Dipolar cycloadditions of imidazoline 3-oxides with N-arylmaleimides. Synthesis and diethylamine induced ring-opening of exo and endo hexahydro-7-oxa-2,5,6a-triaza-cyclopenta[a]pentalene-1,3-diones

1,4-Diarylimidazoline 3-oxides react with N-arylmaleimides in benzene to give predominantly the corresponding endo adducts. Chiral imidazoline 3-oxides react diastereospecifically (cis configuration of the tetrahydroimidazo ring) and diastereoselectively to give cis-endo adducts. The effects of substituents on the aromatic ring of the maleimide was investigated. The presence of electron-withdrawing or releasing groups have minor effect on the total yields but more pronounced is the effect on the ratio of exo and endo diastereomers. The adducts undergo an interesting and unprecedented ring-opening in the presence of secondary amines to give deoxygenated 3-imidazoline 3-oxides instead of the expected double cis elimination products. Tertiary amines did not induce any reaction.     

Regioselective synthesis of poly-substituted naphthalenes via a Pd-catalyzed cyclization of modified Baylis–Hillman adducts: selective 6-endo Heck reaction and an aerobic oxidation cascade

Poly-substituted naphthalenes were synthesized via a Pd-catalyzed cyclization of modified Baylis–Hillman adducts having an o-bromophenyl acetonitrile moiety at the secondary position, in reasonable yields. The reaction involved a sequential 6-endo Heck reaction and an aerobic oxidation process.     

Photocycloaddition of ethylvinylether and cyclopentene to 3.5-dimethylanisole

Photocycloadition of ethylvinylether and cyclopentene to 3,5-dimethylanisole yields derivatives of 1-methoxy-2, 4-dimethyltricyclo [3.3.0.0^2,8]oct-3-ene in which the substituents at positions 6 and/or 7 are endo. Structural proofs are based on 250 MHz ¹H and 62.9 MHz ¹³C NMR spectra.     

Diels-Alder reaction of α-tropolone and electron-deficient dienophiles prompted by Et3N or silica gel: a new synthetic method of highly functionalized homobarrelenone derivatives

A Diels-Alder reaction of α-tropolone and electron-deficient dienophiles prompted by Et₃N or silica gel was performed. Reaction with the highly reactive dienophile, N-methylmaleimide, proceeded smoothly in the presence of Et₃N or silica gel to yield adducts as a mixture of endo and exo isomers. Both catalysts accelerated endo/exo isomerization of the product, and detailed examination of the reaction using hinokitiol and N-methylmaleimide revealed that isomerization proceeds via an intramolecular path without retro Diels-Alder reaction. Successful cycloaddition reactions were established with six other dienophiles: acrylonitrile, methyl acrylate, ethyl vinyl ketone, dimethyl fumalate, dimethyl malate, and dimethyl acetylenedicarboxylate, and the corresponding adducts were obtained in good to moderate yields.     

Mono-Glycosylated 3-N-Alkylcatechols: Direct Synthesis from Glycosylacetates, 1H Nmr Analysis and Conformational Studies

ABSTRACT

The direct coupling of 3-n-alkyl catechols to the acetate or trichloroacetimidate derivatives of β-D- or α-D-glycosides (glucose, galactose, xylose, mannose and maltose) catalyzed by BF₃Ot₂ has been studied. β-Glycosides with an equatorial acetate group at position 2 formed exclusively β adducts with yields of 60–80%. α-Glycosides with an equatorial acetate group at position 2 formed β adducts, while β-glycosides with an axial acetate group formed α adducts when activated as trichloroacetimidates, with yields of 70–85%. This was applied to the coupling of 3-n-alkylcatechols of increasing chain length (up to C15) to sugar derivatives. The coupling position of glycosides on the catechol was determined either by differential NOE experiments and by the regioselective synthesis of 1-(O-β-D-glucopyranosyl)-3-pentadecylcatechol, a water soluble analogue of the poison ivy skin allergen. ¹H NMR of acetylated and deprotected compounds were investigated and the conformational preferences of the C₆ side chain determined using molecular modeling.     

Camphor-derived sulfonylhydrazines: catalysts for Diels-Alder cycloadditions

Camphor-derived sulfonylhydrazines proved to be very active for organocatalyzed Diels-Alder cycloadditions with cyclopentadiene. Good chemical yields and enantiomeric excesses up to 89% and 88% are obtained for endo/exo adducts.     

Oxythallation of norbornene derivatives with thallium(III) acetate in methanol

Treatment of norbornene, norbornadiene, benzonorbornadiene, and chloro- and methoxy-benzonorbornadiene with thallium(III) acetate in methanol affords only the corresponding cis-exo-acetoxythallation adducts in a sharp contrast to oxymercuration of such strained olefins where methoxymercuration prevails. In the cases of substituted benzonorbornadienes the products are obtained as the regioisomeric mixtures, the isomer ratio being determined by ¹³C NMR. In the cases of 5-norbornene-2,3-dicarboxylic anhydride, 5-norbornene-2-methyl-2,3-dicarboxylic anhydride, and 5-norbornen-2-endo-carboxylic acid, lactonization occurs to give a trans-oxythallation adduct having a lactone ring, no introduction of either methoxy or acetoxy groups being observed. ¹H and/or ¹³C NMR data for several new oxythallation adducts are provided. The alkaline sodium borohydride reduction of adducts in methanol affords mainly the parent olefin together with 10–16% yields of the corresponding exo-alcohol.     

Symmetry allowed π4s+π2s additions silacyclopentadienes

π⁴s+π²s cycloaddition of hexaphenylsilacyclopentadiene with ethyl acrylate gives rise to a bicyclosilaheptene derivative. High resolution NMR studies have shown that the ester group in this adduct is in the endo position and that the ester methylene protons are magnetically inequivalent. Similar cycloadditions of hexaphenylsilacyclopentadiene, 1,1-dimethyl-2,3,4,5-tetraphenylsilacyclopentadiene, 1-methyl-1,2,3,4,5-pentaphenylsilacyclopentadiene, and 1-methyl-1-vinyl-2,3,4,5-tetra-phenylsilacyclopentadiene with dienophiles like acrylonitrile, maleic anhydride and dibenzoylacetylene have been carried out. The stereochemistry of these adducts has been deduced on the basis of NMR studies. Mass spectral fragmentation studies of some of the silabicycloheptenes have been carried out.     

Indenyl and fluorenyl transition metal complexes : VII. Innersphere “ricochet” rearrangements on alkylation of η5-indenyl- and η5-fluorenyltricarbonylchromate anions

Alkylation of K[η⁵-C₉H₇Cr(CO)₃] (Xa) with CH₃I and C₆H₅CH₂Br leads to σ-alkyl derivatives of η⁵-C₉H₇Cr(CO)₃Alk type. These complexes undergo innersphere “ricochet” rearrangement, with the alkyl group being shifted to the endo position at C(1) and the chromium tricarbonyl group shifted to the benzene nucleus. The structure of the product of such a rearrangement in the case of η⁵-C₉H₇(CO)₃CrCH₂C₆H₅, i.e. (1-benzyl-3a,4-7,7a-η⁶-indene)chromium tricarbonyl (XVIII), is established by a low temperature X-ray study, indicating an endo position for the benzyl radical.On alkylation of equilibrium tautomeric mixtures of η⁵- and η⁶-fluorenylchromium tricarbonyl anions XIa ? XIb under similar conditions, the η⁵-anion (Xa) yields a σ-alkyl derivative, which is rearranged to (9-endo-alkyl-1-4,4a,9a-η⁶-fluorene)chromium tricarbonyl. Electrophilic attack of the η⁶-anion (XIb) takes place on the outer side at C(9) and leads to a corresponding 9-exo-alkyl derivative.     

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%).     

Correct structures of Diels-Alder adducts from the natural cyclolignan thuriferic acid and its 8-epimer

A detailed analysis of one- and two-dimensional ¹H and ¹³C NMR data for the endo and the exo adducts, obtained by Diels-Alder reaction of thuriferic and epithuriferic acids with cyclopentadiene is described. The unequivocal spectral data assignment of the endo and exo structures was complemented with molecular modelling studies and confirmed through X-ray diffraction studies.     

[4+2]-Cycloadditionen von 1,2-Dicyanocyclobuten und seine thermische Ringöffnung zum 2,3-Dicyanobutadien-1,3

Facile synthetic routes to 1,2-dicyanocyclobutene ( 3 ), cyclobutene-1,2-dicarboxylic acid ( 56 ) and derivatives thereof are presented, starting from 1,2-dicyanocyclobutane ( 1 ), a commercially available acrylonitrile cyclodimer. The favored mode of [4+2]-cycloadditions of 3 to cyclic dienes with sp³carbon atoms is the endo-addition (above 90% relative yields of adducts with endo-cyclobutane ring). Exo-cycloaddition, however, is preferred by dienes having no sp³-carbon atom (e.g. furane). Cyclisation reactions involving cis-vicinal substituents in [4+ 2]-cycloadducts afford (m.n. 2)-azapropellanes 18 , 74 and 77 . ¹H- and ¹³C-NMR. spectra of the stereoisomeric adducts are discussed in detail. The structures of the furane adducts 14 and 15 were determined by ¹H-NMR. using the shift reagent Eu(dpm)₃. Reactive butadienes 32 , 53 - 55 are obtained in high yield and purity by gasphase thermolysis (380–420°) of the correspondingly substituted cyclobutenes. 2,3-Dicyanobutadiene-l, 3 ( 32 ) gives good yields of [4 + 2]-cycloadducts with strained cycloolefines, moderate yields with vinylethers and non-activated olefins, and no adducts at all with electrophilic dienophiles (8.g. maleic anhydride, fumaronitrile). Thus, reactions of 32 are typical Diels-Alder reactions with ‘inverse electron demand’. Some of these primary [4+2]-cycloadducts ( 38 , 39 and 45 ) were dehydrogenated to new aromatic ortho-dinitriles 46 - 48 .     

Stereoselective hetero-Diels-Alder reaction of 3-(trifluoroacetyl)chromones with cyclic enol ethers: synthesis of 3-aroyl-2-(trifluoromethyl)pyridines with ω-hydroxyalkyl groups

3-(Trifluoroacetyl)chromones undergo heterodiene cycloaddition to 3,4-dihydro-2H-pyran and 2,3-dihydrofuran under mild conditions, producing novel fused pyrans with high stereoselectivity and in good yields. These pyrans were transformed into functionalized pyridines on treatment with ammonium acetate in ethanol. The structures of the endo-cycloadducts were established by ¹H NMR spectroscopy and X-ray diffraction analysis.     

Integrity of alkene stereochemistry in the Diels—Alder reaction

The Diels—Alder reaction of hexachlorocyclopentadiene and α-methylstyrene produces both exo-phenyl and endo-phenyl adducts, with the latter in preponderance. A deuterium label at the β position of the alkene provides a probe for determining whether the vicinal stereochemical relationship between groups on the alkene is retained in the adducts. From the alkene labeled 77.6±2.3% E and 22.4±2.3% Z was produced the major (endo-phenyl) isomer with 79.4±1.1% exo-d and 20.6±1.1% endo-d and the minor (exo-phenyl) isomer with 78.9±0.5% endo-d and 21.1±0.5% exo-d. Thus both adducts are produced with complete retention of alkene stereochemistry.     

Bypassing the lack of reactivity of endo-substituted norbornenes with the catalytic rectification–insertion mechanism

The catalytic 1,2-insertion polymerization of polar norbornenes (NBEs) leads to the formation of functional rigid macromolecules with exceptional thermal, optical and mechanical properties. However, this remarkable reaction is plagued by the low reactivity of the polar monomers, and most notably of those bearing a functional group in endo position. We have examined the polymerization mechanism of NBEs bearing one or two CO₂Me groups either in exo or endo position catalyzed by the so-called naked allyl Pd⁺ SbF₆^– catalyst (1). Although endo dimethyl ester of 5-norbornene-2,3-dicarboxylic acid (NBE(CO₂Me)₂) is polymerized by 1, two endo units are never inserted consecutively along the polymer chain. Indeed, 1 is a tandem catalyst which not only catalyzes the insertion of the monomer but also the isomerization of endo and exo isomers. Thus, the polymerization of endo monomers proceeds via a novel mechanism, coined rectification–insertion mechanism, whereby half of the endo monomers are rectified into exo ones prior insertion, leading to the formation of an alternating endo–exo copolymer using an endo only feedstock. With this mechanism, the lack of reactivity of endo norbornenes is bypassed, and the polymerization of predominantly endo polar NBEs bearing a variety of functionalities such as esters, imides, acids, aldehydes, alcohols, anhydrides, or alkyl bromides proceeds with catalyst loadings as low as 0.002 mol%.     

5-Nitroisocoumarins from tandem Castro-Stephens coupling—6-endo-dig cyclisation of 2-iodo-3-nitrobenzoic acid and arylethynes and ring-closure of methyl 2-alkynyl-3-nitrobenzoates with electrophiles

Reaction of 2-iodo-3-nitrobenzoic acid with arylalkynyl copper(I) reagent gave 3-aryl-5-nitroisocoumarins. Castro-Stephens coupling was followed by in situ Cu-catalysed ring-closure. ¹H NMR and X-ray crystallography showed the cyclisations to be 6-endo, contrasting with reports of 5-exo cyclisation of analogous 2-iodobenzoate esters with alkynes. Sonogashira couplings of methyl 2-iodo-3-nitrobenzoate with phenylacetylene and with trimethylsilylacetylene gave the corresponding 2-alkynyl-3-nitrobenzoate esters. With HgSO₄, the phenylalkyne underwent 6-endo cyclisation to give 5-nitro-3-phenylisocoumarin. The disubstituted alkyne esters gave 4-phenylselenylisocoumarins with PhSeCl. 5-Nitro-3-phenyl-4-phenylselenylisocoumarin shows significant sterically-driven distortion of the isocoumarin ring. Reaction of methyl 3-nitro-2-phenylethynylbenzoate with ICl gave the 4-iodoisocoumarin. Thus the nitro group tends to direct these electrophile-driven cyclisations towards the 6-endo mode.     

Thebaine Adducts with Maleimides. Synthesis and Transformations

Diels-Alder reaction of thebaine with maleimides is structurally specific and yields [7,8,3′,4′ ]-succinimido-endo-ethenotetrahydrothebaines containing N′-alkyl, cycloalkyl, aralkyl or aryl substituents. N′-[1(S)-hydroxymethyl-2-methylpropyl]-succinimido-6,14-endo-ethenotetrahydrothebaine formed in reaction of S-valinol with (7α,8α)-anhydrido-6,14-endo-ethenotetrahydrothebaine. The reduction of the adducts by LiAlH₄ afforded N′-substituted 7,8-pyrrolidino-endo-ethenotetrahydrothebaines. The reduction of fused succinimides by NaBH₄ resulted in the corresponding 2′α-hydroxylactam derivatives. O-Demethylation of the tetrahydrothebaine pyrrolidine derivatives effected by BBr₃ afforded compounds of the tetrahydrooripavine series. The O-demethylation of tetrahydrothebaine succinimide derivatives gave rise to the corresponding 6-demethyl-endo-ethenotetrahydrooripavines. Alkylation conditions were found for N′-(4-hydroxyphenethyl)-substituted tetrahydrothebaine succinimide derivatives.     

Regioselective synthesis of naphthalenes from modified Baylis-Hillman adducts via a Pd-catalyzed cyclization: 5-exo-carbopalladation, C(sp)-H activation to cyclopropane, ring-opening, and aromatization cascade

Modified Baylis-Hillman adducts having 2-bromophenyl acetonitrile moiety at the primary position underwent a Pd-catalyzed cascade reaction to provide poly-substituted naphthalene derivatives in reasonable yields. The reaction involved a sequential 5-exo-carbopalladation, C(sp³)-H activation to cyclopropane, ring-opening and concomitant aromatization processes.     

Reaction of quinoid derivatives of 4,4a-Dihydropyrido[1,2-a]-3H-benzimidazole with cyclopentadiene

Diels-Alder reaction between quinone mono-, diimines, and methylenequinone imines of 4,4a-dihydropyrido[1,2-a]-3H-benzimidazole series and cyclopentadiene proceeds endo-stereoselectively at the unsubstituted π-bond of the quinoid ring affording a mixture of diastereomeric cycloaddition adducts.     

Microwave-assisted tandem Wittig-intramolecular Diels-Alder cycloaddition. Product distribution and stereochemical assignment

The IMDA cycloadditions of 10 different ester-tethered 1,3,8-nonatrienes have been examined under controlled microwave heating (MeCN, 180 °C, 30 min), giving 90-99% yields, and the stereochemical outcome of the exo and endo adducts established together with X-ray crystal structural analysis. A microwave-assisted tandem Wittig-IMDA cycloaddition protocol has been established for a modular synthesis of the bicyclic lactones starting from α-bromoacetates of 2,4-pentadien-1-ols and α-oxo carbonyl compounds in the presence of PPh₃ and 2,6-lutidine (MeCN, 180 °C, 30 min). The overall yields of the tandem reactions are 68-80% and the stereoselectivity of the major adducts formed from E-substituted 1,3,8-nonatriene is the same as that observed for the purified 1,3,8-nonatrienes.