Double [3 + 2] cycloaddition of nitrile oxides with allenoates: Synthesis of spirobidihydroisoxazoles

The double [3+2] cycloaddition of allenoates with nitrile oxides was presented. The reaction worked well under mild reaction conditions to give the spirobidihydroisoxazole in moderate to excellent yields with excellent diastereoselectivities.     

Copper-catalyzed γ-selective and stereospecific allylic alkylation of ketene silyl acetals

Copper-catalyzed allylic alkylation of ketene silyl acetals proceeded with excellent γ-E-selectivity. Efficient α-to-γ chirality transfer with anti-selectivity occurred in the reaction of enantioenriched secondary allylic phosphates, affording enantioenriched β-branched γ,δ-unsaturated esters. Excellent functional group compatibility was observed.     

Highly enantioselective Mannich reactions with α-aryl silyl ketene acetals and imines

Mannich reactions with chiral silicon Lewis acid activated acylhydrazones and α-aryl silyl ketene acetals and α-aryl,α-alkyl silyl ketene imines proceed efficiently and with good to excellent levels of both diastereoselectivity and enantioselectivity. The reactions provide access to α-aryl,β-hydrazido esters and α-aryl,α-alkyl,β-hydrazido nitriles, which are valuable analogs of β-amino acids.     

Synthesis of functionalized pyrroles and fused pyrroles through intermolecular [3 + 2] cycloaddition reaction

A facile and efficient synthesis of pyrrole and pyrrole-fused heterocyclic compounds has been demonstrated. The current protocol involves the in situ generation of azomethine ylides which undergoes intermolecular cycloaddition reaction and subsequent treatment with DDQ provides the pyrrole and fused heterocyclic compounds in good yields.     

Tributylphosphane-promoted [3 + 2] annulation of 3-hydroxyoxindoles with acrylates: Synthesis of spirocyclic oxindole-lactones

The tributylphosphane-promoted [3 + 2] annulation reactions of 3-hydroxyoxindoles with acrylates have been developed to give a variety of pharmaceutically attractive spirocyclic oxindole-lactone derivatives in good to excellent yields. The structures of all the compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. This metal-free procedure features low costs of the reagents and materials, mild reaction conditions, non-toxicity and easy handling for scalable synthesis.     

Synthesis of α,α-disubstituted α-amino esters: nucleophilic addition to iminium salts generated from amino ketene silyl acetals

Alkoxycarbonyl iminium species are prepared easily by the oxidation of tetrasubstituted amino ketene silyl acetals, and subsequent nucleophilic addition of Grignard reagents to the iminium salts gives α,α-disubstituted α-amino ester derivatives in moderate to good yields, in which aryl and ethynyl substituents are readily introduced.     

Application of [3 + 2]-Cycloaddition in the Synthesis of Valdecoxib

A large scale synthesis of valdecoxib 1 is described. Our work features potential application of [3 + 2]-dipolar cycloaddition involving enamine and in situ–generated nitrile oxide derivatives.     

Reductive aminopropylation of ketene silyl (thio)acetals leading to the synthesis of δ-amino esters

In the presence of silica gel or titanium tetrachloride, ketene silyl acetals or ketene silyl thioacetals underwent 1,4-addition with α,β unsaturated aldimines which possess a large triphenylmethyl group at the imino nitrogens followed by reduction with sodium cyanoborohydride to give aminopropylated products, δ-amino esters, in good yields.     

The first report of [2+2] ketene–imine cycloaddition reactions (Staudinger) on carbon nanotubes

Several new carbon nanotube-functionalized β-lactams have been synthesized from chiral imines derived from β-d-glucopyranosylamine and a ketene from carbon nanotube-based oxyacetic acid via a [2+2] cycloaddition reaction. The cycloadducts were characterized by thermogravimetric analysis, Raman spectrometry, IR, and N₂ adsorption processes.     

Photoinduced [4?+?2] cycloaddition reactions of benzo[b]thiophene-2,3-dione with alkenes

[4?+?2]-Photocycloadditions of benzo[b]thiophene-2,3-dione with electron-rich and electron-deficient alkenes have been described. Olefins preferentially add at both carbonyl groups to give the head-to-head [4?+?2] cycloadducts, i.e., dioxanes only. Comprehensive molecular orbital calculations at DFT-B3LYP level have been carried out to address the mechanism as well as regiochemical course of the reaction.     

Synthesis of N-heterocycles via [4 + 3] cycloaddition of azomethine imine

Di, tri and tetra-nitrogen containing 7-membered heterocycles are the key building blocks for natural and medicinally active compounds. They are using as antidepressants, antiulcer, antibiotics, antiemetic and also used as herbicides and insecticides. These building blocks can be synthesized easily from [4 + 3] cycloadditon reaction of azomethine imine with the other suitable reacting partner. Research on this area is very much important as this area is not much explored till now. Hence, the synthetic literature survey towards the di-nitrogen containing heterocycles is paramount importance. Herein, we report numerous synthetic routes (metal catalyzed, metal free, asymmetric) of di-nitrogen containing 7-membered heterocycle through [4 + 3] cycloadditon reaction of the last 10 years (2011-2019).     

Iridium-catalyzed [2 + 2 + 2] cycloaddition of α,ω-diynes with nitriles

[Ir(cod)Cl](2)/DPPF or BINAP efficiently catalyzed the cycloaddition of α,ω-diynes with nitriles to give pyridines. The reaction can accommodate a very wide range of nitriles. Both aliphatic and aromatic nitriles smoothly reacted with α,ω-diynes to give pyridines. Ten equivalents of unactivated aliphatic nitrile were enough to give the product in high yield. Aliphatic nitriles bearing an acetal or amino moiety could be used for the reaction. The highly regioselective cycloaddition of unsymmetrical diyne bearing two different internal alkyne moieties was achieved. The observed regioselectivity could be reasonably explained by considering the different reactivities of the α-position in iridacyclopentadiene. Regioselective cycloaddition was successfully applied to the synthesis of terpyridine and quinquepyridine. This chemistry was extended to a new and efficient synthesis of oligoheteroarenes. Five aromatic or heteroaromatic rings were connected in a single operation. [Ir(cod)Cl](2)/chiral diphosphine catalyst can be applied to enantioselective synthesis. Kinetic resolution of the racemic secondary benzyl nitrile catalyzed by [Ir(cod)Cl](2)/SEGPHOS gave a central carbon chiral pyridine in 80% ee. The mechanism was analyzed on the basis of the B3LYP level of density functional calculations.     

Synthesis of Chlorin-Fused Monospirooxindolopyrrolidines Through a Facile [3 + 2]-Cycloaddition of Azomethine Ylides

One-pot synthesis of novel chlorin-fused monospirooxindolopyrrolidines has been accomplished in good yield via a facile [3 + 2]-cycloaddition reaction of azomethine ylides, derived from isatin/N-benzylisatin and sarcosine, with various porphyrin derivatives as dipolarophiles.     

Iridium-catalyzed [2+2+2] cycloaddition of α,ω-diynes with isocyanates

[Ir(cod)Cl](2)/BINAP was found to be an efficient catalyst for the [2+2+2] cycloaddition of α,ω-diynes with isocyanates to give 2-pyridones. A wide range of isocyanates can be used for this reaction. Both aliphatic and aromatic isocyanates smoothly reacted with α,ω-diynes to give 2-pyridones in high yields. Aliphatic isocyanates were more reactive than aromatic isocyanates. For aromatic isocyanates, the electronic properties of the substituents affected the reactivity: electron-donating substituents enhanced the reaction. The reaction of unsymmetrical α,ω-diynes possessing two different internal alkyne moieties with isocyanates was regiospecific and gave a single product. This regioselectivity could be explained by the reaction of iridacyclopentadiene with a nitrogen-carbon double bond. The regioselectivity of the reaction of malonate-derived diyne was controlled by a steric effect, while that of the reaction of ester-tethered diyne was controlled by an electronic effect. [Ir(cod)Cl](2)/chiral diphosphine catalyst could be used for the enantioselective synthesis of C-N axially chiral 2-pyridone. The reaction of diyne 1a with o-methoxyphenyl isocyanate (7a) gave C-N axially chiral 2-pyridone (R)-8aa in 78% yield with 94% ee.     

Microwave-Accelerated Ruthenium-Catalyzed [2π + 2π] Cycloadditions of Dimethylacetylene Dicarboxylate with Norbornenes

An efficient and convenient procedure has been developed for the ruthenium-catalyzed [2π + 2π] cycloadditions of dimethylacetylene dicarboxylate with norbornenes. Reaction is significantly accelerated in microwave conditions, while the commonly used benzene solvent was replaced by environmentally benign tetrahydrofuran.

Cu-catalyzed asymmetric [3+2] cycloaddition of α-iminoamides with activated olefins

A variety of 2-amido pyrrolidines, including Weinreb-type amides, have been prepared with very high exo diastereoselectivity and enantioselectivitiy in the reaction of α-iminoamides with activated alkenes catalyzed by Cu(I)-Segphos ligands.     

Reaction of a chlorovinylcarbene with ketenealkyl silyl acetals. Synthesis of new α- and β-allenic carboxylates.

The reaction of ketenealkylsilylacetals with 1,1-dimethyl-2,2,3-trichlorocyclopropane in the presence of methyllithium leads to cyclopropane compounds, which, when treated with tetrabutylammonium fluoride give α- or β-allenic carboxylates.