Merging Iron Catalysis and Biocatalysis—Iron Carbonyl Complexes as Efficient Hydrogen Autotransfer Catalysts in Dynamic Kinetic Resolutions

A dual catalytic iron/lipase system has been developed and applied in the dynamic kinetic resolution of benzylic and aliphatic secondary alcohols. A detailed study of the Knölker‐type iron complexes demonstrated the hydrogen autotransfer of alcohols to proceed under mild reaction conditions and allowed the combination with the enzymatic resolution. Different racemic alcohols were efficiently converted to chiral acetates in good yields and with excellent enantioselectivities.     

Preparation of Polyfunctionalized Aromatic Nitriles from Aryl Oxazolines

A selective ortho,ortho’-functionalization of readily available aryl oxazolines by two successive magnesiations with sBu₂Mg in toluene followed by trapping reactions with electrophiles, such as (hetero)aryl iodides or bromides, iodine, tosyl cyanide, ethyl cyanoformate or allylic bromides (39 examples, 62–99 % yield) is reported. Treatment of these aryl oxazolines with excess oxalyl chloride and catalytic amounts of DMF (50 °C, 4 h) provided the corresponding nitriles (36 examples, 73–99 % yield). Conversions of these nitriles to valuable heterocycles are reported, and a tentative mechanism is proposed.     

Amide Synthesis by Nickel/Photoredox-Catalyzed Direct Carbamoylation of (Hetero)Aryl Bromides

Herein, we report a one-electron strategy for catalytic amide synthesis that enables the direct carbamoylation of (hetero)aryl bromides. This radical cross-coupling approach, which is based on the combination of nickel and photoredox catalysis, proceeds at ambient temperature and uses readily available dihydropyridines as precursors of carbamoyl radicals. The method's mild reaction conditions make it tolerant of sensitive-functional-group-containing substrates and allow the installation of an amide scaffold within biologically relevant heterocycles. In addition, we installed amide functionalities bearing electron-poor and sterically hindered amine moieties, which would be difficult to prepare with classical dehydrative condensation methods.     

Amide Synthesis by Nickel/Photoredox‐Catalyzed Direct Carbamoylation of (Hetero)Aryl Bromides

Herein, we report a one‐electron strategy for catalytic amide synthesis that enables the direct carbamoylation of (hetero)aryl bromides. This radical cross‐coupling approach, which is based on the combination of nickel and photoredox catalysis, proceeds at ambient temperature and uses readily available dihydropyridines as precursors of carbamoyl radicals. The method's mild reaction conditions make it tolerant of sensitive‐functional‐group‐containing substrates and allow the installation of an amide scaffold within biologically relevant heterocycles. In addition, we installed amide functionalities bearing electron‐poor and sterically hindered amine moieties, which would be difficult to prepare with classical dehydrative condensation methods.     

Metal‐Catalyzed Dealkoxylative CarylC Cross‐Coupling—Replacement of Aromatic Methoxy Groups of Aryl Ethers by Employing a Functionalized Nucleophile

The direct replacement of aromatic methoxy groups with activated carbon nucleophiles would give rise to novel synthetic pathways for targeted and diversity‐oriented syntheses. We demonstrate here that this transformation can be achieved in a one‐step reaction involving a bifunctional organolithium nucleophile in combination with a C_Ar? OMe bond‐cleaving nickel catalyst. The resulting products are stable, α‐CH active, and suitable for various further modifications.     

In Situ Quench Reactions of Enantioenriched Secondary Alkyllithium Reagents in Batch and Continuous Flow Using an I/Li-Exchange

We report a practical in situ quench (ISQ) procedure involving the generation of chiral secondary alkyllithiums from secondary alkyl iodides (including functionalized iodides bearing an ester or a nitrile) in the presence of various electrophiles such as aldehydes, ketones, Weinreb amides, isocyanates, sulfides, or boronates. This ISQ-reaction allowed the preparation of a broad range of optically enriched ketones, alcohols, amides, sulfides and boronic acid esters in typically 90–98 % ee. Remarkably, these reactions were performed at −78 °C or −40 °C in batch. A continuous flow set-up permitted reaction temperatures between −20 °C and 0 °C and allowed a scale-up up to a 40-fold without further optimization.