Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

The palladium-catalyzed enantioselective allylic substitution by carbon or nitrogen nucleophiles is a key transformation that is particularly useful for the synthesis of bioactive compounds. Unfortunately, the selection of a suitable ligand/substrate combination often requires significant screening effort. Here, we show that a transition state force field (TSFF) derived by the quantum-guided molecular mechanics (Q2MM) method can be used to rapidly screen ligand/substrate combinations. Testing of this method on 77 literature reactions revealed several cases where the computationally predicted major enantiomer differed from the one reported. Interestingly, experimental follow-up led to a reassignment of the experimentally observed configuration. This result demonstrates the power of mechanistically based methods to predict and, where necessary, correct the stereochemical outcome.

Selenocyclization by formation of carbon-nitrogen bonds

: Selenium promoted cyclization of unsaturated substrates containing internal nitrogen nucleophiles, such as different amines and amides, including the examples of its application in the synthesis of more complex polycyclic compounds is reviewed. Selenocyclization reactions of some more specific polyfunctional substrates, like Biginelli hybrids and hydantoins, are also covered.

Design, Synthesis, and Evaluation of New Colorimetric Chemosensors Containing Quinazolinones Moiety for some Cations Detection in an Aqueous Medium and Biological Sample

The current project deals with designing and synthesizing of colorimetric chemosensors to detect the cations in the aqueous medium and biological sample. To achieve this goal a new series of quinazolinone derivatives were synthesized via reaction of the novel 6-nitro-2-propyl-4H-benzo[d][1,3]oxazin-4-one (3) with selected nitrogen nucleophiles, namely, formamide, hydrazine hydrate, hydroxylamine hydrochloride, O-phenylendiamine, O-aminophenol and O-aminothiophenol, urea and/or thiourea. Structures of the new compounds have been investigated depending on their spectral data (IR, 1H NMR, 13C NMR and MS) and elemental analyses. Some of the newly synthesized products exhibited a significant response as chemosensors for some cations detection. The synthesized chemosensors 11a and 11b showed high-selectivity and specificity towards cooper (CuII) and mercury (HgII) cations detection through exhibiting colormetric responses. Chemosensors 7 and 10b showed high selectivity toward cadmium (CdII) cation, whilst other examined compounds (9b, c, 10a, 12, 13, and 14) did not exhibit colorimetric response in all cation's samples. Resumen. En el presente proyecto se diseñan y sintetizan quimiosensores colorimétricos para detectar los cationes en el medio acuoso y en la muestra biológica. Para lograr este objetivo se sintetizó una nueva serie de derivados de quinazolinona mediante la reacción de la 6-nitro-2-propil-4H-benzo[d][1,3]oxazin-4-ona (3) con nucleófilos nitrogenados seleccionados, a saber, formamida, hidrato de hidracina, clorhidrato de hidroxilamina, O-fenilendiamina, O-aminofenol y O-aminotiofenol, urea y/o tiourea. Las estructuras de los nuevos compuestos se han comprobado en función de sus datos espectrales (IR, 1H NMR, 13C NMR y MS) y de los análisis elementales. Algunos de los nuevos productos sintetizados mostraron una respuesta significativa como quimiosensores para la detección de algunos cationes. Los quimiosensores sintetizados 11a y 11b mostraron una alta selectividad y especificidad hacia la detección de los cationes cobre (Cu II) y mercurio (Hg II) al mostrar respuestas colormétricas. Los quimiosensores 7 y 10b mostraron una alta selectividad hacia el catión cadmio (Cd II), mientras que otros compuestos examinados (9b, c, 10a, 12, 13 y 14) no mostraron respuesta colorimétrica con los cationes investigados.

The synthesis and crystallographic characterization of 4-methylbenzenesulfonamide derivatives

The sulfonamide moiety is present among a variety of biologically significant compounds. A facile synthesis is necessary to produce a variety of sulfonamides with the potential to improve human health. Herein, we report a facile methodology for the synthesis of 4-methylbenzenesulfonamides, amenable to a broad range of nitrogen nucleophiles. Implementing a semi-miscible biphasic solvent system resulted in higher yields, decreased reaction times, and a simplified workup over preliminary methods. Additionally, the crystal structures of five novel sulfonamide compounds and two polymorphs, have been determined by X-ray diffraction. Results obtained through spectroscopic characterization support the successful formation of the desired 4-methylbenzenesulfonamides.

Proofreading Experimentally Assigned Stereochemistry Through Q2MM Predictions in Pd-Catalyzed Allylic Aminations

The palladium-catalyzed enantioselective allylic substitution by carbon or nitrogen nucleophiles is a key transformation that is particularly useful for the synthesis of bioactive compounds. Unfortunately, the selection of a suitable ligand/substrate combination often requires significant screening effort. Here, we show that a transition state force field (TSFF) derived by the quantum-guided molecular mechanics (Q2MM) method can be used to rapidly screen ligand/substrate combinations. Testing of this method on 77 literature reactions revealed several cases where the computationally predicted major enantiomer differed from the one reported. Interestingly, experimental follow-up led to a reassignment of the experimentally observed configuration. This result demonstrates the power of mechanistically based methods to predict and, where necessary, correct the stereochemical outcome.

Cobalt Hydride Oxidase Catalysis Enabled Hydroamination of Unactivated Olefins

Dioxygen is an abundant, selective, and sustainable oxidant that is considered ideal for organic transformations. Oxidative processes using dioxygen as the electron acceptor without oxygen atom incorporation into the substrate are often referred to as oxidase reactions. However, the ground state triplet nature of dioxygen makes such a synthetically valuable pathway incompatible with simple free alkyl radicals, a ubiquitous class of reactive intermediates in the daily synthesis of pharmaceuticals, agrochemicals, and complex natural products. Here we report that a combination of strong cage effect and bimetallic radical-polar crossover successfully addresses this problem, and opens up an oxidase pathway in cobalt hydride catalysis. This leads to a general and chemoselective method that tackles several key challenges in catalytic hydroamination, a fundamental transformation for amine synthesis. Under balloon pressure of dioxygen at ambient temperature, we demonstrate single-step intra- and intermolecular formal addition of a variety of nitrogen nucleophiles, including free amines, sulfonamides, amides, and carbamates, to unactivated alkenes in the presence of a silane, under solvent-free conditions. Important medicinal chemistry building blocks such as a-branched tertiary amines can be easily accessed, which are often difficult targets otherwise due to their steric hindrance and reducing nature. Mechanistic studies including stoichiometric experiments with well-defined organocobalt complexes provide support for the key hypothesis, which points the way to the development of sustainable processes involving other nucleophiles based on the same design elements.

Cobalt Hydride Oxidase Catalysis Enabled Hydroamination of Unactivated Olefins

Dioxygen is an abundant, selective, and sustainable oxidant that is considered ideal for organic transformations. Oxidative processes using dioxygen as the electron acceptor without oxygen atom incorporation into the substrate are often referred to as oxidase reactions. However, the ground state triplet nature of dioxygen makes such a synthetically valuable pathway incompatible with simple free alkyl radicals, a ubiquitous class of reactive intermediates in the daily synthesis of pharmaceuticals, agrochemicals, and complex natural products. Here we report that a combination of strong cage effect and bimetallic radical-polar crossover successfully addresses this problem, and opens up an oxidase pathway in cobalt hydride catalysis. This leads to a general and chemoselective method that tackles several key challenges in catalytic hydroamination, a fundamental transformation for amine synthesis. Under balloon pressure of dioxygen at ambient temperature, we demonstrate single-step intra- and intermolecular formal addition of a variety of nitrogen nucleophiles, including free amines, sulfonamides, amides, and carbamates, to unactivated alkenes in the presence of a silane, under solvent-free conditions. Important medicinal chemistry building blocks such as a-branched tertiary amines can be easily accessed, which are often difficult targets otherwise due to their steric hindrance and reducing nature. Mechanistic studies including stoichiometric experiments with well-defined organocobalt complexes provide support for the key hypothesis, which points the way to the development of sustainable processes involving other nucleophiles based on the same design elements.

Three Component Photoredox 1,2-Alkylamination of Styrenes with Alkanes and Nitrogen Nucleophiles via C(sp3)-H bond Cleavage

A three component photoredox 1,2-alkylamination of styrenes involving functionalization of the C(sp3)-H bonds in alkyl halides instead of functionalization of C-halogen bonds is disclosed. A variety of commercialized C(sp3)-H alkanes,...