Synthesis of 1,2,4-Triazinones Exploiting the Reactivity of Diazadiene and N-Isocyanate Intermediates.

1,2,4-Triazinones are useful compounds, but their synthesis can be challenging. Herein, we report a strategy to build 1,2,4-triazinones using α-bromohydrazones to access diazadienes and exploiting their ability to undergo facile substitution with nitrogen nucleophiles. The N-isocyanate intermediate formed in situ can then undergo cyclization to give the desired triazinones. This provides access to products with various substituents at the 4-position, and with suitable hydrazone precursors (R2 = Ph), the cascade reaction yields 1,2,4-triazin-3(2H)-ones at room temperature.

Cyclic Ureate Tantalum Catalyst for Preferential Hydroaminoalkylation with Aliphatic Amines: Mechanistic Insights into Substrate Controlled Reactivity.

The efficient and catalytic amination of unactivated alkenes with simple secondary alkyl amines is preferentially achieved. A sterically accessible, N,O-chelated cyclic ureate tantalum catalyst was prepared and characterized by X-ray crystallography. This optimized catalyst can be used for the hydroaminoalkylation of 1-octene with a variety of aryl and alkyl amines, but notably enhanced catalytic activity can be realized with challenging N-alkyl secondary amine substrates. This catalyst offers turnover frequencies of up to 60 h-1, affording full conversion at 5 mol% catalyst loading in approximately 20 min with these nucleophilic amines. Mechanistic investigations, including kinetic isotope effect (KIE) studies, reveal that catalytic turnover is limited by protonolysis of the intermediate 5-membered azametallacycle. A Hammett kinetic analysis shows that catalytic turnover is promoted by electron rich amine substrates that enable catalytic turnover. This more active catalyst is shown to be effective for late stage drug modification.

Photocatalytic Intramolecular C-H Amination Using N-Oxyureas as Nitrene Precursors.

Nitrenes are remarkable high-energy chemical species that enable direct C-N bond formation, typically via controlled reactions of metal-stabilized nitrenes. Here, in contrast, the combined use of photocatalysis with careful engineering of the precursor enabled C-H amination forming imidazolidinones and related nitrogen heterocycles from readily accessible hydroxylamine precursors. Preliminary mechanistic results are consistent with the formation of free carbamoyl triplet nitrenes as reactive intermediates.

Formation of Complex Hydrazine Derivatives via Aza-Lossen Rearrangement.

The development of a broadly applicable procedure for the aza-Lossen rearrangement is reported. This process converts amines into complex hydrazine derivatives in two steps under safe, mild conditions. This method allows the chemoselective formation of N-N bonds, resulting in the synthesis of cyclic and acyclic products while avoiding side reactions of the amphoteric (ambident) nitrogen-substituted isocyanate intermediate.

Synthesis of N-Oxyureas by Substitution and Cope-Type Hydroamination Reactions Using O-Isocyanate Precursors.

Oxy-carbamate O-isocyanate precursors facilitate access to synthetically valuable N-oxyureas via substitution with amines. This work exploits the reactivity of suitable O-isocyanate precursors, identified by a thorough study highlighting the different reactivity of isocyanate masking groups. This led to bench-stable O-isocyanate precursors, offering improved versatility in the synthesis of N-oxyureas, and demonstrates the controlled reactivity of masked O-isocyanates. Suitable precursors also enabled the first example of Cope-type hydroamination of unsaturated hydroxyureas.