Asymmetric Brønsted Base Catalyzed and Directed [3+2] Cycloaddition of 2‐Acyl Cycloheptatrienes with Azomethine Ylides

Conjugated cyclic trienes have the potential for different types of cycloaddition reactions. In the present work, we will, in a novel asymmetric cycloaddition reaction, demonstrate that the organocatalytic reaction of 2‐acyl cycloheptatrienes with azomethine ylides proceeds as a [3+2] cycloaddition, which is in contrast to the Lewis acid‐catalyzed reaction, in which a [3+6] cycloaddition takes place. In the presence of a chiral organosuperbase, 2‐acyl cycloheptatrienes react in a highly enantioselective manner in the [3+2] cycloaddition with azomethine ylides, providing the 1,3‐dipolar cycloaddition product in high yields and up to 99 % ee. It is also shown that the diene formed by the reaction can undergo stereoselective dihydroxylation, bromination, and cycloaddition reactions. Finally, based on experimental observations, some mechanistic considerations are discussed.     

Hetero [6+3] cycloaddition of fulvenes with N-alkylidene glycine esters: a facile synthesis of the delavayine and incarvillateine framework

[reaction: see text] In contrast to the [3+2] or [4+3] cycloaddition of N-metalated azomethine ylides and various alkenes, N-benzylidene glycine ethyl ester reacts with fulvenes to give the hetero [6+3] cycloaddition adducts with high stereoselectivity, constituting an efficient and novel route to [2]pyrindines.     

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.     

Synthesis of ferrocenyl monospirooxindolopyrrolidines—a facile [3+2]-cycloaddition of azomethine ylides

One-pot synthesis of novel ferrocenylmonospirooxindolopyrrolidines has been accomplished in good yield via a facile [3+2]-cycloaddition reaction of several azomethine ylides, derived from isatin/5,7-dibromoisatin and sarcosine, with various ferrocene derivatives as the dipolarophile. The effect of solvent on the [3+2]-dipolar cycloaddition reaction is also studied.     

Highly enantioselective catalytic [6+3] cycloadditions of azomethine ylides

Under control: Highly functionalized chiral annulated piperidines with eight stereocenters are efficiently obtained by means of a highly enantioselective one-pot [6+3]/[4+2] sequence. This sequence included the first enantioselective [6+3] cycloaddition of azomethine ylides with fulvenes.     

A novel Fe(II)/diaryl prolinol catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with alkenes

A novel Fe(II)/diaryl prolinol catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with alkenes has been developed. In the presence of FeCl₂ (10 mol %) and α,α-bis(3,5-bistrifluoromethylphenyl)prolinol L1 (10 mol %), [3+2] cycloaddition of azomethine ylides with electronic-deficient olefins underwent smoothly in CH₃CN at room temperature to generate the desired endo-adducts in moderate to good yields and enantioselectivities. This is the first example of Fe(II)/N,O-ligand (L1) catalyzed 1,3-dipolar enantioselective cycloaddition reaction of azomethine ylides.     

Remote regioselective organocatalytic asymmetric [3+2] cycloaddition of N-2,2,2-trifluoroethyl isatin ketimines with cyclic 2,4-dienones

An organocatalytic asymmetric [3+2] cycloaddition of trifluoromethyl-containing azomethine ylides with cyclic 2,4-dienones was developed.The process enables efficient incorporation of CF3 groups into functionalized spiro [pyrro lid in-3,2'-oxindoles] in high yields with good to excellent enantio-and diastereoselectivities.     

Lewis acid-promoted carbon-carbon bond cleavage of aziridines: divergent cycloaddition pathways of the derived ylides

Lewis acids are shown to cleave the carbon-carbon bond of activated aziridines at ambient temperature. The derived metal-coordinated azomethine ylides undergo cycloaddition reactions with electron-rich alkenes. Cyclic alkenes afford products that are formally [4+2] adducts most likely derived from a Mannich-type addition to the ylide, followed by intramolecular Friedel-Crafts alkylation. Alternatively, acyclic alkenes undergo [3+2] cycloaddition to give new pyrrolidine products.     

Synthesis of novel functionalized 3-spiropyrrolizidine and 3-spiropyrrolidine oxindoles from Baylis-Hillman adducts of isatin and heteroaldehydes with azomethine ylides via [3+2]-cycloaddition

A novel regioselective synthesis of a number of functionalized 3-spiropyrrolizidine and 3-spiropyrrolidine oxindoles from Baylis-Hillman adducts of isatin and heteroaldehydes via [3+2] cycloaddition of azomethine ylides in excellent yields has been reported.     

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.     

3 + 2]-cycloaddition of nonstabilized azomethine ylides. 10. An efficient strategy for the construction of x-Azatricyclo[m.n.0. 0

Various new structural entities related to x-azatricyclo[m.n.0. 0(a)()(,)(b)()]alkanes are constructed by the intramolecular [3 + 2] dipolar cycloaddition of nonstabilized cyclic azomethine ylides. The ylide is generated by the sequential double desilylation of N-alkyl alpha,alpha'-bis(trimethylsilyl)cyclic amines using Ag(I)F as a one-electron oxidant.     

An expedient synthesis of ferrocene grafted spirooxindolopyrrolizidines via [3+2]-cycloaddition of azomethine ylides

A facile and rapid one-pot synthesis of ferrocene bearing novel spiropyrrolizidines has been accomplished by [3+2]-cycloaddition reaction of various azomethine ylides derived from isatin/5,7-dibromoisatin and l-proline with various ferrocene derivatives as dipolarophile in good yield. The protocol is general and applicable to a wide variety of ferrocenyl derived dipolarophiles. Effect of various solvents on [3+2]-dipolar cycloaddition reaction is also studied.     

Pt(II)- or Au(III)-catalyzed [3+2] cycloaddition of metal-containing azomethine ylides: highly efficient synthesis of the mitosene skeleton

[reaction: see text] Only 1-3 mol % of PtCl(2) or AuBr(3) was sufficient to promote generation and [3+2] cycloaddition of transition-metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines bearing an internal alkyne moiety. A highly efficient method for the preparation of synthetically useful tricyclic indole derivatives having a substituent at the 3-position of the indole nucleus was established by this method.     

Lewis acid-catalyzed [3 + 2]cyclo-addition of alkynes with N-tosyl-aziridines via carbon-carbon bond cleavage: synthesis of highly substituted 3-pyrrolines

A novel, efficient, and highly regioselective Lewis acid-catalyzed [3 + 2] cycloaddition of alkynes with azomethine ylides, which are easily obtained from N-tosylaziridines via C-C bond heterolysis at room temperature was developed. Moderate enantioselectivity (70% ee) can be achieved by the application of the commercially available chiral Pybox 7 as the ligand.     

A facile and efficient synthesis of highly functionalised 3,3′-dispiropyrrolidine- and 3,3′-dispiropyrrolizidine bisoxindoles via [3+2] cycloaddition

The [3+2] cycloaddition reaction of azomethine ylides with isomerised Morita-Baylis-Hillman adducts, both dipoles and dipolarophiles are derived from isatin, afforded highly functionalised 3,3′-dispiro pyrrolidine- and 3,3′-dispiropyrrolizidine bisoxindoles in high yields.     

Cycloaddition reactions of thiazolium azomethine ylides: application to pyrrolo[2,1-b]thiazoles

Thiazolium azomethine ylides, equipped with a C-2 methanethiol group, participate in an efficient [3 + 2] cycloaddition reaction with acetylene derivatives to yield unique pyrrolo[2,1-b]thiazoles. The elimination of the methanethiol leaving group from the cycloadduct has replaced the need for a separate oxidation step and suppresses ring-opening side reactions. Products were obtained in short synthetic sequences to demonstrate their use as a scaffold for compound libraries.     

exo- and enantioselective cycloaddition of azomethine ylides generated from N-alkylidene glycine esters using chiral phosphine-copper complexes

High diastereo- and enantioselectivities were obtained for the asymmetric 1,3-dipolar cycloaddition of azomethine ylides generated from N-alkylideneglycine esters with dipolarophiles using chiral phosphine-copper complexes as catalysts. Whereas the cycloaddition of azomethine ylides catalyzed by metal salts generally afforded endo-adducts as the predominant product, the present method is the first example of an exo-selective cycloaddition. [reaction: see text]     

Azomethine ylide cycloaddition/reductive heterocyclization approach to oxindole alkaloids: asymmetric synthesis of (-)-horsfiline.

The intermolecular [3 + 2] annulation of azomethine ylides with 2(2-nitrophenyl)acrylate dienophiles followed by reductive heterocyclization affords the spiro(indole-pyrrolidine) ring system. Hence, this enable us to accomplish a concise and highly enantioselective synthesis of (-)-horsfiline 1, based on chiral auxiliary-directed pi-face discrimination in the 1,3-dipolar cycloaddition of (1S,2R)-2-phenyl-1-cyclohexyl ester 4f with N-methylazomethine ylide.     

ZrOCl2·8H2O mediated microwave induced [3+2] cycloaddition of azomethine ylides—a facile one-pot synthesis of novel dispiroheterocycles

An efficient microwave-assisted, ZrOCl₂·8H₂O mediated, synthesis of novel dispiro-oxindolopyrrolidines and -pyrrolizidines was accomplished through [3+2] cycloaddition reaction of azomethine ylides derived from acenaphthenequinone and sarcosine/l-proline with (E)-2-oxoindolino-3-ylidene acetophenones in good yields.     

Catalytic Enantioselective and Regioselective [3+3] Cycloadditions Using 2‐Indolylmethanols as 3 C Building Blocks

The first catalytic asymmetric cycloaddition using 2‐indolylmethanols as 3C building blocks has been established by a chiral phosphoric acid‐catalyzed enantioselective and regioselective [3+3] cycloaddition of 2‐indolylmethanols with azomethine ylides, which constructed biologically important tetrahydro‐γ‐carboline frameworks in high yields and excellent enantioselectivities (up to 83 % yield, 99:1 e.r.). This reaction not only represents the first application of 2‐indolylmethanols as 3C building blocks in catalytic asymmetric cycloadditions, but also has established an abnormal regioselectivity in indolylmethanol‐involved transformations.