Synthesis and thermolysis of tetrasubstituted cyclopropenes

Photolysis of 5-benzyl-2-methoxy-2,5-dimethyl-³-1, 3,4-oxadiazoline and of the 5,5-dibenzyl analogue with 300-nm light afforded 1-phenyl-2-diazopropane and 1,3-diphenyl-2-diazopropane, respectively. The diazoalkanes were intercepted, in situ, with dimethyl acetylenedicarboxylate to afford 3-benzyl-4,5-bis(methoxycarbonyl)-3-methyl-3H-pyrazole and 3,3-dibenzyl-4,5-bis(methoxycarbonyl)-3H-pyrazole, respectively. Those pyrazoles are short-lived under the reaction conditions and undergo two major reactions. Photolysis prior to rearrangement affords the corresponding 3,3-dialkyI-1,2-bis(methoxycarbonyl)-cyclopropenes. Thermal 1,5-benzyl migration converts the two 3H-pyrazoles in part into the corresponding 4H-pyrazoles, which undergo photolysis to 2,3-dialkyl-1,3-bis(methoxycarbonyl)cyclopropenes.Thermolysis of the 3,3-dialkyl-1,2-bis(methoxycarbonyl) cyclopropenes affords conjugated dienes, presumably through the sequence cyclopropene vinyl carbene diene. The stereochemistry of the dienes was determined and a mechanism consistent with that stereochemistry is proposed.The 2,3-dialkyl-1,3-bis(methoxycarbonyl)cyclopropanes are very stable under conditions that convert isomeric 3,3-dialkyl-1,2-bis(methoxycarbonyl)cyclopropenes to conjugated dienes. It is proposed that the effect of substitution pattern on the thermolysis rate constants is the result of combined ground state and transition state factors.     

Unprecedented Cobalt‐Catalyzed Isomerization Reactions to Single Skipped 2,4,7‐Trienes Applied in the Synthesis of Urushiol

The cobalt‐catalyzed isomerization of 1,3‐dienes to 2Z,4E‐dienes was realized for the very challenging substrates with an additional double bond in the side chain. An isomerization to the conjugated 3,5,7‐triene derivative was not observed, which is in stark contrast to observations with many other isomerization catalysts. Accordingly, the synthesis of the natural product urushiol, which has a sensitive 2Z,4E,7Z‐triene subunit in the side chain, was investigated. The O‐protected urushiol derivative was generated selectively without isomerization to the conjugated 3,5,7‐triene or Z/E‐isomerization of the double bond at position 7.     

Valenzisomerisierung von cis-Dienonen,II. 5-Phenylpenta-2, 4-dienaldehyde [1]

The 5-Phenylpenta-2,4-dienaldehydes 4 , and 7 , show an uncatalized cis-trans-isomerization of the 4,5-double bond above 70 °C. The negative value of the activation entropy for these reactions points to the formation of the bicyclic valence isomeric 2H-Pyrans 5 and 8 respectively in the rate determining step. Intermediate 5 can be trapped as its tetracyanoethylene cycloadduct 11 . The cis-trans isomeric 1,6-diphenyl-hexa-1,3,5-trienes 12a and 12b undergo above 150° a disrotatory ring closure to the bicyclic dienes 13 and 14 respectively.     

Potential use of secondary products of the agri-food industry for topical formulations and comparative analysis of antioxidant activity of grape leaf polyphenols

The aim of the present study was to develop a phytocosmetic using Vitis waste by-products, for use as a topical formulation for skin protection against ultraviolet radiation damage. The study also evaluates the free radical scavenger activity of the crude extracts of dried leaves of Vitis vinifera and Vitis labrusca, as well as the anthocyanins, flavonoid fraction and isolated compounds. Next, release and permeation studies of hydrogels were performed using Franz-type diffusion cells. Flavonoid acted more intensively in TRAP and conjugated dienes antioxidant assays, whereas anthocyanins had higher antioxidant activity in hydroxyl and nitric oxide assay. Only quercetin-3-O-glucuronide (5) was released from hydrogels, and the flavonoid retention in porcine ear skin after eight hours of permeation was below of limit of quantification for this compound. The polyphenols present in Vitis are capable of absorbing UV and visible light, justifying their potential as sunscreens for the development of a phytocosmetic.     

Utilisation d'ylides du phosphore en chimie des sucres. XVIII Synthèse de furannoses à insaturation conjuguée. Communication préliminaire

Several sugars with conjugated unsaturation (dienes or α, β-unsaturated carbonyl compounds) have been synthesised by use of Wittig reactions. Keto-sugars bearing a carbonyl group α to a furanose ring are prone to undergo an elimination leading to conjugated unsaturated systems. This constitutes a novel kind of side-reaction in the application of Wittig reactions to carbonyl sugars. The synthesis of a new kind of acetylenic sugar is also described.     

(2E)-4,4-Dimethoxy-2-butenal in the Synthesis of Conjugated Dienes and Dienals

Using (2E)-4,4-dimethoxy-2-butenal as starting compound, methods were developed for synthesis of (2E,4E)- and (2E,4Z)-dimethoxyalkadienes. Deacetalization of the latter gives with high yield the corresponding dienals which are naturally occurring compounds and also synthons for preparation of conjugated dienes as key compounds for building up other natural products.     

The reduction and hydrolysis of some 7,7-diethylpyrazolo[1,2-a]-pyridazine-6,8(7H)dione derivatives

The chemistry of several of the Diels-Alder adducts formed by the reaction of 4,4-diethylpyrazoline-3,5-dione ( 1 ) with conjugated dienes was studied with respect to reduction (hydride and catalytic) and reaction with base. Reaction of the 2,3-dimethyl-1,3-butadiene adduct with lithium aluminum hydride followed by hydrogenation gave 1,3,5,6,7,8-hexahydro-cis-endo-6,7-dimethyl-2,2-diethylpyrazolo[1,2-a]pyridazine ( 11 ). Attempted conversion of this compound to 3,3-diethyl-cis-7,8-dimethyl-1,5-diazacyclononane ( 12 ) gave instead a compound which has been tentatively identified as N-(2,3-dimethyl-4-aminobutyl)-2-ethyl-2-methylbutanaldimine ( 14 ). Lithium aluminum hydride reduction of 4,4-diethylpyrazolidine-3,5-dione ( 22 ) or the adducts formed from 1 and cyclopentadiene or 1,3-cyclohexadiene gave good yields of 4,4-diethylpyrazolidine ( 21 ). This later reduction gave a new and efficient synthetic route to the pyrazolidine ring system. Lithium aluminum hydride reduction of 5,6,7,8-tetrahydro-5,8-ethano-2,2-diethylpyrazolo[1,2-a]pyridazine-1,3(2H)dione ( 26 ) followed by hydrogenolysis led to a high yield of 4,4-diethyl-2,6-diazabicyclo[5.2.2]undecane ( 28 ) which is the first reported example of this ring system. Reaction of several of the adducts with ethanolic potassium hydroxide resulted in the opening of the five-membered ring.     

Diels-Alder Reactions of 2-Oxazolidinone Dienes in Polar Solvents Using Catalysis or Non-conventional Energy Sources

Summary. The (Z)-N-substituted 4-methylene-5-propylidene-2-oxazolidinone dienes were prepared by a one-step synthesis, starting from 2,3-hexanedione and isocyanates. Diels-Alder cycloadditions of these dienes were carried out in the presence of the dienophiles methyl vinyl ketone, methyl propiolate, and a captodative olefin, under conditions such as solvents of high polarity, Lewis acid catalysis, and non-conventional energy sources. The reactions carried out either with mixtures of H₂O/MeOH or under BF₃·Et₂O catalysis yielded the highest regio- and stereoselectivities. The use of ionic liquids, microwaves, and ultrasound did not significantly increase the selectivity.     

Syntheses of Seven- and Five-Membered Rings from Allyl Cations

The cycloaddition of allyl cations to conjugated dienes offers an efficient and general tool for the construction of seven-membered carbocycles. The silver salt route is highly suitable for generating allyl cations and can be used even in most difficult cases, i. e. for elusive and intractable allyl cations such as 2-methylallyl, 2-methoxyallyl, and the parent allyl cation. Cycloadditions to the 2-methoxyallyl cation come very close to the prototype of a 6π, 7C reaction, since the carbonyl group introduced into the new ring can either be used for further transformations or be removed altogether. The combination of an allyl cation with π reactants, especially conjugated dienes, is a powerful and strongly convergent synthetic method since it permits one-step assembly, from a C₃ and a C₄ unit, of a cluster of up to four chiral centers in a ring which is larger than six-membered. Allyl cations combine with electron-rich 2π systems to form novel five-membered rings. The nature of the organometallic intermediates has been elucidated in many cases.     

Phenanthroline-imine ligands for iron-catalyzed alkene hydrosilylation

Iron-catalyzed organic reactions have been attracting increasing research interest but still have serious limitations on activity, selectivity, functional group tolerance, and stability relative to those of precious metal catalysts. Progress in this area will require two key developments: new ligands that can impart new reactivity to iron catalysts and elucidation of the mechanisms of iron catalysis. Herein, we report the development of novel 2-imino-9-aryl-1,10-phenanthrolinyl iron complexes that catalyze both anti-Markovnikov hydrosilylation of terminal alkenes and 1,2-anti-Markovnikov hydrosilylation of various conjugated dienes. Specifically, we achieved the first examples of highly 1,2-anti-Markovnikov hydrosilylation reactions of aryl-substituted 1,3-dienes and 1,1-dialkyl 1,3-dienes with these newly developed iron catalysts. Mechanistic studies suggest that the reactions may involve an Fe(0)–Fe(ii) catalytic cycle and that the extremely crowded environment around the iron center hinders chelating coordination between the diene and the iron atom, thus driving migration of the hydride from the silane to the less-hindered, terminal end of the conjugated diene and ultimately leading to the observed 1,2-anti-Markovnikov selectivity. Our findings, which have expanded the types of iron catalysts available for hydrosilylation reactions and deepened our understanding of the mechanism of iron catalysis, may inspire the development of new iron catalysts and iron-catalyzed reactions.

Newly developed iron complexes bearing 2-imino-9-aryl-1,10-phenanthroline ligands were successfully used to catalyze hydrosilylation of terminal alkenes and conjugated dienes in high yields with excellent anti-Markovnikov selectivity.     

Dendrimer-Encapsulated Pd Nanoparticles,Immobilized in Silica Pores,as Catalysts for Selective Hydrogenation of Unsaturated Compounds

Heterogeneous Pd-containing nanocatalysts, based on poly (propylene imine) dendrimers immobilized in silica pores and networks, obtained by co-hydrolysis in situ, have been synthesized and examined in the hydrogenation of various unsaturated compounds. The catalyst activity and selectivity were found to strongly depend on the carrier structure as well as on the substrate electron and geometric features. Thus, mesoporous catalyst, synthesized in presence of both polymeric template and tetraethoxysilane, revealed the maximum activity in the hydrogenation of various styrenes, including bulky and rigid stilbene and its isomers, reaching TOF values of about 230000 h⁻¹. Other mesoporous catalyst, synthesized in the presence of polymeric template, but without addition of Si(OEt)₄, provided the trans-cyclooctene formation with the selectivity of 90–95 %, appearing as similar to homogeneous dendrimer-based catalysts. Microporous catalyst, obtained only on the presence of Si(OEt)₄, while dendrimer molecules acting as both anchored ligands and template, demonstrated the maximum activity in the hydrogenation of terminal linear alkynes and conjugated dienes, reaching TOF values up to 400000 h⁻¹. Herein the total selectivity on alkene in the case of terminal alkynes and conjugated dienes reached 95–99 % even at hydrogen pressure of 30 atm. The catalysts synthesized can be easily isolated from reaction products and recycled without significant loss of activity.     

Herstellung substituierter 1,6-Methano[10]annulene durch Cycloadditionsreaktionen des 1H-Cyclopropabenzols

Synthesis of Substituted 1,6-Methano[10]annulenes by Cycloadditions of 1H-Cyclopropabenzene Diels-Alder reactions of 1H-cyclopropabenzene ( 1 ) with electron-poor dienes, leading to substituted 1,6-methano[10]annulenes, are described.     

Iron-Catalyzed Stereoconvergent 1,4-Hydrosilylation of Conjugated Dienes

Stereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron-catalyzed stereoconvergent 1,4-hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z-allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two-electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α-diimine ligand-modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti-π-allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal-hydride species.     

Synthesis of 2,3-dihydroselenazolo[3,2-a]pyridinium salts based on reactions of pyridine-2-selanyl chloride with alkenes and dienes

The reaction of pyridine-2-selanyl chloride with alkenes and dienes gives 2,3-dihydro[1,3]selenazolo- [3,2-a]pyridinium derivatives as addition-cyclization products involving closure of the ring at the pyridine nitrogen atom of the selanylating electrophile.     

Hydride affinities of cumulated, isolated, and conjugated dienes in acetonitrile

The hydride affinities (defined as the enthalpy changes in this work) of 15 polarized dienes [five phenyl sulfone substituted allenes (1a), the corresponding five isolated dienes (1b), and the corresponding five conjugated dienes (1c)] in acetonitrile solution were determined by titration calorimetry for the first time. The results display that the hydride affinity scales of the 15 dienes in acetonitrile range from -71.6 to -73.9 kcal/mol for 1a, from -46.2 to -49.7 kcal/mol for 1b, and from -45.0 to -46.5 kcal/mol for 1c, which indicates that the hydride-obtaining abilities of the cumulated dienes (1a) are not only much larger than those of the corresponding conjugated dienes (1c) but also much larger than those of the corresponding isolated dienes (1b). The hydrogen affinities of the 15 dienes as well as the hydrogen affinities and the proton affinities of the radical anions of the dienes (1(-*)) in acetonitrile were also evaluated by using relative thermodynamic cycles according to Hess's law. The results show that (i) the hydrogen affinities of the neutral dienes 1 cover a range from -44.5 to -45.6 kcal/mol for 1a, from -20.4 to -21.4 kcal/mol for 1b, and from -17.3 to -18.5 kcal/mol for 1c; (ii) the hydrogen affinities of the radical anions of the dienes (1(-*)) in acetonitrile cover a range from -40.6 to -47.2 kcal/mol for 1a(-*), from -21.6 to -29.6 kcal/mol for 1b(-*), and from -10.0 to -15.4 kcal/mol for 1c(-*); (iii) the proton affinities of the 15 1a(-*) in acetonitrile cover a range from -97.0 to -100.6 kcal/mol for 1a(-*), from -77.8 to -83.4 kcal/mol for 1b(-*), and from -66.2 to -68.9 kcal/mol for 1c(-*). The main reasons for the great difference between the cumulated dienes and the corresponding isolated and conjugated dienes in the hydride affinity, hydrogen affinity, and proton affinity have been examined. It is evident that these experimental results should be quite valuable to facilitate the elucidation of the origins of the especially high chemical potencies of the allenes, the choice of suitable hydride reducing agents to reduce the dienes, and the analyses on the reduction mechanisms.     

Amino Acid Derivatives, VI [1]: Synthesis, Antiviral, and Antimicrobial Evaluation of α-Amino Acid Esters Bearing a 1,2,3-Triazolo[4,5-d]pyrimidinedione Side Chain

Summary. A series of peptide and dipeptide derivatives conjugated with a 1,2,3-triazolo[4,5-d]pyrimidinedione residue were synthesized. The new compounds were evaluated in vitro for cytotoxicity against HAV-27 and HSV-1 and showed moderate activity. The prepared compounds were tested for antimicrobial activity against four different bacterial species, and they displayed different degrees of antibacterial activities or inhibitory actions.     

exo-Stereoselectivity in Diels-Alder Addition of Halogenocyclopropenes to Butadienes and Furans

The stereochemistry of the Diels-Alder reaction of 1,2-dichloro-3,3-difluorocyclopropene ( 5a ) to 1,4-diphenyl-1,3-butadiene ( 6 ) and 1,3-diphenylisobenzofuran ( 7 ) was unambiguously established by X-ray structure determination. In all cases known so far, tetrahalogenocyclopropenes add exo to open-chain dienes and furans. The previously reported exo-addition product ( 2a ) of l-bromo-2-chlorocyclopropene ( 5b ) to 7 allows assignments of the stereochemistry of other additions of 5b to furans. exo-Addition usually predominates, but in some cases endo- adducts are also formed. This contrasts with reports in the literature that 5b adds preferentially endo to open-chain dienes.     

Palladium-Catalyzed Hydrosilylation of Unactivated Alkenes and Conjugated Dienes with Tertiary Silanes Controlled by Hemilabile Hybrid P,O Ligand

Novel P,O-type ligands, N-disulfonyl bicyclic bridgehead phosphorus triamides, were synthesized and utilized in Pd-catalyzed hydrosilylation involving tertiary silanes, unactivated alkenes, and conjugated dienes. The ligand displayed a remarkable level of reactivity for alkene hydrosilylation with tertiary silanes and its use resulted in a significant improvement in the regioselectivity of diene hydrosilylation towards 1,2-hydrosilylation. X-ray crystallographic analysis confirmed the bidentate nature of the ligand, with coordination of phosphorus and oxygen. Control experiments provided evidence for the formation of Pd⁰ species and the reversibility of Pd−H insertion in the reaction mechanism. Density functional theory (DFT) computations supported the importance of the hemilabile P,O ligand in stabilizing both the rate-determining transition state of Pd−H insertion and the transition state of reductive elimination that determines the regioselectivity.     

Use of Formic Acid as a CO Surrogate for the Reduction of Nitroarenes in the Presence of Dienes: A Two-Step Synthesis of N-Arylpyrroles via 1,2-Oxazines

Formic acid, activated by acetic anhydride and a base, was employed as a CO surrogate to deoxygenate nitroarenes to nitrosoarenes, a reaction catalyzed by a palladium/phenanthroline complex in the homogeneous phase. Nitrosoarenes were trapped by conjugated dienes to give 3,6-dihydro-2H-[1,2]-oxazines. The latter were then transformed into N-arylpyrroles employing CuCl as the catalyst. The reaction was designed to give the best results for pyrroles lacking any substituent in the 2 and 5 positions, which are difficult to produce employing most pyrrole syntheses.     

Reductions of Benzene Derivatives Whose Benzylic Positions Bear Oxygen Atoms under Mild Conditions

Reductions of compounds whose benzylic positions bear O‐atoms, such as benzyl alcohol, dibenzyl ether, styrene oxide, benzaldehyde, acetophenone, and benzophenone, to the corresponding non‐conjugated dienes were performed by using t‐BuOH, Li, and gaseous NH₃ in THF at room temperature. In these reductions, it was observed that the functional groups at benzylic positions were reduced first.