We describe a combination of catalysts that allows the coupling of titanocene­(III) catalysis with photoredox catalysis. Oxidation of radical intermediates by a photoredox catalyst opens novel catalytic mechanisms for reductive epoxide ring opening and redox-neutral epoxide radical arylation. In the former case, the requirement of metallic reductants and stoichiometric acidic additives is bypassed.

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 Cp TiX-catalysts that are prepared in situ from readily available Cp TiX is achieved by varying the anionic ligand X. Of the complexes investigated, Cp 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.

Described here is atitanocene-catalyzed reaction for the synthesis of acetals and hemiaminals from benzylic ethers and benzylic amines,r espectively,with pendant epoxides.T he reaction proceeds by catalysis in single-electron steps.T he oxidative addition comprises an epoxide opening.AnH-atom transfer,t og enerate ab enzylic radical, serves as ar adical translocation step,a nd an organometallic oxygen rebound as ar eductive elimination. The reaction mechanism was studied by high-level dispersion corrected hybrid functional DFT with implicit solvation. The low-energy conformational space was searched by the efficient CREST program. The stereoselectivity was deduced from the lowest lying benzylic radical structures and their conformations are controlled by hyperconjugative interactions and steric interactions between the titanocene catalyst and the aryl groups of the substrate.A ni nteresting mechanistic aspect is that the oxidation of the benzylic center occurs under reducing conditions. Scheme 1. Atom-economic transformation of benzylic ethers into acetals by titanocene(III) catalysis in single-electrons teps (SET).

Described here is atitanocene-catalyzed reaction for the synthesis of acetals and hemiaminals from benzylic ethers and benzylic amines,r espectively,with pendant epoxides.T he reaction proceeds by catalysis in single-electron steps.T he oxidative addition comprises an epoxide opening.AnH-atom transfer,t og enerate ab enzylic radical, serves as ar adical translocation step,a nd an organometallic oxygen rebound as ar eductive elimination. The reaction mechanism was studied by high-level dispersion corrected hybrid functional DFT with implicit solvation. The low-energy conformational space was searched by the efficient CREST program. The stereoselectivity was deduced from the lowest lying benzylic radical structures and their conformations are controlled by hyperconjugative interactions and steric interactions between the titanocene catalyst and the aryl groups of the substrate.A ni nteresting mechanistic aspect is that the oxidation of the benzylic center occurs under reducing conditions. Scheme 1. Atom-economic transformation of benzylic ethers into acetals by titanocene(III) catalysis in single-electrons teps (SET).

In one word,h ow would you describe your research? Evolving, exciting, rewarding, dynamic! What is the most significant result of this study?Catalysis in single-electron steps merges the advantages of radical chemistry,s uch as high functional group tolerance, mild reaction conditions, and high rates, with those of transition-metal catalysis, such as control of stereoselectivity by the ligands of the metals. The key aspect of our approach is to perform oxidative additions and reductive eliminations in one-electron steps. Therefore, we make use of the same terms as in classical catalysis but significantly broaden the scope of old concepts. How is this approach related to other fields of catalysis?In many cross-coupling reactions and Lewis acid catalyzed processes the variation of the anionic ligands lead to an increase in reactivity and selectivity.F or catalysis in single-electron steps this is also the case. However,w ith cyclic voltammetry,w eh ave an ideal method that allows us to rationally screen the properties essential for reactivity.T his is not always straightforward in other branches of catalysis. Therefore, our approach is both related and unique.How did the collaborationo nt his project start?The collaboration started when Professors Gansäuer and Flowers met at an organic free radical conference in Ottawa in 2009. Since then they have tackled many mechanistic problems often with the aid of theoretical chemistry.