Enantioenriched Molecules out of the Power Outlet

Published in Chemistry
Enantioenriched Molecules out of the Power Outlet

Organic electrosynthesis has recently attracted significant attention as a synthetic platform for redox reactions since the electrons come right out of a battery or electrical outlet instead of relying on stoichiometric amounts of waste-generating chemical oxidants and reductants. Along these lines, it is desirable to combine electrosynthesis with asymmetric catalysis because single enantiomer compounds are in ever increasing demand for the production of drugs, agricultural chemicals, flavors, fragrances, and materials. However, the challenge is to identify suitable catalysts which combine compatibility with the conditions within an electrochemical cell and at the same time provide selective chemical activation and high stereocontrol.

Inspiration for this work came from our previous work on intertwining asymmetric catalysis with photoredox chemistry employing bis-cyclometalated iridium and rhodium complexes as chiral Lewis acid catalysts, in which single electron transfer processes play a central role. For this study we envisioned that our catalyst might be able to selectively activate a bound substrate towards electrochemical oxidation by raising the HOMO and that the hereby formed catalyst-bound reactive intermediates would undergo stereocontrolled chemistry. In this design, the chiral catalyst assists in the anodic oxidation, and hence mild conditions with better tolerance can be expected.

A recently by the company IKA Inc. in collaboration with Prof. Phil Baran developed electrochemical device (ElectraSyn 2.0) facilitated our extensive screening efforts. Specifically, we found that our bis-cyclometalated chiral rhodium catalysts enable the oxidative cross-coupling of 2-acyl imidazoles with silyl enol ethers to provide a sustainable avenue to synthetically useful 1,4-dicarbonyl compounds, including products bearing all-carbon quaternary stereocenters. Using very mild redox conditions, high chemo- and enantioselectivities (up to >99% ee) were obtained.

The chiral Lewis acid catalyst is both involved in the electrochemical step and the asymmetric induction. It fulfils several important functions by facilitating the selective oxidation of the substrate only upon coordination to the catalysts, by staying bound to the oxidatively formed radical intermediate and thereby preventing unwanted side reactions such as homo-coupling, and by providing a high asymmetric induction in the course of the new C-C bond formation. We believe that this work demonstrates the potential of combining asymmetric Lewis acid catalysis with electrochemistry and we anticipate that it will spur the further development of catalytic asymmetric electrosynthesis.

For more details, see our paper: "Electricity Driven Asymmetric Lewis Acid Catalysis".  https://www.nature.com/articles/s41929-018-0198-y

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