Synthesis of a new fluorophore: wavelength-tunable bisbenzo[f]isoindolylidenes.

The creation of new functional molecules is a central task in chemical synthesis. Herein, we report the synthesis of a new type of fluorophore, bisbenzo[f]isoindolylidenes, from easily accessible dipropargyl benzenesulfonamides. Wavelength-tunable fluorophores emitting strong fluorescence of green to red light were obtained in this reaction. Late-stage modifications and incorporation of bioactive molecules into these fluorophores give rise to potential applications in biological studies. Detailed computational and experimental studies were conducted to elucidate the mechanism, and suggest a reaction sequence involving Garratt-Braverman type cyclization, isomerization, fragmentation, dimerization and oxidation.

Radical 1,2,3-tricarbofunctionalization of α-vinyl-ß-ketoesters enabled by a carbon shift from an all-carbon quaternary center.

Herein, we report an intermolecular, radical 1,2,3-tricarbofunctionalization of α-vinyl-ß-ketoesters to achieve the goal of building molecular complexity via the one-pot multifunctionalization of alkenes. This reaction allows the expansion of the carbon ring by a carbon shift from an all-carbon quaternary center, and enables further C-C bond formation on the tertiary carbon intermediate with the aim of reconstructing a new all-carbon quaternary center. The good functional group compatibility ensures diverse synthetic transformations of this method. Experimental and theoretical studies reveal that the excellent diastereoselectivity should be attributed to the hydrogen bonding between the substrates and solvent.

Synthesis of unsymmetrically tetrasubstituted pyrroles and studies of AIEE in pyrrolo[1,2-a]pyrimidine derivatives.

Pyrroles are among the most important heterocycles in pharmaceuticals and agrochemicals. Construction of pyrrole scaffolds with different substituents and a free NH group, however, is challenging. Herein, a metal-free method for the synthesis of unsymmetrically tetrasubstituted NH-pyrroles using a consecutive chemoselective double cyanation is reported. The desired pyrroles were obtained with yields up to 99% and good functional group tolerance. Mechanistic studies identified a reaction mechanism that features a subtle sequence of first cyano-addition and migration, followed by cyano-addition and aromatization to afford the pyrrole skeleton. Pyrrolo[1,2-a]pyrimidines are synthesized as the synthetic applications of NH-pyrroles, and these pyrrolo[1,2-a]pyrimidines exhibit unpredicted time-dependent aggregation-induced emission enhancement (AIEE) properties.

Copper-Catalyzed Radical Enantioselective Carbo-Esterification of Styrenes Enabled by a Perfluoroalkylated-PyBox Ligand.

Chiral lactones are found in many natural products. The reaction of simple alkenes with iodoacetic acid is a powerful method to build lactones, but the enantioselective version of this reaction has not been implemented to date. Herein, we report the efficient catalytic radical enantioselective carbo-esterification of styrenes enabled by a newly developed CuI -perfluoroalkylated PyBox system. Simple styrenes have been converted to useful chiral lactones, whose synthetic applications are showcased. Mechanistic studies reveal that this reaction is a rare example of an efficient ligand-decelerated system, in which the ligand decelerates the reaction, but the reaction is still efficient with reduced amounts of ligand. This uncommon catalytic system may inspire further consideration of the effect of ligands in asymmetric catalysis.

Direct synthesis of pentasubstituted pyrroles and hexasubstituted pyrrolines from propargyl sulfonylamides and allenamides.

Multisubstituted pyrroles are important fragments that appear in many bioactive small molecule scaffolds. Efficient synthesis of multisubstituted pyrroles with different substituents from easily accessible starting materials is challenging. Herein, we describe a metal-free method for the preparation of pentasubstituted pyrroles and hexasubstituted pyrrolines with different substituents and a free amino group by a base-promoted cascade addition-cyclization of propargylamides or allenamides with trimethylsilyl cyanide. This method would complement previous methods and support expansion of the toolbox for the synthesis of valuable, but previously inaccessible, highly substituted pyrroles and pyrrolines. Mechanistic studies to elucidate the reaction pathway have been conducted.

Regioselective Three-Component Synthesis of Vicinal Diamines via 1,2-Diamination of Styrenes.

The vicinal diamine motif plays a significant role in natural products, drug design, and organic synthesis, and development of synthetic methods for the synthesis of diamines is a long-standing interest. Herein, we report a regioselective intermolecular three-component vicinal diamination of styrenes with acetonitrile and azodicarboxylates. The diamination products can be produced in moderate to excellent yields via the Ritter reaction. Synthetic applications and theoretical studies of this reaction have been conducted.

Copper-Catalyzed Enantioselective Radical 1,4-Difunctionalization of 1,3-Enynes.

Chiral allenes are important structural motifs frequently found in natural products, pharmaceuticals, and other organic compounds. Asymmetric 1,4-difunctionalization of 1,3-enynes is a promising strategy to construct axial chirality and produce substituted chiral allenes from achiral substrates. However, the previous state of the art in 1,4-difunctionalization of 1,3-enynes focused on the allenyl anion pathway. Because of this, only electrophiles can be introduced into the allene backbones in the second functionalization step, consequently limiting the reaction and allene product types. The development of asymmetric 1,4-difunctionalization of 1,3-enynes via a radical pathway would complement previous methods and support expansion of the toolbox for the synthesis of asymmetric allenes. Herein, we report the first radical enantioselective allene formation via a group transfer pathway in the context of copper-catalyzed radical 1,4-difunctionalization of 1,3-enynes. This method addresses a longstanding unsolved problem in asymmetric radical chemistry, provides an important strategy for stereocontrol with free allenyl radicals, and offers a novel approach to the valuable, but previously inaccessible, chiral allenes. This work should shed light on asymmetric radical reactions and may lead to other enantioselective group transfer reactions.

1,4-Fluoroamination of 1,3-Enynes en Route to Fluorinated Allenes.

The regioselective synthesis of fluorinated allenes via a metal-free 1,4-fluoroamination of 1,3-enynes is presented. This method employs commercially available N-fluorobenzenesulfonimide serving as both the nitrogen source and the fluorine source, affording access to various tetrasubstituted allenes in a straightforward and atom-economic pathway. Preliminary mechanistic studies and theoretical studies revealed that this reaction might undergo an intimate ion-pair mechanism.

Revealing the Iron-Catalyzed ß-Methyl Scission of tert-Butoxyl Radicals via the Mechanistic Studies of Carboazidation of Alkenes.

We describe here a mechanistic study of the iron-catalyzed carboazidation of alkenes involving an intriguing metal-assisted ß-methyl scission process. Although t-BuO radical has frequently been observed in experiments, the ß-methyl scission from a t-BuO radical into a methyl radical and acetone is still broadly believed to be thermodynamically spontaneous and difficult to control. An iron-catalyzed ß-methyl scission of t-BuO is investigated in this work. Compared to a free t-BuO radical, the coordination at the iron atom reduces the activation energy for the scission from 9.3 to 3.9 ~ 5.2 kcal/mol. The low activation energy makes the iron-catalyzed ß-methyl scission of t-BuO radicals almost an incomparably facile process and explains the selective formation of methyl radicals at low temperature in the presence of some iron catalysts. In addition, a radical relay process and an outer-sphere radical azidation process in the iron-catalyzed carboazidation of alkenes are suggested by density functional theory (DFT) calculations.

The Introduction of the Radical Cascade Reaction into Polymer Chemistry: A One-Step Strategy for Synchronized Polymerization and Modification.

Polymerization and modification play central roles in polymer chemistry and are generally implemented in two steps, which suffer from the time-consuming two-step strategy and present considerable challenge for complete modification. By introducing the radical cascade reaction (RCR) into polymer chemistry, a one-step strategy is demonstrated to achieve synchronized polymerization and complete modification in situ. Attributed to the cascade feature of iron-catalyzed three-component alkene carboazidation RCR exhibiting carbon-carbon bond formation and carbon-azide bond formation with extremely high efficiency and selectivity in one step, radical cascade polymerization therefore enables the in situ synchronized polymerization through continuous carbon-carbon bond formation and complete modification through carbon-azide bond formation simultaneously. This results in a series of α, ß, and γ poly(amino acid) precursors. This result not only expands the methodology library of polymerization, but also the possibility for polymer science to achieve functional polymers with tailored chemical functionality from in situ polymerization.

Synthesis of difluoromethylated allenes through trifunctionalization of 1,3-enynes.

Organofluorine compounds have shown their great value in many aspects. Moreover, allenes are also a class of important compounds. Fluorinated or fluoroalkylated allenes might provide an option as candidates for drug and material developments, as allenes allow a great number of valuable transformations. Herein, we report a metal-free synthesis of difluoromethylated allenes via regioselective trifunctionalization of 1,3-enynes. This method proceeds through double C-F bond formation with concomitant introduction of an amino group to the allene. Synthetic applications are conducted and preliminary mechanistic studies suggest that a two-step pathway is involved. DFT calculations revealed an unusual dibenzenesulfonimide-assisted fluorination/fluoroamination with NFSI. In addition, kinetic reaction study revealed the induction period of both major and side products to support the proposed reaction mechanism. This work offers a convenient approach for the synthesis of a range of difluoromethylated allenes and is also a rare example of trifunctionalization of 1,3-enynes.

Iron-catalyzed carboazidation of alkenes and alkynes.

Carboazidation of alkenes and alkynes holds the promise to construct valuable molecules directly from chemical feedstock therefore is significantly important. Although a few examples have been developed, there are still some unsolved problems and lack of universal methods for carboazidation of both alkenes and alkynes. Here we describe an iron-catalyzed rapid carboazidation of alkenes and alkynes, enabled by the oxidative radical relay precursor t-butyl perbenzoate. This strategy enjoys success with a broad scope of alkenes under mild conditions, and it can also work with aryl alkynes which are challenging substrates for carboazidation. A large number of diverse structures, including many kinds of amino acid precursors, fluoroalkylated vinyl azides, other specific organoazides, and 2H-azirines can be easily produced.

Copper-Catalyzed Radical 1,4-Difunctionalization of 1,3-Enynes with Alkyl Diacyl Peroxides and N-Fluorobenzenesulfonimide.

Many reactions involving allenyl ion species have been studied, but reactions involving allenyl radicals are less well understood, perhaps because of the inconvenience associated with the generation of short-lived allenyl radicals. We describe here a versatile method for the generation of allenyl radicals and their previously unreported applications in the intermolecular 1,4-carbocyanation and 1,4-sulfimidocyanation of 1,3-enynes. With the assistance of the trifunctional reagents, alkyl diacyl peroxides or N-fluorobenzenesulfonimide, a range of synthetically challenging multisubstituted allenes can be prepared with high regioselectivity. These multisubstituted allenes can be easily transformed into synthetically useful structures such as fluorinated vinyl cyanides, lactones, functionalized allenyl amides, 1-aminonaphthalenes, and pyridin-2(1 H)-ones, and several novel transformations are reported. The results of radical scavenger and radical clock experiments are consistent with the proposed allenyl radical pathway. Density functional theory (DFT) and IR spectroscopy studies suggest the formation of an isocyanocopper(II) species in the ligand exchange step. On the basis of the results of IR, DFT, and diastereoselectivity studies, an isocyanocopper(II)/copper(I) catalytic cycle is proposed, which differs from the previously considered Cu(III) mechanism in cyanation reactions.

Impact of the Valence Charge of Transition Metals on the Cobalt- and Rhodium-Catalyzed Synthesis of Indenamines, Indenols, and Isoquinolinium Salts: A Catalytic Cycle Involving MIII/MV [M = Co, Rh] for [4 + 2] Annulation.

Reaction mechanisms for the synthesis of indenamines, indenols, and isoquinolinium salts through cobalt- and rhodium-catalysis were investigated using density functional theory calculations. We found that the valence charge of transition metals dramatically influences the reaction pathways. Catalytic reactions involving lower-oxidation-state transition metals (MI/MIII, M = Co and Rh) generally favor a [3 + 2] cyclization pathway, whereas those involving higher oxidation states (MIII/MV) proceed through a [4 + 2] cyclization pathway. A catalytic cycle with novel MIII/MV as a crucial species was successfully revealed for isoquinolinium salts synthesis, in which highly valent MV was encountered not only in the [RhCp*]-catalysis but also in the [CoCp*]-catalysis.

Multicomponent reactions of phosphines, enynedioates and benzylidene malononitriles generated highly substituted cyclopentenes through an unexpected phosphine α-addition-δ-evolvement of an anion pathway.

Multicomponent reactions of phosphines, enynedioates and benzylidene malononitriles provide highly substituted syn-selective cyclopentenes appending the phosphorus ylide moiety in good yield with a diastereoselectivity of up to 100% through resonance-derived 1,5-dipolar species as the key intermediates, via the nucleophilic α(δ')-attack of phosphines toward enynedioates followed by addition to benzylidene malononitriles and 5-exo-dig cyclization. Through computational analyses, the overall reactions for the formation of syn- and anti-diastereomers are both exothermic with 65.6 and 66.3 kcal mol(-1) at the B3LYP-D3/6-31G(d) level of theory and were found to be kinetically controlled, which favours the formation of syn-diastereomers.

Effects of iodine on the relaxation dynamics of a photoexcited I(-)(H(2)O)(4) cluster.

The Born-Oppenheimer molecular dynamics are used to examine the relaxation dynamics of the charge-transfer-to-solvent (CTTS) photoexcited electron in I(-)(H2O)4. The dynamics are initiated from the C1' cluster configuration, which contains a dangling water molecule. The iodine atom is found to exert a repulsive force on the photoexcited electron at the beginning but an attractive force at later times of the simulation. This dual repulsion-and-attraction role of the iodine atom is found to be dependent on the ratio of the iodine-electron distance to the radius of gyration of the excited electron, d/r. In the region of d/r < ∼0.8, the iodine exerts an exclusion-repulsion force on the excited electron. Conversely, for values of d/r > ∼1.0, the iodine can exert an attractive force on the excited electron due to the induced dipole moment of iodine. However, at large iodine-electron distances, the iodine-electron interaction becomes very weak, and as a result, this attractive force is expected to fade away. Due to the heavy mass of the iodine atom, the evolution of the iodine-electron distance is driven by the motion of solvent molecules and not iodine itself. The dangling water molecules and the dipolar field of water molecules are also important in the solvent dynamics. The influence of temperature on the iodine effects and the experimental implications of the findings are also discussed.

Exploring water binding motifs to an excess electron via X2(-)(H2O) [X = O, F].

X(2)(-)(H(2)O) [X = O, F] is utilized to explore water binding motifs to an excess electron via ab initio calculations at the MP4(SDQ)/aug-cc-pVDZ + diffs(2s2p,2s2p) level of theory. X(2)(-)(H(2)O) can be regarded as a water molecule that binds to an excess electron, the distribution of which is gauged by X(2). By varying the interatomic distance of X(2), r(X1-X2), the distribution of the excess electron is altered, and the water binding motifs to the excess electron is then examined. Depending on r(X1-X2), both binding motifs of C(s) and C(2v) forms are found with a critical distance of ∼1.37 Å and ∼1.71 Å for O(2)(-)(H(2)O) and F(2)(-)(H(2)O), respectively. The energetic and geometrical features of O(2)(-)(H(2)O) and F(2)(-)(H(2)O) are compared. In addition, various electronic properties of X(2)(-)(H(2)O) are examined. For both O(2)(-)(H(2)O) and F(2)(-)(H(2)O), the C(s) binding motif appears to prevail at a compact distribution of the excess electron. However, when the electron is diffuse, characterized by the radius of gyration in the direction of the X(2) bond axis with a threshold of ∼0.84 Å, the C(2v) binding motif is formed.

Potential energy surface of O2-(H2O) and factors controlling water-to-O2- binding motifs.

The potential energy surface (PES) of O(2)(-)(H(2)O) is investigated by varying the interoxygen distance of O(2)(-) via ab initio calculations with a large basis set. Although two stationary points, C(s) and C(2v) conformers, are found along the interoxygen-distance coordinate, only the C(s) conformer is identified as a minimum-energy species. We find a critical distance, r(c), separating these two conformers in the PES. The C(s) conformer prevails at interoxygen distances of O(2)(-) that are less than r(c), while the C(2v) conformer dominates at the distances larger than r(c). The structural features of these two conformers are also discussed. Although the water deformation energy is shown to be the stabilization source responsible for the prevalence of the C(s) cluster conformer at the interoxygen distances of O(2)(-) less than r(c), the ionic hydrogen bonding is the major driving force for transformation of the water binding motif from C(s) to C(2v) when the interoxygen distance of O(2)(-) increases.

Tuning through-bond Fe(III)/Fe(II) coupling by solvent manipulation of a central ruthenium redox couple.

The relationships between the intervalence energy (E(IT)) and the free energy difference (DeltaG) that exists between the minima of redox isomers (Fe(II)-Ru(III)/Fe(III)-Ru(II)) for various heterobimetallic complexes [(R-Fcpy)Ru(NH(3))(5)](2+/3+) (R = H, ethyl, Br, actyl; Fcpy = (4-pyridyl)ferrocenyl; Ru(NH(3))(5) = pentaam(m)ineruthenium) were examined. The changes in DeltaG for the complexes in various solvents were due to the effects of both solvent donicity and the substituents. The intervalence energy versus DeltaG, DeltaG approximately FDeltaE(1/2) (DeltaE(1/2) = E(1/2)(Fe(III/II)) - E(1/2)(Ru(III/II))), plots for the complexes in various solvents suggest a nuclear reorganization energy (lambda) of approximately 6000 cm(-1) (Chen et al. Inorg. Chem. 2000, 39, 189). For [(R-Fcpy)Ru(NH(3))(5)](2+) and [(et-Fcpy)Ru(NH(3))(4)(py)](2+) (Ru(NH(3))(4) = trans-tetraam(m)ineruthenium; py = pyridine) in various solvents, the E(1/2)(Ru(III/II)) of rutheniumam(m)ine typically was less than the E(1/2)(Fe(III/II)) of the ferrocenyl moiety. However, the low-donicity solvents resulted in relatively large values of E(1/2)(Ru(III/II)) for [(et-Fcpy)Ru(NH(3))(4)(py)](2+/3+/4+). Under our unique solvent conditions, a dramatic end-to-end interaction was observed for the trimetal cation, [(et-Fcpy)(2)Ru(NH(3))(4)](4+), in which the [(et-Fcpy)(2)Ru(NH(3))(4)](4+) included a central trans-tetraam(m)ineruthenium(III) and a terminal Fe(II)/Fe(III) pair. In general, results of electrochemical studies of [(et-Fcpy)(2)Ru(NH(3))(4)](2+) indicated both solvent-tunable E(1/2)(Ru(III/II)) (1 e(-)) and solvent-insensitive E(1/2)(Fe(III/II)) (2 e(-)) redox centers. However, in nitriles, two E(1/2)(Fe(III/II)) peaks were found with DeltaE(1/2)(Fe(III/II) - Fe(III/II)) ranging between 83 and 108 mV at a terminal metal-to-metal distance of up to 15.6 A. Furthermore, the bridging dpi orbital of the ruthenium center mediated efficient end-to-end interaction between the combinations of the terminal Fe(II)-Fe(III)/Fe(III)-Fe(II) pair. To our knowledge, this is the first example of solvent-tunable end-to-end interactions in multimetal complexes.