A useful protocol for achieving decarboxylative cross-coupling
(DCC) of redox-active esters (RAE, isolated or generated in situ)
and halo(hetero)arenes is reported. This pragmatically focused study
employs a unique Ag–Ni electrocatalytic platform to overcome
numerous limitations that have plagued this strategically powerful
transformation. In its optimized form, coupling partners can be combined
in a surprisingly simple way: open to the air, using technical-grade
solvents, an inexpensive ligand and Ni source, and substoichiometric
AgNO3, proceeding at room temperature with a simple commercial
potentiostat. Most importantly, all of the results are placed into
context by benchmarking with state-of-the-art methods. Applications
are presented that simplify synthesis and rapidly enable access to
challenging chemical space. Finally, adaptation to multiple scale
regimes, ranging from parallel milligram-based synthesis to decagram
recirculating flow is presented.
A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI 2 (which cannot accomplish the same reaction).
There
is a strong parallel between simple alcohol oxidation and
carbonyl desaturation from both strategic and tactical vantage points.
As they both seek to extract hydrogen from an organic substrate, they
are deceptively simple looking transformations that have been addressed
over the past 70+ years through stoichiometric means. The past decade
has seen an intensifying level of interest in rendering both of these
simple reactions catalytic. In this Perspective, recent advances from
the past 5 years are highlighted featuring both transition-metal-catalyzed
and metal-free approaches to carbonyl desaturation. Through a historical
overview and a detailed look at each of these new developments, we
seek to address the question of in what context a catalytic strategy
emerges as ideal.
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