Substituent effects on the reactivity of the silicon-carbon double bond

Laser flash photolysis of various organosilicon compounds such as aryl-, vinyl-, and alkynyldisilanes, silacyclobutanes and silacyclobutenes, and alpha-silylketenes and -diazomethanes leads to the formation of reactive silenes which can be detected directly in solution, allowing detailed studies of the kinetics and mechanisms of their reactions with nucleophiles. Over 30 transient silenes have now been studied by these methods, providing the opportunity to systematically assess the effects of substituents at silicon and carbon on the reactivity of the Si=C bond.     

Pericyclic Organometallic Reactions. Substituent Effects on Cycloadditions and Rearrangements of (η4-cycloheptatriene)Fe(CO)3 Derivatives

The mechanism of the reactions of (η⁴-cycloheptatrien-1-al)Fe(CO)₃ and its ethyleneglycol acetal with tetracyanoethylene (TCNE) was studied. The aldehyde undergoes a fast reversible 3+2 cycloaddition involving the free aldehyde-substituted double bond, and a slow irreversible 3+2 cycloaddition at the coordinated site. The latter, σ,π-allylic complex undergoes a slow interconversion with the corresponding 5 +2 isomer via the pericyclic [3,3]-sigmahaptotropic rearrangement. In contrast, the acetal reacts with TCNE at the free acetal-substituted double bond to give a single kinetic 3+2 adduct, which, under thermodynamic conditions, undergoes a [4,4]-sigmahaptotropic rearrangement to the 6 + 2 adduct. The reaction kinetics was followed by ¹H NMR. The effect of substituents on the reaction course is discussed, and the detailed mechanism of both the cycloadditions and rearrangements is described.     

Cycloaddition chemistry of organic molecules with semiconductor surfaces

Recent investigations have shown that cycloaddition reactions, widely used in organic chemistry to form ring compounds, can also be applied to link organic molecules to the (001) surfaces of crystalline silicon, germanium, and diamond. While these surfaces are comprised of Si=Si, Ge=Ge, and C=C structural units that resemble the C=C bonds of organic alkenes, the rates and mechanisms of the surface reactions show some distinct differences from those of their organic counterparts This article reviews recent studies of [2 + 2], [4 + 2] Diels-Alder, and other cycloaddition reactions of organic molecules with semiconductor surfaces and summarizes the current understanding of the reaction pathways.     

Synthesis of Multisubstituted Silyloxy-based Donor-Acceptor Cyclobutanes by an Acid-Catalyzed [2+2] Cycloaddition

This account summarizes our recent efforts on the acid-catalyzed [2+2] cycloaddition of silyl enol ethers with α,β-unsaturated esters, giving donor-acceptor (D -A) cyclobutanes and their related reactions. The cycloaddition generally produces multisubstituted cyclobutanes in good yields with high diastereoselectivity. We found that aluminum Lewis acids and triflic imide (Tf₂NH) had good catalytic activity. The retro [2+2] cycloaddition proceeded at higher reaction temperatures, and in some cases, diastereoselectivity switching of cycloadducts was observed. A microflow protocol was established for Tf₂NH-catalyzed [2+2] cycloaddition. Although the cycloaddition usually requires cryogenic conditions in a batch reactor, the microreactor system enabled the production of D -A cyclobutanes, even at ambient temperature. [2+2] Cycloaddition of allylsilanes and alkyl enol ethers, instead of silyl enol ethers, afforded the corresponding D -A cyclobutanes.     

Synthesis of Group 9 Metal‐Olefin Complexes with Identical Ligand Frameworks and Comparison of their Catalytic Activity in [2+2+2] Cycloaddition and other Addition Reactions

The preparation and catalytic evaluation of the three group 9 (cyclopentadienyl)metal(trimethylvinylsilane) complexes of the type C₅H₅M(H₂CCHSiMe₃)₂ (M=cobalt, rhodium and iridium) are reported. The complexes were investigated in [2+2+2] cycloaddition as well as in hydrogenation, hydroformylation and hydroboration reactions. Despite the identical organic frameworks and structural parameters, the complexes display remarkable reactivity and stability differences.     

Combining in situ Generated Chiral Silicon Lewis Acid and Chiral Brønsted Acid Catalysts for [3+2] Cycloadditions: Cooperative Catalysis as a Convenient Enantioselective Route to Pyrazolidines

A facile enantioselective synthesis of chiral pyrazolidines via a [3+2] cycloaddition reaction, involving a BINOL‐derived phosphoric acid and an in situ generated BINOL phosphate‐derived silicon Lewis acid, which may act cooperatively, has been developed.     

Zinc‐Catalyzed Tandem Diels–Alder Reactions of Enynals with Alkenes: Generation and Trapping of Cyclic o‐Quinodimethanes (o‐QDMs)

A systematic investigation of ZnCl₂‐catalyzed reactions of enynals with alkenes has been undertaken. Structurally unique propeller‐like products could be obtained under mild conditions. Cyclic o‐quinodimethanes (o‐QDMs) are generated through [4+2] cycloaddition between enynals and alkenes. Both electron‐poor and electron‐rich dienophiles could be used to trap the active intermediate through [4+2] cycloaddition. But [1,5]‐H shift products could also be observed when electron‐rich alkenes were used as dienophile. DFT calculations were performed to understand the reaction mechanism. A competition between the [4+2] cycloaddition and [1,5]‐H shift was proposed for the transformation of cyclic o‐QDMs. The selectivity could be affected by the properties of the substrates.

     

The Thermal Rearrangement of 1,2,7-Trienes

The thermal rearrangement of 1,6,7-nonatriene and 1,2,7-octatriene at 400°C has been studied. Besides intramolecular [2 + 2] cycloaddition reactions, these hydrocarbons undergo intramolecular ene reactions, furnishing cis-1-methyl-2-(1-propynyl)cyclopentane and cis-1-ethynyl-2-methylcyclopentane, respectively.     

Clickable poly(ionic liquid)s for modification of glass and silicon surfaces

Covalent attachment of poly(ionic liquid)s (PILs) by click chemistry on glass or silicon (Si) surfaces was performed. Poly[1-(4-vinylbenzyl)-3-butylimidazolium bis(trifluoromethylsulfonyl)imide] (polyVBBI⁺Tf₂N⁻), and copolymers of polyVBBI⁺Tf₂N⁻ with fluorescein O-methacrylate were synthesized by conducting an atom transfer radical polymerization (ATRP) from initiators containing azide or thioacetate groups. The azide- and thiol-terminated PILs were then successfully grafted onto alkyne and alkene modified glass/Si wafers by thermal azide–alkyne cycloaddition and photoinitiated thiol-ene click reactions, respectively. The modified surfaces were characterized by contact angle measurements and ellipsometry. The fluorescent PIL functionalized surfaces showed strong fluorescence under UV irradiation. This procedure of tethering PILs to substrates also provides an easy way to change the surface hydrophilicity by replacing the anions in the grafted PILs. The present approach could be readily applied for surface modifications with other types of PILs or their copolymers to achieve different functionalities on various surfaces.     

Incorporation of Metal Ions into Silica-Grafted Imidazolium-Based Ionic Liquids to Efficiently Catalyze Cycloaddition Reactions of CO<Subscript>2</Subscript> and Epoxides

Abstract  

A variety of imidazolium-based ionic liquids (ILs) have been widely developed to effectively catalyze the cycloaddition reactions of CO₂ and epoxides. To further improve the catalytic performance of those IL catalysts, we incorporated various metal chlorides (CoCl₂, NiCl₂, CuCl₂, ZnCl₂, and MnCl₂) into silica-grafted 1-methyl-3-[(triethoxysilyl)propyl] imidazolium chloride to produce a series of heterogeneous catalysts. Catalytic reaction tests demonstrated that the incorporation of such metal ions can significantly enhance the catalytic reactivity of the silica-grafted ILs towards cycloaddition reactions of CO₂ and epoxides that produce cyclic carbonates in solvent-free conditions. In addition, the effects on the catalytic reactivity of reaction parameters including reaction time, reaction temperature and CO₂ pressure were investigated.     

Mg(II)-Catalyzed [4+2] Annulation for the Synthesis of 2-Arylquinoline Motifs: Applications and DFT Studies

Mg-catalyzed [4+2] cycloaddition reactions between 2-aminobenzaldehydes and ynones offered an array of 2-arylquinoline motifs merged with a CF₃-acyl group. Furthermore, with Mg-catalyzed [4+2] annulation as the key step, DDD107498, DDD102542, and Hit analogues were assembled. Finally, a computational study of the reaction mechanism was conducted.     

联烯类化合物[3+2]环加成反应的研究进展

环加成反应是有机化学中非常重要的一类反应,常用于多元环类化合物的合成。联烯是具有丙二烯结构单元的一类不饱和化合物,广泛存在于自然界中,由于其特殊结构与反应活性,可与许多含不饱和键的化合物发生环加成反应来制备吲哚、呋喃或吡啶等多种环状化合物。近年来,联烯及其衍生物已经引起了国内外许多科研工作者的兴趣。综述了近几年联烯类化合物与含各种不饱和键化合物[3+2]环加成反应的研究进展,并对其发展方向进行了展望。     

[4+2] Cycloaddition of ortho‐Quinone Methides Promoted by Ionic Liquids: an Efficient and Mild Protocol for the Synthesis of Tetrahydropyranobenzopyrans

The stereoselective synthesis of trans‐annelated pyrano[3,2‐c]benzopyrans has been achieved by intramolecular [4+2] cycloaddition of o‐benzoquinone methides that are generated in situ from o‐hydroxybenzaldehydes and unsaturated alcohols using an air‐ and moisture‐stable ionic liquid, i.e., 1‐butyl‐3‐methylimidazolium tetrafluoroborate [bmim]BF₄ under mild and neutral conditions.     

Redox Potentials of High-Valent Iron-, Cobalt-, and Nickel-Oxido Complexes: Evidence for Exchange Enhanced Reactivity

The ferrocene titration method has been employed to determine the one-electron reduction potentials of a series of oxido-iron(IV), oxido-cobalt(IV) and oxido/hydroxido-nickel(III) complexes based on the same tetradentate TMG₃tren ligand (TMG₃tren=tris[2-(N-tetramethylguanidyl)ethyl]amine). The S=2 ground state of the [(TMG₃tren)Fe^IV=O]²⁺ complex allows an exchange enhanced reactivity, which enables it to perform efficient oxygen atom transfer (OAT) and hydrogen atom abstraction (HAA) reactions with a low one-electron reduction potential of 270 mV vs. SCE. In the absence of exchange enhanced reactivity, the OAT and HAA abilities of the S=3/2 [(TMG₃tren)Co^IV−O(Sc(OTf)₃)]²⁺, S=1/2 [(TMG₃tren)Ni^III−O(H)]²⁺ and the previously reported S=1 [(TMC)(CH₃CN)Fe^IV=O]²⁺ and [(N4Py)Fe^IV=O]²⁺ complexes can be directly correlated to their reduction potentials. Notably, [(N4Py)Fe^IV=O]²⁺ and [(TMG₃tren)Fe^IV=O]²⁺ exhibit similar OAT and HAA reactivities although the reduction potential of [(N4Py)Fe^IV=O]²⁺ is 0.24 V more positive than that of [(TMG₃tren)Fe^IV=O]²⁺. The present study therefore provides experimental evidence for exchange enhanced reactivity and rationalizes nature's choice for employing S=2 oxido-iron(IV) cores to achieve difficult oxidation reactions at biologically viable potentials.     

A Facile and Efficient Synthesis of Dihydroisobenzofuran Derivatives via Tandem Palladium‐Catalyzed Coupling,Propargyl‐Allenyl Rearrangement, [4+2] Cycloaddition and Aromatization Reaction

A variety of dihydroisobenzofuran derivatives has been prepared in good yields via an interesting sequential reaction consisting of palladium‐catalyzed coupling, propargyl‐allenyl rearrangement, [4+2] cycloaddition and aromatization. A double‐coupling, rearrangement, [4+2] cycloaddition and aromatization process is also described for the synthesis of more complex and diverse structures.     

Functionalization of multi‐walled carbon nanotubes with poly(ε‐caprolactone) using click chemistry

Multi‐walled carbon nanotubes (MWNTs) were covalently functionalized with poly(ε‐caprolactone) (PCL) using click chemistry. First, chlorine moiety‐containing PCL was synthesized by the copolymerization of α‐chloro‐ε‐caprolactone with ε‐caprolactone monomer using ring opening polymerization, and further converted to azide moiety‐containing PCL. The alkyne‐functionalized MWNTs were prepared with the treatment of p‐amino propargyl ether using a solvent free diazotization procedure. The covalent functionalization of alkyne‐derived MWNTs with azide moiety‐containing PCL was accomplished using Cu(I)‐catalyzed [3+2] Huisgen dipolar cycloaddition click chemistry. The PCL‐functionalization of MWNTs was confirmed by the measurements of Fourier transform infra‐red, NMR, Raman spectroscopy, scanning electron microscopy, and transmission electron microscopy. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Interrogation of an Enzyme Library Reveals the Catalytic Plasticity of Naturally Evolved [4+2] Cyclases

Stereoselective carbon-carbon bond forming reactions are quintessential transformations in organic synthesis. One example is the Diels-Alder reaction, a [4+2] cycloaddition between a conjugated diene and a dienophile to form cyclohexenes. The development of biocatalysts for this reaction is paramount for unlocking sustainable routes to a plethora of important molecules. To obtain a comprehensive understanding of naturally evolved [4+2] cyclases, and to identify hitherto uncharacterised biocatalysts for this reaction, we constructed a library comprising forty-five enzymes with reported or predicted [4+2] cycloaddition activity. Thirty-one library members were successfully produced in recombinant form. In vitro assays employing a synthetic substrate incorporating a diene and a dienophile revealed broad-ranging cycloaddition activity amongst these polypeptides. The hypothetical protein Cyc15 was found to catalyse an intramolecular cycloaddition to generate a novel spirotetronate. The crystal structure of this enzyme, along with docking studies, establishes the basis for stereoselectivity in Cyc15, as compared to other spirotetronate cyclases.     

A one-pot approach to dendritic star polymers via double click reactions

A class of well-defined dendritic star polymers with poly (ε-caprolactone) (PCLs) on the periphery has been prepared via one-pot double click reactions (Cu-catalyzed azide/alkyne click chemistry, i.e., CuAAC and Diels–Alder [4+2] cycloaddition reactions). The predecessors for Diels–Alder reaction, maleimide end-functionalized PCLs were produced by ring-opening polymerization (ROP). Obtained dendritic star polymers were characterized by ¹H NMR, size exclusion chromatography (SEC), UV/vis, and fluorescence spectroscopy.     

Aryne-Based Synthesis of Cyclobutadiene-Containing Oligoacenes and Related Extended Biphenylene Derivatives

A previously undescribed aryne derived from a π-extended biphenylene, 2,3-didehydrobenzo[b]biphenylene, has been developed. The participation of this new aryne building block in [4+2] and palladium-catalyzed [2+2+2] cycloaddition reactions has been applied to the synthesis of a variety of polycyclic conjugated hydrocarbons (PCHs) with appealing structures which combine (aromatic) benzene and (antiaromatic) cyclobutadiene (CBD) rings. Among them, a family of unsubstituted (or barely substituted) CBD-oligoacenes has been accessed by iterative Diels-Alder reactions of the new aryne with furans and/or isobenzofurans, followed by deoxygenative aromatization of the resulting epoxy-derivatives. The experimental and computational studies of the newly synthesized PCHs suggest an important degree of electron delocalization along the polycyclic skeleton, more pronounced in the linearly fused derivatives. The computed ACID plots reveal clockwise current density vectors at the peripheral bonds, originating from the σ contributions of the antiaromatic cyclobutadiene rings.     

Synthesis and Pharmacological Properties of Silicon‐Containing GPR81 and GPR109A Agonists

The GPR81 and GPR109A receptors mediate antilipolytic effects and are potential drug targets for the treatment of metabolic disorders such as dyslipidemia and type 2 diabetes. There is still a need to identify potent GPR81 agonists as pharmacological tools. A high‐throughput screen identified an acylurea‐based GPR81 agonist lead series, with activities at the GPR109A receptor as well. To expand the chemical scope and to explore the pharmacological and pharmacokinetic consequences, a series of structurally related organosilicon compounds with a 6‐sila‐4,5,6,7‐tetrahydrobenzo[d]thiazole skeleton was synthesized and studied for their physicochemical properties [octanol/water distribution coefficient (pH 7.4), solubility in HBSS buffer (pH 7.4)], agonistic potency at rat GPR81 and GPR109A receptors, and intrinsic clearance in human liver microsomes and rat hepatocytes. The straightforward synthesis of these organosilicon compounds offered a valuable expansion of the chemical scope in the above‐mentioned GPR81 agonist lead series, provided potency and efficacy SAR, and yielded compounds with sub‐micromolar GPR81 potency. This work supports the value of including silicon chemistry into the toolbox of medicinal chemistry.