Palladium-Catalyzed <i>N</i>-Acylation of Monosubstituted Ureas Using Near-Stoichiometric Carbon Monoxide

The palladium-catalyzed carbonylation of urea derivatives with aryl iodides and bromides afforded <i>N</i>-benzoyl ureas (20 examples) in yields attaining quantitative via the application of near-stoichiometric amounts of carbon monoxide generated from the decarbonylation of the CO precursor, 9-methylfluorene-9-carbonyl chloride. The synthetic protocol displayed good functional group tolerance. The methodology is also highly suitable for ¹³C isotope labeling, which was demonstrated through the synthesis of three benzoyl ureas, including the insecticide triflumuron, whereby ¹³CO was incorporated into the core structure

Palladium-Catalyzed <i>N</i>-Acylation of Monosubstituted Ureas Using Near-Stoichiometric Carbon Monoxide

The palladium-catalyzed carbonylation of urea derivatives with aryl iodides and bromides afforded <i>N</i>-benzoyl ureas (20 examples) in yields attaining quantitative via the application of near-stoichiometric amounts of carbon monoxide generated from the decarbonylation of the CO precursor, 9-methylfluorene-9-carbonyl chloride. The synthetic protocol displayed good functional group tolerance. The methodology is also highly suitable for ¹³C isotope labeling, which was demonstrated through the synthesis of three benzoyl ureas, including the insecticide triflumuron, whereby ¹³CO was incorporated into the core structure

Palladium Catalyzed Carbonylative Heck Reaction Affording Monoprotected 1,3-Ketoaldehydes

The direct carbonylative palladium catalyzed synthesis of monoprotected 1,3-ketoaldehydes is reported starting from aryl iodides applying near stoichiometric amounts of carbon monoxide. Besides representing platforms for a variety of heterocyclic structures, these motives serve as viable precursors for the highly relevant aryl methyl ketones. The presented strategy can also be adapted for the facile and efficient incorporation of ¹³C-labeled carbon monoxide

An Efficient Method for the Preparation of Tertiary Esters by Palladium-Catalyzed Alkoxycarbonylation of Aryl Bromides

The palladium-catalyzed alkoxycarbonylation of aryl bromides is described for the efficient preparation of tertiary esters. The protocol proved compatible with a wide variety of functionalized (hetero)aromatic bromides, as well as several different sterically hindered tertiary alcohols, affording the alkoxycarbonylated products in high yields. Finally, the formation of aromatic trityl esters is discussed

Access to 2‑(Het)aryl and 2‑Styryl Benzoxazoles via Palladium-Catalyzed Aminocarbonylation of Aryl and Vinyl Bromides

A sequential one-pot procedure for the synthesis of either 2-(hetero)­aryl or 2-styryl benzoxazoles is reported, starting from aryl and vinyl bromides, respectively, involving an initial aminocarbonylation with 2-aminophenols as nucleophiles followed by an acid mediated ring closure to generate the heterocycle. The methodology displays a broad substrate scope in moderate to excellent yields and can be exploited for ¹³C-isotope labeling. Finally, this carbonylative protocol was applied to the synthesis of a potential Alzheimer’s plaque binder and a selective PPAR antagonist including site-specific labeling with ¹³C-carbon monoxide

A High Mobility Reactor Unit for R&D Continuous Flow Transfer Hydrogenations

A suitcase sized mobile reactor unit (MRU) weighing in at less than 10 kg was designed for laboratory scale transfer hydrogenations in continuous flow. Simple cyclohexene and a cosolvent in combination with a palladium-on-charcoal packed bed reactor provided a setup with isolation of nearly all products without the need for further purification. Several functional groups including olefins, triple bonds, nitro-groups, carbonyls, and so forth were effectively reduced with retention times as low as 2 min. Additionally, standard protection groups such as Cbz, benzyl, and allyl ether or esters were removed in high yields. To prove the flexibility of the setup an example of the Mizoroki–Heck reaction was also performed on the MRU. Finally, two scale-up transfer hydrogenation experiments were performed affording isolation of the desired target compounds in 0.5 and 0.8 mol scales with less than 4 h of continuous operation on the MRU

Silacarboxylic Acids as Efficient Carbon Monoxide Releasing Molecules: Synthesis and Application in Palladium-Catalyzed Carbonylation Reactions

Silacarboxylic acids have been demonstrated to be easy to handle, air-stable carbon monoxide precursors. Different silacarboxylic acids were synthesized from the corresponding chlorosilanes and carbon dioxide, and their decarbonylation, upon treatment with an array of activators, was evaluated. The release of CO from crystalline MePh₂SiCO₂H proved to be highly efficient, and it was successfully applied in a selection of palladium-catalyzed carbonylative couplings using near-stoichiometric quantities of carbon monoxide precursor. Finally, the synthesis of MePh₂Si¹³CO₂H and its application in carbonyl labeling of two bioactive compounds was demonstrated

Improved Safety during Transfer of Pyrophoric <i>tert</i>-Butyllithium from Flasks with Protective Seals

A simple setup has been devised to facilitate safer transfer of air-sensitive and pyrophoric reagents from Sure/Seal bottles in a fume hood setting. The setup is composed of three parts; a sealed transfer vial, a custom bottle cap for transfer vial alignment, and a metal clip. All of the needed parts are constructed from standard laboratory equipment and by 3D printing. Titration of <i>tert</i>-butyllithium was used as an example of safe transfer of a highly pyrophoric reagent, and an instructional video has been prepared

Improved Safety during Transfer of Pyrophoric <i>tert</i>-Butyllithium from Flasks with Protective Seals

A simple setup has been devised to facilitate safer transfer of air-sensitive and pyrophoric reagents from Sure/Seal bottles in a fume hood setting. The setup is composed of three parts; a sealed transfer vial, a custom bottle cap for transfer vial alignment, and a metal clip. All of the needed parts are constructed from standard laboratory equipment and by 3D printing. Titration of <i>tert</i>-butyllithium was used as an example of safe transfer of a highly pyrophoric reagent, and an instructional video has been prepared

Improved Safety during Transfer of Pyrophoric <i>tert</i>-Butyllithium from Flasks with Protective Seals

A simple setup has been devised to facilitate safer transfer of air-sensitive and pyrophoric reagents from Sure/Seal bottles in a fume hood setting. The setup is composed of three parts; a sealed transfer vial, a custom bottle cap for transfer vial alignment, and a metal clip. All of the needed parts are constructed from standard laboratory equipment and by 3D printing. Titration of <i>tert</i>-butyllithium was used as an example of safe transfer of a highly pyrophoric reagent, and an instructional video has been prepared