One-pot Three-component Cycloaddition Research Articles

Hydrazones as Substrates in the Synthesis of Isoxazolidines via a KOH-Promoted One-Pot Three-Component Cycloaddition with Nitroso Compounds and Olefins.

Hydrazones have been employed as the starting materials in a KOH-mediated one-pot three-component cycloaddition with readily accessible nitroso compounds and olefins to construct various isoxazolidines. Compared with diazo compounds as starting materials, this methodology could afford a wider range of products in good to excellent yields and diastereoselectivities for most substrates, and hydrazones are cheaper, more accessible, and safer substrates. The experimental study shows that the choice of suitable hydrazones is crucial.

NBS/DBU-Promoted One-Pot Three-Component Cycloaddition of Malonic Acid Derivatives, Nitrosoarenes, and Alkenes: Synthesis of Isoxazolidines.

A general DBU-mediated one-pot three-component cycloaddition reaction of easily accessible malonic acid derivatives, nitrosoarenes, and alkenes has been successfully established with the aid of NBS to provide direct access to highly functionalized isoxazolidine derivatives with generally good to excellent yields, broad functional group tolerance, and excellent regio- and diastereo-selectivities under mild conditions. The mechanism study shows that the NBS-mediated formation of bromomalonic acid derivatives from malonic acid derivatives and DBU-promoted synthesis of nitrone intermediates via the reaction of bromomalonic acid derivatives with nitrosoarenes are key steps.

Metal free, I2-catalyzed [3+1+1] cycloaddition reactions to synthesize 1,2,4-trisubstituted imidazoles

We have successfully developed an operationally simple and economical one-pot three-component cycloaddition reaction to synthesize 1,2,4-trisubstituted imidazoles by employing aldehydes, α-amino carbonyl compounds and ammonium acetate. The transformation is environmentally friendly and metal free by employing I2 (10mol%) as a catalyst and EtOH as a solvent, and a wide range of function groups and heterocyclics are well tolerated resulting in moderate to good yields.

Synthesis of glucosylspiro-oxindole derivatives via one-pot three-component cycloaddition of azomethine ylides

Highly regio- and stereoselective synthesis of glucosylspiro-oxindole/acenaphthenone derivatives was accomplished through 1,3-dipolar cycloaddition (1,3-DC) reaction. The glucosyl α,β-unsaturated-7,3-lactone (a sugar lactone) derived from d-glucose was used as a chiral dipolarophile in 1,3-DC reaction for the first time. The azomethine ylides generated from sarcosine/l-proline/thiazolidine-4-carboxylic acid/piperidine-2-carboxylic acid with isatin and acenaphthoquinone were trapped by the sugar lactone to give a series of glucosylspiro-pyrrolidine derivatives in good yields.

Novel Five/Five- and Six/Five-Membered Bicyclic Nitroso Acetals from High-Pressure-Promoted Cyclisation Reactions ofp-Methoxybenzyl Vinyl Ether, 1-Nitro-2-heteroaryl Ethenes, and Mono- and Di-Substituted Olefins

At 15 kbar the 1-nitro-2-heteroarylethenes 2a−c reacted in a one-pot three-component cycloaddition with p-methoxybenzyl vinyl ether (1) and methyl acrylate to yield novel heteroaromatic-substituted six/five-membered bicyclic nitroso acetals. In the reaction of 3-[(E)-2-nitroeth-1-enyl]pyridine (2 equiv.) and 1 a competition between the formation of the tandem [4 + 2]/[3 + 2] cycloadducts and the formation of a novel five-membered cyclic nitronate was observed. The ratio of product formation was strongly pressure and solvent dependent. A mechanistic explanation for the formation of the novel five-membered cyclic nitronate has been proposed. 1-Nitro-4-[(E)-2-nitroeth-1-enyl]benzene (2d) reacted with 1 in the same manner as 2a in accordance with the proposed mechanism. The five-membered cyclic nitronate reacted as an 1,3-dipole in a high-pressure promoted [3 + 2] cycloaddition with both electron-rich and electron-poor olefins and yielded a novel class of pyridyl-substituted five/five-membered bicyclic nitroso acetals.

Solid phase synthesis of diverse isoxazolidines via 1,3-dipolar cycloaddition

Diverse substituted isoxazolidines 2–4 are assembled on solid phase by condensing hydroxylamines with aldehydes and trapping the resulting nitrones with various dipolarophiles. The one-pot three-component cycloaddition reaction yields the isoxazolidines in good to excellent yield. Three different reaction pathways - each dealing with one of the three components attached to the solid support - are evaluated with respect to versatility and yield of the synthesized isoxazolidines. Structures and relative configurations of representative isoxazolidines are elucidated with 1H-NMR, TOCSY, HSQC and NOESY. The reaction of polymer-bound hydroxylamines with aldehydes and alkenes is found to be the most successful. The kinetics of the solid phase reaction are determined by FT-IR-ATR spectroscopy. Polymer-bound nitrones are stable for the split/combine synthesis. A library of isoxazolidines is synthesized by the split/combine method and analyzed by means of HPLC-MS.