Ruthenium‐Catalyzed Reductive Arylation of N‐(2‐Pyridinyl)amides with Isopropanol and Arylboronate Esters

A new three‐component reductive arylation of amides with stable reactants (iPrOH and arylboronate esters), making use of a 2‐pyridinyl (Py) directing group, is described. The N‐Py‐amide substrates are readily prepared from carboxylic acids and PyNH₂, and the resulting N‐Py‐1‐arylalkanamine reaction products are easily transformed into the corresponding chlorides by substitution of the HN‐Py group with HCl. The 1‐aryl‐1‐chloroalkane products allow substitution and cross‐coupling reactions. Therefore, a general protocol for the transformation of carboxylic acids into a variety of functionalities is obtained. The Py‐NH₂ by‐product can be recycled.     

Reusable Nickel Nanoparticles‐Catalyzed Reductive Amination for Selective Synthesis of Primary Amines

The preparation of nickel nanoparticles as efficient reductive amination catalysts by pyrolysis of in situ generated Ni‐tartaric acid complex on silica is presented. The resulting stable and reusable Ni‐nanocatalyst enables the synthesis of functionalized and structurally diverse primary benzylic, heterocyclic and aliphatic amines starting from inexpensive and readily available carbonyl compounds and ammonia in presence of molecular hydrogen. Applying this Ni‐based amination protocol, ‐NH₂ moiety can be introduced in structurally complex compounds, for example, steroid derivatives and pharmaceuticals.     

Transition‐Metal‐Free Hydrogen Autotransfer: Diastereoselective N‐Alkylation of Amines with Racemic Alcohols

A practical method for the synthesis of α‐chiral amines by alkylation of amines with alcohols in the absence of any transition‐metal catalysts has been developed. Under the co‐catalysis of a ketone and NaOH, racemic secondary alcohols reacted with Ellman's chiral tert‐butanesulfinamide by a hydrogen autotransfer process to afford chiral amines with high diastereoselectivities (up to >99:1). Broad substrate scope and up to a 10 gram scale production of chiral amines were demonstrated. The method was applied to the synthesis of chiral deuterium‐labelled amines with high deuterium incorporation and optical purity, including examples of chiral deuterated drugs. The configuration of amine products is found to be determined solely by the configuration of the chiral tert‐butanesulfinamide regardless of that of alcohols, and this is corroborated by DFT calculations. Further mechanistic studies showed that the reaction is initiated by the ketone catalyst and involves a transition state similar to that proposed for the Meerwein–Ponndorf–Verley (MPV) reduction, and importantly, it is the interaction of the sodium cation of the base with both the nitrogen and oxygen atoms of the sulfinamide moiety that makes feasible, and determines the diastereoselectivity of, the reaction.