Organocatalytic Silicon-Free SuFEx reactions for modular synthesis of sulfonate esters and sulfonamides

Sulfur(VI) fluoride exchange (SuFEx) click chemistry provides a powerful tool for rapid construction of modular connections. Here, we report a novel catalytic silicon-free SuFEx reaction with sulfonyl fluorides. Under the catalysis of 10 mol% N-heterocyclic carbene (NHC), a range of phenols and alcohols react with different sulfonyl fluorides to afford sulfonate esters in 49-99% yields. In addition, Under the relay catalysis of 10 mol% N-heterocyclic carbene and 10 mol% 1-hydroxybenzotriazole (HOBt), a variety of primary and secondary amines react with different sulfonyl fluorides to produce sulfonamides in 58%-99% yields. More than 140 sulfonylated products, including 17 natural product derivatives have been prepared through this method. Mechanism study showed that NHCs might act as a carbon-centered Brønsted base to catalyse the SuFEx click reactions via the formation of hydrogen bonding with phenols or alcohols.

Alkene Difunctionalization Directed by Free Amines: Diamine Synthesis via Nickel-Catalyzed 1,2-Carboamination

A versatile method to access differentially substituted 1,3- and 1,4-diamines via a nickel-catalyzed three-component 1,2-carboamination of alkenyl amines with aryl/alkenylboronic ester nucleophiles and N–O electrophiles is reported. The reaction proceeds efficiently with free primary and secondary amines without needing a directing auxiliary or protecting group, and is enabled by fine-tuning the leaving group on the N–O reagent. The transformation is highly regioselective and compatible with a wide range of coupling partners and alkenyl amine substrates, all performed at room temperature. A series of kinetic studies support a mechanism in which alkene coordination to the nickel catalyst is turnover-limiting.

Practical N-Alkylation via Homogeneous Iridium-Catalyzed Direct Reductive Amination

Direct reductive amination (DRA) is one of the most efficient methods for amine synthesis. Herein we report a practical homogeneous DRA procedure utilizing iridium catalysis. Applying simple, readily available and inexpensive PPh3 and alike ligands at as low as 0.003 mol%, aldehydes and ketones reductively coupled with primary and secondary amines to efficiently form structurally and functionally diverse amine products, including a set of drugs and their late-stage manipulation. The reaction conditions were exceptionally mild and additive-free, and they tolerated oxygen, moisture, polar protic groups and multiple other functional groups. For targeted products, this methodology is versatile and could offer multiple synthetic routes in regard to the selection of starting materials. The 10 gram-scale synthesis further demonstrated the potential and promise of this procedure in practical amine synthesis.

Synthesis of Boronated Amidines by Addition of Amines to Nitrilium Derivative of Cobalt Bis(Dicarbollide)

A series of novel cobalt bis(dicarbollide) based amidines were synthesized by the nucleophilic addition of primary and secondary amines to highly activated B-N+≡C–R triple bond of the propionitrilium derivative [8-EtC≡N-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)]. The reactions with primary amines result in the formation of mixtures of E and Z isomers of amidines, whereas the reactions with secondary amines lead selectively to the E-isomers. The crystal molecular structures of E-[8-EtC(NMe2)=HN-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)], E-[8-EtC(NEt2)=HN-3,3′-Co(1,2- C2B9H10)(1′,2′-C2B9H11)] and E-[8-EtC(NC5H10)=HN-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)] were determined by single crystal X-ray diffraction.

Selenoxide Elimination Triggers Enamine Hydrolysis to Primary and Secondary Amines: A Combined Experimental and Theoretical Investigation

We discuss a novel selenium-based reaction mechanism consisting in a selenoxide elimination-triggered enamine hydrolysis. This one-pot model reaction was studied for a set of substrates. Under oxidative conditions, we observed and characterized the formation of primary and secondary amines as elimination products of such compounds, paving the way for a novel strategy to selectively release bioactive molecules. The underlying mechanism was investigated using NMR, mass spectrometry and density functional theory (DFT).