Scalable Electrochemical Decarboxylative Olefination Driven by Alternating Polarity.

A mild, scalable (kg) metal-free electrochemical decarboxylation of alkyl carboxylic acids to olefins is disclosed. Numerous applications are presented wherein this transformation can simplify alkene synthesis and provide alternative synthetic access to valuable olefins from simple carboxylic acid feedstocks. This robust method relies on alternating polarity to maintain the quality of the electrode surface and local pH, providing a deeper understanding of the Hofer-Moest process with unprecedented chemoselectivity.

Overcoming the limitations of Kolbe coupling with waveform-controlled electrosynthesis.

The Kolbe reaction forms carbon-carbon bonds through electrochemical decarboxylative coupling. Despite more than a century of study, the reaction has seen limited applications owing to extremely poor chemoselectivity and reliance on precious metal electrodes. In this work, we present a simple solution to this long-standing challenge: Switching the potential waveform from classical direct current to rapid alternating polarity renders various functional groups compatible and enables the reaction on sustainable carbon-based electrodes (amorphous carbon). This breakthrough enabled access to valuable molecules that range from useful unnatural amino acids to promising polymer building blocks from readily available carboxylic acids, including biomass-derived acids. Preliminary mechanistic studies implicate the role of waveform in modulating the local pH around the electrodes and the crucial role of acetone as an unconventional reaction solvent for Kolbe reaction.

Ni-electrocatalytic Csp3-Csp3 doubly decarboxylative coupling.

Cross-coupling between two similar or identical functional groups to form a new C-C bond is a powerful tool to rapidly assemble complex molecules from readily available building units, as seen with olefin cross-metathesis or various types of cross-electrophile coupling1,2. The Kolbe electrolysis involves the oxidative electrochemical decarboxylation of alkyl carboxylic acids to their corresponding radical species followed by recombination to generate a new C-C bond3-12. As one of the oldest known Csp3-Csp3 bond-forming reactions, it holds incredible promise for organic synthesis, yet its use has been almost non-existent. From the perspective of synthesis design, this transformation could allow one to agnostically execute syntheses without regard to polarity or neighbouring functionality just by coupling ubiquitous carboxylates13. In practice, this promise is undermined by the strongly oxidative electrolytic protocol used traditionally since the nineteenth century5, thereby severely limiting its scope. Here, we show how a mildly reductive Ni-electrocatalytic system can couple two different carboxylates by means of in situ generated redox-active esters, termed doubly decarboxylative cross-coupling. This operationally simple method can be used to heterocouple primary, secondary and even certain tertiary redox-active esters, thereby opening up a powerful new approach for synthesis. The reaction, which cannot be mimicked using stoichiometric metal reductants or photochemical conditions, tolerates a range of functional groups, is scalable and is used for the synthesis of 32 known compounds, reducing overall step counts by 73%.

Catalytic asymmetric synthesis of stable oxetenes via Lewis acid-promoted [2+2] cycloaddition.

A highly enantioselective and atom-economical [2 + 2] cycloaddition of various alkynes with trifluoropyruvate using a dicationic (S)-BINAP-Pd catalyst has been established. This is the first enantioselective synthesis of stable oxetene derivatives, whose structure has been clarified by X-ray analysis. This catalytic process offers a practical synthetic method for oxetene derivatives (catalyst loading: up to 0.1 mol %), which can serve as novel chiral building blocks for pharmaceuticals and agrochemicals and can also be transformed into a variety of enantiomerically enriched CF(3)-substituted compounds with high stereoselectivity.

Highly enantioselective alkynylation of trifluoropyruvate with alkynylsilanes catalyzed by the BINAP-Pd complex: access to α-trifluoromethyl-substituted tertiary alcohols.

A highly enantioselective alkynylation catalyzed by the dicationic (S)-BINAP-Pd complex with a variety of alkynylsilanes and trifluoropyruvate is described. The catalytic reaction is applicable to highly enantioselective addition of polyyne to trifluoropyruvate to construct α-trifluoromethyl-substituted tertiary alcohols as enantiomerically enriched forms. The alkynyl products can be converted into a chiral allene bearing a trifluoromethyl group.

Highly enantioselective alkenylation of glyoxylate with vinylsilane catalyzed by chiral dicationic palladium(II) complexes.

Chiral dicationic palladium complex-catalyzed vinylation and dienylation of glyoxylate with vinylsilanes and dienylsilanes to produce highly optical active allylic alcohols has been achieved. The advantages of this reaction are that the chiral palladium catalyst is readily employed and that vinylsilanes as nucleophiles are easily synthesized, storable, and air- and moisture-stable.