Bifunctional AgOAc-catalyzed asymmetric [3 + 2] cycloaddition of azomethine ylides

[reaction: see text] A bifunctional AgOAc-catalyzed asymmetric cycloaddition of azomethine ylides with electronic-deficient alkenes was developed using ferrocenyloxazoline-derived N,P ligands. The reactive metal-bound azomethine ylide dipole is formed by the deprotonation with acetate, and extra base is not necessary. The reactions proceed with high enantioselectivity. This method provides an efficient and convenient route to optically active pyrrolidine derivatives.     

Thiourea-catalyzed asymmetric formal [3+2] cycloaddition of azomethine ylides with nitroolefins

A chiral thiourea catalyst possessing an amine function catalyzes an asymmetric [3+2] cycloaddition of azomethine ylides to nitroolefins to provide highly functionalized pyrrolidines with high diastereo- and enantioselectivities (up to 98:1:1 dr, 92% ee). The reaction proceeds in a stepwise manner consisting of Michael addition and subsequent intramolecular aza-Henry reaction. Both reactions are promoted by the thiourea catalyst, and the reaction rate of the latter step is efficiently enhanced by the addition of 2,2,2-trifluoroethanol.     

A three-component, one-pot synthesis of indolizidines and related heterocycles via the [3+2] cycloaddition of nonstabilized azomethine ylides

Nonstabilized azomethine ylides (i.e. those bearing only hydrogens or alkyl groups) can be generated from (2-azaallyl)stannanes and (2-azaallyl)silanes through an intramolecular N-alkylation/demetalation cascade. The resulting ylides undergo [3+2] cycloaddition with electron-poor or electron-rich dipolarophiles yielding indolizidines and related 1-aza[m.3.0]bicycloalkane systems in good yield. An in situ protocol allows for a one-pot, three-component synthesis of indolizidines. The (2-azaallyl)stannanes tolerate enolizable hydrogens in these cycloadditions, while (2-azaallyl)silanes do not. The mechanism of the cycloaddition cascade is clarified by a series of control experiments. The same (2-azaallyl)stannanes may be transmetalated by n-butyllithium to generate 2-azaallyllithiums, which also may undergo a [3+2] cycloaddition/N-alkylation cascade to form indolizidines.     

Bis-sulfonyl ethylene as masked acetylene equivalent in catalytic asymmetric [3 + 2] cycloaddition of azomethine ylides

Enantioenriched 3-pyrrolines have been synthesized by highly enantioselective Fesulphos-Cu-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with trans-1,2-bisphenylsulfonyl ethylene, followed by reductive sulfonyl elimination. High levels of reactivity, exoselectivity, and enantioselectivity have been accomplished for a variety of substituted azomethine ylides. This cycloaddition-desulfonylation strategy has been applied as a key step in the enantioselective synthesis of a biologically active C-azanucleoside.     

AgOAc catalyzed asymmetric [3+2] cycloaddition of azomethine ylides with chiral ferrocene derived P,S ligands

Ferrocene derived P,S-heterodonor ligands were effectively used in AgOAc catalyzed asymmetric cycloaddition of azomethine ylides. The roles of planar chirality and electronic properties of the phosphorous substituents have been examined, and up to 93% ee was obtained.     

A facile synthesis of novel dispiroheterocycles through solvent-free microwave-assisted [3+2] cycloaddition of azomethine ylides

A comparative study of the synthesis of novel dispiro pyrrolo/pyrrolizidino ring systems by the cycloaddition of azomethine ylides generated by a decarboxylative route from sarcosine/proline and isatin with the dipolarophile 9-arylidine-fluorene using four different methodologies is described. A solvent-free microwave-assisted approach gave products with the highest yields in a short time. Additionally, our solvent-free approach allowed the use of 4-N,N-dimethylaminobenzaldehyde, which failed to yield the desired cycloadducts under conventional approaches.     

First example of [3+2] cycloaddition of azomethine ylides to 5-methylidene-3-phenylhydantoin

Russian Chemical Bulletin - New type dispiroindolinones, dispiroimidazolidine-4,3′-pyrrolidine-2′,3″-indolinones unsubstituted at position 4′ of the central pyrrolidine...     

One-pot synthesis of macrocycles by a tandem three-component reaction and intramolecular [3+2] cycloaddition

By combining three appropriately designed simple substrates, a programmed sequence involving an alpha-isocyano acetamide-based three-component reaction followed by a copper-catalyzed intramolecular [3+2] cycloaddition of alkyne and azide took place to afford complex macrocycles in moderate to good yields. One macrocycle and two heterocycles were produced with concurrent formation of five chemical bonds in this operationally simple process.     

Microwave-assisted [3 + 2] cycloadditions of azomethine ylides

The microwave-assisted intramolecular [3 + 2] cycloaddition reaction of azomethine ylides to activated and nonactivated alkenes and alkynes is described. The procedure allows the synthesis of pyrrolidines and pyrrole products in good to excellent overall yields in short reaction times. It appears from parallel comparative studies that the microwave procedure favors the reaction times and overall purity of the crude reaction mixture. The reactions can also be performed in the absence of solvent. [reaction: see text]     

Highly enantioselective Ag(i)-catalyzed [3 + 2] cycloaddition of azomethine ylides

A highly reactive Ag(I)-catalyzed [3 + 2] cycloaddition of azomethine ylides is founded using AgOAc as the catalytic precursor and phosphines as ligands. Using a new bis-ferrocenyl amide phosphine (FAP) as the ligand, we found that high enantioselectivities (up to 97% ee) have been achieved in the [3 + 2] cycloaddition of azomethine ylides. Up to four stereogenic centers can be established in this multicomponent coupling reaction from readily available materials such as aldehydes, aminoesters, and dipolarophiles.     

The Lewis acid-catalyzed [3+1+1] cycloaddition of azomethine ylides with isocyanides

A Lewis acid-catalyzed [3+1+1] cycloaddition reaction between aliphatic isocyanides and azomethine ylides generated in situ from aziridines, leading to pyrrolidine derivatives, has been developed. This reaction proceeds smoothly under mild conditions and can also be modified by employing aromatic isocyanides to generate four-membered heterocycles, azetidines, through a [3+1] cycloaddition reaction.     

Intramolecular [3+2] cycloadditions of functionalized azomethine ylides

The use of dithiane chemistry to synthesize functionalized azomethine ylides which are then employed in [3+2] cycloaddition chemistry is described. The advantages of this methodology as well as an approach to the lycorenine alkaloid system are presented.     

An expedient diastereoselective synthesis of pyrrolidinyl spirooxindoles fused to sugar lactone via [3+2] cycloaddition of azomethine ylides

Synthesis of pyrrolidinyl-spirooxindoles fused to sugar lactone has been achieved by a one pot three component 1,3-dipolar cycloaddition (1,3-DC) reaction. A unique dipolarophile (α,β-unsaturated lactone) derived from d-glucose/d-galactose reacted with azomethine ylide generated in situ from isatin/N-substituted isatin and secondary amino acids (sarcosine/proline/piperidine-2-carboxylic acid) to give the corresponding cycloadducts in good yield. The cycloaddition was found to be highly regio- and diastereoselective.     

Catalytic asymmetric synthesis of stable oxetenes via Lewis acid-promoted [2+2] cycloaddition

A highly enantioselective and atom-economical [2 + 2] cycloaddition of various alkynes with trifluoropyruvate using a dicationic (S)-BINAP-Pd catalyst has been established. This is the first enantioselective synthesis of stable oxetene derivatives, whose structure has been clarified by X-ray analysis. This catalytic process offers a practical synthetic method for oxetene derivatives (catalyst loading: up to 0.1 mol %), which can serve as novel chiral building blocks for pharmaceuticals and agrochemicals and can also be transformed into a variety of enantiomerically enriched CF(3)-substituted compounds with high stereoselectivity.     

New chiral ferrocenyl P,S-ligands for highly diastereo- and enantioselective Ag(I)-catalyzed asymmetric [3+2] cycloaddition of azomethine ylides

A new family of chiral ferrocenyl P,S-ligands incorporating an indole ring at the α-ferrocenylmethyl position has been prepared via a Friedel–Crafts alkylation reaction of (R_c,S_Fc)-PPFA with a variety of 2-indole thioethers. These newly developed ferrocenyl P,S-ligands proved to be efficient in the AgOAc-catalyzed asymmetric [3+2] cycloaddition of azomethine ylides with various dipolarophiles, giving cycloadducts with high diastereoselectivities and enantioselectivities (up to 99% ee).     

Thermal [3+2] cycloaddition reaction of azomethine imines with allenoates for dinitrogen-fused heterocycles

The thermal [3+2] cycloaddition reactions of two classes of azomethine imines with allenoates have been investigated. The reactions are operationally simple and proceed smoothly under mild reaction conditions to provide a variety of dinitrogen-fused heterocycles in moderate to excellent yields.