Nitrene-Mediated P–N Coupling Under Iron Catalysis

Abstract

P-N and P=N bonds play important roles in the design and synthesis of functional molecules such as bioactive compounds and organic ligands for catalysis. Existing methods for P-N coupling mostly rely on Staudinger condensation or nucleophilic substitution between phosphorus electrophiles and amine nucleophiles. Herein, we report a nitrene-mediated intermolecular P-N coupling reaction between various phosphorus nucleophiles and dioxazolones under simple iron-catalyzed conditions. These reactions offer an efficient, versatile, and broadly applicable method for synthesis of a range of N-P compounds including amidophosphines, iminophosphonamides, phosphinamides, aminophosphines, and iminophosphoranes from readily available precursors under mild conditions.

Controlled Synthesis of α-CF2H or α-CF2Cl Styrenes from the Same Precursors: Dehydrazinative Hydrogenation or Chlorination of 3,3-Difluoroallyl Hydrazines

“…Based on the aforementioned observations and previous literature reports, a plausible mechanism is proposed in Scheme . The FeCl 3 -mediated hydrogenation would be initiated by the cleavage of the N -Boc group under assistance of FeCl 3 and heating, affording diazene species A .…”

Ligand‐Promoted Iron‐Catalyzed Nitrene Transfer for the Synthesis of Hydrazines and Triazanes through N‐Amidation of Arylamines

“…The presence of P t Bu 3 ligand significantly accelerated the formation of 3 a and the reaction can be completed within 10 minutes (entry 3). Interestingly, our previous studies showed that P t Bu 3 alone could undergo rapid P ‐amidation with 1 to give N ‐acyl iminophosphorane 4 in high yield under similar FeCl 2 ‐catalyzed conditions at rt [15a] . However, the formation of 4 was mostly suppressed (<1 %) in the N ‐amidation of aniline 2 with 1 using 20 mol % of P t Bu 3 as a ligand, suggesting the role of P t Bu 3 has changed in the presence of 2 .…”

“…Functionalities such as sulfide (7), carboxylic acid (8), and sulfanilamide (9) were well tolerated. Substrates containing heterocycle motifs such as dioxane (15), thiazole (17), and coumarin (18) worked well. Aniline-based drug molecules like sulfamethoxazole (14, antibiotic) and lenalidomide (19, anticancer) reacted smoothly with 1 to give the corresponding products in moderate to good yields.…”

“…Subsequently, we reported that various phosphorus compounds such as phosphines could undergo P-amidation with dioxazolones to give NÀ P coupled products under similar FeCl 2 -catalyzed conditions (Scheme 1A). [15] Notably, sterically demanding phosphines also reacted well, indicating the high reactivity of the Fecatalyzed P-amidation. Mechanistic studies suggested that the phosphorus group, likely as an actor ligand, migrates from the Fe center to the N atom of acyl nitrene moiety to form the NÀ P bond.…”

Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols

“…Besides the S -amidation of sulfur, the utility of dioxazolones as acyl nitrene precursors have also been demonstrated in other important transformations such as C–H amidation reactions in recent years 66 – 73 . We previously showed that dioxazolones can enable efficient amidation of arylamines and various phosphorus compounds to construct N–N and P–N bonds under the catalysis of iridium or iron 74 , 75 . Motivated by the prevalence of thiol group in both small molecules and peptides, we questioned whether dioxazolones can react with SH to give the sulfenamide product under proper metal-catalyzed conditions.…”