Catalytic highly enantioselective 1,3-dipolar cycloaddition reaction of nitrones with 3-alkenoyl-2-oxazolidinones by use of a bidentate chiral bis(imine) ligand–Cu(II) triflate complex

A copper(II) triflate complex with bidentate, chiral C₂-symmetric cyclohexane-1,2-bis[(2,6-dichlorophenylmethylene)amine] catalyzed the 1,3-dipolar cycloaddition reactions of nitrones with electron-deficient dipolarophiles, 3-(2-alkenoyl)-1,3-oxazolidin-2-ones to give isoxazolidine cycloadducts with extremely high endo- and enantioselectivities.     

Asymmetric 1,3-dipolar cycloaddition of chiral sulphinylethenes with 1-methyl-3-oxido-pyridinium and some nitrones

1,3-Dipolar cycloaddition of (R)-(+)-p-tolyl vinyl sulphoxide 1 with 1-methyl-3-oxidopyridinium 6 proceeded in a diastereoselective manner to afford the exo and endo cycloadducts 11a,b and 12a in 36%, 7% and 29% yield, respectively. The absolute configuration of 11a was determined by its transformation to (1S)-(−)-2-tropanol (−)-15. Attempts to the cycloaddition of the sulphinylethenes 17–19 with the pyridinium 6 were nsuccessful under several conditions. The reaction of the sulphoxide 20 with pyrroline 1-oxide 21 gave an inseparable mixture of products. The cycloaddition of 20 with 3,4,5,6-tetrahydropyridine 1-oxide22 afforded a mixture of four adducts in ca. 90% yield. High level of diastereoselectivity was achieved for the endo cycloaddition affording the adduct 23 in 33% isolated yield. The absolute configuration of 23 was confirmed by a single-crystal X-ray diffraction study. The stereochemical course of the reaction was discussed based on the absolute configuration of the products.     

Asymmetric 1,3-dipolar cycloaddition reaction of nitrones and acrolein with a bis-titanium catalyst as chiral Lewis acid

A mu-oxo-type chiral bis-Ti(IV) oxide (S,S)-1 can be successfully utilized in the asymmetric 1,3-dipolar cycloaddition reactions between various nitrones 2 and acrolein to give the corresponding isoxazolidines with high to excellent enantioselectivities. For instance, the reaction between nitrone 2 (R = t-Bu) and acrolein in the presence of 10 mol % of bis-Ti(IV) catalyst (S,S)-1 in dichloromethane at -40 degrees C gave the corresponding endo cycloadduct with 97% ee.     

Cu-Fesulphos complexes: efficient chiral catalysts for asymmetric 1,3-dipolar cycloaddition of azomethine ylides

The Cu^I-Fesulphos catalyst system (≤3 mol %) shows an excellent performance in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides. High to very high levels of reactivity, endo/exo selectivity, and enantioselectivity (69->99% ee) are generally achieved with a very wide range of azomethine ylides and dipolarophiles. Based on experimental and computational studies data, a model that accounts for this high enantiocontrol is proposed.     

The 1,3-dipolar cycloaddition of adamantine-derived nitrones with maleimides

Abstract

Adamantane-derived aldo- and ketonitrones react with maleimides giving corresponding isoxazolidines. In the case of aldonitrones reactions proceed giving the diastereomeric mixtures. The ratio of isomers is changing during the reaction process due to the reversibility of the cycloaddition reaction. The cytotoxic and virus-inhibiting activity against influenza virus was investigated for selected adducts.     

Computer-assisted design of asymmetric 1,3-dipolar cycloadditions between dimethylvinylborane and chiral nitrones

This report describes a theoretical study of the 1,3-dipolar cycloadditions between dimethylvinylborane and different chiral nitrones, aimed at identifying the requisite structural features to achieve high levels of selectivity. Excellent regioselectivities towards the formation of the 5-borylisoxazolidines are computed in all cases due to the presence of a strong secondary orbital interaction between the boron of the vinylborane and the oxygen of the nitrones. While these transition structures show [3+3] character, 4-boryl regioisomeric structures have classical [3+2] character with weak carbon-boron secondary orbital interactions. Endo transition structures leading to the favoured products adopt chair-like conformations only, unlike their exo counterparts, which exhibit either boat or twist-boat structures. Placing a stereocentre adjacent to the nitrone nitrogen appears to be an effective strategy to stereodiscriminate the anti and syn approaches of the dipolarophile.     

6,6'-Substituent effect of BINOL in bis-titanium chiral Lewis acid catalyzed 1,3-dipolar cycloaddition of nitrones

By the accommodation of modified BINOLs as chiral ligands, enantioselectivities in the bis-titanium chiral Lewis acid catalyzed 1,3-dipolar cycloaddition of N-diphenylmethyl nitrones and methacrolein could be improved.     

Asymmetric 1,3-dipolar cycloaddition reaction of α,β-unsaturated nitriles with nitrones catalyzed by chiral-at-metal rhodium or iridium complexes

The aqua complexes (S_M,R_C)-[(η⁵-C₅Me₅)M{(R)-Prophos}(H₂O)](SbF₆)₂ (M = Rh, Ir; (R)-Prophos = 1,2-bisdiphenylphosphino propane) catalyze the 1,3-dipolar cycloaddition reaction (DCR) of nitrones with α,β-unsaturated nitriles with low-to-moderate enantioselectivity. The involved catalysts [(η⁵-C₅Me₅)M{(R)-Prophos}(α,β-unsaturated nitrile)](SbF₆)₂, isolated as mixtures of the (S_M,R_C)- and (R_M,R_C)-diastereomers, have been fully characterized, and the molecular structure of the complexes (S_Rh,R_C)-[(η⁵-C₅Me₅)Rh{(R)-Prophos}(cis-2-pentenenitrile)](SbF₆)₂ and (S_Ir,R_C)-[(η⁵-C₅Me₅)Ir{(R)-Prophos}(acrylonitrile)](SbF₆)₂ has been determined by X-ray diffraction. The (R)-at-metal epimers isomerize to the (S)-at-metal counterparts. Diastereopure (S_M,R_C)-[(η⁵-C₅Me₅)M{(R)-Prophos}(α,β-unsaturated nitrile)](SbF₆)₂ complexes catalyze the above-mentioned DCR in a stoichiometric manner with up to 97% ee. The results make clear the influence of the metal configuration on the catalytic stereochemical outcome. The catalysts can be recycled without significant loss of either activity or selectivity.     

Double asymmetric induction in 1,3-dipolar cycloaddition of five-membered cyclic nitrones to 2-(5H)-furanones

The 1,3-dipolar cycloaddition of nitrones 1–4 and their enantiomers 2ent–4ent to α,β-unsaturated γ-lactones, such as achiral 9 and d-glycero 10 provides an interesting example of a double asymmetric induction. The reactions are kinetically controlled. Upon heating and prolonged reaction time, however, the reversibility of the cycloaddition was observed and the presence of more stable thermodynamic products detected. Moreover, in the case of lactone 10, a partial racemization did occur and consequently adducts derived from 10ent were formed. Contrary to the corresponding additions involving δ-lactones, where only the exo approach of the reactants was observed, γ-lactones added nitrones in both exo and endo modes. The high preference of an anti addition to the terminal hydroxymethyl group in lactone 10 and to the 3-tert-butoxy group of the nitrone was observed; the 4-tert-butoxy substituent plays a secondary role. The endo addition of the reactants is energetically more demanding than the exo addition and occurs if none of the substituents present in the lactone or nitrone hinders such an approach. Due to the complex steric interactions a single product was formed in two cases only, 2ent/10 and 3/10. In one case, 3/9, a high preponderance of a single adduct was observed.     

Synthesis of spiroisoxazolidinyl-benzoisothiazolines by 1,3-dipolar cycloaddition of benzoisothiazole-2,2-dioxide-3-ylidenes with nitrones

The spiroisoxazolidinyl-benzoisothiazoline derivatives were synthesized through a highly diastereoselective 1,3-dipolar cycloaddition of benzoisothiazole-2,2-dioxide-3-ylidenes with nitrones. The regiochemistry of cycloaddition was assigned on the ¹H NMR chemical shift of methane-H in 3 and 5. The relative stereochemistry of cycloadducts was determined from the single-crystal X-ray crystallography.     

Synthesis of novel chiral bis(2-oxazolinyl)xanthene (xabox) ligands and their evaluation in catalytic asymmetric 1,3-dipolar cycloaddition reactions of nitrones with 3-crotonoyl-2-oxazolidinone

Chiral 4,5-bis(2-oxazolinyl)-(2,7-di-tert-butyl-9,9-dimethyl)-9H-xanthenes (xabox) were synthesized and the chiral environments were evaluated in catalytic asymmetric 1,3-dipolar cycloaddition reactions of nitrones resulting in good to excellent enantioselectivities. 1,3-Dipolar cycloaddition reactions of nitrones with 3-crotonoyl-2-oxazolidinone in the presence of a bis(2-oxazolinyl)xanthene (4c; xabox-Bn) and Mn(II) or Mg(II) complex as a chiral Lewis acid catalyst proceeded smoothly to give the corresponding cycloadducts ranging from 96:4 to >99:1 of endo:exo ratio and ranging from 91% to 98% ee for the endo adduct.     

CuII-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with a chiral ferrocene-derived P,N-ligand

A ferrocene-derived P,N-heterodonor ligand was effectively used in a Cu(OAc)₂·H₂O-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with maleate derivatives, affording cycloadducts with high yields (up to 96%), diastereoselectivities (>99 dr), and enantioselectivities (up to 99% ee).     

Diastereoselective 1,3-dipolar cycloaddition of pyrylium ylides with chiral enamides

Chiral enamides 5f-i were found to react with pyrylium ylides to give cycloadducts 6d-i in good yields with an excellent level of stereoselectivity. The chiral auxiliary was successfully removed on hydrogenolysis of compound 6f in continuous flow (H-Cube) resulting in the first asymmetric synthesis of complex amine 8.     

Enantioselective 1,3-dipolar cycloaddition of nitrones catalyzed by optically active cationic cobalt(III) complexes

[reaction: see text] The optically active beta-ketoiminato cationic cobalt(III) complexes were employed as efficient Lewis acid catalysts for the enantioselective 1,3-dipolar cycloaddition reaction of alpha,beta-unsaturated aldehydes with nitrones. Excellent endo selectivities and high enantioselectivities were achieved in the cycloaddition reaction of 1-cyclopentene-1-carbaldehyde and the nitrones derived from 2-halobenzaldehyde.     

硝酮1,3-偶极环加成对映选择性配合物催化剂的研究进展

近几年来，1，3-偶极环加成的对映选择性金属配合物催化反应得到了较多研究。人们研制出了一系列控制反应立体选择性的金属配合物催化剂，尤其是对硝酮和链烯烃反应，许多催化剂对Dies-Alder反应和1，3-偶极环加成反应同时具有较高的对映及非对映选择性。     

Stereocontrol in rare earth metal triflate-catalyzed 1,3-dipolar cycloaddition reaction of 2-benzopyrylium-4-olate with aldehydes

Exo-cycloadduct was obtained with high stereoselectivity by the addition of ytterbium triflate (Yb(OTf)(3)) (10 mol %) in the rhodium(II) acetate (Rh(2)(OAc)(4))-catalyzed decomposition of o-(methoxycarbonyl)-alpha-diazoacetophenone in the presence of benzaldehyde. In the reaction in the absence of Yb(OTf)(3), almost no selectivity was obtained. Stereoselectivity in the reactions with p-nitrobenzaldehyde, p-anisaldehyde, and benzyloxyacetaldehyde could be also controlled to high exo preference by the addition of Yb(OTf)(3).     

Electronic effects in 1,3-dipolar cycloaddition reactions of N-alkyl and N-benzyl nitrones with dipolarophiles

1,3-Dipolar cycloadditions afforded fast access to isoxazolidines bearing N-alkyl or N-benzyl substituents. The electronic properties of the substituents in the nitrones define the activity of the dipoles and modulate diastereoselectivity in the non-catalyzed reactions. Using a chiral one-point binding ruthenium Lewis acid catalyst, products were obtained in good yields and with excellent regio-, diastereo-, and enantioselectivity.     

The catalytic asymmetric 1,3-dipolar cycloaddition of ynones with azomethine ylides

The first catalytic asymmetric 1,3-dipolar cycloaddition of electron-deficient carbon-carbon triple bonds with azomethine ylides has been established. This reaction provides an unprecedented approach to access novel 2,5-dihydropyrrole derivatives with potential bioactivities in perfect enantioselectivities of up to >99% ee.