Inverse electron demand asymmetric cycloadditions of cyclic carbonyl ylides catalyzed by chiral Lewis acids—Scope and limitations of diazo and olefinic substrates

High enantioselectivities (94-96% ee) were obtained for the inverse electron-demand 1,3-dipolar cycloadditions between cyclohexyl vinyl ether and 2-benzopyrylium-4-olate generated via Rh₂(OAc)₄-catalyzed decomposition of o-methoxycarbonyl-α-diazoacetophenone. The reactions were effectively catalyzed by Eu(OTf)₃, Ho(OTf)₃, or Gd(OTf)₃ complexes (10 mol %) of chiral 2,6-bis[(4S,5S)-4,5-diphenyl-2-oxazolinyl]pyridine. The reactions with the other electron-rich dipolarophiles such as allyl alcohol, 2,3-dihydrofuran, and butyl-tert-butyldimethylsilylketene acetal showed moderate enanantioselectivities (60-73% ee). Good to high enantioselectivities (73-97% ee) were also obtained for the cycloadditions between 3-acyl-2-benzopyrylium-4-olates, generated from methyl 2-(2-diazo-1,3-dioxoalkyl)benzoates and butyl or cyclohexyl vinyl ethers, in the presence of binaphthyldiimine (BINIM)-Ni(II) complexes (10 mol %). Under similar conditions, the reaction between methyl 2-(2-diazo-1,3-dioxohexyl)benzoate and 2,3-dihydrofuran was highly endo-selective, and moderately enantioselective (70% ee). For the BINIM-Ni(II)-catalyzed reactions of cyclohexyl vinyl ether, the use of an epoxyindanone as the 3-acyl-2-benzopyrylium-4-olate precursor revealed that the chiral Lewis acid can function as a catalyst for asymmetric induction. The scope of the cyclic carbonyl ylides was extended to those generated from 1-diazo-2,5-pentanedione derivatives, which were reacted with butyl or TBS vinyl ether and catalyzed using the (4S,5S)-Pybox-4,5-Ph₂-Lu(OTf)₃ complex to give good levels of asymmetric inductions (75-84% ee).     

Chiral 2,6-bis(oxazolinyl)pyridine-rare earth metal complexes as catalysts for highly enantioselective 1,3-dipolar cycloaddition reactions of 2-benzopyrylium-4-olates

Significant levels of enantioselectivity were obtained in 1,3-dipolar cycloadditions of 2-benzopyrylium-4-olate generated from the Rh(2)(OAc)(4)-catalyzed decomposition of o-methoxycarbonyl-alpha-diazoacetophenone. This reaction utilized chiral 2,6-bis(oxazolinyl)pyridine (Pybox)--rare earth metal triflate complexes as chiral Lewis acid catalysts. The reactions with several benzyloxyacetaldehyde derivatives catalyzed by a Sc(III)--Pybox-i-Pr complex (10 mol %) proceeded smoothly to yield endo-adducts selectively with high enantioselectivity (up to 93% ee). For the reaction with benzyl pyruvate, the Sc(III)-Pybox-i-Pr complex (10 mol %) catalyzed the reaction effectively in the presence of trifluoroacetic acid (10 mol %) to yield an exo-adduct with both high diastereo- and enantioselectivity (94% ee). This catalytic system was efficiently applied to the reactions with several other alpha-keto esters with high exo- and enantioselectivities (up to 95% ee). In contrast to the reaction with carbonyl compounds, Yb(III)--Pybox-Ph complex (10 mol %) was found to be effective to obtain high enantioselectivity (96% ee) of diastereoselectively produced exo-cycloadduct in the reaction with 3-acryloyl-2-oxazolidinone.     

Catalytic asymmetric synthesis of descurainin via 1,3-dipolar cycloaddition of a carbonyl ylide using Rh2(R-TCPTTL)4

A catalytic asymmetric synthesis of descurainin has been achieved by incorporating an enantioselective 1,3-dipolar cycloaddition, a stereoselective alkene hydrogenation, an oxidation with Fremy’s salt and a regioselective demethylation with NbCl₅ as the key step. The 1,3-dipolar cycloaddition of a carbonyl ylide derived from tert-butyl 2-diazo-5-formyl-3-oxopetanoate with 4-hydroxy-3-methoxyphenylacetylene in the presence of dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(R)-tert-leucinate], Rh₂(R-TCPTTL)₄, provided an 8-oxabicyclo[3.2.1]octane skeleton in 95% ee.     

Chiral bis(2-oxazolinyl)xanthene (xabox)/transition-metal complexes catalyzed 1,3-dipolar cycloaddition reactions and Diels-Alder reactions

A series of chiral 4,5-bis(2-oxazolinyl)-(2,7-di-tert-butyl-9,9-dimethyl)-9H-xanthenes (xabox) and their transition-metal complexes were synthesized. The X-ray analysis of xabox-RhCl₃ complex shows a unique facial type structure. Xabox-Bn-Mn(II) and xabox-Bn-Mg(II) complexes were found to be efficient catalysts in nitrone 1,3-dipolar cycloaddition (1,3-D.C.) reaction resulting in good to excellent enantioselectivities ranging from 96:4 to >99:1of endo/exo ratio and 91-96% ee for the endo adduct. The correlation between enantiomeric excess of the ligand and the product in the nitrone 1,3-D.C. reaction shows a clear linear relationship, which suggests xabox-metal catalyst worked as a single molecular catalyst. In addition, xabox-i-Pr-Mn(II) complex was also found to be an active catalyst for Diels-Alder (D-A) reaction of acryloyloxazolidinone and cyclopentadiene affording the corresponding cycloadduct in quantitative yield along with 82% ee and 98:2 endo/exo ratio.     

Sacrificial azomethine ylide cycloaddition controlled chemoselective nitrile oxide cycloaddition to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: formation of mono-spiro-isoxazolines

The 1,3-dipolar cycloaddition of an azomethine ylide to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolidines in good yields. Further cycloaddition of these spiro-pyrrolidines with nitrile oxide afforded mono-spiro-isoxazolines in moderate yields (45-56%), presumably via a di-spiro intermediate, which undergoes a spontaneous cycloreversion of the spiro-pyrrolidine unit. In contrast, the direct cycloaddition of nitrile oxide to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones gave the mono-spiro-isoxazoline as the minor product, while the bis-spiro-isoxazolines are formed predominantly.     

Synthesis of ethyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate via regioselective dipolar cycloaddition

Efforts to prepare ethyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate (1) by developing a regioselective 1,3-dipolar cycloaddition between phenyl nitrile oxide and various 4,4,4-trifluoromethyl crotonates are described. The substitution at the C2-position of crotonate dipolarophile 4 significantly influenced the regiochemistry and yield of the cycloaddition. Enol and enol ether-based crotonates underwent regioselective cycloadditions with phenyl nitrile oxide to provide 4-trifluoromethyl isoxazoles in good yields.     

An expedient approach for the regio- and stereoselective synthesis of novel spiroindolizidines via [3+2] cycloaddition

A new series of spiroindolizidines was synthesized by one-pot, three-component condensation of azomethine ylides, generated from 1,2,3,4-tetrahydroisoquinoline with ninhydrin or isatin derivatives by a 1,5-prototropic shift route, with various derivatives of trans-β-nitrostyrene in a regio- and stereoselective manner. X-ray crystal structure analysis and NMR spectroscopic data confirmed the structure outcome of the cycloaddition reaction.     

An experimental and theoretical investigation of the regio- and stereoselectivity of the polar [3+2] cycloaddition of azomethine ylides to nitrostyrenes

The regio- and stereochemical polar [3+2] cycloaddition of the azomethine ylides, which were generated in situ by the reaction of isatin derivatives and proline, with trans-β-nitrostyrene and (E)-1-phenyl-2-nitropropene were studied using experimental and theoretical methods. In comparison with trans-β-nitrostyrene, when the reactions were performed with (E)-1-phenyl-2-nitropropene, a remarkable inversion in the regioselectively was observed. The regioselectivity of the reactions was investigated using global and local reactivity indices and frontier molecular orbital (FMO) analysis at the B3LYP/6-31G(d,p) level of theory. The effects of the electronic and steric factors on the regioselectivity of the reactions were discussed. The inspection of geometries and energetics of transition states revealed the importance of weak interactions in regioselectivity of the cycloaddition reactions.     

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.     

Chemo-, regio- and stereoselective 1,3-dipolar cycloaddition of C-aryl-N-phenylnitrones over 3,5-bis(arylidene)-1-methylpiperidin-4-ones: synthesis of highly substituted novel spiro-isoxazolidines

1,3-Dipolar cycloaddition of C-aryl-N-phenylnitrones to 3,5-bis-(arylidene)-1-methylpiperidin-4-ones affords novel mono- and bis-spiroisoxazolidines in moderate yields. In general, this reaction predominantly yields mono-spiroisoxazolidine, wherein the oxygen of the nitrone is linked to the β-carbon of the benzylidene moiety, while 3,5-bis-(2-chloro- and 3-nitro-benzylidene)-1-methylpiperidin-4-ones afford predominantly bis-spiroisoxazolidines. The cycloaddition of mono-spiroisoxazolidines occurs with facial diastereoselectivity to furnish bis-spiroisoxazolidines. The nitrogen in the heterocyclic ring of the 3,5-bis-(arylidene)-1-methylpiperidin-4-ones facilitates the cycloaddition through transannular (NCO) and/or homoconjugative (NCC) interactions.     

3-(5-Substituted 2-Methoxyphenyl)-4-Nitro-2-Phenyl-5-Thiophene-2-yl-Isoxazolidines - Synthesis and Conformational Studies

Abstract

The synthesis of a new set of 2,3,4,5-substituted isoxazolidines having a sulfur containing heterocyclic moiety has been described. The structural features of the compounds have been analyzed by ¹H and ¹³C NMR spectroscopy as well as by single crystal X-ray studies.

[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: .cif file.]     

Catalytic bimetalic [Pd(0)/Ag(I) Heck-1,3-dipolar cycloaddition cascade reactions accessing spiro-oxindoles. Concomitant in situ generation of azomethine ylides and dipolarophile

Spiro-oxindoles, epi-Spirotryprostatin A and its analogues were prepared from a tactical combination of cascade catalytic bimetallic Pd (0)/Ag(I), intramolecular Heck and subsequent imine → azomethine ylide → 1,3-Dipolar cycloaddition reactions. The cascade features in situ generation of azomethine ylides and dipolarophiles and produces two new rings together with three stereocentres in good to excellent yields.     

1,3-Dipolar cycloaddition of α-alkoxycarbonylnitrones with vinyl ethers and allyl alcohols in the presence of Eu(fod)3: selective activation of (Z)-isomers of the nitrones

Uncatalyzed cycloaddition of α-alkoxycarbonylnitrones 1 with vinyl ethers 7 gave mixtures of cis- and trans-cycloadducts 8, whereas Eu(fod)₃-catalyzed cycloaddition of 1 with 7 gave the trans-cycloadducts trans-8 in a highly stereoselective manner. NMR studies indicated that Eu(fod)₃ selectively activated (Z)-nitrones (Z)-1 in E,Z-equilibrium mixtures of nitrones 1. In contrast, the reaction of 1 with allyl alcohols 12 in the presence of Eu(fod)₃ resulted in sequential transesterification and intramolecular cycloaddition to give intramolecular cycloadducts 13.     

New cycloaddition reaction between 4-arylidene-2-phenyl-5(4H)-1,3-oxazolones and benzyne; facile synthesis of 1,4(H)-benzoxazepine-2-ones and their N-phenyl derivatives

Reaction of 4-arylidene-2-phenyl-5(4H)-1,3-oxazolones with benzyne afforded predominantly, 3-arylidene-7-hydroxy-7-phenyl-1,4(H)-benzoxazepine-2-ones in addition to their N-phenyl derivatives. However, the reaction of the target oxazolones with an excess of benzyne gave only the N-phenyl derivatives of 1,4(H)-benzoxazepine-2-ones in good yields. The reaction mechanism describing product formation is also explained. Arylation of 1,4(H)-benzoxazepine-2-ones with benzyne proceeded successfully to give the N-phenyl products.     

Parallel Solid-Phase Synthesis of disubstituted 3-(1H-benzo[d]imidazol-2-yl)imidazolidine-2,4-diones and 3-(1H-benzo[d]imidazol-2-yl)-2-thioxoimidazolidin-4-ones

A multistep approach to construct novel 3-(1H-benzo[d]imidazol-2-yl)imidazolidine-2,4-diones and 3-(1H-benzo[d]imidazol-2-yl)-2-thioxoimidazolidin-4-ones from commercially available amino acids, amines, and carboxylic acids is described. Coupling of Fmoc-amino acid to resin-bound aminobenzimidazole provided following Fmoc elimination free amine. Treatment of the free amine with 1,1′-carbonyldiimidazole or 1,1′-thiocarbonyldiimidazole furnished the corresponding hydantoins and thiohydantoins via intramolecular cyclization. The desired aminobenzimidazole tethered hydantoins or thiohydantoins were isolated in good yields.     

在La_2Na_2Sr_6(PO_4)_6Br_2基质中Tb~(3+)的发光及Ce~(3+)对Tb~(3+)的敏化

用高温固相反应法合成了发光材料、研究了Tb~(3+)在La_2Na_2Sr_6(PO_4)_6Br_2基质中的光致发光性质及Ce~(3+)对Tb~(3+)的敏化作用.在254nm紫外光激发下,Tb~(3+)的发光较弱,但Ce~(3+)对Tb~(3+)有强的敏化作用,其能量传递机埋是偶极-偶极相互作用引起的共振能量传递,计算了传递效率。     

Reaction of chromone-3-carbaldehyde with α-amino acids—syntheses of 3- and 4-(2-hydroxybenzoyl)pyrroles

Azomethine ylides generated from the reaction of chromone-3-carbaldehyde with α-amino acids undergo 1,5-electrocyclization reactions to afford 3- and 4-(2-hydroxybenzoyl)pyrroles. These ylides can be trapped with dipolarophiles in 1,3-dipolar cycloaddition reactions to yield chromonyl pyrrolidines. The reaction of chromone-3-carbaldehyde with methyl glycinate gives a mixture of pyrrole, pyridine, and 3-aza-9-xanthenone derivatives.     

Microwave induced one-pot synthesis of fluorenespiro[9.3′]-(4′-aryl)pyrrolidine/pyrrolizidine/tetrahydropyrrolo[1,2-c]thiazolespiro[2′.2″]indan-1″,3″-dione derivatives

A versatile one-pot method for the synthesis of new dispiro heterocycles is described using an intermolecular [3+2] cycloaddition reaction. The reaction gives excellent yields when carried out under solvent-free microwave irradiation.     

Diels-Alder cycloaddition of 2-azadienes to methyl 2-(2,6-dichlorophenyl)-2H-azirine-3-carboxylate in the synthesis of methyl 4-oxo-1,3-diazabicyclo[4.1.0]heptane-6-carboxylates

A number of fused 4-oxo-1,3-diazabicyclo[4.1.0]heptane-6-carboxylates, a new type of compound, have been obtained by Diels-Alder cycloaddition between nucleophilic 2-azadienes and an electrophilic 2H-azirine. The reactions are completely endo- and regioselective, the azirine being added by its less hindered face to the diene. There are two isomers 7 and 8 formed from dienes 1 due either to isomerization of the cycloadducts 7 and 8 or by isomerization of the CN bond of the diene during the reaction. The isomer 10 is formed from diene 2e, and a single diastereoisomer structure 4a-i is formed from dienes 11. Some pyrimidones 8a, 7c/8c, 7e, 10, 11d have been hydrolyzed leading to functionalised aziridines 12, 13 and 15.     

Preorganization in the Nazarov cyclization: the role of adjacent coordination sites in the highly Lewis acidic catalyst [IrMe(CO)(dppe)(DIB)](BAr4)2

The dicationic Ir(III) complex [IrMe(CO)(dppe)(DIB)](BAr₄^f)₂ where dppe=bis(diphenylphosphino)ethane and DIB=o-diiodobenzene possesses adjacent labile sites and is found to be a very active catalyst for the Nazarov cyclization. ³¹P NMR spectroscopy provides evidence for substrate-catalyst binding by chelation, and this is found to be the resting state of the system during catalysis. The efficiency of the cyclization is attributed to the electrophilicity of the Ir(III) complex and substrate activation via O,O′-chelation which employs two substrate carbonyl groups or one carbonyl and an ether function, and encourages the s-trans/s-trans conformation required for cyclization. When two point binding occurs through an oxygen atom and one of the vinyl groups, the s-trans/s-trans conformation is not achieved, and cyclization is not observed. In one case, monodentate binding of substrate occurs, and the rate of cyclization is significantly slower than when O,O′-chelation is possible. The viability of O,O′-chelation is shown by the crystal structure determination of a model substrate-catalyst complex.