Mechanistic Study of the Titanocene(III)‐Catalyzed Radical Arylation of Epoxides

Abstract

An atom-economical and catalytic arylation of epoxide-derived radicals is described. The key step of the catalytic system is a sequential electron and proton transfer for the rearomatization of the radical σ-complex and catalyst regeneration. Kinetic, computational, spectroscopic, and cyclovoltammetric investigations highlight the key issues of the reaction mechanism and catalyst stabilization by collidine hydrochloride. Studies employing radicophiles rule out the participation of cations as reactive intermediates.

Proton-Coupled Electron Transfer in Organic Synthesis: Fundamentals, Applications, and Opportunities

“…It is known that Cp 2 Ti III Cl and TEMPO form a bond of approximately 25 kcal mol −1 ; in light of this, we were unable to observe any conjugate amination at elevated temperatures using these two catalysts or the known complex Cp 2 Ti IV Cl-OTEMP [234][235][236]. Our DFT calculations estimate the strength of the Cp* 2 Ti IV Cl-OTEMP bond to be 23 kcal mol −1 weaker than that of the Cp 2 Ti IV Cl-OTEMP complex, putting an approximate value of this BDFE at 2 kcal mol −1 .…”

Proton-Coupled Electron Transfer in Organic Synthesis: Fundamentals, Applications, and Opportunities

“…It is known that Cp 2 Ti III Cl and TEMPO form a bond of approximately 25 kcal mol −1 ; in light of this, we were unable to observe any conjugate amination at elevated temperatures using these two catalysts or the known complex Cp 2 Ti IV Cl-OTEMP [234-236]. Our DFT calculations estimate the strength of the Cp* 2 Ti IV Cl-OTEMP bond to be 23 kcal mol −1 weaker than that of the Cp 2 Ti IV Cl-OTEMP complex, putting an approximate value of this BDFE at 2 kcal mol −1 .…”

Bond-Weakening Catalysis: Conjugate Aminations Enabled by the Soft Homolysis of Strong N–H Bonds

“…6,12 Conjugate addition of this metalated nucleophile to the pendant olefin acceptor followed by metal migration would result in the formation of titanium enolate 4 that could undergo proton exchange with reduced TEMPO-H to furnish a neutral closed-shell product. 13,14 Electron transfer from the strongly reducing TEMPO anion ( E 1/2 = −1.95 V vs Fc/Fc + in MeCN) 7 to the Ti IV cation ( E p = −1.44 V vs Fc/Fc + in MeCN) 15a is exergonic by ~500 mV and should readily regenerate the Ti III catalyst and TEMPO radical, closing the catalytic cycle.…”

“…Isodesmic calculations indicated that the bonding between Cp* 2 TiCl and TEMPO is 23 kcal/mol less favorable than in the TEMPO complex of Cp 2 TiCl, which Waymouth reported to have a Ti–O BDFE ~25 kcal/mol. 10,15b This implies that the Ti–O bond for the TEMPO complex of Cp* 2 TiCl is exceptionally weak, with a BDFE only ~2 kcal/mol. 18 Additional experimental support for the ability of TEMPO and Cp* 2 TiCl to persist together in solution was obtained through EPR spectroscopy.…”