Cycloaddition of cyclohexa-2,4-dienones with β-nitroacrylates: a short and efficient entry into bicyclo[2.2.2]octanes endowed with β-nitro-ester and β-amino ester functionality

Regio- and stereoselective cycloaddition of β-nitroacrylates with electron deficient cyclohexa-2,4-dienones leading to highly functionalised bicyclo[2.2.2]octanes having the β-nitroester group and their transformation to bicyclo[2.2.2]octanes having β-aminoester functionality is described.     

Elysiapyrones from Elysia diomedea. Do such metabolites evidence an enzymatically assisted electrocyclization cascade for the biosynthesis of their bicyclo[4.2.0]octane core?

[structure: see text] Biogenetically interesting polypropionate-derived metabolites 1 and 2, featuring an unprecedented skeleton, have been isolated from the sea slug Elysia diomedea. Their enantiomeric character indicates that the current spontaneous electrocyclization cascade biogenetic hypothesis for the bicyclo[4.2.0]octane core must be enzymatically aided. These compounds are isomeric with the 15-nor-9,10-deoxytridachione/15-norphotodeoxytridachione pair of metabolites and encourage speculation about their biosynthetic relationship.     

Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives binding to the μ-opioid receptor

Summary Molecular modeling studies were carried out on a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives with the aim to highlight the main factors modulating their affinity for the -opioid receptor. Structure-affinity relationships were developed with the aid of molecular mechanics and semiempirical quantum-mechanics methods. According to our proposed pharmacodynamic model, the binding to the -receptor is promoted by the following physico-chemical features: the presence of hydrocarbon fragments on the nitrogen ring frame capable of interacting with one of two hypothesized hydrophobic receptor pockets; a correct orientation of an N-propionyl side chain so as to avoid a sterically hindered region of the receptor; the possibility of accepting a hydrogen bond from a receptor site complementary to the morphine phenol oxygen.     

Synthesis and structure of manganese(ii) coordination polymers with 1,4-diazabicyclo[2.2.2]octane N,N′-dioxide: solvent and template effects

Russian Chemical Bulletin - New metal-organic frameworks [Mn(DMF)2(odabco)2](ClO4)2 · H2O (1), [Mn(H2O)2? (HCOO)2] · odabco (2), and [Mn(Hodabco)2(odabco)3](NO3)4 (3) were...     

A new rearrangement of spiro[indane-1,3′-thiophene] and spiro[naphthalene-1,3′-thiophene] derivatives accompanied by opening of the cycloalkane ring

Abstract  

The new thioamides 2-oxoindane-1-carbothioamides and 2-oxo-1,2,3,4-tetrahydronaphthalene-1-carbothioamides underwent conjugated addition to (E)-β-nitrostyrenes followed by cyclization to give products containing 5-hydroxyimino-2-aryliminothiophene rings spiro-annulated to the 2-indanone or 2-tetralone system. On treatment with hydrochloric acid in boiling methanol the compounds underwent a new rearrangement, involving transformation of the 2-aryliminothiophene ring to a pyrrole and an opening of the alicyclic ring in the proximity of the carbonyl group, affording 2-(1,3-diaryl-2-oxo-5-thioxopyrrol-4-yl)benzeneacetic or 2-(1,3-diaryl-2-oxo-5-thioxopyrrol-4-yl)benzenepropanoic acid methyl esters. The structures of two selected pyrrole derivatives were determined by X-ray crystal analyses. The thioamides derived from 2-indanone showed unexpected reactivity towards primary alcohols and underwent conversion to 2-hydroxy-1H-indene-3-thiocarboxylic acid O-esters.     

Photoreactions of β-aziridinylacrylonitriles and acrylates with alkenes: the substituent effects on the formation of [3+2] cycloadducts

The photochemical C,C-bond cleavage of trisubstituted aziridines 3-6 and consequent [3+2] cycloaddition with electron-deficient alkenes afforded the novel head-to-head adducts (1,2,3,5-tetrasubstituted pyrrolidines) selectively and efficiently. The aziridines 3 and 5 reacted with molecular oxygen, affording dioxazolidine 26 and cleaved products, respectively. The results may suggest that the C,C-bond of aziridine cleaves biradically. The photoreactions of N-tritylaziridines 7-9 possessing diester, dinitrile, and butadiene groups in the side chain with electron-deficient alkenes yielded 2,3-cis-pyrrolidine derivatives 29, 30, and 33 exclusively. In particular, the dinitrile 8 also reacted with non-electron-deficient alkenes. The formal synthesis of the indolizidine fragment 10 of stellettamides starting from the pyrrolidine (E)-33 was achieved in a convenient manner.     

Reaction of tricarbonyl[(1-4-η)-2-methoxy-5-vinylidene-cyclohexa-1,3-diene]iron derivatives with carbene: (2+1) cycloaddition for the rapid synthesis of spiro[2,5]octane

Tricarbonyl[(1-4-η)-2-methoxy-5-methylene-cyclohexa-1,3-diene]iron (1a) and tricarbonyl[(1-4-η)-2-methoxy-5-isopropylene-cyclohexa-1,3-diene]iron (1b) complexes are unstable 4-vinylidene cyclohexanone equivalents and these react regio- and stereoselectively with carbenes and metallocarbenes to give spiro[2,5]octane ring system. The (2+1) cycloaddition reaction provides a rapid entry into spiro[2,5]octane ring system. In cases where the carbene and metallocarbene contain a good bulky leaving group or an electron-withdrawing group, the cyclopropane ring-opening products are obtained.     

Asymmetric baker’s yeast reductions of bridgehead-substituted bicyclo[2.2.2]octane-2,6-dione derivatives followed by conversion into catalytically active BODOLs for the diethylzinc addition to benzaldehyde

4-Substituted bicyclo[2.2.2]octane-2,6-diones have been synthesized and tested as substrates in the enantioselective reduction with baker’s yeast to give the corresponding hydroxy ketones. It was found that the derivative bearing a TIPSO group at the 4-position was not reduced at all while that with a TBDMSO group gave 87% yield and 46% ee. Other 4-oxy functionalized derivatives were reduced with varying yields (36–87%) and ees (10–82%). The best result was obtained for the 4-Oallyl derivative (80% yield, 82% ee). The hydroxy ketones carrying the benzyloxy and allyloxy groups at the 4-position were converted into the corresponding BODOLs, which were tested as catalysts in the diethylzinc addition to benzaldehyde. In this reaction the ees were 90% and 89%, respectively, which showed that BODOLs substituted at the 4-position are essentially as good catalysts in this reaction as those bearing a hydrogen.     

Mass spectrometry and the amyloid problem—How far can we go in the gas phase?

A number of proteins are capable of converting from their soluble, monomeric form into highly-ordered, insoluble aggregates known as amyloid fibrils. In vivo, these fibrils, which accumulate in organs and tissues, are associated with a wide range of amyloid diseases for which there are currently no therapeutic solutions. The molecular details of the pathway from native monomer through oligomeric intermediates to the final amyloid fibril remain a challenging enigma. Over the past few years, mass spectrometry has been applied to investigate the various stages of amyloid fibril formation, and this report summarizes the key steps achieved to date.     

Regio- and stereoselectivity in the concatenated enyne cross metathesis–metallotropic [1,3]-shift of terminal 1,3-diyne

Enyne cross metathesis of terminal 1,3-diynes with various alkenes afforded two products of distinctive connectivity, as the result of a uniform mode of initiation but different modes of termination events with or without metallotropic [1,3]-shift. Steric and electronic factors of the substituents on the 1,3-diynes play an important role in controlling the metallotropic [1,3]-shift of the propagating alkylidene intermediates and their regioselective trapping to the final products.     

Zinc(II) metal-organic frameworks with 1,4-diazabicyclo[2.2.2]octane N,N′-dioxide: control of the parameters of the cationic porous framework and optical properties

Russian Chemical Bulletin - Four zinc metal-organic frameworks (MOFs) with 1,4-diazabicyclo[2.2.2]octane N,N′-dioxide (odabco) as a bridging ligand were synthesized by varying the solvent and...     

Exploring effects of the trifluoromethyl substituent on the chemoselectivity and regioselectivity of [3+2] cycloadditions of thiocarbonyl S-methanides with α, β-unsaturated ketones

A [3+2] cycloaddition (32CA) reaction between a thiocarbonyl ylide ( TCY 2 ) and an electron-deficient enone ( TFB 3 ) in tetrahydrofuran (THF) was studied in the light of molecular electron density theory at the DFT-B3LYP/6-31G(d) computational level to probe energetics and selectivities. The reaction was investigated in four competitive reaction paths associated with the CC and CO chemoselectivities in TFB 3 . An analysis of the density functional theory-based reactivity indices shows that TCY 2 is a strong nucleophile, and TFB 3 is also a strong electrophile. Although both C4─C5 and C6─O7 double bonds of TFB 3 can potentially be involved in 32CA reaction toward TCY 2 , computed relative Gibbs free energies obviously demonstrate that C6─O7 involvement in a quite regioselective manner is entirely preferred over the C4─C5 one in an excellent agreement with the chemoselectivity and regioselectivity observed experimentally. Interestingly, such a chemoselectivity could not be rationalized through assessment of the electrophilic Parr functions calculated at the C4, C5, C6, and O7 centers of TFB 3 . The global electron density transfer value, 0.31 e, calculated at the most energetically preferred transition state structure TS 1 involved within the C6─O7 chemoselective reaction channel demonstrates that this pseudodiradical type (pdr-type) 32CA reaction has a notable polar character.     

Iodoplumbate(Ⅱ)-based Hybrid Templated by 1,4-Diazabicyclo[2.2.2]octane Derivative:Structure,Photocurrent Response Behavior and Photocatalytic Activity for the Degradation of Organic Dye

A new iodoplumbate/organic hybrid,[(Et_2DABCO)_2(Pb_3I_(11))(H3 O)]n(1,Et_2DABCO = N,N?-diethyl-1,4-diazabicyclo[2.2.2] octane) has been synthesized using solution method.According to X-ray diffraction structural analysis,the unique(Pb_3I_(11))_n~(5n-) chain in 1 is constructed from face-and edge-sharing PbI_6 octahedra,which is templated by(Et_2DABCO)~(2+) dication possessing both rigidity and flexibility.C–H···I hydrogen bonds contribute to the structure extending from 1D chains to a 3D network.Its energy band gap of 2.64 eV indicates its broad-gap semiconductor nature.It exhibits both photocurrent response property and photocatalytic activity for the degradation of rhodamine B.     

Amberlyst-15? in PEG: A novel catalytic system for the facile and efficient one-pot synthesis of benzothiazolo-[2,3-b]-quinazolinone derivatives

A simple and convenient approach for the synthesis of tetraheterocyclic benzothiazolo-[2,3-b]-quinazolin-1-ones has been developed utilizing the MCR methodology, which involves the condensation of 2-aminobenzothiazole, cyclic-diketones and various aldehydes using Amberlyst-15 in PEG 400 as an environmentally benign and reusable catalyst system. Environmental benignity, recyclability, cost-effectiveness, easy workup and excellent yields are the major attributes of this one-pot procedure.     

Catalyst and solvent-free cyclopropanation of electron-deficient olefins with cyclic diazoamides for the synthesis of spiro[cyclopropane-1,3′-indolin]-2′-one derivatives

A novel series of spirooxindolylcyclopropane derivatives have been synthesized in high yields from 3-diazooxindole and electron deficient olefins under catalyst/solvent-free conditions.     

Effects of bulky substituent groups on the Si–Si triple bonding in RSiSiR and the short Ga–Ga distance in Na2[RGaGaR]: A theoretical study

The steric and electronic effects of bulky aryl and silyl groups on the Si–Si triple bonding in RSiSiR and the short Ga–Ga distance in Na₂[RGaGaR] are investigated by density functional calculations. As typical bulky groups, Tbt = C₆H₂-2,4,6-{CH(SiMe₃)₂}₃, Ar′ = C₆H₃-2,6-(C₆H₃-2,6-iPr₂)₂, Ar¹ = C₆H₃-2,6-(C₆H₂-2,4,6-iPr₃)₂, SiMe(SitBu₃)₂, and SiiPrDis₂ (Dis = CH(SiMe₃)₂) are investigated and characterized. The importance of large basis sets is emphasized for density functional calculations.     

Theoretical study of the substituent effect of hydroxy group on tandem Cope rearrangement and [2 + 2] cycloaddition in cis-1,2-diethynylcyclopropane and its mono-hetero analogues

The tandem Cope rearrangement and [2?+?2] cycloaddition of cis-1,2-diethynyl-1,2-dihydroxycyclopropane and its mono-hetero analogues have been investigated at the B3LYP/6-31+G* level. The presence of the hydroxy group lowers the activation enthalpies for the Cope rearrangement, whereas activation enthalpies for the [2?+?2] cycloaddition are raised as compared to those for their non-hydroxy derivatives. The NBO analysis indicates that in the transition structure involved in the Cope rearrangement, lone pairs of the oxygen atoms of the hydroxy groups are transferred into the σ* C–C bond undergoing migration, as a result of which it is weakened. On the other hand, the lone pairs of the oxygen atoms interact with the π* C=C orbitals of the bis-allenic systems in the intermediate thereby stabilizing it and, thus, suppressing its driving ability for the [2?+?2] cycloaddition. In the products so formed, 6π electrons are delocalized conferring stability on them, which is further augmented by extended conjugation with the hydroxy groups. Due to high stability of these products, activation barrier for the change of enol into ketone is very high.

     

Catalyst-free synthesis of 3-hydroxyimidazo[1,2-a]pyridine zwitterion derivatives via the three-component reaction of ethyl glyoxalate, 2‑aminopyridines and cyclic 1,3-dicarbonyls

The three-component reaction of ethyl glyoxalate, 2-aminopyridines, and cyclic 1,3-dicarbonyl compounds such as 4-hydroxycoumarin, N,N-dimethylbarbituric acid and 4-hydroxy-6-methyl-2H-pyran-2-one is described for the synthesis of 3-hydroxyimidazo[1,2-a]pyridine zwitterion derivatives.