Dual behavior of masked o-benzoquinones in intramolecular Diels-Alder reactions. Expedient synthesis of highly functionalized cis-decalins from 2-methoxyphenols

[Reaction: see text]. The potential dual behavior as dienes and dienophiles of the diene moieties of masked o-benzoquinones (MOBs) 10a-e-12a-e, generated upon oxidation of 2-methoxyphenols 1-3 with BTIB in the presence of appropriate dienols, in their intramolecular Diels-Alder (IMDA) reactions has been examined. The IMDA reactions of MOBs 10a-d, 11a,b,d, and 12a,b,d resulted in highly functionalized oxatricyclic compounds 18a-d, 19a,b,d, and 20a,b,d, respectively, with concomitant formation of cis-decalin derivatives 21a-d, 22a,b,d, and 23a,b,d in a highly regio- and stereoselective manner. However, the MOBs 10e-12e provided exclusively oxatricyclic compounds 18e-20e. The formation of cis-decalins in these IMDA reactions illustrates the dienophilic character of MOBs, in addition to their behavior as dienes. The ratio of the two cycloadducts obtained in each reaction as a result of the dual character of MOBs depends on the nature and/or position of the substituents on both the cyclohexadienone moiety and the added 2,4-dienol. The majority of the cycloadducts resulted from the diene property of MOBs in intramolecular Diels-Alder reactions smoothly underwent Cope rearrangement to furnish cis-decalins as sole products in excellent to quantitative yields that provides a short and efficient entry to polyfunctionized cis-decalins from 2-methoxyphenols. Furthermore, the variation of dienophilic and diene characters of MOBs in the IMDA reactions with the electron-donating or electron-withdrawing substituent of both cyclohexadienone moiety and the added conjugated acyclic diene or 2,4-dienol has been studied in detail.     

Sur l'orientation et les anomalies de l'acetylation des Bz-méthoxy nitro-2 benzofurannes

4-Methoxy-, 5-methoxy- and 7-methoxy-2-nitrobenzofurans have been acetylated via the Friedel-Crafts reaction under the same reaction conditions. 2-Nitrobenzofuran does not undergo acetylation while 6-methoxy-2-nitrobenzofuran only produces decomposition products. As a result of the positive acetylation reactions, 7-acetyl-4-methoxy-, 4-acetyl-5-methoxy- and 4-acetyl-7-methoxy-2-nitrobenzofuran have been prepared. As side products in the acetylation reactions, 4-methoxy-3-(4′-methoxy-2′-nitro-7′-benzofuranyl)-2,3-dihydrobenzofuran-2-one was isolated when 4-methoxy-2-nitrobenzofuran was the starting material and, likewise, when 5-methoxy-2-nitrobenzofuran was the starting material, 3-chloro-5-methoxy-2,3-dihydrobenzofuran-2-one was obtained. Furthermore, 5-methoxy-2-nitrobenzofuran participated in an unexpected chlorination leading to 4-chloro-5-methoxy-2-nitrobenzofuran.     

Cyclische gekreuzt-konjugierte Bindungssysteme. XV. Cycloadditionen mit 5,6-Dimethyl-1,2;3,4-dibenzo- und 5,6-Dimethyl-1,2,3,4-tetraphenyl-calicen

Cycloaddition reactions of 5,6-dimethyl-1,2,3,4-dibenzo- and 5,6-dimethyl-1,2,3,4-tetraphenyl-calicene with diazo compounds, with dienes, and with dienophilic reagents are described.     

Reactivity of 1-nitronaphthalene and 1,3-dinitronaphthalene with conjugated dienes. An easy access to N-naphthylpyrroles

1-Nitronaphthalene reacts at high temperature with poor and moderately reactive dienes affording N-naphthylpyrroles while, with the same dienes, 1,3-dinitronaphthalene exhibits the dienophilic character of naphthalenic C3C4 bond producing the corresponding phenanthrenes through a classical Diels-Alder process.     

Dual behavior of masked o-benzoquinones in intermolecular Diels-Alder reactions with acyclic dienes: a rapid entry to polyfunctionalized bicyclo[2.2.2]oct-5-en-2-ones and cis-decalins

The potentiality of the masked o-benzoquinones, i.e., 6,6-dimethoxy-2,4-cyclohexadienones 5-8, to react both as dienes and dienophiles in their intermolecular reactions has been demonstrated. The masked o-benzoquinones (MOBs) 5-8 generated in situ from 2-methoxyphenols 1-4 underwent intermolecular Diels-Alder cycloadditions with acyclic 1,3-dienes 9a-e to provide bicyclo[2.2.2]octenones 10a-f-13a-f along with cis-decalin derivatives 14a-f-17a-f with regio- and stereoselectivity, except in the case of MOB 8. The formation of cis-decalins in these Diels-Alder reactions illustrates the dienophilic character of MOBs, in addition to their general behavior as dienes. The ratio of the two cycloadducts obtained in each reaction as a result of the dual character of MOBs depends on the nature and/or position of the substituents on both the cyclohexadienone moiety and the added conjugated acyclic diene. All of the cycloadducts resulted from the diene property of MOBs in intermolecular Diels-Alder reactions smoothly underwent Cope rearrangement to furnish cis-decalins as sole products in excellent to quantitative yields.     

A novel application of the Diels-Alder reaction: nitronaphthalenes as normal electron demand dienophiles

Thermal reactions between nitronaphthalenes and butadienes were studied. It was demonstrated that these reactions are capable of undergoing the normal electron demand Diels-Alder reaction, with a variety of dienes affording the phenanthrene derivatives. The influence of the extension and type of substitution was also discussed. When the electron-withdrawing activation of the naphthalenic nucleus or the donor properties of the dienes were not enough, N-naphthylpyrroles were detected as main product, suggesting that a competitive reaction would probably take place. The results clearly confirmed the dienophilic nature of nitronaphthalenic double bonds and provided an alternative procedure for phenanthrene derivatives and N-naphthylpyrroles' synthesis. The relative reactivity of the reactants and the viability of the reactions were discussed from a theoretical point of view.     

Comparison of the reactivity between 2- and 3-nitropyrroles in cycloaddition reactions. A simple indole synthesis

N-Tosyl-2-nitropyrroles react at high temperature with poorly and strongly activated dienes. They exhibit a dienophilic character similar to N-tosyl-3-nitropyrroles producing the corresponding indoles through a classical Diels-Alder process. A similar behaviour was observed in disubstituted N-tosyl-pyrroles.     

Unexpected hydrobromic acid-catalyzed C-C bond-forming reactions and facile synthesis of coumarins and benzofurans based on ketene dithioacetals

Hydrobromic acid was found to be a unique catalyst in C? C bond‐forming reactions with ketene dithioacetals. Distinctly different from other acids (including Lewis and Brønsted acids), the remarkable catalytic performance of hydrobromic acid in catalytic amounts was observed in the “acid”‐catalyzed reactions of readily available functionalized ketene dithioacetals 1 with various electrophiles. Under the catalysis of 0.1 equivalents of hydrobromic acid, the reaction of 1 with carbonyl compounds 2 a – l gave polyfunctionalized penta‐1,4‐dienes 3 or conjugated dienes 4 in good to excellent yields. The reaction tolerated a broad range of substituents on both the ketene dithioacetals 1 and the carbonyl compounds 2 . Application of this efficient C? C bond‐forming method generated coumarins 5 and benzofurans 7 under mild, metal‐free conditions by hydrobromic acid‐catalyzed reactions of 1 with salicylaldehydes 2 m – o and p‐quinones 6 a – d , respectively. A new reactive species, a sulfur‐stabilized carbonium ylide, formed depending on the nature of the counterion, and this was proposed as the key intermediate in the unique catalysis of hydrobromic acid.     

Cyclic vinyl p-tolyl sulfilimines as chiral dienophiles: Diels-Alder reactions with furan and acyclic dienes

The dienophilic behavior of the sulfilimine 2, synthesized from (Z)-3-p-tolylsulfinylacrylonitrile 1, in its Diels-Alder reactions with furan and acyclic dienes has been investigated. A complete pi-facial selectivity for 2, opposite to that observed from its precursor 1, is the main feature of all these cycloadditions. Moreover, the high exo selectivity observed in reactions of 2 with furan (not observed for 1) contrasts with the almost complete endo selectivity with other cyclic and acyclic dienes. Additionally, the opposite regioselectivities obtained for 2 with Dane's diene and 1-substituted butadienes (not observed for 1) are also noteworthy. This behavior allows dienophiles 1 and 2 to be considered as complementary precursors from a synthetic point of view.     

Phosphine-Catalyzed Annulations between Modified Allylic Derivatives and Polar Dienes and Substituent Effect on the Annulation Mode

in this work, the phosphine-catalyzed annulation reactions between modified allylic derivatives and polar 1,1-dicyano-1,3-dienes have been studied. In the catalysis of PPh3 （20 mol%）, a [4 ＋ 1 ] annulation reaction is realized between a series of l,l-dicyano-2,4-diaryl-1,3-dienes and ethoxycarbonyl-activated allylic acetate, producing polysubstituted cyclopentenes in modest to excellent yields. It is also observed that the substituents of both 1,3-dienes and allylic derivatives have a significant influence on the annulation mode： under the catalysis of PPh3 or PBu3 （20 mol%）, regioselective [3 ＋ 2] annulation products are formed from differently substituted substratcs.     

Rhodium-catalyzed cascade reactions of triazoles with organoselenium compounds – a combined experimental and mechanistic study

Herein, we report on our studies on the reaction of organoselenium compounds with triazoles under thermal conditions using simple Rh(ii) catalysts. These reactions do not provide the product of classic rearrangement reactions. Instead two different cascade reactions were uncovered. While allyl selenides react in a cascade of sigmatropic rearrangement and selenium-mediated radical cyclization reaction to give dihydropyrroles, cinnamyl selenides undergo a double rearrangement reaction cascade involving a final aza-Cope reaction to give the product of 1,3-difunctionalization. Theoretical and experimental studies were conducted to provide an understanding of the reaction mechanism of these cascade reactions. The former provide an important insight into fundamental question on the nature of the ylide intermediate in rearrangement reactions and reveal that organoselenium compounds take up multiple roles in rearrangement reactions and mediate a free ylide reaction mechanism.

Herein, we report on our studies on the reaction of organoselenium compounds with triazoles under thermal conditions using simple Rh(ii) catalysts.     

Au-catalyzed synthesis of (1Z,3E)-2-pivaloxy-1,3-dienes from propargylic pivalates

Propargylic pivalates with electronically unbiased internal alkynes are selectively transformed into (1Z,3E)-2-pivaloxy-1,3-dienes containing various functionalities. The unusual selectivity of 1,2-acyloxy migration over the structurally preferred 3,3-rearrangement is realized. This reaction is highly stereoselective and offers rapid access to dienes for one-pot intra-/intermolecular Diels-Alder reactions either under thermal conditions or with Lewis acid catalysis.     

A theoretical study of the mechanisms and regiochemistry of the reactions of 5-alkoxyoxazole with thioaldehydes,nitroso compounds,and aldehydes

A theoretical study based on B3LYP/6-31G calculations has been applied to the mechanisms and regiochemistry of reactions of 5-alkoxyoxazole with thioaldehydes, nitroso compounds, and aldehydes. All three reactions adopt similar mechanisms, which start with Diels-Alder (DA) reactions, followed by either a novel, concerted ring-opening-ring-closing (RORC) step to transfer the DA adduct to 2-alkoxycarbonyl-3-thiazoline and 2-alkoxycarbonyl-3-oxazoline for thioaldehydes and aldehydes, respectively, or stepwise ring-opening and ring-closing steps to generate 1,2,4-oxadiazoline for nitroso compounds. The reactions of 5-alkoxyoxazole with thioaldehydes and nitroso compounds can be conducted under thermal reaction conditions due to the 10 kcal/mol activation barriers for their rate-determining DA reactions. By contrast, the reaction of 5-alkoxyoxazole with aldehydes cannot take place under thermal conditions, since this bimolecular reaction has the rate-determining RORC transition state higher than the reactants by 30.5 kcal/mol.     

Domino reaction to functionalized 2-hydroxybenzophenones from electron-deficient chromones and 1,3-dicarbonyl compounds

A base-promoted one-pot tandem reaction sequence has been developed to transform electron-deficient chromone-fused dienes 1 and 1,3-dicarbonyl compounds 2 to functionalized 2-hydroxybenzophenones 3 under mild conditions. This domino process, which involves multiple reactions, including Michael addition/cyclization/elimination, serves as an efficient, economic, and eco-friendly method for the construction of diversified 2-hydroxybenzophenone scaffolds without a transition-metal catalyst and inert atmosphere.     

Synthesis and Diels-Alder Reactions of a New Kind of Chiral Dienophiles: Cyclic Vinyl-p-tolylsulfilimines

A new kind of chiral dienophiles, cyclic vinyl-p-tolylsulfilimines (2a and 2b), were obtained from the corresponding (Z)-sulfinylacrylonitriles with HBF(4) and methanol. The asymmetric Diels-Alder reaction of optically pure 2a with cyclopentadiene under mild thermal or catalyzed conditions afforded only the endo-4a adduct with complete endo and pi-facial selectivities. The ability of the sulfilimine moiety to enhance the dienophilic reactivity of the double bond is similar to that of the sulfinyl group.     

Solid-supported nitroso hetero Diels-Alder reactions. 1. Acylnitroso dienophiles: scope and limitations

Polymer-supported acylnitroso dienophiles were prepared and used in hetero Diels-Alder (HDA) reactions with a variety of dienes. The transient acylnitroso dienophiles were prepared in situ from immobilized hydroxamates, which were attached to solid supports via several linkers each cleavable by different cleavage reagents, and served for the synthesis of both N-unsubstituted and N-derivatized HDA adducts. Model compounds were used to (i) optimize reaction conditions for solid-supported HDA reactions, (ii) evaluate the outcome of the reactions with various dienes, (iii) compare relative reactivities of dienes, and (iv) assess the stability of HDA adducts toward cleavage conditions typically used in solid-phase syntheses. Cleaved products were submitted to biological assays, and the results are reported. The accompanying paper, focused on complementary arylnitroso HDA reactions, includes a comparison of both HDA reactions.     

Benzofuran derivatives. Part 3 On the reactivities of the intermediates in benzofuran synthesis

3-Methyl-5-nitrobenzofuran ( 2 ) and 3-methyl-5-nitrobenzofuran-2-carboxylic acid ( 3 ) were obtained by heating 2-acetyl-4-nitrophenoxyacetic acid ( 1 ) with various bases in acetic anhydride. It appeared that 3-hydroxy-3-methyl-5-nitro-2,3-dihydrobenzofuran-2-carboxylic acid ( 4 ) was the intermediate in the benzofuran synthesis. The properties of 4 were examined under various conditions. Using strong bases such as triethyl-amine in place of sodium acetate, 3-methyl-5-nitrobenzofuran-2-carboxylic acid ( 3 ) was obtained exclusively. However, in the presence of acetic acid in the reaction mixture 3-methyl-5-nitrobenzofuran ( 2 ) was obtained in good yield. The reaction pathways for the formation of 2 and 3 are discussed.     

Cationic copolymerization of isobutene and conjugated small-ring dienes

1-Methyl-3-methylenecyclobutene (MMCB) and 1,2-dimethylenecyclobutane (DMCB) copolymerized readily with isobutene with aluminum chloride as initiator in methyl chloride solution at temperatures from ?95 to ?78°C. No polymers were obtained with methylenecyclobutene (MCB) under similar conditions. The copolymerization of MMCB with isobutene took place through a 1,5-addition reaction while that of DMCB through both 1,2- and 1,4-addition reactions. Large amounts of gel were present in the copolymers obtained from DMCB if the reaction was carried to high conversion. The commonly observed effects of dienes (i.e., rate retardation and molecular weight depression) on cationic copolymerization reactions were observed but to a much higher degree with these small ring dienes. The thermal crosslinking behavior of the resulting copolymers was investigated. In conjunction with the copolymerization studies, homopolymers of MMCB, DMCB, and 3,3-dimethyl-1-isopropylidene-2-methylenecyclobutane (IMCB) were prepared and their chemical structures examined.     

Sequential aza-Baylis-Hillman/ring closing metathesis/aromatization as a novel route for the synthesis of substituted pyrroles

A new route to diverse 2-substituted-3-methoxycarbonyl pyrroles has been developed. Diverse SES protected alpha-methylene beta-aminoesters were obtained by a 3-component aza-Baylis-Hillman reaction. Diversity arose from the aryl aldehydes which can be used in this reaction. N-Alkylation with allyl bromide under mild conditions provided the corresponding dienes. These substituted dienes were cyclized by ring closing metathesis at room temperature or under microwave-activation with Grubbs-type II catalyst to yield SES-protected pyrroline intermediates. The final pyrroles were obtained by base-promoted dehydrodesulfinylation/aromatization. The scope of each of these reactions was explored.     

Diels-Alder Reactions of Ethyl α-Bromoacrylate with Open-chain Dienes——Synthesis of Ethyl 1,3-/1,4-Cyclohexadienecarboxylates

The Diels‐Alder reactions of ethyl α‐bromoacrylate 1 with open‐chain dienes 2 were conducted under thermal or Lewis acid‐catalysis conditions. In most cases, the cyclic adducts of 1‐bromocyclohex‐3‐enecarboxylates 3 were formed in high yields with good regio‐ and stereoselectivity. Subsequent E2‐elimination by treatment with DBU provided the corresponding 1,3‐ or 1,4‐cyclohexadienecarboxylates depending on the relative configuration of the products. Starting from myrcene (7‐methyl‐3‐methyleneocta‐1,6‐diene) the reaction sequence afforded the ester precursor of Georgywood with good yields.