1,3-dipolar cycloaddition reactions of porphyrins with azomethine ylides

[reaction: see text] The behavior of porphyrins as dipolarophiles in 1,3-dipolar cycloadditions with azomethine ylides was studied. Depending on the nature of the substituent groups on the porphyrin macrocycles, the reaction can give monoadducts (chlorins) or bisadducts (isobacteriochlorins and bacteriochlorins). When a large excess of azomethine ylide is used, trisadducts can also be obtained. Mixed isobacteriochlorin derivatives were prepared from the reaction of azomethine ylides with the chlorin monoadducts previously obtained via Diels-Alder reactions.     

Synthesis of non-aggregating chlorins and isobacteriochlorins from meso-tetrakis(pentafluorophenyl)porphyrin: a study using 1,3-dipolar cycloadditions under mild conditions

The 1,3-dipolar cycloaddition of meso-tetrakis(pentafluorophenyl)porphyrin and its nickel complex, with the bulky azomethine ylide dipole was studied under mild conditions, and yielded chlorin and isobacteriochlorin derivatives self-prevented from aggregation. The reactions were performed at room temperature or 0 °C, and we were able to establish a set of reaction conditions to obtain only the chlorin or the isobacteriochlorin. These compounds were evaluated in solution, and no aggregation was observed at less than 25 mM (∼30 mg mL⁻¹) using ¹H NMR experiments.     

1,3-偶极环加成反应修饰卟啉化合物

利用1,3-偶极环加成反应对卟啉大环进行修饰是近年来卟啉研究的一个新热点。环加成产物因在可见光谱长波段范围的特征吸收,在构筑人工光反应体系和用作光动力疗法中的光敏剂等领域有重要应用价值。本文综述了1,3-偶极环加成反应在修饰卟啉化合物方面的研究进展,包括：卟啉作为亲偶极体能与甲亚胺叶立德、硝酮、重氮烷、羰基叶立德、腈氧化物等1,3-偶极子反应生成各种新型杂环稠合卟吩类化合物;卟啉化合物作为1,3-偶极子能与C₆₀等亲偶极体反应,生成β位取代的各种新型卟啉化合物;以及扩展卟啉也可以作为亲偶极体与甲亚胺偶极子发生1,3-偶极环加成反应等。     

1,3-Dipolar cycloaddition of azomethine ylide with ethene and 2-butene: a computational study

B3LYP/6-311 + G(d,p) has been used to calculate the relative energies and geometrical parameters of the respective reactants, transition states, and cycloadducts from the cycloadditions of azomethine ylide and ethene, (Z)-2-butene, and (E)-2-butene. The half-chair (envelope) transition state structures are consistent with a synchronous concerted cycloaddition mechanism.     

Catalytic asymmetric [3+2] cycloaddition of azomethine ylides. Development of a versatile stepwise,three-component reaction for diversity-oriented synthesis

We report a new catalyst system that should enhance the use of enantioselective 1,3-dipolar cycloadditions of azomethine ylides with electronic-deficient olefins in the divergent pathways of diversity-oriented synthesis (DOS). The underlying reaction is of considerable interest in DOS because its stereospecificity enables stereochemical diversification of up to four tetrahedral centers on pyrrolidine rings. This new catalyst system extends the scope and selectivity of the azomethine ylide cycloaddition and is compatible with reagents used in a one-bead/one-stock solution technology platform for DOS.     

Porphyrin derivatives: Synthesis and potential applications

Porphyrin‐porphyrin and porphyrin‐chlorin dimers have been synthesized and evaluated for their photo‐physical and in vivo photodynamic therapy properties. Two of them can become potential new photosensitizers. Study of the reactivity of meso‐tetraaryl porphyrins, as dienophiles, in Diels‐Alder transformations and as dipolarophiles in 1,3‐dipolar cycloadditions, has been undertaken. New synthetic methodologies for certain chlorin, bacteriochlorin and isobacteriochlorin type macrocycles, with potential biological significance, have been established.     

Regioselective [3+4] cycloaddition of an azomethine ylide to meso-meso, β-β, β′-β′ triply linked diporphyrins

Thermal reaction of meso-meso, β-β, β′-β′ triply linked diporphyrins with an azomethine ylide produced seven-membered cycloadducts via formal [3+4] cycloaddition at the bay-area. Bischlorin structures of the cycloadducts are characterized on the basis of spectroscopic data and confirmed by single crystal X-ray diffraction analysis. Interestingly, the stability of the cycloadducts depends on the central metal ions in the porphyrin core.     

Diastereoselective addition of chiral azomethine ylides to cinnamoyl moieties,attached to chiral auxiliaries

Doubly diastereoselective 1,3-dipolar cycloadditions of chiral azomethine ylides to cinnamoyl moieties, attached to chiral auxiliaries, were investigated. The resulting trans-3,4-disubstituted pyrrolidines were obtained in diastereomeric ratios of up to 78:22. The influence on this ratio by the constitution of the chiral ylide was found to be rather small.     

Four-component Pd-catalysed cascade/ring closing metathesis. Synthesis of heterocyclic enones

A palladium-catalysed four-component process is described involving carbon monoxide, allene and aryl/heteroaryl iodides generating (π-allyl) palladium species, which are intercepted by alkene tethered nitrogen nucleophiles to afford 1,6- and 1,7-dienones. Subsequent ring closing metathesis affords five- and six-membered N-heterocyclic enones. The N-heterocyclic enones are active dipolarophiles in 1,3-dipolar cycloaddition reactions as exemplified by azomethine ylide and nitrone cycloadditions.     

Synthesis of highly functionalized pyrrolidines via a mild one-pot, three-component 1,3-dipolar cycloaddition process

[reaction: see text] A simple and efficient one-pot, three-component synthesis of highly functionalized pyrrolidines via cascade imine --> azomethine ylide --> 1,3-dipolar cycloadditions is reported. Admixing a variety of aldehydes, dimethyl 2-aminomalonate, and electron deficient alkenes in THF leads to the clean production of pyrrolidines in good to excellent yields. The mild reaction conditions enabled the generation of previously inaccessible azomethine ylides from enolizable aldehydes. Endo selectivity was exclusive with N-phenyl maleimide and maleic anhydride. Good chemo-, regio-, and stereoselectivities were observed with methyl acrylate, though catalysis by Ag(I) was necessary with this dipolarophile.     

Asymmetric 1,3-dipolar cycloadditions of a chiral nonracemic glyoxylic azomethine imine

The reactivity of a chiral nonracemic glyoxylic azomethine imine has been investigated. This species reacts with a wide range of dipolarophiles, with a complete regio- and facial stereoselectivity. The introduction of an electron-withdrawing substituent on the ylide leads to a lower endo selectivity with electron-withdrawing dipolarophiles, but to an improved exo selectivity with styrene derivatives when compared to the reactivity of aliphatic- or aromatic-substituted ylides.     

Novel Entry to the Tricyclic Core of Stemofoline and Didehydrostemofoline

A novel approach to the tricyclic core of the Stemona alkaloids stemofoline and didehydrostemofoline has been discovered that features an intramolecular (3+2) dipolar cycloaddition of an unactivated carbon-carbon double bond with an azomethine ylide; the azomethine ylide was generated by an unprecedented reaction that occurred during a Swern oxidation of an α-(N-cyanomethyl)-β-hydroxy ester. In separate experiments, the efficacy of introducing the requisite oxygen functionality at C(8) and the 1-butenyl side chain at C(3) was established.     

Catalytic Asymmetric Formal [3+3] Cycloaddition of an Azomethine Ylide with 3‐Indolylmethanol: Enantioselective Construction of a Six‐Membered Piperidine Framework

A catalytic asymmetric formal [3+3] cycloaddition of 3‐indolylmethanol and an in situ‐generated azomethine ylide has been established to construct a chiral six‐membered piperidine framework with two stereogenic centers. This approach not only represents the first enantioselective cycloaddition of isatin‐derived 3‐indolylmethanol, but also has realized an unusual enantioselective formal [3+3] cycloaddition of azomethine ylide rather than its common [3+2] cycloadditions. Besides, this protocol combines the merits of a multicomponent reaction and organocatalysis, which efficiently assembles a variety of isatin‐derived 3‐indolylmethanols, aldehydes, and amino esters into structurally diverse spiro[indoline‐3,4′‐pyridoindoles] with one all‐carbon quaternary stereogenic center in high yields and excellent enantioselectivities (up to 93 % yield, >99 % enantiomeric excess (ee)). Although the diastereoselectivity of the reaction is generally moderate, most of the diastereomers can be separated by using column chromatography followed by preparative TLC.     

Porphyrins in 1,3-dipolar cycloaddition reactions. Synthesis of new porphyrin-chlorin and porphyrin-tetraazachlorin dyads

N-(Porphyrin-2-ylmethyl)glycine was synthesized and used as precursor of azomethine ylide, which was trapped with several dipolarophiles. The reaction of that azomethine ylide with dimethyl fumarate afforded the expected adduct. However, with 1,4-benzo- and 1,4-naphthoquinones only dehydrogenated adducts were isolated. Also, the reaction of that ylide with meso-tetrakis(pentafluorophenyl)porphyrin and tetraazaporphine allowed access to novel porphyrin-chlorin and porphyrin-tetraazachlorin dyads.     

One‐pot Regioselective Synthesis of Novel 1‐N‐Methyl‐spiro[2,3′]oxindole‐spiro[3,3″]‐1″‐N‐arylpyrrolidine‐2″,5″‐dione‐4‐arylpyrrolidines through Multicomponent 1,3‐Dipolar Cycloaddition Reaction of Azomethine Ylide

An atom economic and facile synthesis of novel dispiro–oxindole–pyrrolidines has been achieved via a three‐component tandem cycloaddition of azomethine ylide generated in situ from isatin and sarcosine by decarboxylative condensation with N‐aryl‐3‐benzylidene‐pyrrolidine‐2,5‐dione derivatives as dipolarophiles. The salient features of synthetic procedure are characterized by the mild reaction conditions, high yields, high regioselectivity and stereoselectivity, one‐pot procedure, and operational simplicity. This regioselectivity was assumed to be under the influence of π–π stacking interactions between the aromatic rings of azomethine ylide and N‐aryl‐3‐benzylidene‐pyrrolidine‐2,5‐diones that further control the exo–endo selectivity of the reaction 1,3‐dipolar cycloaddition. The regiochemistry and structures of the cycloadducts were determined with spectroscopic data.     

Nucleophilic properties of a nonstabilized azomethine ylide derived from sarcosine and cyclohexanone. A novel domino reaction leading to substituted 4-aryl-2-pyrrolidones

A nonstabilized asymmetric azomethine ylide derived from sarcosine and cyclohexanone reacts with 3-substituted coumarins and ethyl benzylidene malonate to give 4-aryl-2-pyrrolidones in moderate yields, and the adducts of classical 1,3-dipolar cycloadditions as the minor products. The main reaction proceeds via a domino process, starting with 1,4-nucleophilic addition to the conjugated double bond, and represents the first example of the nucleophilic properties of a nonstabilized azomethine ylide.     

A greener approach for the synthesis of 1-N-methyl-(spiro[2.3′]oxindolespiro[3.2″]/spiro[2.3′]indan-1,3-dionespiro[2.2″])cyclopentanone-4-aryl pyrrolidines

N,N-Dimethylammonium N′,N′-dimethyl carbamate (DIMCARB), a reusable reaction medium, has been used in the synthesis of a number of monoarylidene cyclopentanones. These compounds are used as dipolarophiles in the 1,3-dipolar cycloaddition reaction of an azomethine ylide, generated in situ by the decarboxylation method for the synthesis of spiropyrrolidines by the application of microwave methodology.     

Synthesis of acridinedione derived mono spiro-pyrrolidine/pyrrolizidine derivatives—a facile approach via intermolecular [3+2] cycloaddition reaction

A facile synthesis of acridinedione derived mono spiro-pyrrolidine and pyrrolizidine derivatives has been accomplished by 1,3-dipolar cycloaddition reaction. The O-acryloylacridinediones, as dipolarophiles reacted with azomethine ylide derived from di-/tri-ketones and sec-amino acids to give acridinedione derived mono spiropyrrolidine/pyrrolizidine derivatives in good yield.     

Reactivity of allenoates toward aziridines: [3+2] and formal [3+2] cycloadditions

The reactivity of buta-2,3-dienoates toward aziridines is reported. Allenoates react as 2π-component in the [3+2] cycloaddition with the azomethine ylide generated from cis-1-benzyl-2-benzoyl-3-phenylaziridine affording 4-methylenepyrrolidines in a site-, regio-, and stereoselective fashion. Under conventional thermolysis, cis- and trans-2-benzoyl-1-cyclohexyl-3-phenylaziridines showed a different reactivity. These aziridines participate in formal [3+2] cycloadditions with allenes via C-N bond cleavage of the three-membered ring leading to functionalized pyrroles.     

Stereoselective synthesis of novel glyco-pyrano pyrrolidines/pyrrolizidines/indolizidines through intramolecular [3+2] cycloaddition approach

An efficient and stereoselective synthesis of novel furo-pyrano pyrrolidine/pyrrolizidine/indolizidine derivatives has been achieved by intramolecular [3+2] cycloaddition reaction of azomethine ylide generated in situ from O-allyl sugar-derived aldehyde and different secondary amino acids.