Cycloaddition Of Nitrones Research Articles

Isoxazolidine Derivatives of Lappaconitine and Talatisamine

Isoxazolidine derivatives of lappaconitine and talatisamine were prepared by [3 + 2]-cycloaddition of lappaconitine and talatisamine nitrones to allyl alcohol.

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.

Formal Synthesis of (-)-Codeine by Application of Temporary Thio Derivatization.

Desymmetrization of a p-quinone monoacetal by organocatalytic sulfa-Michael addition provided rapid access to a C-ring building block for a formal synthesis of (-)-codeine. By means of a diastereoselective 1,2-addition for A/C-ring union, an intramolecular nitrone cycloaddition for construction of the phenanthrene core, and a sulfoxide elimination, an enantiopure key intermediate of the authors' previous synthesis of racemic codeine was available in 12 steps from isovanillin.

Alkenylazaarenes as dipolarophiles in 1,3-dipolar cycloaddition of nitrones: regioselectivity-switchable and highly diastereoselective synthesis of multisubstituted isoxazolidines

Metal free 1,3-dipolar cycloaddition between alkenylazaarenes and nitrones has been developed for the synthesis of 4-substituted isoxazolidines and 5-substituted isoxazolidines in good yields and selectivities.

Accessing benzooxadiazepines via formal [4 + 3] cycloadditions of aza-o-quinone methides with nitrones.

An unprecedented and efficient [4 + 3] cycloaddition of N-(ortho-chloromethyl)aryl amides with nitrones has been developed. This approach provides easy access to a series of seven-membered benzooxadiazepine derivatives in good to excellent yields (up to 99% yield) under mild reaction conditions.

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.

Organocatalytic Enantioselective Synthesis of Trifluoromethyl‐Containing Tetralin Derivatives by Sequential (Hetero)Michael Reaction–Intramolecular Nitrone Cycloaddition

AbstractThe enantioselective synthesis of tetralin derivatives bearing a trifluoromethylated all‐carbon quaternary stereocenter has been accomplished through a synthetic sequence comprising an organocatalytic β‐functionalization of ortho‐1‐trifluoromethylvinyl‐(hetero)aromatic conjugated aldehydes followed by the intramolecular nitrone 1,3‐cycloaddition reaction (INCR). Both nitromethane and N‐Cbz‐hydroxylamine were employed as nucleophiles in the initial organocatalytic conjugate addition step, which provided the chiral information required for the subsequent diastereoselective INCR. Although diastereoselectivity was moderate, good yields and enantioselectivities were, in general, obtained. Interestingly, an inversion of the selectivity in the intramolecular cycloaddition step was observed when either nitromethane or N‐Cbz‐hydroxylamine was employed. This outcome was studied by means of theoretical calculations, which were in agreement with the experimental results. In addition, the ring opening of the isoxazolidine moiety furnished the corresponding fluorinated diamino alcohols in a very efficient manner.magnified image

Visible-Light-Mediated Anti-Regioselective Nitrone 1,3-Dipolar Cycloaddition Reaction and Synthesis of Bisindolylmethanes.

The development of photoredox reactions of 1,3-dipolar cycloaddition of nitrones with alkenes is reported. It offers an efficient synthetic method to obtain isoxazolidine derivatives under mild conditions in synthetically useful yields. The nitrones are cyclized with oxidizable styrenes and aliphatic alkenes via a polar radical crossover cycloaddition reaction through photocatalytic reaction without additives. In addition, bis(indole)methanes can also be prepared through this method.

Conceptual DFT analysis of the regioselectivity of 1,3-dipolar cycloadditions: nitrones as a case of study.

The regioselectivity of the 1,3-dipolar cycloaddition of a model nitrone with a set of dipolarophiles, presenting diverse electronic effects, is analyzed using conceptual density functional theory (DFT) methods. We deviate from standard approaches based on frontier molecular orbitals and formulations of the local hard/soft acid/base principle and use instead the dual descriptor. A detailed analysis is carried out to determine the influence of the way to calculate the dual descriptor, the computational procedure, basis set and choice of method to condensate the values of this descriptor. We show that the qualitative regioselectivity predictions depend on the choice of "computational conditions", something that indicates the danger of using black-box computational set-ups in conceptual DFT studies.

Synthesis of Spirocyclic Amines by Using Dipolar Cycloadditions of Nitrones.

Aliphatic ketones containing a chloride and alkene were heated with hydroxylamine to promote cascade, tandem condensation to oximes, cyclization to nitrones, and 1,3-dipolar cycloaddition to tricyclic isoxazolidines as single stereoisomers. Single regioisomers were obtained when three atoms linked the ketone and dipolarophile to give five-membered rings but mixtures resulted with four atoms in the tether unless a terminal ester was located on the alkene. The N-O bond in the products could be reduced to give spirocyclic amines and diamines.

γ-Cyclodextrin as a Catalyst for the Synthesis of 2-Methyl-3,5-diarylisoxazolidines in Water.

A green and efficient 1,3-dipolar cycloaddition of nitrones with different styrenes and cinnamates using a catalytic amount of γ-cyclodextrin (γ-CD) in water has been developed to give substituted isoxazolidines. γ-CD was found to be highly efficacious in carrying out this reaction under an eco-friendly environment, affording moderate to excellent yields and, in some cases, excellent diastereomeric excess (up to >95%) at 100 °C in 8-12 h. The catalyst can be easily recuperated and recycled for several times without loss of activity. Water, an eco-friendly reaction medium, has been utilized for the first time, to the best of our knowledge, in this reaction. The credit of the presented protocol includes high yields and catalyst reusability, and precludes the use of organic solvents. The use of in silico calculations allowed us to rationalize the obtained results and to improve the stereoselectivity.

Metal‐Catalyzed Synthesis of Functionalized 1,2,4‐Oxadiazoles from Silyl Nitronates and Nitriles

AbstractThe metal‐catalyzed cycloaddition of silyl nitronates and nitriles leading to 1,2,4‐oxadiazoles is described. Silver(I) triflate (AgOTf) and and ytterbium(III) triflate [Yb(OTf)3] are suitable catalysts. A variety of functional groups is tolerated in the nitrile. The reaction works well for alkenyl and aryl silyl nitronates while the use of alkyl silyl nitronates is less efficient. Mechanistic studies are in favour of an elimination of tert‐butyl(dimethyl)silanol (TBSOH) after the cycloaddition step. The new approach has also been applied for the synthesis of the drug ataluren.magnified image

Cu(II)-catalyzed enantioselective 1,3-dipolar cycloaddition of nitrones with α, β-unsaturated acyl phosphonates

A highly enantioselective 1, 3-dipolar cycloaddition of nitrone with α, β-unsaturated acyl phosphonate was developed for the first time by using a chiral indane-bis(oxazoline)-copper(II) complex. The reaction proceeded smoothly under mild conditions to provide isoxazolidines with multi-stereocenters in good yields with high to excellent diastereo- (>20:1 dr) and enantioselectivities (up to 99% ee). The resulting products were readily converted to multi-functional isoxazolidines or γ-amino alcohol compounds.

3 + 3] Formal Cycloadditions of Nitrones from Isatins and Azaoxyallyl Cations for Construction of Spirooxindoles

A [3 + 3] formal cycloaddition reaction between in situ formed azaoxyallyl cations and nitrones from isatins has been developed, furnishing a spectrum of spiro[1,2,4‐oxadiazinan‐5‐one]oxindoles in good to excellent yields with excellent diastereoselectivity. This method provides direct and efficient access to potentially bioactive spirooxindoles incorporating a six‐membered heterocyclic scaffold.

Synthesis of novel d-glucose based anionic bolaamphiphiles and their catalytic application in 1,3-dipolar nitrone cycloaddition reactions

Three d-glucose based bolaamphiphiles have been synthesized by a simple and efficient synthetic methodology utilizing the free C-3 hydroxyl group of diisopropylidene glucose. The resulting bolaamphiphiles showed unique aggregation behavior in aqueous solution, e.g. transformation of vesicle to tubular morphology on aging. The chiral hydrophobic interior of these vesicles was utilized as tiny reaction vessels to carry out 1,3-dipolar nitrone cycloadditions in water. The corresponding isoxazolidine derivatives were formed with high diastereoselectivity in several cases. The bolaamphiphile with 12 carbon spacer (5c) showed better diastereoselectivity among the rest with just 2mol% of catalyst loading and can be reused.

Intramolecular Nitrone Cycloaddition of α-(Trifluoromethyl)styrenes. Role of the CF3 Group in the Regioselectivity.

The intramolecular 1,3-dipolar cycloaddition of ortho-substituted 1,1,1-trifluoromethylstyrene-derived nitrones is described. Tricyclic fused isoxazolidines were obtained as major or exclusive products, in contrast to the case for nonfluorinated substrates, which rendered the bridged derivatives. This change in the regioselectivity was attributed to the electronic and, particularly, steric requirements of the trifluoromethyl group in comparison to the methyl group. It is worth mentioning that trifluoromethylstyrenes have been employed for the first time as dipolarophiles in a 1,3-dipolar intramolecular cycloaddition reaction, leading to the corresponding isoxazolidines bearing a quaternary trifluoromethyl moiety. Finally, the synthetic utility of the developed methodology has been illustrated with the synthesis of a family of bicyclic fluorinated 1,3-amino alcohols.

Copper-Catalyzed Asymmetric [3+4] Cycloaddition of Nitrones to Azoalkenes

Copper-Catalyzed Asymmetric [3+4] Cycloaddition of Nitrones to Azoalkenes

Regio- and stereoselective (3 + 2)-cycloaddition of nitrile oxides and nitrones to N-vinylindole

1,3-Dipolar cycloaddition of nitrile oxides and nitrones to N-vinylindole proceeds regioselectively at the exocyclic multiple bond to form 5-indolyl-substituted isoxazolines and isoxazolidines in good yields.

Efficient method for the synthesis of 1,2,3-triazole functionalized isoxazolidine derivatives by 1,3-dipolar cycloaddition of nitrones with terminal olefins

ABSTRACT1-Phenyl-1,2,3-triazole-4-carbaldehyde 1 was treated with different N-alkyl hydroxylamine hydrochlorides 2 using NaHCO3 to obtain 1,2,3-triazole substituted N-alkyl nitrones 3a–c. The nitrones 3a–c were further reacted with different substituted olefins and furnished 2-alkyl-3-(1-phenyl-1H-1,2,3-triazol-4-yl)-5-(substituted)isoxazolidine derivatives 4a–p in high yields via 1,3-dipolar cycloaddition reaction.

Nickel(II)‐Catalyzed Enantioselective 1,3‐Dipolar Cycloaddition of Nitrones with α,β‐Unsaturated Acylcarboxylates

The highly enantioselective 1,3‐dipolar cycloaddition of nitrones with α,β‐unsaturated acylcarboxylates was realized for the first time by using a chiral bis(indano‐oxazoline)‐based Ni complex. The reaction proceeded smoothly under mild conditions and provided isoxazolidines with three contiguous stereocenters in high yields with excellent diastereoselectivities (>20:1 dr) and enantioselectivities (up to 99 % ee). The reaction was scaled up to the gram scale, and the products were readily transformed into γ‐amino alcohols and other potentially bioactive compounds.