Sequential One-Pot Research Articles

Sequential One-Pot Transformation to R-CF2-Embedded 1,5-Diketones Enabled by Nickel: Access to 4-Perfluoroalkylpyridines.

Herein, we have demonstrated the application of bench-stable polyfluorinated alcohols as fluoroalkylating reagents for a sequential one-pot transformation with ketones to R-CF2-embedded 1,5-diketones and pyridines enabled by a nickel catalyst. The protocol is tolerant to a range of functional groups (>31 examples and up to 85% yield) and perfluoro alcohols and releases H2 and H2O as byproducts. Preliminary mechanistic studies, EPR analyses, and deuterium scrambling experiments were performed, and observed PC-H/PC-D = 2.12.

Sequential One-Pot Synthesis of β-Amino-γ-keto-malonates from Nitro-Substituted Donor–Acceptor Cyclopropanes

AbstractA sequential one-pot procedure has been developed to access β-amino-γ-keto-malonates from nitro-substituted donor–acceptor cyclopropanes and four different nitrogen heterocycles. The reaction proceeds through in situ generation of aroylmethylidene malonates from 1-aryl-2-nitrocyclopropanes via Kornblum-type ring-opening oxidation using DMSO and subsequent aza-Michael addition with the nitrogen heterocycles. To prove the synthetic utility of the resulting products, one of them was transformed into a pyridazinone derivative.

Sequential One-Pot (Het)arene Thioetherification and Amination with Nickel and Visible Light

Sequential One-Pot (Het)arene Thioetherification and Amination with Nickel and Visible Light

Sequential One-Pot Synthesis of 3-Arylbenzofurans from N-Tosylhydrazones and Bromophenol Derivatives.

A divergent and efficient one-pot sequence allowing direct access to 3-arylbenzofuran derivatives has been developed. The process, involving N-tosylhydrazones and bromophenols, proceeds via a palladium-catalyzed Barluenga-Valdés cross-coupling, followed by an aerobic, copper-catalyzed, radical cyclization to form Csp2-Csp2 and O-Csp2 bonds. 3-Arylated benzofurans bearing various substituents were obtained with good to excellent yields (up to 90%). Mechanistic investigation strongly supports a radical process for the cyclization step.

Sequential One-Pot Vilsmeier-Haack and Organocatalyzed Mannich Cyclizations to Functionalized Benzoindolizidines and Benzoquinolizidines.

The development of new one-pot sequential cyclizations involving a Vilsmeier-Haack reaction followed by an organocatalyzed Mannich reaction is reported. This synthetic strategy gives access to functionalized indolizidines and quinolizidines in one operation from readily synthesized precursors. Yields and diastereoselectivities are good to excellent when formamides are used to trigger the key step, bearing either an electron-rich aryl or a pyrrole as the nucleophilic partner in the first cyclization.

A Highly Efficient and Green Synthesis of Pyrimido-Fused Benzophenazines via Microwave-Assisted and H3PW12O40@Nano-ZnO Catalyzed a Sequential One-Pot Cyclization in Aqueous Medium

A rapid, efficient, and environmentally benign procedure for the synthesis of novel heteroaryl-substititued dihydrobenzo[a]pyrimido[5′,4′:5,6]pyrido[2,3-c]phenazines has been developed via condensation/Knoevenagel/Michael/heterocyclization reactions of 2-hydroxynaphthalene-1,4-dione, o-phenylenediamine, aromatic aldehydes, and 6-amino-1,3-dimethyluracil in the presence of H3PW12O40@nano-ZnO as a recyclable heterogeneous catalyst in aqueous medium under microwave irradiation. This sequential green process with main aspects such as: operational simplicity, high yields, low cost, easy handling, eco-friendly and reusability of the catalyst, absence of any tedious workup, or purification and avoidance of hazardous or toxic reagents/catalysts/solvents opens an effective and convenient way to pyrimido-functionalized benzophenazine systems, which are promising compounds for different biomedical applications.

Polyelectrolyte Capping As Straightforward Approach toward Manipulation of Diffusive Transport in MOF Films.

We present experimental results demonstrating the suitability of polyelectrolyte capping as a simple and straightforward procedure to modify hydrophilic/hydrophobic character of porous films, thus allowing additional control on transport properties. In particular, we synthesized ZIF-8 metal organic framework (MOF) films, an archetypal hydrophobic zeolitic imidazolate framework, constituted by Zn2+ ions tetrahedrally coordinated with bidentate 2-methylimidazolate organic linker, and poly(4-styrenesulfonic acid) as capping agent (PSS). MOF films were synthesized via sequential one pot (SOP) steps over conductive substrates conveniently modified with primer agents known to enhance heterogeneous nucleation, followed by dip-coating with PSS aqueous solutions. Crystallinity, morphology, and chemical composition of ZIF-8 films were confirmed with traditional methods. Continuous electron density depth profile obtained with synchrotron light X-ray reflectivity (XRR) technique, suggest that PSS capped-films do not adopt segregated configurations in which PSS remains surface-confined. This affects functional properties conferred by PSS capping, which were assessed using cyclic voltammetry with both positively and negatively charged redox probe molecules. Furthermore, taking advantage of the control attained, we successfully carried in situ synthesis of film-hosted d-block metal nanoparticles (Au and Pt-NPT@5x-ZIF-8+PSS) via direct aqueous chemical reduction of precursors (diffusion-reaction approach).

An N-Heterocyclic Carbene-Mediated, Enantioselective and Multicatalytic Strategy to Access Dihydropyranones in a Sequential Three-Component One-Pot Reaction.

The multicatalytic generation of 3,5,6-trisubstituted 3,4-dihydropyranones with high enantioselectivity using a highly convergent strategy starting from commercially available precursors is reported. The operationally simple three-step, one-pot protocol merges H-bond and NHC catalysis to provide crucial, reactive β-unsubstituted enones from nitroalkenes as latent 1,2-biselectrophiles. These intermediates are directly funneled into a further NHC-catalyzed formal hetero-Diels-Alder reaction to deliver manifold chiral C(4)-unsubstituted dihydropyranones (typical ee >98%), allowing aliphatic and heteroaromatic substituents and hence expanding the scope of this Michael addition/lactonization.

Sequential One-Pot Synthesis of Dipeptides through the Transient Formation of CDI-N--Protected alpha--Aminoesters

Sequential One-Pot Synthesis of Dipeptides through the Transient Formation of CDI-N--Protected alpha--Aminoesters

Sequential One-Pot Multienzyme Chemoenzymatic Synthesis of Glycosphingolipid Glycans.

Glycosphingolipids are a diverse family of biologically important glycolipids. In addition to variations on the lipid component, more than 300 glycosphingolipid glycans have been characterized. These glycans are directly involved in various molecular recognition events. Several naturally occurring sialic acid forms have been found in sialic acid-containing glycosphingolipids, namely gangliosides. However, ganglioside glycans containing less common sialic acid forms are currently not available. Herein, highly effective one-pot multienzyme (OPME) systems are used in sequential for high-yield and cost-effective production of glycosphingolipid glycans, including those containing different sialic acid forms such as N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), 2-keto-3-deoxy-d-glycero-d-galacto-nononic acid (Kdn), and 8-O-methyl-N-acetylneuraminic acid (Neu5Ac8OMe). A library of 64 structurally distinct glycosphingolipid glycans belonging to ganglio-series, lacto-/neolacto-series, and globo-/isoglobo-series glycosphingolipid glycans is constructed. These glycans are essential standards and invaluable probes for bioassays and biomedical studies.

ChemInform Abstract: Boron Trifluoride‐Promoted Indium(III) Triflate‐Catalyzed Sequential One‐Pot Synthesis of (1,2‐Diaryl‐2‐oxoethyl)malonates from trans‐2‐Aryl‐3‐nitrocyclopropane‐1,1‐dicarboxylates and Activated Arenes.

ChemInform Abstract: Boron Trifluoride‐Promoted Indium(III) Triflate‐Catalyzed Sequential One‐Pot Synthesis of (1,2‐Diaryl‐2‐oxoethyl)malonates from trans‐2‐Aryl‐3‐nitrocyclopropane‐1,1‐dicarboxylates and Activated Arenes.

Amine-Mediated Sequential One-Pot Synthesis of Highly Substituted Thiophenes from β-Keto Esters, Aryl Isothiocyanates and 4-Chloroacetoacetate

GRAPHICAL ABSTRACT

A Facile, Superacid-Promoted Sequential Domino One-Pot Dual C–C Bond Formation and Fischer Indole Synthesis: Rapid Access to 10-Phenyl-5,10-dihydroindeno[1,2-b]indoles

A superacid-promoted sequential domino one-pot approach for the synthesis of novel 10-phenyl-5,10-dihydroindeno[1,2-b]indoles, ubiquitous core structure present in many alkaloid natural products, is presented. The entire sequential process involves a domino intermolecular Friedel–Crafts alkylation and intramolecular acylation of simple and easily accessible ethyl cinnamates, to furnish the corresponding indanones, followed by the Fischer indole reaction. Interestingly, this method enabled the synthesis of various dihydroindeno[1,2-b]indoles possessing tertiary or quaternary centers at the 10th position.

Sequential One-Pot Synthesis of Tri- and Tetrasubstituted Thiophenes and Fluorescent Push-Pull Thiophene Acrylates Involving (Het)aryl Dithioesters as Thiocarbonyl Precursors.

An efficient, one-pot three component synthesis of highly functionalized tri- and tetrasubstituted thiophenes has been reported involving (het)aryl dithioesters as thiocarbonyl precursors. Thus, sequential base mediated condensation of readily available (het)aryl active methylene ketones with (het)aryl dithioesters followed by S-alkylation of the resulting enethiolate salts with activated halomethylene compounds and concurrent intramolecular aldol-type condensation of S-alkylated compounds affords substituted thiophenes in excellent yields. The methodology has also been extended for the synthesis of highly fluorescent push-pull substituted thiophene-5-acrylates by using bromocrotonate as the activated methylene alkylating agent.

Sequential one-pot access to molecular diversity through aniline aqueous borylation.

On the basis of our recently reported aniline aqueous borylation, molecular diversity was achieved in a one-pot process by combining other reactions such as esterification, Suzuki-Miyaura coupling, hydrogenolysis, or Petasis borono-Mannich.

Synthesis of β-Aryl-β-sulfanyl Ketones by a Sequential One-Pot Reaction Using KF/Al2O3 in Glycerol

The title compounds were synthesized by a sequential one-pot reaction of aryl aldehydes, aryl-methyl ketones, and thiols promoted by KF/Al2O3. This methodology affords a large number of β-aryl-β-sulfanyl ketone derivatives from aliphatic and aromatic thiols in good yields and is also applicable for solid substrates. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

Step-Economical Access to Valuable Weinreb Amide 2,5-Disubstituted Pyrrolidines by a Sequential One-Pot Two-Directional Cross-Metathesis/Cyclizing Aza-Michael Process

Double cross-metathesis of 1,5-hexadiene with a variety of electron-deficient alkenes including the reluctant Weinreb acrylamide has been successfully accomplished. It was found that the process is quite general, and microwave irradiation effectively accelerates cross-coupling metathesis. This promotes a very versatile and high yielding methodology for the synthesis of symmetric Michael acceptors, which can be transformed into 2,5-disubstituted pyrrolidines through a sequential one-pot two-directional cross-metathesis/ring-closing double aza-Michael process.

Synthesis of an H3 Antagonist via Sequential One-Pot Additions of a Magnesium Ate Complex and an Amine to a 1,4-Ketoester followed by Carbonyl-Directed Fluoride Addition

We describe the development of an efficient and scalable process for the preparation of fluorocyclobutane-containing H3 antagonist, 1. The synthesis was accomplished by the chemoselective addition of a magnesium ate complex and an amine to a 1,4-ketoester in a one-pot sequence, followed by a diastereoselective carbonyl-directed fluorination. The chemoselective addition of the magnesium ate complex to the ketoester benefited from tight stoichiometric control, short addition times, and lower reaction temperatures, and thus was amenable to rapid mixing and excellent heat transfer in a flow reactor.

Efficient Synthesis of Urea Derivatives via a Sequential One-Pot Nucleophilic Addition/Ugi Five-Component Reaction Under Solvent-Free Conditions

Urea polyfunctional derivatives were successfully synthesized via a one-pot, five-component nucleophilic addition/Ugi reaction sequence. Simplicity, solvent-free conditions, and good yields of products are advantages of this method.

Sequential One-Pot Reactions of Thioformamides with Organolithium and Zinc Reagents

Sequential one-pot reactions of thioformamides with organolithium and zinc reagents were carried out. As thioformamides, N,N-dimethylthioformamide and N-ethoxycarbonyl N′-thioformyl piperazine were used. A variety of organolithium reagents such as alkyl, aryl, and heteroaryllithiums were used to give the corresponding amines in moderate to high yields. The efficiency of the reaction was influenced by the substituents on the aromatic rings. Thienyllithium gave the product in good yield, whereas the reaction of furyllithium was less efficient. A similar reaction with lithium acetylides was not successful. As an alternative method, methyl iodide was added to the reaction mixture of thioformamides and lithium silylacetylide to form S,N-acetals as intermediates, and to this were added organozinc reagents to lead to propargylamines. For organozinc reagents, dialkyl zincs and 3-ethoxycarbonylpropylzinc bromide were used. The former reagents showed high efficiency when combined with several organolithium reagents, but the latter gave the corresponding product only when lithium silylacetylide was used as an initial reagent.