Cp2 TiX Complexes for Sustainable Catalysis in Single-Electron Steps.

We present a combined electrochemical, kinetic, and synthetic study with a novel and easily accessible class of titanocene catalysts for catalysis in single-electron steps. The tailoring of the electronic properties of our Cp2 TiX-catalysts that are prepared in situ from readily available Cp2 TiX2 is achieved by varying the anionic ligand X. Of the complexes investigated, Cp2 TiOMs proved to be either equal or substantially superior to the best catalysts developed earlier. The kinetic and thermodynamic properties pertinent to catalysis have been determined. They allow a mechanistic understanding of the subtle interplay of properties required for an efficient oxidative addition and reduction. Therefore, our study highlights that efficient catalysts do not require the elaborate covalent modification of the cyclopentadienyl ligands.

Demystifying Cp2Ti(H)Cl and its Enigmatic Role in the Reactions of Epoxides with Cp2TiCl.

The role of Cp2Ti(H)Cl in the reactions of Cp2TiCl with trisubstituted epoxides has been investigated in a combined experimental and computational study. Although Cp2Ti(H)Cl has generally been regarded as a robust species, its decomposition to Cp2TiCl and molecular hydrogen was found to be exothermic (ΔG = -11 kcal/mol when the effects of THF solvation are considered). In laboratory studies, Cp2Ti(H)Cl was generated using the reaction of 1,2-epoxy-1-methylcyclohexane with Cp2TiCl as a model. Rapid evolution of hydrogen gas was demonstrated, indicating that Cp2Ti(H)Cl is indeed a thermally unstable molecule, which undergoes intermolecular reductive elimination of hydrogen under the reaction conditions. The stoichiometry of the reaction (Cp2TiCl:epoxide = 1:1) and the quantity of hydrogen produced (1 mole per 2 moles of epoxide) is consistent with this assertion. The diminished yield of allylic alcohol from these reactions under the conditions of protic versus aprotic catalysis can be understood in terms of the predominant titanium(III) present in solution. Under the conditions of protic catalysis, Cp2TiCl complexes with collidine hydrochloride and the titanium(III) center is less available for "cross-disproportionation" with carbon-centered radicals; this leads to by-products from radical capture by hydrogen atom transfer, resulting in a saturated alcohol.

Prophylactic treatment of hereditary severe factor VII deficiency in pregnancy.

: Severe hereditary factor VII deficiency is a rare bleeding disorder and may be associated with a severe bleeding phenotype. We describe a pregnancy in a 33-year-old woman with compound heterozygous factor VII deficiency and a history of severe menorrhagia and mucocutaneous bleedings. After discontinuation of contraceptives, menstruation was covered with recombinant activated factor VII (rFVIIa), and during pregnancy, rFVIIa had to be administered in first trimester in doses ranging from 15 to 90 µg/kg per day because of recurrent retroplacental hematomas and vaginal bleedings. Thrombin generation was measured in first trimester at different doses of rFVIIa and showed an increase in lag time when doses of less than 30 µg/kg/day were administered, whereas time to thrombin peak and peak thrombin were not influenced. A low-dose rFVIIa prophylactic treatment of 15 µg/kg every other day in the late second and in the third trimester was sufficient to allow a successful childbirth in this patient with severe factor VII deficiency.

Synthesis of Dihydropyrrolizine and Tetrahydroindolizine Scaffolds from Pyrroles by Titanocene(III) Catalysis.

A synthetic approach to dihydropyrrolizine and tetrahydroindolizine scaffolds from pyrroles has been developed. The key step, a titanocene(III)-catalyzed radical arylation that proceeds by C-H functionalization is atom-economical and tolerates a large variety of functional groups. The reaction is therefore attractive for the swift assembly of functional and structural diversity.

Cationic Titanocene(III) Complexes for Catalysis in Single-Electron Steps.

By exploiting solvent and anion effects, [Cp2Ti](+) complexes for atom-economical catalysis in single-electron steps were developed and applied for the first time. These complexes constitute remarkably stable and active catalysts for radical arylations. The reaction kinetics and catalyst composition were studied by cyclic voltammetry and in situ IR spectroscopy.