Regio- and diastereoselectivity of the cycloaddition of nitrones with N-propadienylindole and pyrroles

The 1,3-dipolar cycloaddition of nitrones to N-propadienyl indoles and pyrroles proceeds predominantly via the C1-C2 bond to form 4-methyleneisoxazolidines. In the case of aldonitrones, the cis-isomers are predominantly formed.     

Stereoselective 1,3-dipolar cycloadditions of nitrones derived from amino acids. Asymmetric synthesis of N-(alkoxycarbonylmethyl)-3-hydroxypyrrolidin-2-ones

Diastereoselective asymmetric 1,3-dipolar cycloadditions of N-(alkoxycarbonylmethyl) nitrones derived from glycine, alanine and phenylalanine have been studied both experimentally and theoretically. Asymmetric induction is evaluated by either introducing a chiral group at the nitrone nitrogen atom or by using Oppolzer's sultam acrylamide. In both cases the sense of the asymmetric induction is the same, the (3R,5R)-isomer being preferentially obtained. The best results were observed with the chiral dipolarophile, which afforded an only isomer in all cases. The obtained isoxazolidines are easily transformed into the corresponding 5-substituted-3-hydroxypyrrolidin-2-ones. DFT studies are in a qualitative agreement with the observed experimental results.     

One-pot synthesis of α-acyloxyaminoamides via nitrones as imine surrogates in the Ugi MCR

α-acyloxyaminoamides can be prepared, with yields ranging from fair to very good (up to 89%), through an Ugi four component reaction by mixing a carbonyl component, a carboxylic acid, an isocyanide and an N-alkylated hydroxylamine in methanol. Preformed nitrones furnish the same final compounds with comparable yields.     

The reaction of nitrones with pyrroles and furan: an easy access to heteroaromatic hydroxylamines and bis(heteroaryl)alkanes

N-Benzylnitrones react with heteroaromatic compounds such as pyrroles or furan in the presence of hydrogen chloride. Either heteroaromatic N-benzylhydroxylamines, symmetrical or unsymmetrical 2,2′-bis(heteroaryl)alkanes could be selectively produced depending on the experimental conditions.     

A new organocatalyst for 1,3-dipolar cycloadditions of nitrones to α,β-unsaturated aldehydes

The triflate salt resulting from the treatment of diphenyl-S-prolinol with trimethylsilyl triflate, catalyzes the addition of nitrones to α,β-unsaturated aldehydes to provide isoxazolidines in high yields and excellent diastereo- and enantioselectivities.     

Experimental and theoretical evidences of 2-aza-Cope rearrangement of nitrones

Both the intramolecular cycloaddition of diastereomeric homochiral N-alkenyl nitrones and the corresponding theoretical calculations using DFT and ab initio methods provided evidences of a thermal [3,3] sigmatropic rearrangement of the nitrones with a complete chirality transfer.     

Intra-molecular nitrone-olefin cycloaddition of d-glucose derived allylic alcohol: synthesis of new aminocyclohexitols

Diastereo- and regioselelective intra-molecular nitrone-olefin cycloaddition reaction of in situ generated N-benzylnitrones, obtained from d-glucose derived precursors 5a/5b furnished dihydroxy functionalized isoxazolidines. The N-O bond reductive cleavage and removal of N/O-benzyl groups led to the formation of stereochemically well defined aminocyclohexitols.     

The first report of unusual flipping of the cycloadducts from 1,3-dipolar cycloaddition of 3,4,5,6-tetrahydropyridine N-oxide to N-cinnamoyl piperidines

A series of cycloadducts possessing unusual flipping modes have been isolated from the 1,3-dipolar cycloaddition of 3,4,5,6-tetrahydropyridine N-oxide to piperidides of cinnamic acid and para-substituted cinnamic acids and these were analyzed by X-ray crystallography to reveal novel solid-state structures. The presence of two different flippomers arising due to flipping of the six/five bicyclic ring was confirmed both in solid state and in solution. This is the first observation of 1,3-dipolar cycloadducts having two different flippomers arising due to flipping of the isoxazolidine ring.     

A highly efficient and stereoselective cycloaddition of nitrones to N-arylitaconimides

The 1,3-dipolar cycloaddition of keto- and aldonitrones with N-arylitaconimides proceeds regioselectively giving only 5-spiroisoxazolidines. In the case of aldonitrones the reaction proceeds with high diastereoselectivity. A range of the obtained adducts were subjected to reductive cleavage of the NO bond using zinc powder in acetic acid to give the corresponding spirolactones and 1,3-amino alcohols.     

Allenyloxime—a new source of heterocyclizations to stable cyclic nitrones

A variety of conditions including reductive and/or basic reagents in aqueous or alcoholic solution was applied to 2,2-dimethylpenta-3,4-dienal oxime. Formation of various five-membered heterocycles with excellent chemical selectivity was observed. Most of the reactions yielded cyclic nitrones with stable dipolar structure and unique functionalities present. All products of cyclization were isolated and fully characterized.     

Highly efficient and stereoselective cycloaddition of nitrones to indolyl- and pyrrolylacrylates

The reactions of various nitrones with indolyl- and pyrrolylacrylates proceeds regioselectively with high diastereoselectivity in the case of aldonitrones, and represents an effective method for obtaining new indolyl- and pyrrolyl-substituted isoxazolidine carboxylates stabilized by weak (CH?O) and moderate (NH?N) strength intramolecular hydrogen bonding. The resulting cycloadducts exhibit promising in vitro anti-influenza activities.     

Regio- and diastereoselectivity of the cycloaddition of aldonitrones with benzylidenecyclopropane: An experimental and theoretical study

1,3-Dipolar cycloaddition of benzylidenecyclopropane with various aldonitrones proceeds regioselectively giving good yields of 4-spirocyclopropane isoxazolidines. In the case of aldonitrones, bearing carbamoyl- or aryl-groups on the carbon atom, only the cis-isomer is formed. The compounds synthesized were tested for their virus-inhibiting activity.     

The first example of 1,3-dipolar cycloaddition reactions of nitrones to vinylidenecyclopropanes

The first example of 1,3-dipolar cycloaddition reactions of nitrones to vinylidenecyclopropanes is described. The nitrones react with the C1′-C2′ double bond of vinylidenecyclopropanes to give the corresponding 4-cyclopropylidene-isoxazolidines in moderate yields.     

Diastereoselectivity of Chiral Nitrone 1,3-Dipolar Cycloaddition to <Emphasis Type="Italic">Baylis-Hillman</Emphasis> Adducts

Summary. 1,3-Dipolar cycloadditions of chiral nitrones to Baylis-Hillman adducts (-hydroxy--methylene esters) proceed with complete regioselectivity in good yields to afford the corresponding diastereomeric 3,5,5-trisubstituted isoxazolidines. Attack of the dipole from the less sterically hindered side of the dipolarophiles affords C-3/C-5 cis isoxazolidines as the predominant isomers. The strong preference for the C-3/C-5 cis isoxazolidines provided more sterically demanding O-tert-butyldimethylsilylsubstituted nitrone 2. Addition of Lewis acids accelerates the reaction and increases the portion of C-3/C-5 trans isoxazolidines. Microwave irradiation accelerates the reaction, but it produces only a small effect on the diastereoisomeric product ratio.     

Regioselectivity of cycloadditions of nitrile oxides and nitrones to 4-methylene-tetrahydrothiopyrane

Summary The cycloaddition of nitrile oxides and nitrones to 4-methylene-tetrahydrothiopyrane proceeds regioselectively under the formation of spiro-substituted isoxazole derivatives4 and9. Semiempirical calculations (AM1) were used to analyze the electronic structure of reactants, energies of products, and activation barriers leading to these products in order to rationalize this exclusive regioselectivity. It was shown that the main factor responsible for the high stereoselectivity of this reaction is not frontier orbital control, but mainly electrostatic and steric interactions. The spiro compounds4 were cleaved by hydrogenolysis to -amino-alcohols11, which were recyclized to spiro-oxazines12 and13.4 and9 as well as12 and13 are derivatives of novel heterocylic systems.

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Regioselektive Cycloadditionen von Nitriloxiden und Nitronen an 4-Methylen-tetrahydrothiopyran

Zusammenfassung Die Cycloaddition von Nitrilen und Nitriloxiden an 4-Methylen-tetrahydrothiopyran zeigt einen regioselektiven Verlauf unter Bildung der spiro-substituierten Isoxazolderivate4 und9. Die elektronischen Strukturen von Reaktanden, Energien von möglichen Reaktionsprodukten und die Aktivierungsbarrieren der durchgeführten Reaktionen wurden mittels semiempirischer Verfahren (AM1) untersucht, um die beobachteten eindeutigen Regioselektivitäten zu interpretieren. Es zeigte sich, daß dafür nicht ausschließlich Frontorbitalkontrolle, sondern vor allem elektrostatische und sterische Wechselwirkungen verantwortlich sind.Die Spiroverbindungen4 wurden in weiterer Folge durch Reduktion zu den entsprechenden -Aminoalkoholen11 gespalten, welche wiederum zu Spiro-oxazinen des Typs12 und13 recyclisiert wurden. Die Verbindungen4 und9 sind ebenso wie12 und13 Derivate von neuen heterocyclischen Grundsystemen.

     

Carboazidation of chiral allylsilanes: experimental and theoretical investigations

The carboazidation of chiral allylsilanes has been investigated by varying the nature of the substituents at the silicon center and on the carbon framework. The influence of temperature and the nature of the sulfonyl azide, as well as the stereochemistry of the remote stereogenic center, on the 1,2-diastereocontrol of the process were considered. Good to excellent levels of diastereocontrol were generally observed, with the syn-beta-azidosilane always being formed as the major isomer. An illustration of the value of this methodology has been provided with a short and efficient synthesis of an analogue of castanospermine. EPR spectroscopy was carried out on various beta-silyl radicals providing useful information about their conformations in the ground state. Based on this experimental evidence and DFT calculations, reactant-like transition state models were finally proposed that rationalize the observed 1,2-stereoinduction.     

Intramolecular 1,3-dipolar cycloaddition of N-alkenyl nitrones en route to glycosyl piperidines

Stereoselective intramolecular 1,3-dipolar cycloaddition of homochiral N-(alkenylglycosyl)nitrones, prepared by allylation of C-(glycosyl)nitrones and subsequent oxidation, is described. The previously described 2-aza-Cope rearrangement was not observed for these substrates, but evidences of E/Z isomerism during the cycloaddition were obtained. The obtained cycloadducts can serve as key precursors of imino disaccharide analogues. This is exemplified by a short route to a protected 2-furanosyl-4-hydroxy-6-phenyl piperidine.     

Synthesis and structure of nitrones derived from 2-trifluoromethyl bornane 3-imines

Upon treatment with (trifluoromethyl)trimethylsilane (CF₃SiMe₃), 3-(N-alkyl or 3-N-aryl)imines of camphorquinone of type 1 smoothly undergo stereoselective conversion to yield 2-endo-trifluoromethylated 1:1 adducts 2, which, after subsequent desilylation with sodium borohydride in boiling alcoholic solutions, were converted into imino alcohols 3. Unexpectedly, oxidation of 3 with m-CPBA resulted in the formation of a new type of trifluoromethylated nitrones 5 (and not the expected oxaziridines) in a stereoselective manner. In the case of 5a, the (Z)-configuration of the CN double bond of the nitrone unit was unambiguously established by an X-ray crystal-structure determination. However, photolysis of 5a led to the exo,exo/exo,endo mixture of the isomeric oxaziridine 7; the two stereoisomers were separated chromatographically.     

1,3-Cycloaddition of nitrones in ionic liquids catalyzed by Er(III): an easy access to isoxazolidines

1,3-Dipolar cycloadditions of nitrones with alkenes afforded the corresponding isoxazolidines in ionic liquids in the presence of Er(OTf)₃. The ionic liquid and the catalyst are recycled up to five times without any specific treatment or loss of activity. Extension of the procedure to the synthesis of isoxazolidinyl nucleosides has been investigated.     

Calcined MgAICO3-HT Catalysed Cyanosilylation of Carbonyl Compounds and Nucleophilic Ring Opening of Oxiranes Using TMSCN

Nucleophilic addition of TMSCN to carbonyl compounds is found to be catalysed efficiently using hydrotalcite as a solid base. The catalyst is also found to be active in the nucleophilic ring opening of oxiranes giving high regioselectivity.