The scope and limitations of a germole-to-borole rearrangement are reported. Double salt metathesis reactions of dipotassium germolediides with amino-, aryl-, and ferrocenyl-substituted boron dihalides allow for the preparation of borole complexes of Ge(II) in synthetically useful yields and quantities. The analogous silole-to-borole transformation is viable but is less selective and of limited synthetic use. The analysis of the molecular and electronic structure of the obtained Ge(II) borole complexes classifies them as boragerma[5]pyramidanes, molecular nido-type clusters. The molecular structure can be fine-tuned as strongly electron-donating substituents at the boron atom induce an opening of the cluster. The boragerma[5]pyramidanes bind via the germanium atom to transition metal complexes and behave as σ-donors with only insignificant π-acceptor abilities. Their reduction with elemental lithium and their reaction with strong nucleophiles such as N-heterocylic carbenes (NHCs) lead to the elimination of germanium and isolation of borole derivatives.

Bicyclic perhydro-pentalene, -indene, and -azulene, as well as decaline skeletons were accessed by aerobic manganese(III)-mediated radical cyclizations of cyclic beta-oxoesters with five-, six-, and seven-membered rings and omega-alkenyl-omega-phenyl C4-C6 side chains in the beta '-position. After treatment of the intermediately formed peroxides with acetyl chloride and pyridine, Kornblum-DeLaMare fragmentation furnished the racemic bicyclic compounds with a 1,4-dicarbonyl structural motif. In five out of eight cases investigated, the cyclization reactions were successful with 56%-72% yields. Diastereoisomers could be separated in most cases and their relative configuration established by X-ray single crystal analysis, either directly or after derivatization with an aryl hydrazine. In the case of the pentalene and indane skeletons, conversion of their 1,4-dicarbonyl motif with seven aryl hydrazines gave a pyridazine ring system with 62%-96% yields. Products are pentaleno[1,6-cd]pyridazines or cyclopenta[de]cinnolines. A compound with a para-bromophenyl residue could be further derivatized in either a Suzuki cross-coupling (84% yield) or a Heck reaction (88% yield).

Phosphinamides are reported as a new class of P-bridged kappa 2 N,O-chelating ligand precursors for titanium-catalyzed hydroaminoalkylation reactions of alkenes and for the synthesis of new titanium complexes. To evaluate the catalytic activity in six different hydroaminoalkylation reactions, TiBn4 is used as a catalyst precursor in combination with a ligand precursor library obtained by a systematic variation of the P- and N-bound phenyl substituents of the phosphinamides. The catalyst screening reveals the beneficial role of para-methoxy- and meta-tert-butyl-substitution on the P- and N-bound benzene rings of the phosphinamides. The combination of both substitution patterns in a single ligand precursor leads to a significant synergistic effect, which, in combination with TiBn4, results in a highly active catalyst system for the intermolecular hydroaminoalkylation of alkenes. As a result, the reaction of 1-octene with N-methylaniline, performed with a catalyst loading of 5 mol % at 160 degrees C, delivers the branched hydroaminoalkylation product in 94% yield after 2 h. The same conditions can also be applied to other alkene and amine substrates. Furthermore, the synthesis of five new titanium complexes obtained from selected phosphinamide ligand precursors and Ti(NMe2)4 is described, and in each case, single-crystal X-ray diffraction confirms the expected kappa 2 N,O-coordination of the ligand.

The reactions of the Rosenthal reagent Cp2Ti(η2-BTMSA) with cyclopropenes and allenes were systematically investigated. With cyclopropenes, selective 1,2-insertion into the Ti-C bond induces a ring expansion from three- to five-membered frameworks, affording titanacyclopentenes. These bicyclic complexes undergo rearrangement under mild conditions to generate highly reactive titanium carbene species, which subsequently participate in [2 + 2] cycloaddition reactions with alkynes (BTMSA and 1,2-diphenylacetylene), yielding titanacyclobutenes. In contrast, reactions with allenes proceed via ligand exchange of the alkyne ligand, giving titanacyclopentane derivatives. In addition to these transformations, the titanium complex was found to catalyze the isomerization of cyclotrideca-1,2-diene to cyclotrideca-1,3-diene. All isolated complexes were comprehensively characterized by NMR spectroscopy, and the solid-state structures of most species were identified by single-crystal X-ray diffraction.

Titanocene-based complexes are among the most prominent organometallic anticancer drugs. Since the discovery of titanocene dichloride, numerous derivatives have been tested as potential chemotherapeutic agents. We previously reported on titanocene-based drug carriers by using substitution-labile triflato ligands to generate cationic complexes with cytotoxic thiosemicarbazones (TSCN). Building on this, we posed the question of whether the larger cyclopentadiene derivative, pentamethylcyclopentadiene (Cp*), might further stabilize the organometallic drug carriers or provide other benefits such as increased lipophilicity. In this work, we describe the synthesis of titanocene-based complexes bearing Cp* and TSCN ligands and discuss how the Cp* ligands affect the water solubility and stability. Our findings are supported by DFT calculations, which enable a rational approach for the design of novel organometallic drug carriers.

Alkylbenzene derivatives react with two equivalents of pivaloyl chloride (PivCl) in the presence of aluminum trichloride under formation of indene derivatives with up to 92% yield. Monosubstituted benzenes undergo this cyclopentannulation reaction with quantitative regioselectivity, which was proved by X‐ray single crystal structure analysis. A mechanistic proposal is based on the in situ‐formation of 2,2,5‐trimethyl‐4‐hexene‐3‐one from the acid chloride. This enone forms the indene derivatives in a sequence of two Friedel–Crafts alkylation reactions. Indeed, the 2,2,5‐trimethyl‐4‐hexene‐3‐one can be prepared from PivCl and AlCl3 in 68% yield. It can then be directly converted to the indene derivatives with yields up to 99%.

Bicyclic diketones and lactones are obtained in up to 60% yield in the aerobic, manganese‐catalyzed intramolecular radical cyclization of β‐oxoesters with a six‐membered ring and phenyl or diphenyl allyl substituents in the γ‐position. Intermediate products of this transformation are peroxides, which are processed either reductively with zinc–acetic acid or by Kornblum‐DeLaMare fragmentation (with acetyl chloride–pyridine). The respective congeners with five‐ or seven‐membered rings either undergo only α‐hydroxylation reactions or mixtures of various cyclization products are obtained in low yields. In this study, also cerium‐catalysis was investigated, however, the yields are lower compared to manganese catalysis. The relative configurations of all racemic products were established by X‐ray single crystal structure analyses.

The formation of titanium(IV) complexes with Cp,N,N and Cp,O,N tridentate ligands via insertion of the pyridine-containing precursors into the pentafulvene moiety of the titanium complexes is reported. After consecutive methylation and treatment with B(C6F5)3 according to a well-established method, cationic complexes with the weakly coordinating MeB(C6F5)3- anion were obtained. Further introduction of moderately strong coordinating triflato ligands provides insight into the nucleophilicity of the respective pyridinyl ligands. The Lewis acidity of the complexes is determined by well-established protocols. Depending on the donor strength, the triflato ligand is displaced by the pyridinyl ligand to produce a cationic complex with a triflate anion. The highly Lewis acidic cationic titanium(IV) complexes are able to perform reactions such as H2 functionalization and C-H activation reactions. The additional 15N NMR values of the pyridine-based ligand and UV/Vis spectra are key features of these ligand systems and further support the coordination mode determination.

Reactions of bis(π-η5:σ-η1-pentafulvene)titanium complexes with isocyanates result in selective insertions of either one or two equivalents of RN═C═O into the two frustrated Ti-Cexo bonds under mild conditions. Depending on the pentafulvene ligand, K1O- and K1N-amidato titanium complexes are obtained and comprehensively characterized by single crystal X-ray diffraction and NMR and IR spectroscopy. In case of single insertion products, the reactivity of the second pentafulvene ligand is investigated with respect to E-H cleavage reactions (alcohols, amines) and insertion reactions of multiple-bond-containing substrates (ketones, nitriles). Transformations of the obtained K1N- to the respective K1O-amidato complexes are observed and investigated by DFT studies and variable temperature NMR experiments.

The synthesis of a series of selanyl-stabilized cationic silyl Lewis acids with naphthalene or acenaphthalene scaffolds is described. The influence of scaffold modifications, substitution variations at the selanyl donor and at the silicon atom on the strengths of the silyl Lewis acid is evaluated using the p-fluorobenzonitrile (FBN) method. These simple variations of the principal structure allow to adjust the Lewis acidity of the cationic silyl Lewis acids from weak ones to examples that are significantly stronger than tris(pentafluorophenyl)borane (BCF). The solid-state structure of the cationic FBN complex [11(FBN)]+ with an acenaphthene backbone and a pentafluorophenylselanyl donor provides evidence for the penta-coordination of the silicon atom in this complex, in agreement with the results of nuclear magnetic resonance (NMR) studies in solution. Finally, this study suggests that the FBN method is well suited to assess even very subtle differences in the strength of Lewis acids.

We have synthesized two Preyssler-type polyoxometalate ({NaP5W30O110}14-)-based compounds [{CoII(C10H8N2)3}4{CoIII(C10H8N2)}0.74H4NaP5W30O110]·24H2O (1) and [{CuII(C10H8N2)2}4(C10H10N2)3NaP5W30O110]·6H2O (2) by solvothermal synthesis. The crystal structure of compound 1 consists of Preyssler polyoxometalate (POM) coordinated to {CoIII(2,2'-bpy)} (bpy = 2,2'-bipyridine, C10H8N2) complex and two uncoordinated {CoII(2,2'-bpy)3} complexes. The molecular structure of compound 2 consists of four {CuII(2,2'-bpy)2} complexes coordinated to terminal oxygens of Preyssler polyanion and three 2,2'-bipyridinium cations. Compounds 1 and 2 have been characterized unambiguously by single-crystal X-ray crystallography including PXRD, FT-IR, TGA, and DRS spectroscopy. In this work, compounds 1 and 2 are used as photocatalysts in the degradation of environmentally hazardous methylene blue (MB) dye via UV light irradiation. Compound 2 outperforms compound 1 in catalytic efficiency for the degradation of MB dye, achieving 78.1% efficiency compared to 72.3% for compound 1. The redox activities of compounds 1 and 2 have been investigated by electrochemical studies. Interestingly, compounds 1 and 2 exhibit solid-state fluorescence at room temperature.

The synthesis of an anionic [Ge,N]-bidentate ligand based on the combination of an amidopyridinato group with an anionic germolide ring is reported. The potential of the germolide part of this ligand to switch between η1-(via Ge) and η5-(via C4Ge) coordination modes makes this ligand an interesting synthetic target. Salt metathesis reactions of the potassium salt of this ligand with GeCl2 dioxane and SnCl2 allow the synthesis of bis-germolyl-substituted germylenes and stannylenes with the tetrel atoms in a distorted square pyramidal coordination environment.

A series of titanium amidinato complexes were synthesized by stoichiometric insertion reactions of carbodiimides into bis(pi-eta 5:sigma-eta 1-pentafulvene)titanium complexes. NMR studies and single-crystal X-ray diffraction showed kappa 1N coordination of the former carbodiimides to the metal center. DFT calculations were performed, confirming the clear preference for a single nitrogen atom coordinating to the metal center with a high energy transition state for the formation of a chelating heteroallyl ligand. Depending on the pentafulvene ligand, additional insertion reactions of carbodiimides into the remaining Ti-Cexo bond were observed. This allows for a stepwise insertion of the corresponding carbodiimides and offers the possibility to further functionalize the complexes. The reactivity of the remaining pentafulvene ligand is further demonstrated in reactions with H-acidic and multiple bond substrates.

As part of the activation of small molecules by transition metal complexes, reactions of bis(pi-eta 5:sigma-eta 1-pentafulvene)titanium complexes with various isothiocyanates are performed. Despite the presence of two double bonds, only the C=S bond reacts in this competing reaction, resulting in the selective formation of titanium kappa 1S thioamidato complexes. The insertion reaction occurs under mild conditions by the attack of the nucleophilic Ti-Cexo atom of the pentafulvene moiety on the central carbon atom of the isothiocyanate. Besides the reaction with an additional equivalent of isothiocyanate to form bis-kappa 1S thioamidato complexes, the reaction with H-acidic and multiple-bond-containing substrates leads to further functionalized complexes. The selective formation of the kappa 1S binding mode compared to a possible kappa 1N binding mode is further supported by DFT calculations, while the structures are confirmed by NMR spectroscopy and single-crystal X-ray diffraction.

Prodrugs that improve drug delivery in the body are highly desirable because they increase drug solubility and activity, thereby reducing drug concentration and side effects compared to the actual active compound. In this work, we demonstrate the impact of titanocene scaffolds on active thiosemicarbazones (TSCN). Two routes toward cationic Ti-(IV) TSCN complexes were established either by the reaction of titanocene bis-(trimethylsilyl)-acetylene with TSCN and subsequent oxidation of the resulting Ti-(III) complex with ferrocenium triflate or by ligand exchange of the triflato ligands in titanocene-(IV) triflate with TSCN. The solubility and stability of the complexes in aqueous media were evaluated by NMR and ultraviolet/visible (UV/vis) spectroscopy. A selection of cationic Ti-(IV) TSCN complexes exhibit improved water solubility, stability and increased cytotoxicity at lower concentrations compared to pure TSCN, cisplatin and 5-FU in human colon cancer cells in vitro.

Addition of gaseous CO2 to solutions of bis(pi-eta 5:sigma-eta 1-pentafulvene)titanium complexes results in the selective insertion reaction of one equivalent of O=C=O into one of the two frustrated Ti-Cexo bonds under mild conditions. The formation of kappa 1 O- and kappa 2 O,O-carboxylate titanium complexes is observed and characterized by single crystal X-ray analysis, NMR and IR spectroscopy. The nature of Ti-O interactions is established by computational studies. The reactivity of the remaining pentafulvene ligand is demonstrated in reactions with H-acidic and multiple-bond-containing substrates. The reactions with etheric HCl results in the selective formation of Ti-Cl complexes by protonation of the second pentafulvene moiety, disregarding the carboxylate ligand. The formed chlorido complexes are used in follow-up reactions with methyllithium, resulting in the methylation of the complexes via salt metathesis reactions, and reduction of the chloride complexes with sodium amalgam results in the formation of dimeric kappa 1 O-mu-O/bridged-carboxylate Ti(III) complexes.

The reactivity analysis of dipotassiumgermoldiides K2[1] with aluminum trichloride in the presence of donors uncovers an unexpectedly broad range of products. The specific product formed varies, based on the donor's characteristics, its size, and the stoichiometric ratio between the donor and the aluminium trichloride. This leads to the formation of various products, including alumole complexes of germanium 3(Do) (with Do = OEt2, iPr2Me2Im), cationic germole complexes of aluminylenes [14]+, and 2H‐germole derivatives such as 15a. The alumole complexes of germanium 3 are structurally best described as nido‐type clusters or aluminagerma[5]pyramidanes. They show significant Lewis acidity and can be isolated only in the form of their donor complexes 3(Do). The 2H‐germole derivative 15a promises a high synthetic potential due to its unprecedented germenide (R2C = Ge(:)‐R) group group, which is part of a butadiene system and substituted with a reactive C–Al functionality.

A four step sequence for the preparation of optically active (R,R)-ethyl 4-phenyl-3,4-dihydroisocoumarin-3-carboxylate is reported. In the first step the first stereocenter was installed by palladium catalyzed asymmetric conjugate addition of PhB(OH)2 to indenone (88 % ee). After deprotonation, the ester moiety was introduced with Mander's reagent. The alpha-hydroxylation of the resulting beta-oxoester was then achieved with cerium-catalysis under an air atmosphere. Key transformation was the cyanide-catalyzed ring transformation of alpha-hydroxy-beta-oxoester furnishing the delta-lactone moiety of the target compound, which was formed as a mixture of separable cis- and trans-diastereoisomers, both with 88 % ee. The cis-isomer could be epimerized to the trans-compound. The relative trans and the absolute (R,R)-configuration of the target compound was established by X-ray single crystal structure analysis. Isocoumarins by Ring Transformation: The cyanide catalyzed ring transformation of an alpha-hydroxy-beta-oxoester is the key transformation for the preparation of an optically active isocoumarin derivative. image

The reaction of hydrazones with bis(pi-eta(5):sigma-eta(1)-pentafulvene)titanium complexes leads to both hydrazonido and hydrazido complexes depending on the interaction of the hydrazone with the fulvene ligand of the metal complex. The molecular structures mostly reveal kappa N-2,N side-on coordination of the hydrazonido ligand due to the deprotonation of the N-H bond by one of the fulvene moieties. Instead of deprotonation, the reaction of the bis(adamantylidene fulvene)titanium complexes with cinnamon aldehyde phenylhydrazone leads to kappa N-1 coordination. By using donating groups in the backbone of the hydrazone ligands, there are exceptions to this coordination mode due to the insertion of the C & boxH;N double bond into the Ti-C-exo bond of the pentafulvene moiety. Using 2-pyridinecarboxaldehyde phenylhydrazone, a formal kappa N-3,N,N ligand system is formed by the coordination of the pyridine nitrogen atom to the metal center via consecutive N-H deprotonation and insertion. Finally, the use of salicylaldehyde phenylhydrazone ultimately produces a complex with the kappa N-3,N,O coordination mode by double deprotonation of the hydrazone N-H and O-H functions. Because of its slow conversion to the final product, the intermediate was isolated as an insertion product with consecutive O-H deprotonation, showing a kappa N-2,O coordination mode of the hydrazido ligand.