save the planet and is working on the development of sustainable cross-coupling reactions.

He completed a Ph.D. looking at novel applications of NHCs and isothioureas as Lewis base organocatalysts and he is also interested in all things involving samarium diiodide, especially it’s application in total synthesis.

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Enantioselective α-Vinylation of Aldehydes via the Synergistic Combination of Copper and Amine Catalysis

Eduardas Skucas and David W. C. MacMillan
J. Am. Chem. Soc.
DOI: 10.1021/ja303116v

The stereoselective preparation of α-vinyl carbonyl compounds is a challenging task for synthetic chemists mainly due to their tendency to racemize under reaction conditions. MacMillan and Skucas report a multicatalysis protocol for the enantioselective α-vinylation of aldehydes under very mild conditions. Using vinyl iodonium triflate species as starting materials, an imidazolidinone organocatalyst to induce stereoselectivity, and a Cu(I) salt, they have devised an efficient and useful synthetic tool for the enantioselective preparation of β,γ-unsaturated aldehydes.

They propose that the Cu(I) catalyst undergoes an oxidative addition to the vinyl iodonium triflate substrate to form a highly electrophilic Cu(III) vinyl complex. At the same time, the imidazolidinone organocatalyst reacts with the aldehyde substrate to form the corresponding enamine. Complexation of the enamine with the Cu(III) species and subsequent reductive ellimination liberates the Cu(I) metal completing one of the catalytic cycles. Hydrolysis of the resulting imminium species yields the desired α-vinyl aldehyde and the imidazolidinone organocatalyst completing the second catalstic cycle.

The authors also investigated the scope of the reaction for both the aldehyde and vinyl coupling partners demonstrating that the protocol can tolerate sterically demanding β-branched aldehydes, protected heteroatoms, electron-poor styrenes as well as trisubstituted carbocycles. The stereochemical induction has been demonstrated to be completely under control of the organocatalyst as preexisting stereocentres do not influence the stereochemical outcome.

Utilising routine reactions, α-vinyl aldehydes can be transformed into a variety of compounds and used as versatile precursors for the synthesis of larger molecules.