Applications of Transition Metal-Catalyzed ortho-Fluorine-Directed C-H Functionalization of (Poly)fluoroarenes in Organic Synthesis.

The synthesis of organic compounds efficiently via fewer steps but in higher yields is desirable as this reduces energy and reagent use, waste production, and thus environmental impact as well as cost. The reactivity of C-H bonds ortho to fluorine substituents in (poly)fluoroarenes with metal centers is enhanced relative to meta and para positions. Thus, direct C-H functionalization of (poly)fluoroarenes without prefunctionalization is becoming a significant area of research in organic chemistry. Novel and selective methodologies to functionalize (poly)fluorinated arenes by taking advantage of the reactivity of C-H bonds ortho to C-F bonds are continuously being developed. This review summarizes the reasons for the enhanced reactivity and the consequent developments in the synthesis of valuable (poly)fluoroarene-containing organic compounds.

Synthesis, Photophysical and Electronic Properties of a D-π-A Julolidine-Like Pyrenyl-o-Carborane.

We synthesized 2-(1-1,2-dicarbadodecaboranyl(12))-6,6,12,12-tetramethyl-7,8,11,12-tetrahydro-6H,10H-phenaleno[1,9-fg]pyrido[3,2,1-ij]quinoline (4), a julolidine-like pyrenyl-o-carborane, with pyrene substituted at the 2,7-positions on the HOMO/LUMO nodal plane. Using solid state molecular structures, photophysical data, cyclic voltammetry, DFT and LR-TDDFT calculations, we compare o-carborane and B(Mes)2 (Mes=2,4,6-Me3C6H2) as acceptor groups. Whereas the π-acceptor strength of B(Mes)2 is sufficient to drop the pyrene LUMO+1 below the LUMO, the carborane does not do this. We confirm the π-donor strength of the julolidine-like moiety, however, which raises the pyrene HOMO-1 above the HOMO. In contrast to the analogous pyrene-2-yl-o-carborane, 2-(1-1,2-dicarbadodecaboranyl(12))-pyrene VI, which exhibits dual fluorescence, because the rate of internal conversion between locally-excited (LE) and charge transfer (CT) (from the pyrene to the carborane) states is faster than the radiative decay rate, leading to a thermodynamic equilibrium between the 2 states, 4 shows only single fluorescence, as the CT state involving the carborane as the acceptor moiety in not kinetically accessible, so a more localized CT emission involving the julolidine-like pyrene moiety is observed.

Phosphine-Catalyzed 1,2-cis-Diboration of 1,3-Butadiynes.

Trialkyl phosphines PMe3 and PEt3 catalyze the 1,2-cis-diboration of 1,3-butadiynes to give 1,2-diboryl enynes. The products were utilized to synthesize 1,1,2,4-tetraaryl enynes using a Suzuki-Miyaura protocol and can readily undergo proto-deborylation.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77 K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

Invited for the cover of this issue are the groups of Holger Braunschweig at the Julius-Maximilians-Universität Würzburg, Germany and Eufrânio N. da Silva Júnior at the Universidade Federal de Minas Gerais, UFMG, Brazil. The image depicts the electrochemical synthesis of selenium-containing BODIPY molecules with lightning symbolizing the electrifying synthetic process, while the surrounding elemental chaos hints at the red-shifted absorption and emission and the transformative photophysical properties of these new compounds. Read the full text of the article at 10.1002/chem.202303883.

Photoredox/Cu-Catalyzed Decarboxylative C(sp3)-C(sp3) Coupling to Access C(sp3)-Rich gem-Diborylalkanes.

gem-Diborylalkanes are highly valuable building blocks in organic synthesis and the pharmaceutical chemistry due to their ability to participate in multi-step cross-coupling transformations, allowing for the rapid generation of molecular complexity. While progress has been made in their synthetic metholodology, the construction of ß-tertiary and C(sp3)-rich gem-diborylalkanes remains a synthetic challenge due to substrate limitations and steric hindrance issues. An approach is presented that utilizes synergistic photoredox and copper catalysis to achieve efficient C(sp3)-C(sp3) cross-coupling of alkyl N-hydroxyphthalimide esters, which can be easily obtained from alkyl carboxylic acids, with diborylmethyl species, providing a series of C(sp3)-rich gem-diborylalkanes with 1°, 2°, and even 3° ß positions. Furthermore, this approach can also be applied to complex medicinal compounds and natural products, offering rapid access to molecular complexity and late-stage functionalization of C(sp3)-rich drug candidates. Mechanistic experiments revealed that diborylmethyl Cu(I) species participated in both the photoredox process and the key C(sp3)-C(sp3) bond-forming step.

On the Reactivity of a NHC Nickel Bis-Boryl Complex: Reductive Elimination and Formation of Mono-Boryl Complexes.

The synthesis of the first terminal mono-boryl complexes of nickel, which are not stabilized by a pincer ligand, is reported. The reaction of the nickel bis-boryl complex cis-[Ni(i Pr2 ImMe )2 (Bcat)2 ] 1 (cat=1,2-O2 C6 H4 ) with the small donor ligand PMe3 led to a complete ligand exchange at nickel with reductive elimination of B2 cat2 and formation of the bis-NHC adduct [B2 cat2 ⋅ (i Pr2 ImMe )2 ] 3 and [Ni(PMe3 )4 ] 2 as the metal-containing species. Electrophilic attack of MeI on complex 1 or ligand dismutation of 1 with trans-[Ni(i Pr2 ImMe )2 Br2 ] led to loss of only one boryl ligand of 1 and afforded the nickel mono-boryl complexes trans-[Ni(i Pr2 ImMe )2 (Bcat)Br] 4 a and trans-[Ni(i Pr2 ImMe )2 (Bcat)I] 4 b.

Controlled Formation of Porous 2D Lattices from C3 -symmetric Ph6 -Me-Tribenzotriquinacene-OAc3.

The on-surface self-assembly of molecules to form holey nanographenes is a promising approach to control the properties of the resulting 2D lattice. Usually, planar molecules are utilized to prepare flat, structurally confined molecular layers, with only a few recent examples of warped precursors. However, control of the superstructures is limited thus far. Herein, we report the temperature-controlled self-assembly of a bowl-shaped, acetylated C3 -symmetric hexaphenyltribenzotriquinacene derivative on Cu(111). Combining scanning tunneling microscopy (STM) and density functional theory (DFT) confirms the formation of highly differing arrangements starting with π-stacked bowl-to-bowl dimers at low coverage at room temperature via chiral honeycomb structures, an intermediate trigonal superstructure, followed by a fully carbon-based, flattened hexagonal superstructure formed by on-surface deacetylation, which is proposed as a precursor for holey graphene networks with unique defect structures.

Regioselective Iridium-Catalyzed C8-H Borylation of 4-Quinolones via Transient O-Borylated Quinolines.

The quinolone-quinoline tautomerization is harnessed to effect the regioselective C8-borylation of biologically important 4-quinolones by using [Ir(OMe)(cod)]2 as the catalyst precursor, the silica-supported monodentate phosphine Si-SMAP as the ligand, and B2 pin2 as the boron source. Initially, O-borylation of the quinoline tautomer takes place. Critically, the newly formed 4-(pinBO)-quinolines then undergo N-directed selective Ir-catalyzed borylation at C8. Hydrolysis of the OBpin moiety on workup returns the system to the quinolone tautomer. The C8-borylated quinolines were converted to their corresponding potassium trifluoroborate (BF3 K) salts and to their C8-chlorinated quinolone derivatives. The two-step C-H borylation-chlorination reaction sequence resulted in various C8-Cl quinolones in good yields. Conversion to C8-OH-, C8-NH2 -, and C8-Ar-substituted quinolones was also feasible by using this methodology.

The Radical Anion and Dianion of Benzo[3,4]cyclobuta[1,2-b]phenazine.

We present the reduction of two azaacenes (a benzo-[3,4]cyclobuta[1,2-b]phenazine and a benzo[3,4]cyclobuta[1,2-b]naphtho[2,3-i]phenazine derivative), featuring a single cyclobutadiene unit, to their radical anions and dianions. The reduced species were produced using potassium naphthalenide in the presence of 18-crown-6 in THF. Crystal structures of the reduced representatives were obtained and their optoelectronic properties evaluated. Charging these 4n Hückel systems gives dianionic 4n + 2 π-electron systems with increased antiaromaticity, according to NICS(1.7)zz calculations, featuring unusually red-shifted absorption spectra.

Photoinduced Borylation for the Synthesis of Organoboron Compounds.

Organoboron compounds have important synthetic value and can be applied in numerous transformations. The development of practical and convenient ways to synthesize boronate esters has thus attracted significant interest. Photoinduced borylations originated from stoichiometric reactions of alkanes and arenes with well-defined metal-boryl complexes. Now, photoredox-initiated borylations, catalyzed by either transition metal or organic photocatalysts, and photochemical borylations with high efficiency have become a burgeoning area of research. In this Focus Review, we summarize research on photoinduced borylations, especially emphasizing recent developments and trends. This includes the photoinduced borylation of arenes, alkanes, aryl/alkyl halides, activated carboxylic acids, amines, alcohols, and so on based on transition metal catalysis, metal-free organocatalysis, and direct photochemical activation. We focus on reaction mechanisms involving single-electron transfer, triplet-energy transfer, and other radical processes.

First-Row d-Block Element-Catalyzed Carbon-Boron Bond Formation and Related Processes.

Organoboron reagents represent a unique class of compounds because of their utility in modern synthetic organic chemistry, often affording unprecedented reactivity. The transformation of the carbon-boron bond into a carbon-X (X = C, N, and O) bond in a stereocontrolled fashion has become invaluable in medicinal chemistry, agrochemistry, and natural products chemistry as well as materials science. Over the past decade, first-row d-block transition metals have become increasingly widely used as catalysts for the formation of a carbon-boron bond, a transformation traditionally catalyzed by expensive precious metals. This recent focus on alternative transition metals has enabled growth in fundamental methods in organoboron chemistry. This review surveys the current state-of-the-art in the use of first-row d-block element-based catalysts for the formation of carbon-boron bonds.

The Nature of the (Oligo/Hetero)Arene Linker Connecting Two Triarylborane Cations Controls Fluorimetric and Circular Dichroism Sensing of Various ds-DNAs and ds-RNAs.

A series of tetracationic bis-triarylborane dyes, differing in the aromatic linker connecting two dicationic triarylborane moieties, showed very high submicromolar affinities toward ds-DNA and ds-RNA. The linker strongly influenced the emissive properties of triarylborane cations and controlled the fluorimetric response of dyes. The fluorene-analog shows the most selective fluorescence response between AT-DNA, GC-DNA, and AU-RNA, the pyrene-analog's emission is non-selectively enhanced by all DNA/RNA, and the dithienyl-diketopyrrolopyrrole analog's emission is strongly quenched upon DNA/RNA binding. The emission properties of the biphenyl-analog were not applicable, but the compound showed specific induced circular dichroism (ICD) signals only for AT-sequence-containing ds-DNAs, whereas the pyrene-analog ICD signals were specific for AT-DNA with respect to GC-DNA, and also recognized AU-RNA by giving a different ICD pattern from that observed upon interaction with AT-DNA. The fluorene- and dithienyl-diketopyrrolopyrrole analogs were ICD-signal silent. Thus, fine-tuning of the aromatic linker properties connecting two triarylborane dications can be used for the dual sensing (fluorimetric and CD) of various ds-DNA/RNA secondary structures, depending on the steric properties of the DNA/RNA grooves.

Photocatalyzed Borylcyclopropanation of Alkenes with a (Diborylmethyl)iodide Reagent.

Cyclopropane skeletons play a prominent role in the development of organic synthesis and pharmaceutical chemistry. Herein, we report the design and synthesis of a stable, multifunctional (diborylmethyl)iodide reagent (CHI(Bpin)2 ) for the photoinduced cyclopropanation of alkenes, providing an array of 1,2-substituted cyclopropylboronates in good yields. This α-haloboronic ester can be readily synthesized on a multigram scale from commercially available starting materials. Furthermore, the protocol displays high chemo- and diastereoselectivity, excellent functional-group tolerance, and allows for late-stage borylcyclopropanation of complex molecules. Mechanistic studies reveal that the borylcyclopropanation proceeds through a radical addition/polar cyclization pathway mediated by the photocatalyst fac-Ir(ppy)3 and visible light.

Efficient Narrowband Circularly Polarized Light Emitters Based on 1,4-B,N-embedded Rigid Donor-Acceptor Helicenes.

Narrow-band emission is essential for applicable circularly polarized luminescence (CPL) active materials in ultrahigh-definition CP-OLEDs. One of the most promising classes of CPL active molecules, helicenes, however, typically exhibit broad emission with a large Stokes shift. We present, herein, a design strategy capitalizing on intramolecular donor-acceptor interactions between nitrogen and boron atoms to address this issue. 1,4-B,N-embedded configurationally stable single- and double helicenes were synthesized straightforwardly. Both helicenes show unprecedentedly narrow fluorescence and CPL bands (full width at half maximum between 17-28 nm, 0.07-0.13 eV) along with high fluorescence quantum yields (72-85 %). Quantum chemical calculations revealed that the relative localization of the natural transition orbitals, mainly on the rigid core of the molecule, and small values of root-mean-square displacements between S0 and S1 state geometries, contribute to the narrower emission.

Electrophilic C-H Borylation of Aza[5]helicenes Leading to Bowl-Shaped Quasi-[7]Circulenes with Switchable Dynamics.

The intrinsic relationship between helicenes and circulenes is of fundamental interest and importance in molecular engineering. Herein, electrophilic borylation of phenanthroline-derived aza[5]helicenes is presented, resulting in the incorporation of a boryl unit into two termini of helicenes to afford quasi-[7]circulenes. Their bowl-shaped structures were determined by X-ray diffraction. UV-vis absorption and fluorescence spectroscopy, as well as electrochemical measurements and DFT calculations, gave insight into their electronic properties. Variable-temperature NMR studies and DFT calculations revealed bowl-to-bowl inversion at room temperature and bowl-to-helix equilibria at elevated temperature, highlighting the important role of B ← N bond strength in tuning their dynamic properties.

Copper-Catalyzed Borylation of Acyl Chlorides with an Alkoxy Diboron Reagent: A Facile Route to Acylboron Compounds.

Herein, the copper-catalyzed borylation of readily available acyl chlorides with bis(pinacolato)diboron, (B2 pin2 ) or bis(neopentane glycolato)diboron (B2 neop2 ) is reported, which provides stable potassium acyltrifluoroborates (KATs) in good yields from the acylboronate esters. A variety of functional groups are tolerated under the mild reaction conditions (room temperature) and substrates containing different carbon-skeletons, such as aryl, heteroaryl and primary, secondary, tertiary alkyl are applicable. Acyl N-methyliminodiacetic acid (MIDA) boronates can also been accessed by modification of the workup procedures. This process is scalable and also amenable to the late-stage conversion of carboxylic acid-containing drugs into their acylboron analogues, which have been challenging to prepare previously. A catalytic mechanism is proposed based on in situ monitoring of the reaction between p-toluoyl chloride and an NHC-copper(I) boryl complex as well as the isolation of an unusual lithium acylBpinOBpin compound as a key intermediate.

Selective, Transition Metal-free 1,2-Diboration of Alkyl Halides, Tosylates, and Alcohols.

Defunctionalization of readily available feedstocks to provide alkenes for the synthesis of multifunctional molecules represents an extremely useful process in organic synthesis. Herein, we describe a transition metal-free, simple and efficient strategy to access alkyl 1,2-bis(boronate esters) via regio- and diastereoselective diboration of secondary and tertiary alkyl halides (Br, Cl, I), tosylates, and alcohols. Control experiments demonstrated that the key to this high reactivity and selectivity is the addition of a combination of potassium iodide and N,N-dimethylacetamide (DMA). The practicality and industrial potential of this transformation are demonstrated by its operational simplicity, wide functional group tolerance, and the late-stage modification of complex molecules. From a drug discovery perspective, this synthetic method offers control of the position of diversification and diastereoselectivity in complex ring scaffolds, which would be especially useful in a lead optimization program.

Aggregation-Induced Dual Phosphorescence from (o-Bromophenyl)-Bis(2,6-Dimethylphenyl)Borane at Room Temperature.

Designing highly efficient purely organic phosphors at room temperature remains a challenge because of fast non-radiative processes and slow intersystem crossing (ISC) rates. The majority of them emit only single component phosphorescence. Herein, we have prepared 3 isomers (o, m, p-bromophenyl)-bis(2,6-dimethylphenyl)boranes. Among the 3 isomers (o-, m- and p-BrTAB) synthesized, the ortho-one is the only one which shows dual phosphorescence, with a short lifetime of 0.8 ms and a long lifetime of 234 ms in the crystalline state at room temperature. Based on theoretical calculations and crystal structure analysis of o-BrTAB, the short lifetime component is ascribed to the T1 M state of the monomer which emits the higher energy phosphorescence. The long-lived, lower energy phosphorescence emission is attributed to the T1 A state of an aggregate, with multiple intermolecular interactions existing in crystalline o-BrTAB inhibiting nonradiative decay and stabilizing the triplet states efficiently.

Base-Mediated Radical Borylation of Alkyl Sulfones.

A practical and direct method was developed for the production of versatile alkyl boronate esters via transition metal-free borylation of primary and secondary alkyl sulfones. The key to the success of the strategy is the use of bis(neopentyl glycolato) diboron (B2 neop2 ), with a stoichiometric amount of base as a promoter. The practicality and industrial potential of this protocol are highlighted by its wide functional group tolerance, the late-stage modification of complex compounds, no need for further transesterification, and operational simplicity. Radical clock, radical trap experiments, and EPR studies were conducted which show that the borylation process involves radical intermediates.