One-pot Operation Research Articles

Metal-Free Iodine-Catalyzed Synthesis of Fully Substituted Pyrazoles and Its Sulphenylation.

A direct and metal-free access toward fully substituted pyrazoles and its sulphenylation has been established through an iodine-mediated three-component [3 + 2] annulation of β-ketonitrile (or pentane-2,4-dione), arylhydrazines, and aryl sulfonyl hydrazides. The reaction allows the formation of one C-S and two C-N bonds by the multiple bond cleavage including sulfur-oxygen, sulfur-nitrogen, and carbon-oxygen bonds. The method features low-cost and readily accessible substrates, bond-forming efficiency, and broad substrate scopes as well as simple one-pot operation, which makes this strategy highly attractive.

Catalyst-Free One-Pot Access to 3-Pyrazolylisoindolinone Derivatives

A series of 3-pyrazolylisoindolinone derivatives were synthesized by a concise, efficient, three-component reaction of a 2-formylbenzoic acid, a primary amine (or ammonium hydroxide), and a pyrazolone under catalyst-free conditions. This novel procedure has the advantages of easy handling, mild reaction conditions, and a wide substrate scope, and can be performed as a one-pot operation.

Practical Synthesis of N-(Diphenylmethyl)- and N-(1-Adamantyl)amides Directly from Aldehydes via a One-Pot Schmidt and Ritter Reaction Sequence

Nonoxidative and noncoupling reaction conditions have been developed for the synthesis of <i>N</i>-(diphenylmethyl)- and <i>N</i>-(1-adamantyl)amide derivatives directly from aldehydes by employing the concept of a Schmidt and Ritter reaction sequence in a one-pot operation. The reagent mixture consisting of sodium azide and HBF₄·OEt₂ in acetic acid converts the aldehydes into their respective nitrile analogues which in situ undergo the Ritter reaction with diphenylmethanol or 1-adamantanol to afford the corresponding <i>N</i>-(diphenylmethyl)- or <i>N</i>-(1-adamantyl)amide derivatives in very good yields. The method does not require column chromatographic purification for isolation of the products. With its simple reaction procedure and easy product purification technique, this method outshines earlier conventional two-step methods.

ChemInform Abstract: Synthesis of Enaminones and Their Difluoroboron Complexes Through Domino Aryl Migration.

AbstractThis new domino strategy allows the selective synthesis of boron complexes.

ChemInform Abstract: Synthesis of Quinolino[2′,3′:8,7]cyclooct[b]indole.

A rapid and efficient synthetic route for the synthesis of 7,8,9,10-tetrahydroquinolino[2 ′ ,3 ′ :8,7] cyclooct[b]indole analogues has been developed by reaction of 1-oxo-1,2,3,4,5,6-hexahydrocyclooct[b]indole with anthranilic acid and 3-amino pyrazine acid under POCl3 condition and the synthesis of 7,8,9,10-tetrahydroquinolino[2 ′ ,3 ′ :8,7]cyclooct[b]indole-6-carboxylic acid has been designed by reaction of 1-oxo-1,2,3,4,5,6-hexahydrocyclooct[b]indole with isatin in the presence of NaOH via Pfitzinger reaction. These methods are more satisfactory in terms of the yield and simple one-pot operation. Structures of the products thus obtained were confirmed by spectral studies.

A Facile Stereoselective Domino Approach for the Construction of Novel Bis(spiropiperidone)–Tetrahydrothiophene Hybrid Heterocycles

A library of novel bis-spiropiperidone–tetrahydrothiophene hybrid heterocycles have been synthesized via pseudo-three-component domino reaction of (3 E ,5 E )-3,5-bis(arylidene)-1-methyl/benzyl piperidin-4-ones and 1,4-dithiane-2,5-diol in the presence of triethylamine. This transformation presumably proceeds via two annulations each involving the generation of 2-mercaptoacetaldehyde from 1,4-dithiane-2,5-diol–Michael addition–intramolecular aldol sequence which result in the creation of four new bonds in a one-pot operation. The advantages of this protocol are high atom economy, high stereoselectivity, short reaction time, and operational simplicity.

Synthesis of 3-Iminoindol-2-amines and Cyclic Enaminones via Palladium-Catalyzed Isocyanide Insertion-Cyclization.

A palladium-catalyzed isocyanide insertion-cyclization using low-cost and readily accessible 2-haloanilines, 2-iodophenylethanones, and isocyanides for efficient synthesis of 3-iminoindol-2-amine and cyclic enaminone derivatives has been developed. The method features low-cost and readily accessible starting materials, reliable scalability, and bond-forming efficiency as well as simple one-pot operation, which makes this strategy highly attractive. A reasonable mechanism for forming 3-iminoindol-2-amine involved double isocyanide insertion/cyclization process is proposed.

ChemInform Abstract: Stereoselective Synthesis of Spiro[tetrahydropyran‐3,3′‐oxindole] Derivatives Employing Prins Cascade Strategy.

A variety of aldehydes undergo smooth coupling with 4-hydroxy-N-methyl-2-methylene-N-phenylbutanamide in the presence of BF3·OEt2 under ambient conditions to produce the corresponding spiro-oxindole derivatives in good yields with excellent selectivity. It is an entirely new strategy to construct the spirocycles in a one-pot operation through a Prins cascade process.

Synthesis of 2,3-Benzodiazepines and 2,3-Benzodiazepin-4-ones from Arynes and β-Diketones

Abstract 2,3-Benzodiazepines were synthesized by two-step or one-pot reactions from aryne precursors. Reaction of 2-(trimethylsilyl)aryl triflates with β-diketones in the presence of CsF gave ortho-substituted benzophenones. Treatment of benzophenones with hydrazine hydrate resulted in the formation of 2,3-benzodiazepines in moderate yields. Tofisopam, a well known anxiolytic, could be synthesized via C–C bond insertion of 3,4-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)butane-1,3-dione, followed by the reaction with hydrazine hydrate in one-pot operation. 2,3-Benzodiazepin-4-ones were also synthesized by the reaction of β-keto esters with triflates in the presence of CsF, followed by the addition of hydrazine hydrate. Substituted isoquinolines were synthesized by the reaction of ortho-substituted benzophenones with ammonium hydroxide.

ChemInform Abstract: Modular, Flexible, and Stereoselective Synthesis of Pyrroloquinolines: Rapid Assembly of Complex Heterocyclic Scaffolds.

A novel 1,2-dinucleophile engages two imines in a sequential vinylogous Mannich-Mannich-Pictet-Spengler process to generate complex hexahydropyrrolo[3,2-c]quinolines in a one-pot operation. This methodology provides a rapid, highly modular, and flexible access toward a wide range of products and forms four new σ-bonds and chiral centers each. The diastereoselectivity may be inverted by fine-tuning of reaction conditions and the electronic nature of the imines.

Tandem aziridine ring opening-disulfide formation-reduction-Michael addition in one-pot mediated by tetrathiomolybdate

A detailed study of tetrathiomolybdate mediated tandem regio- and stereoselective ring opening of aziridine, disulfide formation, reduction of disulfide bond and Michael reaction in a one-pot operation is reported. This constitutes four reactions that take place in one-pot operation. In the reaction of [BnEt3N]4MoS4 with an aziridine derived from cyclohexene and in the absence of Michael acceptor intermediates sulfonamidodisulfide and sulfonamidothiol were isolated and fully characterized. It has also been shown that it is possible to carry out selective opening of the aziridine ring in the presence of an epoxide. By incorporating a suitable Michael acceptor as part of the substrate, intramolecular 1,4-addition could be performed, to achieve the synthesis of sulfur containing acyclic, cyclic amino acid ester derivatives and thia-bicyclo[3.3.1]nonane derivatives in good yields.

ChemInform Abstract: Asymmetric Organocatalyzed Michael Addition of Nitromethane to a 2‐Oxoindoline‐3‐ylidene Acetaldehyde and the Three One‐Pot Sequential Synthesis of (‐)‐Horsfiline and (‐)‐Coerulescine.

(−)-Horsfiline and (−)-coerulescine were synthesized through three one-pot operations in 33 and 46 % overall yield, respectively. Key to the success was the efficient use of a diarylprolinol silyl ether to catalyze the asymmetric Michael addition of nitromethane to a 2-oxoindoline-3-ylidene acetaldehyde. This allowed the all-carbon quaternary, spirocyclic carbon stereocenter to be constructed in good yield with excellent enantioselectivity.

ChemInform Abstract: A Step‐Economical Route to Fused 1,2,3‐Triazoles via an Intramolecular 1,3‐Dipolar Cycloaddition Between a Nitrile and an in situ Generated Aryldiazomethane.

An intramolecular 1,3-dipolar cycloaddition strategy for rapid entry into triazole-fused heterocyclic compounds without recourse to the traditional Cu(1)-catalyzed azide–alkyne cycloadditions is described. Central to the strategy is the in situ generation of substituted diazomethanes in a two-step sequence from the corresponding aldehydes, which then undergo smooth cycloaddition with a cyano group to generate the desired fused 1,2,3-triazoles in good overall yields. The entire sequence can be carried out in a one-pot operation.

ChemInform Abstract: Facile Four‐Component Domino Reactions for the Synthesis of 2,6‐Diaryl‐4‐(1H‐indol‐3‐yl)‐3‐cyanopyridines.

Abstract A series of novel 2,6-diaryl-4-(1H-indol-3-yl)-3-cyanopyridines was obtained in good yields from the domino reactions of 3-(1H-indol-3-yl)-3-oxopropanenitrile, 4,4,4-trifluoro-1-phenylbutane-1,3-dione, and aromatic aldehydes in the presence of ammonium acetate under solvent-free condition. This transformation involves the formation of two C C and two C N bonds leading to the creation of a six-membered ring in a one-pot operation.

Enantioselective Synthesis of Allenylenol Silyl Ethers via Chiral Lithium Amide Mediated Reduction of Ynenoyl Silanes and Their Diels–Alder Reactions

An enantioselective Meerwein-Ponndorf-Verley-type reduction of ynenoylsilanes by a chiral lithium amide followed by a Brook rearrangement and anti-mode protonation across conjugated 1,3-enynes provides allene derivatives bearing a 2-siloxyvinyl moiety in high enantioselectivity. The E/Z geometry of enol silyl ethers is controlled by the geometry of the starting enyne moiety. Thus, (E)- and (Z)-enol silyl ethers are obtained from (Z)- and (E)-ynenoylsilans, respectively. The 2-siloxyvinylallene products can participate in Diels-Alder reactions with reactive dienophiles such as PTAD, which can be achieved in a one-pot operation from ynenoylsilanes.

ChemInform Abstract: Synthesis of Hexacyclic Fused Isocoumarin Framework Through Selective Domino Multicyclizations under Catalyst and Solvent Free Conditions.

Abstract A novel fused isocoumarin skeleton has been synthesized through selective domino multicyclizations by mixing homothallic acid and 2,3-diphenylacryloyl chloride at 200 °C under catalyst and solvent free reaction conditions. Six fused rings with two stereogenic centers were assembled in a convenient one-pot operation in good yield. The resulting hexacyclic fused isocoumarin skeleton and its stereochemistry was fully characterized and unambiguously confirmed by X-ray diffraction analysis.

Directing group assisted nucleophilic substitution of propargylic alcohols via o-quinone methide intermediates: Brønsted acid catalyzed, highly enantio- and diastereoselective synthesis of 7-alkynyl-12a-acetamido-substituted benzoxanthenes.

BINOL-based, chiral phosphoric acids catalyze the substitution of 1-(o-hydroxyphenyl)propargylic alcohols with enamides to furnish 7-alkynyl-12a-acetamido-substituted benzo[c]xanthenes and related heterocycles in a one-pot operation with excellent diastereo- and enantioselectivity. Ambient reaction temperature, operationally simple reaction conditions, low catalyst loading, high yields, and excellent stereocontrol are attractive features of this process and make it a highly practical and versatile transformation.

Two Neglected Multicomponent Reactions: Asinger and Groebke Reaction for Constructing Thiazolines and Imidazolines

The multicomponent reaction (MCR) is an important research field in the organic synthetic methodology. In 1956, Professor Friedrich Asinger reported a method for synthesizing thiazoline scaffold, in which a ketone was treated by sulfur and ammonia in one-pot operation. In 1998, Professor Katrin Groebke, Hugues Bienayme, and Christopher Blackburn reported a method for preparing imidazo[1,2-a]pyridine, in which an annulation took place among α- aminopyridine, aldehyde, and isocyanide in one-pot operation, and then the reaction was entitled as Groebke reaction. Comparing with the bloom in the research of other MCRs such as Strecker (found in 1850), Hantzsch (1882), Biginelli (1891), Mannich (1912), Passerini (1921) and Ugi (1959) MCR, as newcomers in the family of MCR, Asinger and Groebke reactions are not reported as usually as other MCRs. The aim of the present review is to emphasize the importance of these two MCRs in the synthesis of thiazolines and imidazolines. Although the Asinger protocol is innovated as the reaction of α-halogensubstituted ketone with thioamide, or, the C-S bond in thiazoline is contributed from mercapto or thiocarbonyl groups, as well as β- aminothiol as the synthon reacts with carbonyl compounds to form the thiazoline scaffold, the advantage of Asinger reaction is still worthy to be noted because four bonds in thiazoline are produced simultaneously from the reaction of ketone with the simple reactants, sulfur and ammonia. On the other hand, the review on the Groebke reaction is herein catalogued as substrates and catalysts. The 2- aminopyridine-type substrates are the necessary reagents for the Groebke reaction and therefore limit the applicability of the reaction, but some efforts succeed in applying catalysts for enlarging the suitable substrates or agitating the following reactions based on the Groebke adducts. To sum up the present achievements on Asinger and Groebke reaction, it can be concluded that the exploration on catalysts will break the limitation of the substrates and bring them with wide application in the synthesis of thiazolines and imidazolines. Keywords: Asinger reaction, Groebke reaction, imidazoline, multicomponent reaction, thiazoline.

Stereoselective synthesis of epoxyisoprostanes: an organocatalytic and "pot-economy" approach.

An efficient and direct synthetic route to epoxyisoprostane EC methyl ester has been accomplished in 8 steps (10% overall yield) from readily available starting materials using a series of asymmetric organocatalytic reactions and one-pot operations.

One-pot protocol to functionalized benzopyrrolizidine catalyzed successively by Rh2(OAc)4 and Cu(OTf)2: a transition metal-Lewis acid catalysis relay.

4-N-allylarylpropylamino-1-sulfonyl triazoles are converted to structurally unique benzopyrrolizidinyl sulfonamides in a one-pot operation. Intramolecular capture of rhodium carbene with arylamino nitrogen gives rise to the formation of an ammonium ylide immediate. A [2,3]- or [1,2]-rearrangement occurs to give a 2-allylpyrrolidinyl-2-carbimine intermediate which undergoes Cu(OTf)2 catalyzed aza-Friedel-Crafts cyclization to finish a highly functionalized tricyclic system decorated with a synthetically difficult quaternary carbon center, a sulfonamide group, and an allyl segment.