Expedient Protocol Research Articles

Ultrasound-Mediated Green Synthesis of Imidazo[1,2-a]pyridines and Imidazo[2,1-b]thiazoles through C(sp3)–H Functionalization

AbstractAn ultrasound-assisted expedient protocol has been developed for the synthesis of imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazoles by the C–H functionalization of ketones using a KI/tert-butyl hydroperoxide catalytic system. The reaction takes place in water, a green solvent, and does not require a metal catalyst; it also gives good yields of the products. The method offers numerous noteworthy characteristics, including mild reaction conditions, the absence of a base, broad functional-group compatibility, and excellent reaction yields. Moreover, it avoids the use of costly and air-sensitive chemicals, and can be conducted under ambient reaction conditions.

Two-Step Construction of Thiophene-Oxazole Dyads with Fluorescent Properties by the Ring Expansion of Aziridines.

A general approach toward 2-thiophenylsubstituted oxazoles using aziridination of a double bond of (acyl)alkenyl thiophenes with the subsequent expansion of the aziridine ring is developed. The isolation of intermediate aziridine is not necessary. This expedient protocol covers a broad scope of readily available 2-, 3-, and benzothiophene derivatives, is practical and reliable, requires short reaction times, and is simple to set up and work up reaction mixtures. Thiophenyloxazoles, obtained by this method, exhibit fluorescence with high quantum yields.

Asymmetric Synthesis of Chiral Aza-macrodiolides via Iridium-Catalyzed Cascade Allylation/Macrolactonization.

Iridium-catalyzed cascade allylation/macrolactonization between vinylethylene carbonate (VEC) and isatoic anhydride derivatives was successfully developed, readily generating a wide range of C2-symmetric chiral macrodiolides bearing 14-membered rings in moderate to good yields with excellent diastereoselectivities and enantioselectivities (generally 99% ee). Control experiments revealed that racemic VEC as the precursor of electrophilic iridium-π-allyl species underwent kinetic resolution process. This expedient protocol features easily available substrates, excellent stereoselective control, and high step economy.

An expedient, efficient and solvent-free synthesis of T3P®-mediated amidation of benzhydrols with poorly reactive N-nucleophiles under MW irradiation

An expedient, efficient, economical, environmentally benign, and solvent free amidation protocol of benzhydrols with less reactive nitrogen nucleophiles assisted by propylphosphonic anhydride (T3P®) under microwave irradiation has been developed.

A Mild Method for Electrochemical Reduction of Heterocyclic N‐Oxides

Deoxygenation of heteroaromatic N‐oxides is commonly accomplished using chemical or enzymatic methods. In this work, we report on an expedient protocol for electrochemical reduction of pyridine N‐oxide derivatives under mild conditions. A diverse range of mono‐ and bis N‐oxides were converted into the corresponding nitrogen bases in good yields. Importantly, the method is highly selective towards N‐oxides and tolerates challenging halo and nitro substituents in the heteroaromatic ring.

Novel N‐(benzo[d]oxazol‐2‐yl)alkanamides; synthesis and carbonic anhydrase II inhibition studies

AbstractCarbonic anhydrase (CA II) inhibitors are very important therapeutic targets in drug design for treatment of neuropathic pain and in eradication of glaucoma, cancer, epilepsy, ulcer and obesity. In this study, some two2‐substituted benzoxazoles (3a‐j) were developed as a new family of carbonic anhydrase II inhibitors by employing acyl thiourea chemistry via a simple and expedient protocol and evaluated for CA II inhibitor activity and radical scavenging ability. Compounds 3f and 3j were found to be the most potent inhibitors, with IC50 values of 0.00564 and 0.00596 μM, respectively which are several times better than that of the standard, acetazolamide (IC50 value 0.997 ± 0.0586 μM). Docking experiments were carried out against the carbonic anhydrase II crystal structure to better rationalize the inhibitory activities of these new structures. Moreover, the results of a DPPH radical scavenging assay showed that the antioxidant profile of compound 3i is superior to those of other derivatives. The results have revealed that derivatives 3f and 3j behave as CA‐II inhibitors significantly better than standard and 3i has good anti‐oxidation potential.

Facile Synthesis of Nitrogen-Containing Six-Membered Benzofuzed Phenophosphazinine Oxides and Studies of the Photophysical Properties.

A facile synthesis of nitrogen-containing six-membered benzofuzed phosphacycles has been described. This cyclization reaction triggered by Tf2O provides an expedient protocol of phosphacycles with a simple operation at mild conditions. The preliminary photophysical studies of these novel materials reveal that the fluorescence intensity enhances with the molecular aggregation in the solid state and that the introduction of the sterically bulky phenanthrene group into the phosphacycles allows a significant increase in the fluorescence quantum yield.

Multiple Absolute Stereocontrol in Cascade Lactone Formation via Dynamic Kinetic Resolution Driven by the Asymmetric Transfer Hydrogenation of Keto Acids with Oxo-Tethered Ruthenium Catalysts.

A straightforward asymmetric construction of chiral fused γ- and δ-lactones containing multiple contiguous stereocenters was successfully developed by either (1) the dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) reaction using oxo-tethered Ru(II) complexes followed by syn-selective lactonization or (2) the tandem DKR-ATH/lactonization in combination with asymmetric hydrogenation catalyzed by Ru-chiral diphosphine complexes. The expedient protocol is applicable to the enantioselective synthesis of natural wine lactone and a biologically active benzo-fused lactone with an unprecedented level of diastereo- and enantioselectivity.

Development of a Synthesis of Kinase Inhibitor AKN028

The novel tyrosine kinase inhibitor AKN028 has demonstrated promising results in preclinical trials. An expedient protocol for the synthesis of the compound at kilogram scale is described, including an SNAr reaction with high regioselectivity and a Suzuki coupling. Furthermore, an efficient method for purification and removal of residual palladium is described.

Dehydration of Amides to Nitriles under Conditions of a Catalytic Appel Reaction.

A highly expedient protocol for a catalytic Appel-type dehydration of amides to nitriles has been developed that employs oxalyl chloride and triethylamine along with triphenylphosphine oxide as a catalyst. The reactions are usually complete in less than 10 min with only a 1 mol % catalyst loading. The reaction scope includes aromatic, heteroaromatic, and aliphatic amides, including derivatives of α-hydroxy and α-amino acids.

A Sustainable and Efficient Synthesis of Benzyl Phosphonates Using PEG/KI Catalytic System.

An efficient and expedient protocol for the synthesis of benzyl phosphonates using KI/K2CO3 as a catalytic system and PEG-400 as benign solvent has been developed. The reaction proceeds smoothly at room temperature achieving excellent selectivity and yield of the corresponding products. The combination of PEG-400, KI, and K2CO3 in this reaction avoids the need of volatile/toxic organic solvents and reactive alkali metals or metal nanoparticles/hydrides. We believe that this benign combination (PEG-400 and KI) could be used for other related organic transformations.

ChemInform Abstract: K2S2O8‐Mediated Nitration of Alkenes with NaNO2 and 2,2,6,6‐Tetramethylpiperidine‐1‐oxyl: Stereoselective Synthesis of (E)‐Nitroalkenes.

Abstract A transition-metal-free nitration of alkenes with NaNO2 in the presence of K2S2O8 and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) is developed. The transformation exhibits a broad substrate scope and good functional group tolerance, thus providing a new and expedient protocol for stereoselective synthesis of (E)-nitroalkenes with moderate to good yields. Moreover, the nitration processes of (E)- and (Z)-stilbene are also studied: even though the proportion of substrates is different, the E/Z ratio of the products is basically the same. Based upon experimental observations, a possible reaction mechanism is proposed.

Decarboxylative/Sonogashira-type cross-coupling using PdCl2(Cy*Phine)2

Expedient protocol to access a wide range of internal alkynes and symmetrical di(heteroaryl)alkynesviatandem decarboxylative–Sonogashira cross-coupling.

K2S2O8-mediated nitration of alkenes with NaNO2 and 2,2,6,6-tetramethylpiperidine-1-oxyl: stereoselective synthesis of (E)-nitroalkenes

A transition-metal-free nitration of alkenes with NaNO2 in the presence of K2S2O8 and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) is developed. The transformation exhibits a broad substrate scope and good functional group tolerance, thus providing a new and expedient protocol for stereoselective synthesis of (E)-nitroalkenes with moderate to good yields. Moreover, the nitration processes of (E)- and (Z)-stilbene are also studied: even though the proportion of substrates is different, the E/Z ratio of the products is basically the same. Based upon experimental observations, a possible reaction mechanism is proposed.

Application of Pfitzinger Reaction to the Facile One‐Pot Access of the Novel (5,6‐b)‐Quinolino‐8‐carboxylic‐acid‐Annulated Analogs of (2,3‐d)‐Azepino‐benzimidazol‐2,6‐diones of Medicinal Interest

The potential of the Pfitzinger reaction has been explored to provide an expedient protocol to the synthesis of novel (5,6‐b)‐quinolino‐8‐carboxylic acid annulated analogues of (2,3‐d)‐azepino benzimidazol‐2,6‐diones 6a, 6b, 6c, 6d, 6e, 6f, 6g from (2,3‐d)‐azepino‐benzimidazol‐2,6,9‐triones 4 and isatins 5a, 5b, 5c, 5d, 5e, 5f, 5g.

ChemInform Abstract: Synthesis of Dihydropyrrole Derivatives by a Palladium‐Catalyzed Heck and Suzuki Cross‐Coupling Cascade Reaction.

An expedient protocol for the synthesis of 5-aryl-2,3-dihydropyrroles, starting from N-tosyl-protected 2-methylprop-2-en-1-amine, alkynyl bromides, and arylboronic acids, is described. The sequential reaction sequence involves nucleophilic addition of the sulfonamide to the alkynyl bromide, followed by a palladium-catalyzed tandem intramolecular Heck and intermolecular Suzuki cross-coupling reaction of the bromoalkene adduct.

ChemInform Abstract: Stereoselective Construction of 2,8‐Dioxabicyclo[3.3.1]nonane/nonene Systems from 3‐C‐Branched Glycals.

A stereoselective approach for the formation of 2,8-dioxabicyclo[3.3.1]nonane/nonene frameworks through the formation of 3-C-branched glycals encompassing the Claisen rearrangement of the carbohydrate-derived allyl-vinyl ethers and TMSOTf-catalyzed acetalization reactions as key steps is revealed. A novel acetalization of 3-C-branched glycals with a tentative mechanism is proposed. The expedient protocol is evaluated by synthesizing a number of 2,8-dioxabicyclo[3.3.1]nonane/nonene architectures.

Synthesis of Dihydropyrrole Derivatives by a Palladium-Catalyzed Heck and Suzuki Cross-Coupling Cascade Reaction

An expedient protocol for the synthesis of 5-aryl-2,3-dihydropyrroles, starting from N-tosyl-protected 2-methylprop-2-en-1-amine, alkynyl bromides, and arylboronic acids, is described. The sequential reaction sequence involves nucleophilic addition of the sulfonamide to the alkynyl bromide, followed by a palladium-catalyzed tandem intramolecular Heck and intermolecular Suzuki cross-coupling reaction of the bromoalkene adduct.

Salt‐Free Preparation of Trimethylsilyl Ethers by B(C6F5)3‐Catalyzed Transfer Silylation by Using a Me3SiH Surrogate

AbstractAn unprecedented transfer silylation of alcohols catalyzed by the strong Lewis acid B(C6F5)3 is described. Gaseous Me3SiH is released in situ by B(C6F5)3‐catalyzed decomposition of 3‐trimethylsilylcyclohexa‐1,4‐diene and subsequently reacts with an alcohol in a dehydrogenative Si–O coupling promoted by the same boron catalyst. Benzene and dihydrogen are formed during the reaction, but no salt waste is. This expedient protocol is applicable to several silicon groups, and the preparation of trimethylsilyl ethers presented here is potentially useful for alcohol derivatization prior to GLC analysis.

Pd‐catalyzed homocoupling of arylhydrazines via C―N cleavage under O2

An efficient and simple synthetic method for biaryl synthesis was developed using Pd(OAc)2 as catalyst from aryl hydrazides under O2. Various biaryls were synthesized in good yields, offering an expedient protocol for the synthesis of symmetrical biaryl molecules via C―N cleavage. The reactions were performed in component solvent of toluene and acetone without using any pro‐oxidant. Copyright © 2014 John Wiley & Sons, Ltd.