Investigation of Masked N-Acyl-N-isocyanates: Support for Oxadiazolones as Blocked N-Isocyanate Precursors.

In contrast to carbon-substituted isocyanates that are common building blocks, N-substituted isocyanates remain underdeveloped and reports on their N-acyl derivatives (i. e. amido-isocyanates) are exceedingly rare.

Photocatalytic Intramolecular C-H Amination Using -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.

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, ,-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 -alkyl secondary amine substrates.

O-Isocyanates as Uncharged 1,3-Dipole Equivalents in [3+2] Cycloadditions.

1,3-Dipoles are commonly used in [3+2] cycloadditions, whereas isoelectronic uncharged dipole variants remain underdeveloped. In contrast to conventional 1,3-dipoles, uncharged dipole equivalents form zwitterionic cycloadducts, which can be exploited to build further molecular complexity. In this work, the first cycloadditions of oxygen-substituted isocyanates (O-isocyanates) were studied experimentally and by DFT calculations.

Aminimide Synthesis Using Concerted Amination Reactions of Alkenes: Scope and Mechanistic Information.

Aminimides are key intermediates in the thermal cycloadditions of suitable alkenyl-hydrazine derivatives. Substrate modifications (β-,-dialkyl) allowed the isolation of these reactive intermediates, and the analysis of their stereochemistry provided support for concerted (Cope-type) hydroamination and concerted [3 + 2] aminocarbonylation reaction pathways. This work also establishes the applicability of these approaches to form complex aminimides in moderate to excellent yields.

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.

Intramolecular Alkene Aminocarbonylation Using Concerted Cycloadditions of Amino-Isocyanates.

The ubiquity of nitrogen heterocycles in biologically active molecules challenges synthetic chemists to develop a variety of tools for their construction. While developing metal-free hydroamination reactions of hydrazine derivatives, it was discovered that carbazates and semicarbazides can also lead to alkene aminocarbonylation products if nitrogen-substituted isocyanates (N-isocyanates) are formed in situ as reactive intermediates. At first this reaction required high temperatures (150-200 °C), and issues included competing hydroamination and N-isocyanate dimerization pathways.

Cascade reactions of nitrogen-substituted isocyanates: a new tool in heterocyclic chemistry.

In contrast to normal -substituted isocyanates, nitrogen-substituted isocyanates (-isocyanates) are rare. Their high reactivity and amphoteric/ambident nature has prevented the scientific community from exploiting their synthetic potential. Recently, we have developed an formation approach using a reversible equilibrium, which allows controlled generation and reactivity of -isocyanates and prevents the dimerization that is typically observed with these intermediates.

One-Pot Synthesis of Aza-Diketopiperazines Enabled by Controlled Reactivity of N-Isocyanate Precursors.

A one-pot sequence for the synthesis of aza-diketopiperazines is reported, involving carbazate acylation with chloroacetyl chloride, SN2 with a primary amine, N-isocyanate formation, and cyclization. Nitrogen-substituted isocyanates (N-isocyanates) are a rare class of amphoteric isocyanate with high, but severely underdeveloped synthetic potential. This approach highlights that βN-acyl carbazates can act as blocked (masked) N-isocyanates, thus allowing a challenging intermolecular SN2 reaction of a primary amine to proceed while the N-isocyanate is "protected", and then cyclization once it is unmasked.