Catalytic, Highly Regio- and Chemoselective Generation of Radicals from Epoxides: Titanocene Dichloride as an Electron Transfer Catalyst in Transition Metal Catalyzed Radical Reactions

A Catalytic System for Reductive Transformations via One-Electron Transfer

“…The titanium-catalyzed intramolecular cyclization of the olefinic epoxide 14 occurs without deoxygenation (Scheme 17). 29 The intermolecular radical addition of the epoxide 15 to methyl acrylate affords the lactone 16. Zn as the co-reductant is used in methanol since the complexation of the generated ZnCl 2 with methanol reduces Lewis acidity.…”

Titanocene(III)-Catalyzed Formation of Indolines and Azaindolines

“…2b,c While the vast majority of known protocols for indoline synthesis utilize nucleophilic, Lewis acid and transition metal cross-coupling techniques, we envisioned a radical process that installs a quaternary carbon simultaneous with pyrrolidine formation from readily available epoxidized allylic amines. 10 The reductive opening of epoxides using either stoichiometric 11 or catalytic 12 titanocene(III) chloride was particularly attractive toward this goal. Nearly two decades after the first reports of using in situ prepared titanocene(III) chloride to generate reactive radical intermediates from epoxides, novel applications of this reagent continue to emerge.…”

“…Sub-stoichiometric amounts of manganese metal increased the ratio in favor of indoline 5a ; a possible indication of reversible radical pathways. 12c Addition of a methyl group to the epoxide in substrate 4b (R 2 =CH 3 ) improved the efficiency of the titanocene(III) chloride catalyzed process and afforded 5b as a single product in 82% yield (entry 2). With 1,1-disubstituted epoxides, sonication was not essential and conventional magnetic stirring also afforded the product in good yield (entry 3).…”

“…As a mechanism for the titanocene(III) chloride catalyzed epoxide-opening annulation, we propose that the formation of the β -titanoxy radical 30 11,12 is followed by a reversible cyclization onto the aromatic ring, forming the cyclohexadienyl radical intermediate 31 (Figure 2). 21 Oxidation of the dienyl radical by trace amounts of dioxygen and proton loss affords the indoline 32 .…”

“…23 Furthermore, it has previously been shown that the MnCl 2 produced in the reaction is not Lewis-acidic enough to promote epoxide-opening reactions. 12a …”