Pd-catalyzed Aminocarbonylation Research Articles

Synthesis of Bis-P,N,P-hybrid Ligands and Application to Pd-Catalyzed Aminocarbonylation of Phenylacetylene with Aniline Free of Additive and Solvent

Synthesis of Bis-P,N,P-hybrid Ligands and Application to Pd-Catalyzed Aminocarbonylation of Phenylacetylene with Aniline Free of Additive and Solvent

Acyl Amidines by Pd-Catalyzed Aminocarbonylation: One-Pot Cyclizations and 11C Labeling.

A protocol for the carbonylative synthesis of acyl amidines from aryl halides, amidines, and carbon monoxide catalyzed by Pd(0) is reported herein. Notably, carbon monoxide is generated ex situ from a solid CO source, and several productive palladium ligands were identified with complementary benefits and substrate scope. Furthermore, sequential one-pot, two-step protocols for the synthesis of 1,2,4-triazoles and 1,2,4-oxadiazoles via acyl amidine intermediates are reported. In addition, this approach was extended to isotopic labeling using [11C]carbon monoxide to allow, for the first time, synthesis of 11C-labeled acyl amidines as well as a 11C-labeled 1,2,4-oxadiazole.

"Walking the nitrogen around the ring": Chemical synthesis and spectroscopic characterization of novel 4-, 5-, 6-, and 7-azaindazole analogs of the synthetic cannabinoid receptor agonist MDMB-PINACA.

Over the past decade, synthetic cannabinoid receptor agonists (SCRAs) have rapidly evolved to encompass a wide range of structurally diverse new psychoactive substances (NPS), including derivatives that incorporate indole, indazole, 7-azaindole, γ-carbolinone, or carbazole heterocyclic scaffolds. The introduction of legislative measures seeking to control the availability of NPS on the recreational drug scene has likely contributed to the continued emergence of novel SCRA analogs, which often evade regulatory control. However, the detection and/or identification of azaindazole-type SCRAs in seized material has not yet been reported (September, 2021). It is plausible that SCRAs bearing a 1,3-disubstituted azaindazole scaffold may possess cannabimimetic activity, given their structural similarity with known indole, indazole, and azaindole SCRAs. In view of these antecedents, a set of four novel isomeric 4-, 5-, 6-, and 7-azaindazole analogs of the known potent indazole SCRA, MDMB-PINACA, were synthesized using a Pd-catalyzed aminocarbonylation strategy. The complementary use of ultraviolet (UV) and infrared (IR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), high resolution mass spectrometry (HRMS), 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy, and high performance liquid chromatography (HPLC) has permitted the spectroscopic differentiation, unambiguous structural assignment, and rapid separation of novel isomeric 4-, 5-, 6-, and 7-azaindazole analogs of the indazole SCRA, MDMB-PINACA.

Synthesis of Secondary Aromatic Amides via Pd-Catalyzed Aminocarbonylation of Aryl Halides Using Carbamoylsilane as an Amide Source.

Using N-methoxymethyl-N-organylcarbamoyl(trimethyl)silanes as secondary amides source, the direct transformation of aryl halides into the corresponding secondary aromatic amides via palladium-catalyzed aminocarbonylation is described. The reactions tolerated a broad range of functional groups on the aryl ring except big steric hindrance of substituent. The types and the relative position of substituents on the aryl ring impact the coupling efficiency.

Ligand- and Additive-Controlled Pd-Catalyzed Aminocarbonylation of Alkynes with Aminophenols: Highly Chemo- and Regioselective Synthesis of α,β-Unsaturated Amides

This work describes the chemo- and regioselective direct aminocarbonylation of alkynes and aminophenols to form hydroxy-substituted α,β-unsaturated amides in good to excellent yields. The latter are valuable compounds in pharmaceuticals and natural products. By a simple choice of different ligands and additives, branched or linear isomers could be selectively formed in excellent regioselectivity. Using a combination of boronic acid and 5-chlorosalicylic acid (“BCSA”) as the additives, linear amides were obtained in high yields and selectivities using 1,2-bis(di-tert-butylphosphinomethyl)benzene (DTBPMB) as the ligand. On the other hand, branched amides could be approached by introducing 1,3-bis(diphenylphosphino)propane as the ligand and p-TsOH·H2O as the additive. In addition to the hydroxyl group, other functional substituents, such as carboxyl and vinyl groups, could also be tolerated using this method. As an application of this strategy, the natural product avenanthramide A could be synthesized direct...

Dioxygen-Promoted Pd-Catalyzed Aminocarbonylation of Organoboronic Acids with Amines and CO: A Direct Approach to Tertiary Amides.

A direct approach from organoboronic acids and amines to tertiary amides via Pd-catalyzed aerobic aminocarbonylation has been developed. The presence of O2 significantly promotes the efficiency of this transformation. This method uses commercially available organoboronic acids and cheap CO and O2 (1 atm), which renders amides an easy synthesis with broad substrate scope and high functional group tolerance.

Application of γ-Valerolactone as an Alternative Biomass-Based Medium for Aminocarbonylation Reactions.

γ-Valerolactone (GVL) was proposed as a renewable, nontoxic reaction medium with negligible vapor pressure for homogeneous Pd-catalyzed aminocarbonylation reactions. Iodobenzene as a model substrate and its 4-substituted derivatives were converted to the corresponding 2-ketocarboxamides with high conversions and chemoselectivities in γ-valerolactone. The effect of carbon monoxide pressure and reaction temperature on the conversion and selectivities were studied in the range 1-50 bar and 25-100 °C, respectively. The highest conversion and selectivity was achieved at 25 bar and 50 °C for iodobenzene in GVL for 24 h.

Mo(CO)6 as a Solid CO Source in the Synthesis of Aryl/Heteroaryl Weinreb Amides under Microwave-Enhanced Condition

The facile transformation of aryl/heteroaryl nonaflates into corresponding amides via Pd-catalyzed aminocarbonylation using Mo(CO)6 as a solid CO source under microwave-enhanced condition is reported. The method was found to be tolerant with respect to a diverse range of electronically biased aryl/heteroaryl nonaflates, and exceptional yields were obtained. The optimized protocol was further extended to a diverse range of amines.

Highly Ligand-Controlled Regioselective Pd-Catalyzed Aminocarbonylation of Styrenes with Aminophenols.

Achieving chemo- and regioselectivity simultaneously is challenging in organic synthesis. Transition metal-catalyzed reactions are effective in addressing this problem by the diverse ligand effect on the catalyst center. Ligand-controlled regioselective Pd-catalyzed carbonylation of styrenes with aminophenols was realized, chemoselectively affording amides. Using a combination of boronic acid and 5-chlorosalicylic acid as the additives, linear amides were obtained in high yields and selectivity using tris(4-methoxyphenyl)phosphine (L3) in acetonitrile, while branched amides were obtained in high yields and selectivity in butanone by changing the ligand to 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phosphaadamantane (L5). Further studies show that the nature of the ligand is key to the regioselectivity. Cone angle and Tolman electronic parameter (TEP) have been correlated to the reactivity and regioselectivity. Studies on the acid additives show that different acids act as the proton source and the corresponding counterion can help enhance the reactivity and selectivity.

Pd-catalyzed aminocarbonylation of alkynes with amines using Co2(CO)8 as a carbonyl source

A facile protocol for aminocarbonylation of alkynes with amines at room temperature was developed using a metal carbonyl source.

Kinetics analysis and automated online screening of aminocarbonylation of aryl halides in flow

The Pd-catalyzed aminocarbonylation of aromatic bromides was investigated in both a silicon microreactor and a packed-bed tubular reactor. An automated transient temperature ramp method with in-line IR analysis led to significantly more rapid determination of reaction kinetics than traditional steady-state screening for offline GC analysis.

A highly-efficient palladium-catalyzed aminocarbonylation/SNAr approach to dibenzoxazepinones

A practical protocol for the synthesis of dibenzo[b,e][1,4]oxazepin-11(5H)-ones has been developed. By virtue of Pd-catalyzed aminocarbonylation and aromatic nucleophilic substitution, 61 examples of the desired dibenzoxazepinones were obtained in moderate to excellent isolated yields (54–92%).

ChemInform Abstract: Sequential One‐Pot Synthesis of Benzoxazoles from Aryl Bromides: Successive Palladium‐ and Copper‐Catalyzed Reactions.

AbstractThe Pd‐catalyzed aminocarbonylation of aryl bromides causes formation of intermediate amides.

Development of a Second Generation Palladium Catalyst System for the Aminocarbonylation of Aryl Halides with CO and Ammonia

An improved and general method for the Pd-catalyzed aminocarbonylation of aryl halides (I) with CO and ammonia is established.

Palladium-catalyzed aminocarbonylation of heteroaryl halides using di- tert-butylphosphinoferrocene

Pd-catalyzed aminocarbonylation of heteroaryl halides, using monodentate ligand di- tert-butylphosphinoferrocene tetrafluoroborate is reported. Good to high yields were obtained with chiral amines on a variety of substrates including 2-bromo heteroaryls.

High-Efficiency Aminocarbonylation by Introducing CO to a Pressurized Continuous Flow Reactor

Halogenated aryl carboxylic acids were efficiently converted to the corresponding dicarboxylic acid monoamides by a one-step Pd-catalyzed aminocarbonylation in a micro/meso fluidic continuous flow reactor (X-Cube) operated at high pressure and high temperature with CO gas introduction. Reaction parameters (solvent, base, catalyst, pressure, temperature) were rapidly optimized in the reactions, which required less than 2 min. The method gave improved results over comparable batch techniques and is also suited to automated parallel syntheses of compound libraries.

Synthesis of Weinreb Amides via Pd-Catalyzed Aminocarbonylation of Heterocyclic-Derived Triflates

The direct transformation of lactam-, lactone-, and thiolactone-derived triflates into N-methoxy-N-methyl or morpholine Weinreb amides has been realized using Pd-catalyzed aminocarbonylation under CO atmospheric pressure and at room temperature. The carbonylative coupling can be efficiently carried out with 2% of catalyst in the presence of Xantphos as a ligand. The amides smoothly react with nucleophiles to afford acylated aza-, oxa-, and thio-heterocycles. The proposed methodology could be advantageously exploited for the synthesis of dienones in which one of the double bonds is embedded in a heterocyclic moiety, as useful substrates for Nazarov cyclization.

Aminocarbonylation route to tolvaptan

Pd-catalyzed aminocarbonylation between aryl bromide and NH-benzazepinone was effectively carried out to furnish the key intermediate for tolvaptan (up to 85%) in one step.

Convenient Method for the Preparation of Weinreb Amides via Pd‐Catalyzed Aminocarbonylation of Aryl Bromides at Atmospheric Pressure.

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Convenient Method for the Preparation of Weinreb Amides via Pd-Catalyzed Aminocarbonylation of Aryl Bromides at Atmospheric Pressure

[reaction: see text] The direct transformation of aryl bromides into the corresponding Weinreb amides via Pd-catalyzed aminocarbonylation at atmospheric pressure is reported.