Conversion of anilines to chiral benzylic amines via formal one-carbon insertion into aromatic C–N bonds

Insertion of atoms into aromatic carbon-nitrogen bonds is an appealing method for the synthesis of nitrogen-containing molecules and it has the advantage of the availability and abundance of anilines. However, the direct cleavage of aromatic carbon-nitrogen bonds is challenging due to the particularly inert and stable nature of these bonds. Here we report a formal, enantioselective one-carbon insertion into an aromatic carbon-nitrogen bond via an aromaticity dissembly-reconstruction process to directly convert anilines to chiral α-branched benzylic amines. The process involves oxidative dearomatization of para-substituted anilines, chiral sulfur ylide-mediated asymmetric aziridination, and subsequent rearrangement. Chiral sulfur ylides serve as one-carbon insertion units.

Expedient Method for Direct Mono-amidation of Phosphonic and Phosphoric Acids

Mono-amidated P(V) pro-drugs predominately contribute to the vastly improved delivery of phosphate and phosphonate-containing anti-viral/cancer nucleotide analogues. However, synthetic approaches towards their formation are often harsh and unreliable, which may hamper the identification of novel, more effective amine pro-drugs. Here, we show that direct mono-amidation of structurally complex phosphonic and phosphoric acids may be accomplished in as quickly as seconds by re-purposing the PPh₃/DIAD redox pair. Where the triphenylphosphine oxide byproduct is often cited as a vulnerability, we use its formation as an asset. Juxtaposing the anionic nature of the generated mono-amidated product, the desired product may be isolated with a single water extraction. Compared to state-of-the-art strategies towards phosphoramidates, our approach is mild, reliable, and enables access to a variety of aliphatic and benzylic amines for pro-drug attachment.

Expedient Method for Direct Mono-amidation of Phosphonic and Phosphoric Acids

Mono-amidated P(V) pro-drugs predominately contribute to the vastly improved delivery of phosphate and phosphonate-containing anti-viral/cancer nucleotide analogues. However, synthetic approaches towards their formation are often harsh and unreliable, which may hamper the identification of novel, more effective amine pro-drugs. Here, we show that direct mono-amidation of structurally complex phosphonic and phosphoric acids may be accomplished in as quickly as seconds by re-purposing the PPh₃/DIAD redox pair. Where the triphenylphosphine oxide byproduct is often cited as a vulnerability, we use its formation as an asset. Juxtaposing the anionic nature of the generated mono-amidated product, the desired product may be isolated with a single water extraction. Compared to state-of-the-art strategies towards phosphoramidates, our approach is mild, reliable, and enables access to a variety of aliphatic and benzylic amines for pro-drug attachment.

Aerobic oxidation of primary benzylic amines to amides and nitriles catalyzed by ruthenium carbonyl clusters carrying N,O-bidentate ligands

An efficient method for direct oxygenation of primary arylamines to nitriles and amides with switchable selectivity was developed using N,O-bidentate Ru3 clusters as catalysts.

Iron-Catalyzed Direct Transformation of Benzylic Amines into Carbonyl Compounds in Water

Fe-catalyzed direct transformation of benzylic amines into carbonyl compounds was performed in H2O. The reaction of benzylic amines with formaldehyde in the presence of FeCl3·6H2O in H2O afforded the corresponding carbonyl compounds (80 °C to reflux conditions; 14 examples, up to 94% yield). O18-labeling experiments indicated that the O atom in the generated carbonyl is derived from H2O.