Stereodivergent, Kinetically Controlled Isomerization of Terminal Alkenes via Nickel Catalysis.

Because internal alkenes are more challenging synthetic targets than terminal alkenes, metal-catalyzed olefin mono-transposition (i.e., positional isomerization) approaches have emerged to afford valuable E- or Z- internal alkenes from their complementary terminal alkene feedstocks. However, the applicability of these methods has been hampered by lack of generality, commercial availability of precatalysts, and scalability. Here, we report a nickel-catalyzed platform for the stereodivergent E/Z-selective synthesis of internal alkenes at room temperature. Commercial reagents enable this one-carbon transposition of terminal alkenes to valuable E- or Z-internal alkenes via a Ni-H-mediated insertion/elimination mechanism. Though the mechanistic regime is the same in both systems, the underlying pathways that lead to each of the active catalysts are distinct, with the Z-selective catalyst forming from comproportionation of an oxidative addition complex followed by oxidative addition with substrate and the E-selective catalyst forming from protonation of the metal by the trialkylphosphonium salt additive. In each case, ligand sterics and denticity control stereochemistry and prevent over-isomerization.

Rapid Access to Carbon-Isotope-Labeled Alkyl and Aryl Carboxylates Applying Palladacarboxylates.

Herein, we report a strategy for the formation of isotopically labeled carboxylic esters from boronic esters/acids using a readily accessible palladium carboxylate complex as an organometallic source of isotopically labeled functional groups. The reaction allows access to either unlabeled or full 13C- or 14C-isotopically labeled carboxylic esters, and the method is characterized by its operational simplicity, mild conditions, and general substrate scope. Our protocol is further extended to a carbon isotope replacement strategy, involving an initial decarbonylative borylation procedure. Such an approach allows access to isotopically labeled compounds directly from the unlabeled pharmaceutical, which can have implications for drug discovery programs.

Regioselective Hydroalkylation of Vinylarenes by Cooperative Cu and Ni Catalysis.

Disclosed here is a dual copper and nickel catalytic system with a silyl hydride source for promoting the linear selective hydroalkylation of vinylarenes. This carbon-carbon bond-forming protocol is applied to couple a variety of functionalized vinylarenes with alkyl halides applying a nickel(II) NNN pincer complex in the presence of an NHC-ligated copper catalyst. This combination allows for a 1 mol % loading of the nickel catalyst leading to turnover numbers of up to 72. Over 40 examples are presented, including applications for pharmaceutical diversification. Labeling experiments demonstrated the regioselectivity of the reaction and revealed that the copper catalyst plays a crucial role in enhancing the rate for formation of the reactive linear alkyl nickel complex. Overall, the presented work provides a complimentary approach for hydroalkylation reactions, whilst providing a preliminary mechanistic understanding of the cooperativity between the copper and nickel complexes.

Controlled Release of Reactive Gases: A Tale of Taming Carbon Monoxide.

This Personal Account describes the development of air-stable and solid precursors for on-demand release of carbon monoxide. In combination with the development of a two-chamber reactor, COware®, CO liberation can be achieved under safe working conditions, as well as allowing transition metal-mediated carbonylations with stoichiometric carbon monoxide. Particularly appealing is the adaptability of this chemical technology for the preparation of carbon isotope labeled bioactive compounds.

Carbon Isotope Labeling Strategy for ß-Amino Acid Derivatives via Carbonylation of Azanickellacycles.

A series of 4-membered azametallacycles have been prepared by the oxidative addition of Ni(0) with aziridines. Stoichiometric 13C-labeled carbon monoxide could be efficiently incorporated via Ni-C bond insertion to generate air stable and isolable cyclic Ni-acyl complexes. Upon subjection to a range of C-, N-, O-, and S-nucleophiles, 13C-labeled ß-amino acids and derivatives thereof, as well as ß-aminoketones, could be rapidly accessed. The methodology proved highly adaptable for the synthesis of the antidiabetic drug, sitagliptin, with a single carbon isotope label.

Scalable carbon dioxide electroreduction coupled to carbonylation chemistry.

Significant efforts have been devoted over the last few years to develop efficient molecular electrocatalysts for the electrochemical reduction of carbon dioxide to carbon monoxide, the latter being an industrially important feedstock for the synthesis of bulk and fine chemicals. Whereas these efforts primarily focus on this formal oxygen abstraction step, there are no reports on the exploitation of the chemistry for scalable applications in carbonylation reactions. Here we describe the design and application of an inexpensive and user-friendly electrochemical set-up combined with the two-chamber technology for performing Pd-catalysed carbonylation reactions including amino- and alkoxycarbonylations, as well as carbonylative Sonogashira and Suzuki couplings with near stoichiometric carbon monoxide. The combined two-reaction process allows for milligram to gram synthesis of pharmaceutically relevant compounds. Moreover, this technology can be adapted to the use of atmospheric carbon dioxide.Electroreduction of CO2 to CO is a potential valorisation pathway of carbon dioxide for fine chemicals production. Here, the authors show a user-friendly device that couples CO2 electroreduction with carbonylation chemistry for up to gram scale synthesis of pharmaceuticals even under atmospheric CO2.