Ni-Electrocatalytic C(sp3)–C(sp3) Doubly Decarboxylative Coupling

This work presents a modern spin on one of the oldest known Csp3–Csp3 bond forming reactions in synthetic chemistry: the Kolbe electrolysis. This reaction holds incredible promise for synthesis, yet its use has been near non-existent in mainstream organic synthesis. In contrast to the strongly oxidative electrolytic protocol employed traditionally since the 19th century, the present method utilizes in situ generated redox-active esters (RAEs) which are combined with a mildly reductive Ni-electrocatalytic cycle. It can be used to heterocouple 1o, 2o, and even certain 3o RAEs with a protocol reminiscent of amide bond formation in terms of simplicity. Due to its mild nature the reaction tolerates a range of functional groups, is scalable, and was strategically enlisted for the synthesis of 25 known compounds to reduce overall step-counts by 74%.

Carbene and Photocatalyst-Catalyzed Decarboxylative Radical Coupling of Carboxylic Acids and Acyl Imidazoles to Form Ketones

The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile and a radical precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized radical precursors and two-component coupling. Herein, an N-heterocyclic carbene and photocatalyst catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles is disclosed, in which the carboxylic acids were directly used as radical precursors. The acyl imidazoles could also be generated in situ by reaction of a carboxylic acid with CDI thus furnishing a formally decarboxylative coupling of two carboxylic acids. In addition, the reaction was successfully extended to three-component coupling by using alkene as a third coupling partner via a radical relay process. The mild conditions, operational simplicity, and use of carboxylic acids as the reacting partners make our method a powerful strategy for construction of complex ketones from readily available starting materials, and late-stage modification of natural products and medicines.

Modular Terpene Synthesis Enabled by Mild Electrocatalytic Couplings

The synthesis of terpenes is a large field of research that is woven deeply into the history of chemistry. Terpene biosynthesis is a case-study of how the logic of a modular design can lead to diverse structures with unparalleled efficiency. This work mimics Nature by leveraging modern Ni-catalyzed electrochemical sp2–sp3 decarboxylative coupling reactions—enabled by Ag-nanoparticle modified electrodes—to intuitively assemble terpene natural products and complex polyenes. The step-change in efficiency of this approach is exemplified through the scalable preparation of 13 complex terpenes, which minimized protecting group manipulations, functional group interconversions, and redox fluctuations. Finally, the mechanistic aspects of the essential functionalized electrodes are studied in depth through a variety of spectroscopic and analytical techniques.

Modular Terpene Synthesis Enabled by Mild Electrocatalytic Couplings

The synthesis of terpenes is a large field of research that is woven deeply into the history of chemistry. Terpene biosynthesis is a case-study of how the logic of a modular design can lead to diverse structures with unparalleled efficiency. This work mimics Nature by leveraging modern Ni-catalyzed electrochemical sp2–sp3 decarboxylative coupling reactions—enabled by Ag-nanoparticle modified electrodes—to intuitively assemble terpene natural products and complex polyenes. The step-change in efficiency of this approach is exemplified through the scalable preparation of 13 complex terpenes, which minimized protecting group manipulations, functional group interconversions, and redox fluctuations. Finally, the mechanistic aspects of the essential functionalized electrodes are studied in depth through a variety of spectroscopic and analytical techniques.

Nickel-Catalyzed Decarboxylative Coupling of Redox-Active Esters with Aliphatic Aldehydes

The addition of alkyl fragments to aliphatic aldehydes is a highly desirable transformation for fragment couplings, yet existing methods come with operational challenges related to the basicity and instability of the nucleophilic reagents commonly employed. We report herein that nickel catalysis using a readily available bioxazoline (BiOx) ligand can catalyze the reductive coupling of redox-active esters with aliphatic aldehydes using zinc metal as the reducing agent to deliver silyl-protected secondary alcohols. This protocol is operationally simple, proceeds under mild conditions, and tolerates a variety of functional groups. Initial mechanistic studies suggest a radical chain pathway. Additionally, alkyl tosylates and epoxides are suitable alkyl precursors to this transformation providing a versatile suite of catalytic reactions for the functionalization of aliphatic aldehydes.

Recent Developments in the Synthesis of β-Diketones

Apart from being one of the most important intermediates in chemical synthesis, broadly used in the formation of C–C bonds among other processes, the β-dicarbonyl structure is present in a huge number of biologically and pharmaceutically active compounds. In fact, mainly derived from the well-known antioxidant capability associated with the corresponding enol tautomer, β-diketones are valuable compounds in the treatment of many pathological disorders, such as cardiovascular and liver diseases, hypertension, obesity, diabetes, neurological disorders, inflammation, skin diseases, fibrosis, or arthritis; therefore, the synthesis of these structures is an area of overwhelming interest for organic chemists. This paper is devoted to the advances achieved in the last ten years for the preparation of 1,3-diketones, using different chemical (Claisen, hydration of alkynones, decarboxylative coupling) or catalytic (biocatalysis, organocatalytic, metal-based catalysis) methodologies: Additionally, the preparation of branched β-dicarbonyl compounds by means of α-functionalization of non-substituted 1,3-diketones are also discussed.