Synthesis of 2‑Aminoquinazolinones via Carbonylative Coupling of <i>ortho</i>-Iodoanilines and Cyanamide

Herein, we describe a convenient and efficient synthesis of 2-aminoquinazolin-4­(3<i>H</i>)-ones and N1-substituted 2-aminoquinazolin-4­(1<i>H</i>)-ones by a domino carbonylation/cyclization process. The reaction proceeds via carbonylative coupling of readily available <i>ortho</i>-iodoanilines with cyanamide followed by in situ ring closure of an <i>N</i>-cyanobenzamide intermediate. The products were easily isolated by precipitation in moderate to excellent yields for a wide range of substrates, making this a highly attractive method for the synthesis of 2-aminoquinazolinones

Synthesis of 2‑Aminoquinazolinones via Carbonylative Coupling of <i>ortho</i>-Iodoanilines and Cyanamide

Herein, we describe a convenient and efficient synthesis of 2-aminoquinazolin-4­(3<i>H</i>)-ones and N1-substituted 2-aminoquinazolin-4­(1<i>H</i>)-ones by a domino carbonylation/cyclization process. The reaction proceeds via carbonylative coupling of readily available <i>ortho</i>-iodoanilines with cyanamide followed by in situ ring closure of an <i>N</i>-cyanobenzamide intermediate. The products were easily isolated by precipitation in moderate to excellent yields for a wide range of substrates, making this a highly attractive method for the synthesis of 2-aminoquinazolinones

Synthesis of N‑Sulfonyl Amidines and Acyl Sulfonyl Ureas from Sulfonyl Azides, Carbon Monoxide, and Amides

A Pd-catalyzed and ligand-free carbonylation/cycloaddition/decarboxylation cascade synthesis of sulfonyl amidines from sulfonyl azides and substituted amides at low CO pressure is reported. The reaction proceeds via an initial Pd-catalyzed carbonylative generation of sulfonyl isocyanates from sulfonyl azides, followed by a [2 + 2] cycloaddition with amides and subsequent decarboxylation, which liberates the desired sulfonyl amidines, generating N₂ and CO₂ as the only reaction byproducts. Using this simple protocol, a diverse range of sulfonyl amidines was obtained in moderate to excellent yields. In addition, the reaction can also be directed through a more conventional amidocarbonylation pathway by employing N-monosubstituted amide nucleophiles to afford acyl sulfonyl ureas in good yields

Aminocarbonylations Employing Mo(CO)₆ and a Bridged Two-Vial System: Allowing the Use of Nitro Group Substituted Aryl Iodides and Aryl Bromides

A bridged two-vial system aminocarbonylation protocol where Mo­(CO)₆ functions as an external <i>in situ</i> solid source of CO has been developed. For the first time both nitro group containing aryl/heteroaryl iodides and bromides gave good to excellent yields in the Mo­(CO)₆-mediated and palladium(0)-catalyzed conversion to benzamides, while the identical one-vessel protocol afforded extensive reduction of the nitro functionality. The above-mentioned bridged two-compartment protocol furnished good results with both primary amines and secondary amines and sluggish aniline nucleophiles at 65–85 °C reaction temperatures

Palladium(0)-Catalyzed Carbonylative One-Pot Synthesis of N‑Acylguanidines

A convenient synthetic strategy toward <i>N</i>-acylguanidines via a sequential one-pot multicomponent carbonylation/amination reaction has been developed. The compounds were readily obtained via an <i>N</i>-cyanobenzamide intermediate formed from the Pd(0)-catalyzed carbonylative coupling of cyanamide and aryl iodides or bromides. Subsequent amination with a large variety of amines provided the final <i>N</i>-acylguanidines, with the overall formation of one C–C and two C–N bonds, in moderate to excellent yields. The substrate scope was found to be wide and the methodology was used to produce over 50 compounds, including 29 novel molecules. Furthermore, three separate nitrogen-containing heterocycles were prepared from the <i>N</i>-acylguanidines synthesized using the developed multicomponent, carbonylative method

Synthesis of Sulfonyl Azides via Diazotransfer using an Imidazole-1-sulfonyl Azide Salt: Scope and ¹⁵N NMR Labeling Experiments

Imidazole-1-sulfonyl azide hydrogen sulfate is presented as an efficient reagent for the synthesis of sulfonyl azides from primary sulfonamides. The described method is experimentally simple and high-yielding and does not require the addition of Cu salts. Furthermore, ¹⁵N NMR mechanistic studies show the reaction proceeds via a diazo transfer mechanism. Imidazole-1-sulfonyl azide hydrogen sulfate provides a considerable advantage over existing diazo transfer reagents in terms of impact stability, cost, and ease of use

Microwave-Assisted Branching Cascades: A Route to Diverse 3,4-Dihydroquinazolinone-Embedded Polyheterocyclic Scaffolds

A novel metal-free microwave-assisted branching cascades strategy for the efficient synthesis of 3,4-dihydro­quinazolinone-embedded polyheterocyclic scaffolds is reported. Starting from in situ generated key <i>N</i>-acyliminium ion precursors, 12 distinct and skeletally diverse polycyclic frameworks were accessed in a single step/pot via adjustment of the nucleophile(s) and reaction conditions. Postcascade functionalization of these compounds was also demonstrated, proving the utility of this method in accessing structurally diverse chemical entities

Synthesis of 4‑Quinolones via a Carbonylative Sonogashira Cross-Coupling Using Molybdenum Hexacarbonyl as a CO Source

A palladium-catalyzed CO gas-free carbonylative Sonogashira/cyclization sequence for the preparation of functionalized 4-quinolones from 2-iodoanilines and alkynes via two different protocols is described. The first method (A) yields the cyclized products after only 20 min of microwave (MW) heating at 120 °C. The second method (B) is a gas-free one-pot two-step sequence which runs at room temperature, allowing the use of sensitive substituents (e.g., nitro and bromide groups). For both protocols, molybdenum hexacarbonyl was used as a solid source of CO

Direct Palladium(II)-Catalyzed Synthesis of Arylamidines from Aryltrifluoroborates

A fast and convenient synthesis of arylamidines starting from readily available potassium aryltrifluoroborates and cyanamides is reported. The coupling was achieved by Pd(II)-catalysis in a one step 20 min microwave protocol using Pd(O₂CCF₃), 6-methyl-2,2′-bipyridyl, TFA, and MeOH, providing the corresponding arylamidines in moderate to excellent yields

Route to 3‑Amidino Indoles via Pd(II)-Catalyzed C–H Bond Activation

We report a facile synthesis of 3-amidino indoles from indoles and cyanamides. The reaction is Pd­(II)-catalyzed and proceeds via C–H bond activation of the indole in its 3-position followed by a 1,2-addition of the resulting indole–palladium σ-complex to a cyanamide, which provides the corresponding amidine. The preference for 4,5-diazafluoren-9-one (DAF) as the ligand is investigated using DFT calculations, and a plausible reaction pathway is presented