Diels—Alder-Reaktionen am Thebain mit cyclischen Azodienophilen

Zusammenfassung Diels-Alder-Reaktion von Thebain mit einer Reihe von cyclischen Azo-oxoverbindungen lieferte die erwarteten Addukte. Hydrierung der aus der Addition resultierenden Äthenobrücke führte zu den Äthanoverbindungen. Die Carbonylgruppen des Thebain—3-Indazolon-Addukts und der entsprechenden hydrierten Äthanoverbindung konnten durch LiAlH₄-Reaktion zur Methylengruppe reduziert werden.

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Diels—alder reactions of thebaine with cyclic azodienophiles

Diels-Alder reaction of thebaine and a number of cyclic azooxo dienophiles gave the corresponding adducts. Hydrogenation of the etheno bridge of the adducts resulting from addition yielded the ethano derivatives. The carbonyl groups of the thebaine—3-indazolone adduct and its hydrogenated ethano derivative were reduced by LiAlH₄ reaction to the methylene group.

     

The Synthesis of Naphthosultine and Benzodisultines and Their Pyrolysis with Dienophiles: Studies on o‐Naphthoquinodimethane and Bis‐o‐Quinodimethane

Sealed tube reactions of the naphthosultine 8 with a series of electron‐deficient dienophiles (fumaronitrile, N‐phenylmaleimide, dimethyl fumarate, and dimethyl acetylenedicarboxylate) in toluene at 180 °C gave corresponding 1:1 cycloadducts 11–14 in various amounts along with rearranged naphthosulfolene 7 in 67–95% yields. The reaction of 1,2,4,5‐tetra(bromomethyl)benzene with Rongalite (sodium form aldehyde sulfoxylate) and tetrabutylammonium bromide in DMF gave benzodisultines 17 and 18 in a combined yield of 56%. Sealed tube reactions of benzodisultines 17 and 18 with a series of dienophiles in xylene at 200 °C gave corresponding 1:1 and 1:2 cycloadducts 20–27 . The results suggested that thermal extrusion of sulfurdioxide from these sultines led to either o‐naphthoquinodimethane 6 (from 8 ) or bis‐o‐quinodimethane 19 (from 17 and 18 ); sub sequent trapping of these reactive intermediates by dienophiles and SO₂ gave various 1:1 and 1:2 Diels‐Alder ad ducts in modest to excellent yields.     

Syntheses of Amino-dideoxyallose and Amino-deoxyribose Derivatives Using Acylnitroso Dienophiles

The dimethyl acetals 4 of (E)-2,4-pentadienal and of (E,E)- and (E,Z)-2,4-hexadienals undergo regio- and stereospecific cycloaddition reactions with in-situ-generated acylnitroso dienophiles 5a and 5b , leading thereby to the corresponding dihydrooxazines 7a–d and 8c–d . cis-Glycolization of these latter adducts stereospecifically gave the dihydro derivatives 9a–d and 10d which, after sequential hydrogenolysis, deacetalization, and instant cyclization, led to the aminodeoxyribose derivatives 17a, 17f , and 18 , and to the amino-dideoxyallose compounds 17c and 17h . These piperidino-deoxysugar derivatives exhibit a strong anomeric effect, i.e. OH? C(1) is always axial, which is explained in terms of a n_N(π)-σ*(C? OH) orbital compression, as compared to the less pronounced one in the more classical pyranose series.     

Camphor-Derived N-Acryloyl and N-Crotonoyl Sultams: Practical Activated Dienophiles in Asymmetric Diels-alder Reactions. Preliminary Communication

Starting from (+)-camphor-10-sulfonyl chloride ( 5 ), the crystalline sultam 8 was easily prepared. Lewis-acid-promoted Diels-Alder additions of the crystalline N-acry-loyl and N-crotonoyl derivatives 9 and 10, respectively, to cyclopentadiene and 1,3-butadiene at ?130 to ?78° furnished adducts 11 , 12 and 17 with high chiral efficiency. Crystallization of the adducts and nondestructive removal of 8 gave either alcohols 13 , 14 and 18 ir acid 19 in 99% enantiomeric purity. The sense of induction was reversed on using the enantiomer of 8 as the auxiliary. The structure of 10 was established by X-ray diffraction analysis.     

Reactions of 2-aminooxazoles and 2-aminothiazoles with dienophiles. Isolation of stable diels-alder adducts

Room temperature reaction of 2-aminooxazole 1 and its 4- and 4,5-substituted derivatives, with dimethyl acetylenedicarboxylate gave good yields of Diels-Alder adducts 2 , isolated as stable crystalline compounds. A competing process produced oxazole[3,2-a]pyrimidines 3 , also in good yield. Minor products were also identified. 2-Amino-4-methylthiazole ( 6 ) reacted in a similar manner and gave the Diels-Alder adduct 7 and a thia-zolo[3,2-a]pyrimidine 8 as main products with a lesser amount of a thiazole [3,2-d][1:3]diazepine ( 9 ). The aminooxazoles reacted with olefinic dienophiles to give pyridine derivative, formed by breakdown of the original unstable adducts.     

Diels–Alder Reactions of Novel (1′‐Arylallylidene)cyclopropanes with Heterodienophiles

Palladium‐catalyzed cross‐coupling of various aryl iodides with bicyclopropylidene provided isolable (1′‐arylallylidene)cyclopropanes, which reacted with a number of carbonyl compounds in the presence of Eu(fod)₃ under high pressure to furnish oxaspiro[2.5]octene derivatives in moderate to good yields (22–69 %). The reactions of the allylidenecyclopropanes with two azo compounds as dienophiles afforded diazaspiro[2.5]octenes in high yields (82 and 99 %) even at ambient pressure. When treated with nitrosobenzene, two of the allylidenecyclopropanes gave the Diels–Alder adducts in up to 83 and 40 % yield. 2,5‐Diiodo‐p‐xylene coupled twice with bicyclopropylidene, and the product underwent a twofold Diels–Alder reaction with nitrosobenzene to produce the bis(spirocyclopropaneoxazine) derivative in 88 % yield. This overall transformation can be brought about in a one‐pot, two‐step operation by addition of the nitrosoarene to the reaction mixture immediately after formation of the allylidenecyclopropanes to furnish various 5‐oxa‐4‐azaspiro[2.5]oct‐7‐ene derivatives in 22–77 % yield. The coupling of methyl bicyclopropylidenecarboxylate with 2,6‐dimethylphenyl iodide produced a mixture of very stable regioisomeric allylidenecyclopropane derivatives in 90 % yield. The reaction of this mixture with N‐phenyltriazolinedione gave a corresponding mixture of the spirocyclopropanated heterobicycles in 61 % yield.     

Effects of Remote Substitution on the Photo-oxidation of Exocyclic s-cis-Butadienes Grafted onto Bicyclo [2.2.1]heptanes. Thermal and Rhodium Catalyzed Rearrangements of 3,6-Dihydro-1,2-dioxines

The rates of photo-oxidation of exocyclic S-cis-butadienes grafted onto bicyclo-[2.2.1]heptanes and 7-oxabicyclo[2.2.1]heptanes ( 1–6 ) are dependent upon remote modifications of the bicyclic skeletons. They correlate with the rates of Diels-Alder additions of these dienes to strong dienophiles. The 2,3-dimethylidenenorbornane ( 1 ), 5,6-dimethylidene-2-norbornene ( 2 ) and 2,3-dimethylidene-7-oxanorbornane ( 3 ) gave the corresponding endo-peroxides (3,6-dihydro-1,2-dioxines) 7–9 in good yield. The 2, 3, 5, 6-tetramethylidene-7-oxanorbornane ( 4 ) gave the mono-endo-pe-roxide 6 , the latter did not react with a second equivalent of oxygen. Similarly, 5, 6-dimethylidene-7-oxa-2-norbornene ( 5 ) was unreactive toward photo-oxidation. Thermal isomerization of the endo-peroxides 7 and 9 gave, the trans-diepoxides 10 and 14 , respectively, with high stereoselectivity. The endo-peroxides 6 , 7 and 9 were cleanly isomerized into the corresponding α, β-unsaturated γ-hydroxy aldehydes in the presence of catalytic amounts of Rh₂(CO)₄Cl₂.     

Synthesis of heterocyclic compounds from 2-phenyl-1,2,3-triazole-4-formylhydrazine

2-Phenyl-1, 2, 3-triazole-4-formylhydrazine (2) was prepared by hydrazinolysis of the corresponding ester 1. Reaction of 2 with CS₂/KOH gave the oxadiazole derivatives (3) which via Mannich reaction with different dialkyl amines furnished 3-N, N-dialkyl derivatives (4a–c). Also, condensation of 2 with appropriate aromatic acid in POCI₃ yielded oxadiazole derivatives (5a–c), or with aldehydes and ketones afforded hydrazones (6a–c). Cyclization of (6a–c) with acetic anhydride gave the desired dihydroxadiazole derivatives (7a–c). On the other hand, reaction of dithiocarbazate (8) with hydrazine hydrate gave the corresponding triazole derivative (9) which on treatment with carboxylic acids in refluxing POCI₃ yielded s-triazole [3, 4–b]-1, 3, 4-thiadiazole derivatives (10a–b). The structures of all the above compounds were confirmed by means of IR, ¹H NMR, MS and elemental analysis.     

Cycloaddition of 2H-Pyran-2-thiones with Nitroso Derivatives. An Unexpected Cycloaddition-Rearrangement Reaction

Reaction of pyran-2-thiones 4 with nitroso derivatives led surprisingly to type- 8 ( 19 ) adducts which proved to be isomeric with the initially expected primary Diels-Alder cycloadducts 5 . Methyl 2-thioxo-2H-pyran-5-carboxylate ( 4f ), when reacted with nitrosobenzene at -10°, led quantitatively to the thieto-oxazine intermediate 13 , which turned out to be the cornerstone of the complex cycloaddition-rearrangement 5 → 8 reaction pathway (Scheme 3). Differential scanning calorimetry, as performed for the 18a → 19a conversion, permitted to demonstrate that this multistep rearrangement is overall a higly exothermal process, the final product 19 representing an energy-sink along this reaction pathway.     

Synthetic transformations of higher terpenoids: XXIII. Synthesis of diterpenoid-based dihydroisoindolones

Vilsmeier-Haak reaction of phlomisoic acid methyl ester gave a mixture of 15- and 16-formyllabdanoids. In addition, methyl 2-formyldodecahydrophenanthro[1,2-b]furan-6-carboxylate was isolated, and its structure was determined by X-ray analysis. Reductive amination of 16-formyllabdanoid with benzylamine or α-amino acid methyl esters led to the formation of labdanoid furfurylamines which reacted with maleic anhydride to produce N-substituted 4-oxo-10-oxa-3-azatricyclo[5.2.1.0^1,5]dec-8-ene-6-carboxylic acids. Acylation of labdanoid furfurylamines with (E)-but-2-enoyl chloride afforded the corresponding unsaturated amides which were converted into 10-oxa-3-azatricyclo[5.2.1.0^1,5]dec-8-en-4-ones via intramolecular Diels-Alder reaction. Treatment of the oxa adducts with boron trifluoride-diethyl ether complex gave dihydroisoindol-1-one derivatives containing a diterpene fragment.     

Photochemische Umwandlungen, 45. Mitteilung [1] die 3σ → 3π-route zu oxepin-derivaten

Exemplifying with the 4.5-dicarbomethoxy oxepin 6a the authors describe an oxepin synthesis from furanes and acetylenic dienophiles via Diels-Alder reaction ( 4a ), photochemical oxanorbornadiene-oxaquadricyclane transformation ( 4a → 5a ), and thermal 3σ → 3π opening of the highly strained oxaquadricyclane 5a . With dimethylacetylenedicarboxylate, methylpropiolate, maleic anhydride, and di-methoxycarbonyl-oxanorbornadiene ( 4a ) 5a yields the 1:1 adducts 19a, 19b, 22, 23 and 26 (unstable) by strictly stereospecific addition to the α-positions of the oxygen bridge. With the same dienophiles the oxepin 6a reacts only through its valence-tautomeric benzene-oxide form 7a giving stereospecifically 27, 29, 30 and 31 . No definite conclusions are drawn with regard to the mechanistic implications of the photostep 4a → 5a , the thermal 3σ → 3π-transformation 5a → 6a/7a , and the bishomofurane cycloaddition reactions. Scope and limitations of this oxepin synthesis are briefly discussed.     

From 1-(Silyloxy)Butadiene to 4-Amino-4-Deoxy-DL-Erythrose and to 1-Amino-1-Deoxy-DL-Erythritol Derivatives via Hetero-Diels-Alder Reactions with Acylnitroso Dienophiles

Acylnitroso dienophiles 4 reacted instantly with 1-(silyloxy)butadiene 5α and led in good yield to the regioisomeric cycloadducts 6 (major) and 7 (minor; Scheme 2, Table 1). cis-Hydroxylation of these primary cycloadducts with OsO₄ (catalyst) occurred stereospecifically and in high yield (→ 8 and 9 , resp.; Scheme 2). It was followed by reductive ring cleavage to give either 1-amino-1-deoxy-DL -erythritol or 4-amino-4-deoxy-DL -erythrose derivatives 10 and 14 , respectively, depending on the nature of the reducing agent (Schemes 3 and 4).     

Ring closure of 1-[4-(imidazol-1-yl)phenyl]-3-phenyl-2-propen-1-one derivatives to potential biologically active compounds

1-[4-(Imidazol-1-yl)phenyl]-3-phenyl-2-propen-1-one 1 reacted with acetone cyanohydrin, ethyl phenylacetate and cyanoacetamide to give the adducts 2, 8 and 10 respectively. Action of hydrazine hydrate on both the γ-ketonitrile 2 and the corresponding γ-ketoacid 4 led to pyridazine derivatives 3 and 5 . 4,5-Dihydropyridazinone 5 was dehydrogenated by the action of bromine in acetic acid to give pyridazinone 6 . Cyclization of acid 8 in acetic medium resulted in α-pyrone 9 . Cyanopentanamide 10 was converted with hydrochloric acid into δ-ketoacid 13 which led to α-pyrone 14 via an intramolecular dehydration. Refluxing 10 in the presence of acetic acid and ammonium acetate gave 3,4-dihydropyridone 11 which was dehydrogenated to produce pyridone 12 .     

Stereospecificity of Diels–Alder Reactions Validated Using Ab Initio Calculations: Synthesis of Novel Coumarin and Phenanthridine Derivatives

A new series of coumarin derivatives (2–5) was synthesized by reaction of phenylsulfonylacetonitrile (1) with 2-hydroxy-1-naphthaldehyde and/or salicyaldehyde. Compounds 3 and 5 were converted to the corresponding phenanthridine analogs 6 and 7, respectively. Compound 9a was treated with different dienophiles to furnish the endo adducts of compounds (11a–d) rather than the exo adducts. Ab initio calculations at the Hartree-Fock (HF) level using the basis set 6-31 G (d,p) was used to study and validate the stereospecificity of compounds 11a–d and showed clearly that the endo adducts were thermodynamically favorable. PM3 parameters also showed that the endo adducts are thermodynamically and kinetically favorable. Tetrahydrobenzochromenone (11) was synthesized and allowed to react with different aromatic diazonium salts to give the corresponding 4-arylazo derivatives (13), which were converted to the corresponding diazaindenophenanthrene derivatives (14) by reaction with o-diamines.     

Participation of Non-Conjugated Double Bonds in Diels-Alder Reactions. A kinetic study of the addition of tropone to norbornens

A kinetic study of Diels-Alder additions between norbornene derivatives acting as dienophiles and the dienes tropone, perchlorocyclopentadiene and 9,10-dimethylanthracene is presented. The results suggest that tropone thereby acts as an electron acceptor, classifying these reactions then as Diels-Alder additions with ‘inverse electron demand’. The role of non-reacting double bonds was investigated using 7-alkylidenorbornene derivatives as dienophiles. These show comparable reactivity in ‘normal’ but enhanced reactivity in ‘inverse electron demand’ Diels-Alder additions. This outcome is interpreted in terms of frontier orbital interactions between the reactants using photoelectron spectroscopical results as a basis for the qualitative perturbation treatment. It is suggested that the enhanced reactivity in the case of the 7-alkylidene derivatives does not necessitate the consideration of a direct (‘through-space’) participation of the non-reacting double bond.     

Stereospecific Synthesis of 2-Oxazinyl-4-oxoazetidinecarbamates Starting from a 1,2-Diazepine. A new type of intramolecular transbenzoylation

Azeitidinodiazepines 4b and 4c react with acylnitroso dienophiles 5a–c , specifically from their convexe α-side, but in a non-regiospecific way, leading thereby stereospecifically to the expected adducts 6a–d and 7a–d . The three-dimensional structures of 6a and 7a were determined by X-ray analyses which corroborated their NMR data. OsO₄ cis-glycolization occurred in good yield with the inverse adducts 7a and 7e and led to the rearranged products 10 . These latter ones result from an intramolecular N- to O-transbenzoylation of the short-lived intermediates 9 followed by fragmentation of the animal function. X-Ray analysis of 7a showed the N(10) atom to be pyramidal, a result which demonstrates that it does not have any pronounced benzamide character; otherwise no such N- to O-transbenzoylation would have taken place. Structure and relative configuration of 10a were ascertained by X-ray analysis which confirmed its NMR data as well as the stereochemical outcome of its formation.     

Studies on sulfinato-dehalogenation: XII. Sodium dithionite-initiated addition of N,N-diethyliododifluoroacetamide to multiple bonds

N, N-deithyl-iododifluoroacetamide 1 reacted with alkenes, alkynes in aqueous acetonitrile solutions of sodium dithionite and sodium hydrogen carbonate at room temperature to give the corresponding adducts, thus constituting a new method for introducing the CF₂ group into organic molecules. Compound 1 reacted with conjugated olefins 2b, c to afford the iodine-free adducts 7b, c. The adducts 3d—f, from addition of 1 to alkenes 2d—f, could be converted into α,α-difluoro-γ-lactones 5d—f by treatment with silica gel. Compound 1 reacted with ethyl vinyl ether 2i to give aldehyde 8, and perfluoroalkyl or polyfluoroalkyl iodides reacted similarly. A radical mechanism was proposed for the addition reaction. Under the same condition, N,N-diethyl-bromodifluoroacetamide produced only the corresponding sulfinate Et₂NC(O)CF₂SO₂Na.     

Diels-Alder-Reaktionen von 2,4-Bis{[(tert-butyl)dimethylsilyl]oxy}-3-aza-1,3-pentadien mit Heterodienophilen

Diels-Alder Reactions of 2,4-Bis{[(tert-Butyl)dimethylsilyl]oxy}-3-aza--1,3-pentadien with Heterodienophiles The 2,4-bis{[(tert-butyl)dimethylsilyl]oxy}-3-aza-1,3-pentadien( 2 ) reacts via the Diels-Alder adducts 3 , 6a-c , and 8a , b , which cannot be isolated, giving the triazines 4 , 7a-c , and the oxadiazines 9a , b . The hydrolysis of 4 in MeOH affords the N-acetyl-acetamid derivative 5 . The formula of 9a is proven by an X-ray-structure analysis.     

Synthesis of main‐chain hydrogen‐bonded supramolecular liquid crystalline complexes: The effects of spacer on thermal behavior of mesophase

Two series of difunctional proton acceptors, stilbazole derivatives 4a – c and 6a – c with different spacers, oligo(methylene) and oligo(ethylene glycol), respectively, were synthesized. Hydrogen‐bonded polymeric complexes 4 / 7 and 6 / 7 and trimeric complexes 4 / 8₂ and 6 / 82 ( 7 and 8 are aromatic dicarboxylic acids and monocarboxylic acids, respectively) were prepared, and their liquid crystallinity was examined. The effects of the spacer in 4 , 6 , and 7 and the terminal group in 8 on the thermal behaviors of hydrogen‐bonded complexes were investigated using differential scanning calorimetry and polarizing optical microscopy. X‐ray diffraction at elevated temperatures was used to verify liquid crystal phases. The study showed that the phase transition temperatures for isotropic to nematic (T_I–Ns) of polymeric complexes 4 / 7 and 6 / 7 in general decreased with the increase in length of spacer in the corresponding proton donors 7 . The increase in length of the proton acceptors 6 led to a drop of T_I–Ns of the corresponding complexes 6 / 7 ; however, the T_I–Ns of complexes 4 / 7 did not show any correlation with the spacer length in 4 . In contrast, the increase in length of the terminal group in 8 resulted in a slight decrease in T_I–Ns of trimeric complexes 4 / 8₂ , but had a negligible effect on the T_I–Ns of 6 / 8₂ because of the presence of the more flexible spacer in the proton acceptors 6 . © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4731–4743, 2005     

A new domino reaction based on [4+2]-cycloadditions of pyrido[1,2-a]pyrazines with azadienophiles

The reaction of pyrido[1,2-a]pyrazines 1 with nitroso compounds 2 provides pyridyl substituted 1,2,4-triazinones 4 via a domino reaction which involves a cycloaddition and a ring transformation reaction. The intermediate and regioselective formed oxadiazines 4′ were trapped by complexation yielding the (CO)₄Mo-complex 5. Derivatives of diazene such as N-phenyltriazolindione 6a , phthalazinedione 6b or esters of azodicarboxylic acid 6c-6f reacted with 1 to give different derivatives of 1,2,4-triazine 7a-f . The use of oxygen gave oxadiazinones 8 .