Merging Regiodivergent Catalysis with Atom‐Economical Radical Arylation

Abstract

A titanocene‐catalyzed regiodivergent radical arylation is described that allows access to either enantiomerically pure tetrahydroquinolines or indolines from a common starting material. The regioselectivity of epoxide opening that results in the high selectivity of heterocycle formation is controlled by two factors, the absolute configuration of the enantiopure ligands of the (C5H4R)2TiX2 catalyst and the inorganic ligand X (X=Cl, OTs). The overall reaction is atom‐economical and constitutes a radical Friedel–Crafts alkylation.

Titanocene-Catalyzed Regiodivergent Epoxide Opening – From Desymmetrizing meso-Epoxides to Regiodivergent Arylation of Epoxides

“…33 Scheme 7 Scope of the regiodivergent arylation of epoxides (rr and dr were determined by 13 C NMR spectroscopy of the crude reaction mixture). 29 All products are obtained as single enantiomers.…”

“…The second generation of REOs further aims at a subsequent C-C bond-forming event by means of an intramolecular radical arylation after regiodivergent ring opening and is hence referred to as REO-arylation (Table 6). 29 The overall transformation is an atom-economic process not requiring any stoichiometric additives and is therefore highly sustainable. The products of the REO-arylation are two constitutionally isomeric heterocycles, which facilitates product separation and purification.…”

Shining Light on TiIV Complexes: Exceptional Tools for Metallaphotoredox Catalysis

“…[22][23][24][25][26] Specifically, the Ti IV/III redox couple facilitates the access to radical intermediates with peculiar regio-and chemoselectivity otherwise not feasible by using other metal complexes. [27,28] Titanocenes (and mainly titanocene dichloride, Cp 2 Ti IV Cl 2 ) offer a wide range of possible applications. [29] Cp 2 Ti III Cl is generated by reduction of commercially available Cp 2 Ti IV Cl 2 (stage a, Figure 1).…”

“…Gansäuer and co-workers reported an intramolecular redoxrelay transformation based on tertiary epoxides with pendant π-aromatic substituents (Scheme 7A). [28,56] A catalytic amount of Mn (20 mol-%) is sufficient to reduce the Ti IV to the active Cp 2 Ti III X, which induces the opening of the epoxide. The tertiary C-centered radical is then able to attack the π-aromatic system by a sort of Minisci-type reaction, forming a persistent aryl radical.…”

“…[ 22–26 ] Specifically, the Ti IV/III redox couple facilitates the access to radical intermediates with peculiar regio‐ and chemoselectivity otherwise not feasible by using other metal complexes. [ 27,28 ]…”