Reactivity of the 4,5‐Didehydroisoquinolinium Cation

The chemical properties of a 1,8‐didehydronaphthalene derivative, the 4,5‐didehydroisoquinolinium cation, were examined in the gas phase in a dual‐cell Fourier‐transform ion cyclotron resonance (FT‐ICR) mass spectrometer. This is an interesting biradical because it has two radical sites in close proximity, yet their coupling is very weak. In fact, the biradical is calculated to have approximately degenerate singlet and triplet states. This biradical was found to exclusively undergo radical reactions, as opposed to other related biradicals with nearby radical sites. The first bond formation occurs at the radical site in the 4‐position, followed by that in the 5‐position. The proximity of the radical sites leads to reactions that have not been observed for related mono‐ or biradicals. Interestingly, some ortho‐benzynes have been found to yield similar products. Since ortho‐benzynes do not react via radical mechanisms, these products must be especially favorable thermodynamically.     

Photocurable and thermally stable polymers based on 1,4‐pentadien‐3‐one‐1‐p‐hydroxyphenyl‐5‐p‐phenyl methacrylate: Copolymerization with ethyl acrylate

1,4‐Pentadien‐3‐one‐1,5‐bis(p‐hydroxyphenyl) (PBHP) was prepared by reacting p‐hydroxybenzaldehyde and acetone in the presence of an acid catalyst. 1,4‐Pentadiene‐3‐one‐1‐p‐hydroxyphenyl‐5‐p‐phenyl methacrylate (PHPPMA) monomer was prepared by reacting PBHP dissolved in ethyl methyl ketone (EMK) with methacryloyl chloride in the presence of triethylamine. A free‐radical solution polymerization technique was used for synthesizing homo‐ and copolymers of different feed compositions of PHPPMA and ethyl acrylate (EA) in EMK as a solvent with benzoyl peroxide as a free‐radical initiator at 70 ± 1 °C. All the polymers were characterized with IR and ¹H NMR techniques. The compositions of the copolymers were determined with the ¹H NMR technique. The copolymer reactivity ratios were evolved with Kelen–Tudos (EA = 1.25 and PHPPMA = 0.09) and extended Kelen–Tudos (EA = 1.30 and PHPPMA = 0.09) methods. Q (0.48) and e (1.68) values for the new monomer (PHPPMA) were calculated with the Alfrey–Price method. UV absorption spectra for poly(PHPPMA) showed two absorption bands at 302 and 315 nm. The photocrosslinking properties of the polymer samples were examined with the solvent method. Thermal analyses of the polymers were performed with the thermogravimetric‐differential thermogravimetric technique. First, the decomposition temperatures started for poly(PHPPMA), copoly(EA‐PHPPMA) (62:38), and copoly(EA‐PHPPMA) (41:59) were at 350, 410, and 417 °C, respectively. A gel permeation chromatographic method was used for determining the polymer molecular weights (weight‐average molecular weight: 2.67 × 10⁴ and number‐average molecular weight: 1.41 × 10⁴) and polydispersity index (1.89). The solubility of the monomer and the copolymers occurred at 30 °C with solvents having different polarities. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1632–1640, 2003     

A Benzene‐1,3,5‐Triaminyl Radical Fused with ZnII‐Porphyrins: Remarkable Stability and a High‐Spin Quartet Ground State

A benzene‐1,3,5‐triaminyl radical fused with three Zn^II‐porphyrins was synthesized through a three‐fold oxidative fusion reaction of 1,3,5‐tris(Zn^II‐porphyrinylamino)benzene followed by oxidation with PbO₂ as key steps. This triaminyl radical has been shown to possess a quartet ground state with a doublet–quartet energy gap of 3.1 kJ mol^?1 by superconducting quantum interference device (SQUID) studies. Despite its high‐spin nature, this triradical is remarkably stable, which allows its separation and recrystallization under ambient conditions. Moreover, this triradical can be stored as a solid for more than one year without serious deterioration. The high stability of the triradical is attributed to effective spin delocalization over the porphyrin segments and steric protection at the nitrogen centers and the porphyrin meso positions.     

Photoinduced and thermal reactions of α‐cyano‐β‐bromomethylcinnamide with 1‐benzyl‐1,4‐dihydronicotinamide

The photoinduced reaction of a mixture of (Z)‐α‐cyano‐β‐bromomethylcinnamide (1) and (E)‐α‐cyano‐β‐bromomethylcinnamide (2) with 1‐benzyl‐1, 4‐dihydronicotinamide produces a mixture of the (E)‐ and (Z)‐ isomers of α‐cyano‐β‐methylcinnamide (3 and 4). Using spin‐trapping technique for monitoring reactive intermediate, it is shown that the reaction proceeds via electron transfer‐debromination‐H abstraction mechanism. The thermal reaction of the same substrate with BNAH at 60°C in the dark gives three products: the (E)‐ and (Z)‐isomers of α‐cyano‐β‐methylcinnamide and a dehydrodimeric product; 2, 7‐dicyano‐3, 6‐diphenylocta‐2, 4, 6‐trien‐1, 8‐dioic amide (7). Based on product analysis, scavenger experiment and cyclic voltammetry, an electron transfer‐debromination‐disproportionation mechanism is proposed.     

Ligand‐Enabled β‐Methylene C(sp3)−H Arylation of Masked Aliphatic Alcohols

Despite recent advances, reactivity and site‐selectivity remain significant obstacles for the practical application of C(sp³)?H bond functionalization methods. Here, we describe a system that combines a salicylic‐aldehyde‐derived L,X‐type directing group with an electron‐deficient 2‐pyridone ligand to enable the β‐methylene C(sp³)?H arylation of aliphatic alcohols, which has not been possible previously. Notably, this protocol is compatible with heterocycles embedded in both alcohol substrates and aryl coupling partners. A site‐ and stereo‐specific annulation of dihydrocholesterol and the synthesis of a key intermediate of englitazone illustrate the practicality of this method.     

Atom‐Efficient Synthesis of Alkynylfluoroborates Using BF3‐Based Frustrated Lewis Pairs

A sterically demanding amine, 1,2,2,6,6‐pentamethylpiperidine (PMP), forms a highly reactive Lewis acid–base pair with boron trifluoride. This pair reacts with terminal acetylenes to give the products of C(sp)?H borylation, previously unknown tri‐ and tetraalkynylboron compounds. Trialkynylfluoroborates can serve as surrogates of alkynyltrifluoroborates for C?C coupling reactions. Using aqueous NaOH, PMP can be recovered from its tetrafluoroborate salt, which is formed as a C?H borylation byproduct. Combining the discovered borylation reactivity with the PMP recovery provides a straightforward and atom‐efficient approach to synthetically useful alkynylfluoroborates.     

Density functional study of H2 molecule and H atom adsorption on α‐U(001) surface

Density functional theory method has been employed to investigate the adsorption of H₂ molecule and H atom on α‐U(001) surface. There exist four initial sites [top (A), triangle‐center (B), long‐bridge (C), and short‐bridge (D)] for H₂ and H atom adsorptions on α‐U(001) surface. The E_ads (adsorption energy) values on the top sites of H₂‐U(001) configurations are around ?0.666 eV, and H₂ molecule has been elongated but not broken into H atoms. For the other three sites, the E_ads values are around ?1.521 eV. The long‐bridge site is the most reactive site for H₂ decomposing. For the H‐U(001) configurations, the E_ads are around ?2.904 eV. Top site and short‐bridge site are the most reactive sites for the H atom react on the α‐U(001) surface. Our work reveals that the different reactive sites play discrepant effects on hydrogenation process. Geometric deformations, diffusion paths, and partial density of states of H₂‐U(001) and H‐U(001) configurations have also been analyzed. Copyright © 2016 John Wiley & Sons, Ltd.     

Electron Attachment to Hydrated Oligonucleotide Dimers: Guanylyl‐3′,5′‐Cytidine and Cytidylyl‐3′,5′‐Guanosine

The dinucleoside phosphate deoxycytidylyl‐3′,5′‐deoxyguanosine (dCpdG) and deoxyguanylyl‐3′,5′‐deoxycytidine (dGpdC) systems are among the largest to be studied by reliable theoretical methods. Exploring electron attachment to these subunits of DNA single strands provides significant progress toward definitive predictions of the electron affinities of DNA single strands. The adiabatic electron affinities of the oligonucleotides are found to be sequence dependent. Deoxycytidine (dC) on the 5′ end, dCpdG, has larger adiabatic electron affinity (AEA, 0.90 eV) than dC on the 3′ end of the oligomer (dGpdC, 0.66 eV). The geometric features, molecular orbital analyses, and charge distribution studies for the radical anions of the cytidine‐containing oligonucleotides demonstrate that the excess electron in these anionic systems is dominantly located on the cytosine nucleobase moiety. The π‐stacking interaction between nucleobases G and C seems unlikely to improve the electron‐capturing ability of the oligonucleotide dimers. The influence of the neighboring base on the electron‐capturing ability of cytosine should be attributed to the intensified proton accepting–donating interaction between the bases. The present investigation demonstrates that the vertical detachment energies (VDEs) of the radical anions of the oligonucleotides dGpdC and dCpdG are significantly larger than those of the corresponding nucleotides. Consequently, reactions with low activation barriers, such as those for O? C σ bond and N‐glycosidic bond breakage, might be expected for the radical anions of the guanosine–cytosine mixed oligonucleotides.     

Highly Enantioselective Synthesis of 1,2,3‐Substituted Cyclopropanes by Using α‐Iodo‐ and α‐Chloromethylzinc Carbenoids

Herein, we report the enantio‐ and diastereoselective formation of trans‐iodo‐ and trans‐chlorocyclopropanes from α‐iodo‐ and α‐chlorozinc carbenoids by using a dioxaborolane‐derived chiral ligand. The synthetically useful iodocyclopropane building blocks were derivatized by an electrophilic trapping of the corresponding cyclopropyl lithium species or a Negishi coupling to give access to a variety of enantioenriched 1,2,3‐substituted cyclopropanes. The synthetic utility of this method was demonstrated by the formal synthesis of an HIV‐1 protease inhibitor. In addition, the related stereoselective bromocyclopropanation was also investigated. New insights about the relative electrophilicity of haloiodomethylzinc carbenoids are also presented.     

Difluorobenzenes revisited: an experimental and theoretical study of spin–spin coupling constants for 1,2‐, 1,3‐, and 1,4‐difluorobenzene

The experimental spin–spin coupling constants (SSCCs) for 1,3‐ and 1,4‐difluorobenzene have been determined anew, and found to be consistent with previously determined values. SSCCs for 1,2‐, 1,3‐, and 1,4‐difluorobenzene have been analyzed by comparing them with the coupling constants computed using the second‐order polarization propagator approximation (SOPPA) and the equation‐of‐motion coupled cluster singles and doubles method (EOM‐CCSD). Eighty experimental values have been analyzed using SOPPA calculations, and a subset of 40 values using both SOPPA and EOM‐CCSD approaches. One‐bond coupling constants ¹J(C? C) and ¹J(C? F) are better described by EOM‐CCSD, whereas one‐bond ¹J(C? H) values are better described by SOPPA. An empirical equation is presented which allows for the prediction of unknown coupling constants from computed SOPPA values. A similar approach may prove useful for predicting coupling constants in larger systems. Copyright © 2009 John Wiley & Sons, Ltd.     

The tropolone–isobutylamine complex: a hydrogen‐bonded troponoid without dominant π–π interactions

Tropolone long has served as a model system for unraveling the ubiquitous phenomena of proton transfer and hydrogen bonding. This molecule, which juxtaposes ketonic, hydroxylic, and aromatic functionalities in a framework of minimal complexity, also has provided a versatile platform for investigating the synergism among competing intermolecular forces, including those generated by hydrogen bonding and aryl coupling. Small members of the troponoid family typically produce crystals that are stabilized strongly by pervasive π–π, C—H…π, or ion–π interactions. The organic salt (TrOH·iBA) formed by a facile proton‐transfer reaction between tropolone (TrOH) and isobutylamine (iBA), namely isobutylammonium 7‐oxocyclohepta‐1,3,5‐trien‐1‐olate, C₄H₁₂N⁺·C₇H₅O₂⁻, has been investigated by X‐ray crystallography, with complementary quantum‐chemical and statistical‐database analyses serving to elucidate the nature of attendant intermolecular interactions and their synergistic effects upon lattice‐packing phenomena. The crystal structure deduced from low‐temperature diffraction measurements displays extensive hydrogen‐bonding networks, yet shows little evidence of the aryl forces (viz. π–π, C—H…π, and ion–π interactions) that typically dominate this class of compounds. Density functional calculations performed with and without the imposition of periodic boundary conditions (the latter entailing isolated subunits) documented the specificity and directionality of noncovalent interactions occurring between the proton‐donating and proton‐accepting sites of TrOH and iBA, as well as the absence of aromatic coupling mediated by the seven‐membered ring of TrOH. A statistical comparison of the structural parameters extracted for key hydrogen‐bond linkages to those reported for 44 previously known crystals that support similar binding motifs revealed TrOH·iBA to possess the shortest donor–acceptor distances of any troponoid‐based complex, combined with unambiguous signatures of enhanced proton‐delocalization processes that putatively stabilize the corresponding crystalline lattice and facilitate its surprisingly rapid formation under ambient conditions.     

Can One Assess the π Character of a C–C Bond with the Help of the NMR Spin–Spin Coupling Constants?

Measured one‐bond spin–spin coupling constants (SSCC) ¹J(CC) can be used to describe the nature of the C–C bond, provided one is able to separate the various coupling mechanisms leading to ¹J(CC). The Fermi‐contact (FC) term probes the first‐order density at the positions of the coupling nuclei, whereas the noncontact terms (the paramagnetic spin orbit (PSO) and the spin–dipole (SD) terms) probe the π character of the C–C bond (the diamagnetic spin orbit (DSO) term can mostly be neglected). A model is tested, in which the value of the FC(CC) term is estimated with the help of measured SSCCs ¹J(CH). The difference between the measured J(CC) and the estimated FC(CC) values, Δ(CC)=PSO(CC)+SD(CC)+DSO(CC), provides a semiquantitative measure of the π character of a C–C multiple bond. The applicability and limitations of this approach are discussed by partitioning the four Ramsey terms of the SSCC ¹J(CC) into one‐ and two‐orbital contributions. The FC, PSO, and SD terms of ¹J(CC) are explained and analyzed with regard to their relationship to other C–C bond properties. It is shown that empirical relationships between measured SSCCs and the s character of a bond need reconsideration.     

Degradable multisegmented polymers synthesized by consecutive radical addition‐coupling reaction of α,ω‐macrobiradicals and nitroso compound

A consecutive radical addition‐coupling reaction induced by spin‐trapping agent is applied to produce degradable multisegmented polymer using α,ω‐dibromo polymer as a precursor. The macroradical generated by single electron transfer process catalyzed by Cu/PMDETA from α,ω‐dibromo polymer can be efficiently captured by 2‐methyl‐2‐nitrosopropane (MNP), which results in nitroxide radical. The in situ formed nitroxide radical immediately undergoes cross‐coupling reaction with polymeric radical, generating block polymer bridged with alkoxyamine moiety. The consecutive radical addition‐coupling reaction generates multisegmented polymer via step‐growth mechanism. Different multisegmented polymers have been prepared from α,ω‐dibromo‐PS, PtBA, and PtBA‐PS‐PtBA. The block number of multisegmented polymers can be tailored by varying the feed ratio of α,ω‐dibromo precursor to MNP. The multisegmented polymer can be degraded in the presence of hydrogen atom donor or air, and the molecular weight distribution transformed back into shape of its original precursor as it is conjugated by alkoxyamine moieties. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Mono‐ and Bis(tetrathiafulvalene)‐1,3,5‐Triazines as Covalently Linked Donor–Acceptor Systems: Structural,Spectroscopic, and Theoretical Investigations

Reaction of 2,4,6‐trichloro‐1,3,5‐triazine with lithiated tetrathiafulvalene (TTF) in stoichiometric conditions, followed by treatment with sodium methanolate, provides mono‐ and bis(TTF)–triazines as new covalently linked (multi)donor–acceptor systems. Single‐crystal X‐ray analyses reveal planar structures for both compounds, with formation of peculiar segregated donor and acceptor stacks for the mono(TTF)–triazine compound, while mixed TTF–triazine stacks establish in the case of the bis(TTF) derivative. Cyclic voltammetry measurements show reversible oxidation of the TTF units, at rather low potential, with no splitting of the oxidation waves in the case of the dimeric TTF, whereas irreversible reduction of the triazine core is observed. Intramolecular charge transfer is experimentally evidenced through solution electronic absorption spectroscopy. Time‐dependent DFT calculations allow the assignment of the charge transfer band to singlet transitions from the HOMO of the donor(s) to the LUMO of the acceptor. Solution EPR measurements correlated with theoretical calculations were performed in order to characterize the oxidized species. In both cases the spectra show very stable radical species and contain a triplet of doublet pattern, in agreement with the coupling of the unpaired electron with the three TTF protons. The dication of the bis(TTF)–triazine is paramagnetic, but no spin–spin exchange interaction could be detected.     

Diastereo‐ and Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of 3‐(ω′‐Alkenyl)‐ and 3‐(ω′‐Alkenyloxy)‐Substituted 5,6‐Dihydro‐1H‐pyridin‐2‐ones

3‐(ω′‐Alkenyl)‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones 2 – 4 were prepared as photocycloaddition precursors either by cross‐coupling from 3‐iodo‐5,6‐dihydro‐1H‐pyridin‐2‐one ( 8 ) or—more favorably—from the corresponding α‐(ω′‐alkenyl)‐substituted δ‐valerolactams 9 – 11 by a selenylation/elimination sequence (56–62 % overall yield). 3‐(ω′‐Alkenyloxy)‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones 5 and 6 were accessible in 43 and 37 % overall yield from 3‐diazopiperidin‐2‐one ( 15 ) by an α,α‐chloroselenylation reaction at the 3‐position followed by nucleophilic displacement of a chloride ion with an ω‐alkenolate and oxidative elimination of selenoxide. Upon irradiation at λ=254 nm, the precursor compounds underwent a clean intramolecular [2+2] photocycloaddition reaction. Substrates 2 and 5 , tethered by a two‐atom chain, exclusively delivered the respective crossed products 19 and 20 , and substrates 3 , 5 , and 6 , tethered by longer chains, gave the straight products 21 – 23 . The completely regio‐ and diastereoselective photocycloaddition reactions proceeded in 63–83 % yield. Irradiation in the presence of the chiral templates (?)‐ 1 and (+)‐ 31 at ?75 °C in toluene rendered the reactions enantioselective with selectivities varying between 40 and 85 % ee. Truncated template rac‐ 31 was prepared as a noranalogue of the well‐established template 1 in eight steps and 56 % yield from the Kemp triacid ( 24 ). Subsequent resolution delivered the enantiomerically pure templates (?)‐ 31 and (+)‐ 31 . The outcome of the reactions is compared to the results achieved with 4‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones and quinolones.     

gem‐Dihalocyclopropanes as Building Blocks in Natural‐Product Synthesis: Enantioselective Total Syntheses of ent‐Erythramine and 3‐epi‐Erythramine

ent‐Erythramine ((?)‐ 1 ), the enantiomer of the alkaloid erythramine, was prepared in 15 steps from known compounds. The first of three pivotal bond‐forming steps in the synthesis was a Suzuki–Miyaura cross‐coupling reaction of the starting materials to give a bis‐silyl ether. The second involved silver(I)‐induced electrocyclic ring opening of the gem‐dichlorocyclopropane formed in the next step and trapping of the ensuing π‐allyl cation by the tethered nitrogen atom to give, following cleavage of the allyloxycarbonyl protecting group, an approximately 5:6 mixture of the chromatographically separable diastereoisomeric spirocyclic products. In the third critical bond‐forming reaction, the iodide formed from one of the diastereoisomers underwent a radical‐addition/elimination reaction sequence that led to (?)‐ 1 in 89 % yield. The application of the same sequence of transformations to the other diastereoisomer afforded 3‐epi‐(+)‐erythramine (3‐epi‐(+)‐ 1 ).     

Effects of a hydroxyl substituent on the reactivity of the 2,4,6-tridehydropyridinium cation, an aromatic σ,σ,σ-triradical

The reactivity of 3-hydroxy-2,4,6-tridehydropyridinium cation was found to be drastically different from the reactivity of 2,4,6-tridehydropyridinium cation. While the latter triradical reacts with tetrahydrofuran, dimethyl disulfide and ally iodide via three consecutive atom or group abstractions, the former triradical exhibits this behavior only with tetrahydrofuran. Only a single atom or group abstraction was observed for the 3-hydroxy-2,4,6-tridehydropyridinium cation upon interaction with dimethyl disulfide and allyl iodide. This change in reactivity is caused by the hydroxyl group that strengthens the interactions between the two radical sites adjacent to it, thus reducing their reactivity. This explanation is supported by the observation of similar behavior for related biradicals.     

Photochemical Reactions of Regioisomeric 2,2‐Dimethyl‐5,5‐diphenyl‐ and 5,5‐Dimethyl‐2,2‐diphenyl‐Substituted Diazo Ketones of a Tetrahydrofuran Series

The principal direction of conventional photolysis of the regioisomeric 2,2‐dimethyl‐5,5‐diphenyl‐ and 5,5‐dimethyl‐2,2‐diphenyl‐substituted 4‐diazodihydrofuran‐3(2H)‐ones 1a and 1b , respectively, is the Wolff rearrangement, while other photochemical processes, which are giving rise to the formation of C? H‐insertion, 1,2‐alkyl‐ or ‐aryl‐shifts, as well as H‐atom‐abstraction products occur to a much lower degree (Schemes 2 and 3). The ratio of similar reaction products from both regioisomers 1a and 1b is essentially independent of their structure, and a substantial effect of the relative position of the Ph and diazo group to each other on the yield of C? H‐insertion products does not occur. Based on stereochemical considerations, the Wolff rearrangement of diazodihydrofuran‐3(2H)‐ones apparently proceeds in a concerted manner, whereas the appearance in the reaction mixture of 1,2‐shift and H‐atom‐abstraction products points to the parallel generation during photolysis of singlet and triplet carbenes (Schemes 4 and 5).     

Organocatalytic Domino Michael–Knoevenagel Condensation Reaction for the Synthesis of Optically Active 3‐Diethoxyphosphoryl‐2‐oxocyclohex‐3‐enecarboxylates

Versatile dominoes : A novel, organocatalytic, Michael–Knoevenagel condensation domino reaction of ethyl 4‐diethoxyphosphoryl‐3‐oxobutanoate with various aryl‐ and aliphatic‐substituted α,β‐unsaturated aldehydes catalyzed by a chiral diarylprolinol ether has been successfully performed. The reaction proceeds in a highly enantio‐ and diastereoselective manner giving access to optically active 6‐substituted‐3‐diethoxyphosphoryl‐2‐oxocyclohex‐3‐enecarboxylates (see scheme).

     

Trapping σ‐Alkyl–Palladium(II) Intermediates with Arynes Encompassing Intramolecular C−H Activation: Spirobiaryls through Pd‐Catalyzed Cascade Reactions

A palladium‐catalyzed cascade reaction based on the trapping of transient alkyl–Pd^II intermediates with arynes encompassing a C?H activation step has been developed. This synthetic pathway gives rise to hetero‐spirocyclic scaffolds containing a biaryl motif, and opens up new synthetic strategies in the design of cascade reactions since it gathers several aspects of Pd chemistry, i.e., intra‐ and intermolecular carbopalladation of unsaturated species, C?H activation and C?C coupling processes.