Titanocene(III)-Catalyzed Precision Deuteration of Epoxides.

We describe a titanocene(III)-catalyzed deuterosilylation of epoxides that provides ß-deuterated anti-Markovnikov alcohols with excellent D-incorporation, in high yield, and often excellent diastereoselectivity after desilylation. The key to the success of the reaction is a novel activation method of Cp2 TiCl2 and (tBuC5 H4 )2 TiCl2 with BnMgBr and PhSiD3 to provide [(RC5 H4 )2 Ti(III)D] without isotope scrambling. It was developed after discovering an off-cycle scrambling with the previously described method. Our precision deuteration can be applied to the synthesis of drug precursors and highlights the power of combining radical chemistry with organometallic catalysis.

Design Platform for Sustainable Catalysis with Radicals: Electrochemical Activation of Cp2 TiCl2 for Catalysis Unveiled.

The combination of synthesis, rotating ring-disk electrode (RRDE) and cyclic voltammetry (CV) measurements, and computational investigations with the aid of DFT methods shows how a thiourea, a squaramide, and a bissulfonamide as additives affect the Eq Cr equilibrium of Cp2 TiCl2 . We have, for the first time, provided quantitative data for the Eq Cr equilibrium and have determined the stoichiometry of adduct formation of [Cp2 Ti(III)Cl2 ]- , [Cp2 Ti(III)Cl] and [Cp2 Ti(IV)Cl2 ] and the additives. By studying the structures of the complexes formed by DFT methods, we have established the Gibbs energies and enthalpies of complex formation as well as the adduct structures. The results not only demonstrate the correctness of our use of the Eq Cr equilibrium as predictor for sustainable catalysis. They are also a design platform for the development of novel additives in particular for enantioselective catalysis.

Condition Screening for Sustainable Catalysis in Single-Electron Steps by Cyclic Voltammetry: Additives and Solvents.

Cyclic voltammetry-based screening method for Cp2 TiX-catalyzed reactions is extended to the screening of solvents other than tetrahydrofuran for bulk electrolysis of the catalyst and radical arylation. It was found that CH3 CN can be used as a solvent for both processes without additives. Furthermore, in tetrahydrofuran, squaramide L2 is more efficient than the previously reported supramolecular halide binder, Schreiner's thiourea L1. The results extend the usefulness of the proposed time and resource-efficient screening method for designing catalysis reactions in single-electron steps.

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.

Highly Active Titanocene Catalysts for Epoxide Hydrosilylation: Synthesis, Theory, Kinetics, EPR Spectroscopy.

A catalytic system for titanocene-catalyzed epoxide hydrosilylation is described. It features a straightforward preparation of titanocene hydrides that leads to a reaction with low catalyst loading, high yields, and high selectivity of radical reduction. The mechanism was studied by a suite of methods, including kinetic studies, EPR spectroscopy, and computational methods. An unusual resting state leads to the observation of an inverse rate order with respect to the epoxide.

Amide-Substituted Titanocenes in Hydrogen-Atom Transfer Catalysis.

Two new catalytic systems for hydrogen-atom transfer (HAT) catalysis involving the N-H bonds of titanocene(III) complexes with pendant amide ligands are reported. In a monometallic system, a bifunctional catalyst for radical generation and reduction through HAT catalysis depending on the coordination of the amide ligand is employed. The pendant amide ligand is used to activate Crabtree's catalyst to yield an efficient bimetallic system for radical generation and HAT catalysis.