Chiral Diels–Alder reaction between cyclopentadiene and nitroso derivatives: thermal isomerisation/racemisation of the adducts

Cyclopentadiene nitroso adducts 1a and ent-1a were synthesised in good yields and good enantiomeric excess from chiral chloro-nitroso derivatives 4 and 5 in the d-mannose and d-ribose series, respectively. The thermal racemisation of these adducts occurred below room temperature. Some other chiral Diels–Alder nitroso adducts were prepared in the d-mandelic, l-prolinol and d-O-methylprolinol series and their thermal isomerisation was specified according to the N-substitution. A simple synthesis of the chiral amido-cyclopentenol (+)-2b, an important precursor for biological interesting compounds, is presented from ent-1a.     

Asymmetric catalysis. Part 153: Metal-catalysed enantioselective α-ketol rearrangement

Promoted by catalytic amounts of Ni complexes tertiary α-hydroxyketones 1a, 3a–5a undergo rearrangement, forming chiral isomers 1b, 3b–5b. The best enantioselection was obtained with the model system 1-benzoylcyclopentanol 4a/2-hydroxy-2-phenylcyclohexanone 4b. In a ligand screening 2-[4-(S)-tert-butyloxazolin-2-yl]pyridine gave the highest enantiomeric excess of 46% (S)-4b. The analogous isomerisation reactions of α-hydroxyimines 6a, 7a forming chiral α-aminoketones 6b, 7b were established.     

Asymmetric polymerization via cycloaddition reactions

The reaction of N‐phthaloyl‐L ‐leucine acid chloride (1) with isoeugenol (2) was carried out in chloroform, and novel optically active isoeugenol ester derivative 3 as a chiral monomer was obtained in high yield. Compound 3 was characterized by ¹H‐NMR, IR, and mass and elemental analysis and then was used for the preparation of model compound 5 and polymerization reactions. 4‐Phenyl‐1,2,4‐triazoline‐3,5‐dione, PhTD (4), was allowed to react with compound 3. The reaction is very fast and gives only one diastereomer of 5 via Diels–Alder and ene pathways in quantitative yield. In order to explain this diastereoselectivity, a nonconcerted two‐step mechanism involving benzylic cation (BC) and aziridinium (AI) have been proposed for the Diels–Alder and ene reactions, respectively. The polymerization reactions of novel monomer 3 with bis(triazolinedione)s [bis(p‐3,5‐dioxo‐1,2,4‐triazolin‐4‐ylphenyl)methane (8) and 1,6‐bis(3,5‐dioxo‐1,2,4‐triazolin‐4‐yl)hexane] (9)] were performed in N,N‐dimethylacetamide (DMAc) at room temperature. The reactions are exothermic, fast, and gave novel optically active polymers 10 and 11 via repetitive Diels–Alder–ene polyaddition reactions. These polymers have inherent viscosities in a range about 0.18–0.22 dL/g. Some physical properties and structural characterizations of these new polymers have been studied and are reported. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1211–1219, 1999     

Diastereomeric process-based chiral resolution of helical quinone derivatives using (−)-menthyl chloroformate

Diastereomeric resolution of helically distorted polycondensed bisphenols (1,1′-bibenzo[c]phenanthrene-2,2′-diols: HEBPOLs) 2a–b was conducted utilizing (1R)-(?)-menthyl chloroformate as a chiral resolving agent. Subsequent manipulation produced highly optically pure [>99% enantiomeric excess (ee)] quinone derivatives (P) and (M)-1a–b in very good yields. The absolute configuration of each product was confirmed based on circular dichroism (CD) spectra and X-ray crystal structure analysis.     

Heterogeneous asymmetric Diels–Alder reactions using a copper–chiral bis(oxazoline) complex immobilized on mesoporous silica

A chiral bis(oxazoline)–copper complex was immobilized onto mesoporous silica and the resulting heterogeneous catalyst was employed in asymmetric Diels–Alder reactions. Reactions using the catalyst exhibited good enantioselectivity of 78% enantiomeric excess and endo/exo-selectivity (17:1) better than the corresponding homogeneous reaction. The catalyst could be easily recovered and reused several times without significant loss of the remarkable reactivity, diastereoselectivity and enantioselectivity.     

Enantioselective Diels–Alder reaction of o-quinodimethanes by utilizing tartaric acid ester as a chiral auxiliary

The asymmetric Diels–Alder reaction of o-quinodimethanes, generated from benzocyclobutenols in situ, with fumaric acid esters was achieved by utilizing diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding optically active 1,2-cis-substituted 1-hydroxy tetrahydronaphthalene derivatives with enantioselectivities up to 83% ee.     

Asymmetric hetero-Diels–Alder reaction of 1-alkyl-3-silyloxy-1,3-dienes with ethyl glyoxylate catalyzed by a chiral (salen)cobalt(II) complex

The hetero-Diels–Alder reactions of 1-alkyl-3-(tert-butyldimethylsilyl)oxy-1,3-butadienes with ethyl glyoxylate catalyzed by chiral salen–metal complexes have been studied. With a cobalt(II) complex as the catalyst, the reaction of 1-(2-benzyloxyethyl)-3-(tert-butyldimethylsilyl)oxy-1,3-butadiene with ethyl glyoxylate gave the Diels–Alder product in 75% isolated yield with the endo:exo ratio >99:1 and the enantiomeric excess ≥52%. The effects of temperature, catalyst and solvent are also discussed.     

New chiral amino acid-derived α-acyloxynitroso reagents for asymmetric nitroso Diels–Alder reactions

The preparation of new chiral α-acyloxynitroso derivatives 4a–e as chiral dienophiles for the nitroso Diels–Alder reaction is reported. These compounds are obtained from amino acid-derived iodobenzene dicarboxylates and ketoximes, and are stable and easy-to-handle reagents. Initial studies for their nitroso Diels–Alder reactions with cyclohexadiene are also reported.     

Synthesis and applications of (1R,5S,6S)-6-(2,2-dimethylpropanamido)spiro[4.4]nonan-1-ol as a chiral auxiliary in Diels–Alder reactions

A short asymmetric synthesis of (1R,5S,6S)-6-(2,2-dimethylpropanamido)spiro[4.4]nonan-1-ol 7 is described along with its application as a chiral auxiliary in various Diels–Alder reactions. The enantioselectivity of the Diels–Alder adducts ranged from 86–98% ee. The Diels–Alder adducts were easily removed from the chiral auxiliary and the latter was recyclized. The absolute and relative stereochemistry of 7 was determined from an X-ray crystal structure of the p-bromobenzoate derivative of 7.     

Asymmetric Diels–Alder addition of cyclopentadiene to chiral naphthoquinones

Diels–Alder reactions of 1,4-naphthoquinones bearing a chiral auxiliary at C-2, with cyclopentadiene under Lewis acid conditions afforded the corresponding Diels–Alder adducts. High levels of diastereomeric excess were obtained using (R)-pantolactone, (S)-N-methyl-2-hydroxysuccinimide and trans-2-phenylcyclohexanol as auxiliaries. Moderate asymmetric induction was achieved using Oppolzer's camphorsultam and (R)-(+)-4-benzyl-2-oxazolidinone as auxiliaries. X-Ray crystallographic analysis of the pantolactone adduct enabled determination of the stereochemistry of all adducts obtained.     

Asymmetric synthesis of new chiral long chain alcohols

Sixteen new chiral alcohols with alkyl (C₁₁–C₁₉) and aryl, substituted aryl, hetero aryl and biaryl groups 2a–2t were synthesized by three different asymmetric reduction methods from their corresponding ketones 1a–1t. Chiral NaBH₄ (method A), chiral BH₃ (method B) and chiral AIP (method C) were used as asymmetric reduction catalysts. Chiral NaBH₄ was modified by four different ligands 3a–3d, chiral BH₃ and chiral AIP by four different ligands 4a–4d. Ligand 4c was synthesized for the first time in this work. Chiral NaBH₄ generated chiral alcohols of (R)-configuration and chiral BH₃ and chiral AIP of (S)-configuration with high enantiomeric excesses, were analysed by chiral HPLC. In order to determine the ee values by chiral HPLC, sixteen corresponding racemic alcohols, synthesized by reducing their corresponding ketones via NaBH₄, were used for chiral resolution on a Daicel OD HPLC column. The sixteen starting ketones were synthesized in this study by Friedel–Craft acylation. The new chiral alcohols were characterized by IR, NMR, (¹H and ¹³C), MS, elemental analyses and specific rotation. The reduction methods A, B and C were applied to these ketones for the first time in this study and were compared with each other. The relationship between the structure of the ketone and the yield and the enantiomeric excess was discussed.     

Synthesis of chiral 1,3-bis(1-(diarylphosphoryl)ethyl)-benzenes via Ir-catalyzed double asymmetric hydrogenation of bis(diarylvinylphosphine oxides)

<正>1 General methods Unless otherwise noted, all reactions and manipulations involving air- or moisture-sensitive compounds were performed using standard Schlenk techniques or in a glovebox. All solvents were purified and dried using standard procedures. Melting points were measured on a RY-I apparatus and uncorrected. 1H, 13 C, 31 P and 19 F NMR spectra were recorded on Varian Mercury 300 or 400 MHz spectrometers. Chemical shifts(δ values) were reported in ppm downfield from internal TMS(1H NMR), CDCl3(13C NMR), external 85% H3PO4(31P NMR), and external CF3CO2H(19F NMR), respectively. Optical rotations were determined using a Perkin Elmer 341 MC polarimeter. The IR spectra were measured on a BRUKER TENSOR 27     

Highly enantioselective hetero Diels–Alder reactions of N-sulfinyl dienophiles promoted by copper(II)- and zinc(II)-chiral bis(oxazoline) complexes

Hetero Diels–Alder reactions of 1,3-cyclohexadiene with N-sulfinyl dienophiles 1a or 1b, promoted by Cu(II)- or Zn(II)-chiral bis(oxazoline) complexes, afforded endo adducts in high yields (up to 85%) and enantiomeric excess (e.e. of up to >98%) under stoichiometric conditions. With 10 mol% loading of the Zn(II) catalyst up to 75% e.e. was obtained for the endo adduct (endo:exo=10:1, total yield 68%).     

Highly stereoselective reduction of chiral α-keto-β, γ-unsaturated acetals: Synthesis of both epimeric allyl alcohols by proper choice of additive

Highly stereoselective reduction of chiral α-keto-β, γ-unsaturated acetals (1a-3a) into each two epimeric optically active allyl alcohols (1b-3b and1c-3c) was attained by LiAlH₄ using additive (LiBr, MgBr₂).     

Allylsilane Reagent-Controlled Divergent Asymmetric Catalytic Reactions of 2-Naphthoquinone-1-methide

Herein, the first allylsilane reagent-controlled divergent asymmetric Hosomi–Sakurai conjugate allylation and hetero-Diels–Alder (HDA) with 2-naphthoquinone-1-methide (2-Nap-Q-1-M) under the catalysis of Sc^III/Feng ligand complex is reported. With these methods, a variety of uniquely substituted chiral allyl-functionalized diaryl compounds and naphthopyran products were obtained in a straightforward and highly stereoselective (up to 96.5:3.5 e.r.) manner under mild conditions. Moreover, it is demonstrated that 2-Nap-Q-1-M can serve as an efficient diene for a side asymmetric Diels–Alder (D-A) reaction. This principle can provide a straightforward access to hydrophenalene in an optically active form, which represents a structural core of various natural products and bioactive molecules.     

Stereoselective synthesis of enantiopure condensed [2.2]paracyclophanes

The Diels–Alder reaction of (S)-(+)-4-ethenyl[2.2]paracyclophane with 1,4-benzoquinone, N-phenylmaleimide and 3-nitrocyclohexen-1-one has been investigated under atmospheric and high pressure conditions. The synthesis of five optically active [2.2]paracyclophanes containing condensed polycyclic aromatic subunits is described. A structural analysis of the reaction products by ¹H and ¹³C NMR spectroscopy is also presented.     

Optically active 1-(benzofuran-2-yl)ethanols and ethane-1,2-diols by enantiotopic selective bioreductions

Enantiotopic selective reduction of 1-(benzofuran-2-yl)ethanones 1a–d, 1-(benzofuran-2-yl)-2-hydroxyethanones 4a–c and 2-acetoxy-1-(benzofuran-2-yl)ethanones 3a–c was performed by baker's yeast for preparation of optically active (benzofuran-2-yl)carbinols [(S)-5a–d, (S)-6a–c and (R)-6a–c, enantiomeric excess from 55 to 93% ee].     

Diels–Alder Cycloadditions of 1,2-Dihydrophosphinine Oxides and Fragmentation-Related Phosphorylations with 2-Phosphabicyclo[2.2.2]Octadiene Oxides Under Green Chemical Conditions—The Role of Microwave and Ionic Liquids

Abstract

The effect of the use of microwave (MW) and solvents including ionic liquids on the Diels–Alder reaction of 1,2-dihydrophosphinine oxides (1) and fragmentation-related phosphorylation of phenols with 2-phosphabicyclo[2.2.2]octadiene oxides (4) was studied. The MW-assisted Diels–Alder reaction of dihydrophosphinine oxides (1) with N-phenylmaleimide may be advantageous to carry out in [bmim][BF₄] due to shorter reaction times, but the dimerization of the double-bond isomers (A and B) of the dihydrophosphinine oxides (1) may be best accomplished under MW in the absence of any solvent. The fragmentation-related phosphorylations may also be carried out under MW, which with the P-phenyl precursor (4a) became more efficient in [bmim][BF₄].

GRAPHICAL ABSTRACT      

Ready access to the 6,8-dioxabicyclo[3.2.1]octane ring system using asymmetric heterocycloaddition induced by a chiral sulfoxide: application to the total synthesis of the Mus musculus pheromone

A new stereocontrolled total synthesis of the (1R,5S,7R)-exo-6,8-dioxabicyclo[3.2.1]oct-3-ene skeleton of the Mus musculus pheromone has been achieved via an asymmetric intermolecular Diels–Alder reaction and an intramolecular conjugated addition, controlled by a chiral auxiliary.     

Synthesis of Bis(indole) Alkaloids from Arundo donax: The Ynindole Diels–Alder Reaction,Conformational Chirality,and Absolute Stereochemistry

Bis(indole) alkaloids from Arundo donax were synthesized using the first ynindole Diels–Alder reaction. The alkaloids are chiral, having stable enantiomeric conformations with half‐lives of racemization of t_1/2=4150–25100 seconds at room temperature. Their absolute stereochemistry was determined using the exciton chirality method.