Stereoselective synthesis of chiral oxepanes and pyrans through intramolecular nitrone cycloaddition in organized aqueous media

[reaction: see text] A highly stereoselective surfactant-catalyzed intramolecular nitrone (formed by dehydration in water) cycloaddition in aqueous media leading to exclusive formation of a single isomer is reported. Either oxepane or pyran is formed from 3-O-allyl furanoside derivatives, which constitute the framework of a large number of biologically active compounds. Therefore, the environmentally friendly, efficient, and highly stereoselective syntheses of these chiral intermediates are still a meaningful pursuit.     

Synthesis and 1,3-dipolar cycloadditions of a new enantiopure cyclic nitrone

A new enantiopure cyclic nitrone has been efficiently synthesized from a d-glyceraldehyde derivative. Its 1,3-dipolar cycloaddition to different classes of dipolarophiles show complete antifacial selectivity, furnishing highly functionalized enantiopure bicyclic isoxazolidines.     

Catalytic enantioselective three-component hetero-[4+2] cycloaddition/allylboration approach to alpha-hydroxyalkyl pyrans: scope, limitations, and mechanistic proposal

This article describes the design and optimization of a catalytic enantioselective three-component hetero-[4+2] cycloaddition/allylboration reaction between 3-boronoacrolein, enol ethers, and aldehydes to afford alpha-hydroxyalkyl dihydropyrans. The key substrate, 3-boronoacrolein pinacolate (2) was found to be an exceptionally reactive heterodiene in the hetero-[4+2] cycloaddition catalyzed by Jacobsen's chiral Cr(III) catalyst 1. The scope and limitations of this process were thoroughly examined. The adduct of 3-boronoacrolein pinacolate and ethyl vinyl ether was obtained in high yield and with over 95 % enantioselectivity. This cyclic alpha-chiral allylboronate adds to a very wide variety of aldehyde substrates, including unsaturated aldehydes and alpha-chiral aldehydes to give diastereomerically pure products. Acyclic 2-substituted enol ethers can be employed, in which case the catalyst promotes a kinetically selective reaction that favors Z enol ethers over the E isomers. Surprisingly, 3-boronoacrolein pinacolate was found to be a superior heterodiene than ethyl (E)-4-oxobutenoate, and a mechanistic interpretation based on a possible [5+2] transition state is proposed.     

A convenient synthesis of new enantiomerically pure trihydroxypyrrolizidines using l-erythrose glycosylhydroxylamine as a masked acyclic chiral nitrone

A route has been developed for the synthesis of enantiomerically pure trihydroxylated pyrrolizidines starting from l-erythrose glycosylhydroxylamine. The latter acts as a masked acyclic nitrone and reacts diastereoselectively from its Re-face with methyl acrylate to give the corresponding isoxazolidines, which after reductive N-O cleavage are recyclized to trihydroxypyrrolizidines via a Mitsunobu condensation.     

Efficient One-Pot,Four-Component Synthesis of 1,2,3-Triazole-Linked Tetrahydrobenzo[b]pyrans

A one-pot procedure has been developed for the synthesis of (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4H-chromene derivatives by concurrent reaction of aryloxy propargylated aldehydes, various azides, active methylene compounds, and 1,3-cyclohexanediones using catalytic amounts of Cu(OAc)₂ / sodium ascorbate and diammonium hydrogen phosphate in aqueous ethanol media. Excellent conversion of starting materials was achieved to the desired (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4H-chromene products.     

Convenient synthesis of epimeric indolizidines by the intramolecular 1,3-dipolar cycloaddition of a sugar derived N-(3-alkenyl)nitrone

The stereoselective synthesis of two epimeric penta-hydroxylated indolizidines was accomplished from 2,3:5,6-di-O-isopropylidene-α-d-mannofuranose and N-(2-methylpent-4-en-2-yl)hydroxylamine. The transformation of these substrates into the corresponding 7-oxa-1-azabicyclo[2.2.1]heptane by the intramolecular 1,3-dipolar cycloaddition was the key step of the synthesis. The adduct was transformed into the tricyclic ammonium salt by intramolecular N-alkylation. The tricyclic ammonium salt was converted to the target compounds by: (route 1) the catalytic hydrogenation; or (route 2) the reaction with sodium azide, followed by the enantioselective reduction of the resulting indolizidinone.     

Synthesis of (±)-camptothecin using a [3+2] nitrone cycloaddition to construct the CDE ring moiety

A novel synthesis to camptothecin is described. A Friedlander condensation of o-aminobenzaldehye 2 with tricylclic ketone 3 affords camptothecin after further elaboration. Tricyclic ketone 3 is prepared via a route employing a [3+2] nitrone cycloaddition and an intramolecular Knoevenagel condensation.     

Synthesis and properties of azoles and their derivatives. 57. Unexpected results of 3-nitropropene-1 [2+3] cycloaddition to C,C,N-triphenylnitrone

[2+3] Cycloaddition of 3-nitropropene-1 with C,C,N-triphenylnitrone leads to a mixture of 5-nitromethyl-2,3,3-triphenylisoxazolidine and 5-methyl-4-nitro-2,3,3-triphenylisoxazolidine. The results obtained can be explained assuming that 3-nitropropene-1 isomerizes to 1-nitropropene-1 under reaction conditions. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1545–1548, October, 2006.     

Dehydrative intramolecular nitrone cycloaddition in confined aqueous media: a green chemical route to cis-fused chromano[4,3-c]isoxazoles

An efficient synthetic route to the formation of cis-fused chromano[4,3-c]isoxazoles via dehydrative intramolecular 1,3-dipolar nitrone cycloaddition in organized aqueous media in the presence of a surfactant (viz. CTAB) as catalyst was developed, which indeed appeared to be green and a more sustainable method than the existing methods with the additional advantage of easy isolation of products.     

Synthesis of (3′R,5′S)-3′-hydroxycotinine using 1,3-dipolar cycloaddition of a nitrone

To synthesize (3′R,5′S)-3′-hydroxycotinine [(+)-1], the main metabolite of nicotine (2), cycloaddition of C-(3-pyridyl)nitrones 3a, 3c, and 15 with (2R)- and (2S)-N-(acryloyl)bornane-10,2-sultam [(2R)- and (2S)-8] was examined. Among them, l-gulose-derived nitrone 15 underwent stereoselective cycloaddition with (2S)-8 to afford cycloadduct 16, which was elaborated to (+)-1.     

Synthesis of dinucleotides containing nitrone, hydroxylamine and amidoxime linkages

Three new thymidine dinucleotides with nitrone, hydroxylamine and amidoxime backbone linkages, suitable for incorporation into oligonucleotide chains, were easily synthesized, by coupling of readily available thymidine monomers and applying short, simple and efficient procedures.     

Total syntheses of hyacinthacine A2 and 7-deoxycasuarine by cycloaddition to a carbohydrate derived nitrone

Practical syntheses of nitrone 8 by two different approaches from sugars are reported. Its use as a versatile intermediate in highly selective 1,3-dipolar cycloaddition reactions constitutes the key step for novel total syntheses of hyacinthacine A₂ (3) and 7-deoxycasuarine (20) by simple transformations of a common isoxazolidine adduct.     

Cu(Ⅱ),Zn(Ⅱ)-手性二噁唑啉配合物催化硝酮与烯烃环加成反应立体选择性的理论研究

用理论计算方法研究了Cu(Ⅱ)和Zn(Ⅱ)-手性二恶唑啉络合物与N-苄基-α-乙氧酰基硝酮形成的反应前驱体与乙基乙烯基醚的1,3-偶极环加成反应过程.讨论了反应前驱体的前线轨道和优化的分子结构对环加成反应的速度和立体选择性的影响,对手性金属催化剂存在下的1,3-偶极环加成反应的立体选择性进行合理解释.还讨论了催化反应和非催化反应速度对反应立体选择性的影响.     

Synthesis of a novel bifunctional oxyammonium-based ionic liquid: Application for the synthesis of pyrano[4,3-b]pyrans and tetrahydrobenzo[b]pyrans

In the present investigation, a novel bifunctional oxyammonium-based ionic liquid, namely, 2,2′-(ethane-1,2-diylbis[oxy])bis(ethan-1-aminium)-2,2,2-trifluoroacetate, was designed and synthesized. The structure of the titled ionic liquid was characterized using Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹HNMR), carbon nuclear magnetic resonance (¹³CNMR), fluorine nuclear magnetic resonance (¹⁹FNMR), homonuclear COSY nuclear magnetic resonance (NMR), thermogravimetry (TG), derivative thermogravimetry (DTG) analysis, X-ray diffraction patterns (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The described ionic liquid demonstrated robust catalytic performance in the synthesis of pyrano[4,3-b]pyrans and tetrahydrobenzo[b]pyran derivatives. The ionic liquid presents a high potential of recycling and reusing capability in both types of model 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.     

Chiral metal-containing ionic liquid:Synthesis and applications in the enantioselective cycloaddition of carbon dioxide to epoxides

A series of novel chiral metal-containing ionic liquids(CMILs) consisting of the cation of crown ether-chelated potassium/sodium and the anion of chiral amino acids were designed and synthesized.These new CMILs were used to catalyze the enantioselective cycloaddition of epoxides and carbon dioxide incorporating with the salenCo(OOCCCl3) to generate corresponding chiral cyclic carbonates under mild conditions.These new catalysts can be recycled at least five times without significant loss of activity and ena...     

Synthesis of 3-thienyl substituted 2-pyrazolines by 1,3-dipolar cycloaddition

1,3,5-Trisubstituted 3-thienylpyrazolines have been prepared in high yields by the reaction of substituted,N-(P;-nitrophenyl)-3-thiophenecarbohydrazonoyl chlorides with Et₃N in CH₂Cl₂ in the presence of an excess of a monosubstituted olefin. The reaction probably occurs as 1,3-dipolar cycloaddition of the corresponding 3-thiophenecarbonitrile imines formedin situ at the double bond of the olefin.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 114–117, January, 1994.