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.

While SN2 based desymmetrization of meso-epoxides has been extensively researched, the more general regioselective opening of cis-1,2 substituted epoxides via SN2 mechanism remains elusive. This short review outlines, how this limitation could be overcome by parting with SN2 and moving towards a radical-based mechanism. The development and refinement of the titanocene(III)-catalyzed regiodivergent epoxide opening (REO) is described.1 Introduction to Asymmetric Catalysis2 From Enantiodivergent to Regiodivergent Epoxide Opening3 Regiodivergent Arylation of Epoxides4 Conclusion

At itanocene-catalyzed regiodivergent radical arylation is described that allows access to either enantiomerically pure tetrahydroquinolines or indolines from ac ommon starting material. The regioselectivity of epoxideo pening that results in the high selectivity of heterocycle formation is controlled by two factors,t he absolute configuration of the enantiopure ligands of the (C 5 H 4 R) 2 TiX 2 catalyst and the inorganic ligand X( X = Cl, OTs). The overall reaction is atom-economical and constitutes ar adical Friedel-Crafts alkylation.The design of catalytic methods to efficiently and highly chemo-and stereoselectively access small molecules with potential biological activity is atopic central to chemistry.T o be attractive for potential applications,such processes have to meet the key requirements of sustainable chemistry.Essential points are that the reaction is atom-economical and, thus, proceeds without the generation of waste,t he use of readily available substrates,and mild reaction conditions.The choice of the catalyst is equally important. Theuse of earth-abundant 3d transition metals [1] that shuttle between neighboring oxidation states is particularly appealing. [2] Herein, we show the validity of these points in at itanocene-catalyzed [3] regiodivergent radical arylation that allows access to enantiomerically pure tetrahydroquinolines or indolines from ac ommon starting material through choice of the appropriate titanocene catalyst. In regiodivergent reactions,o ne constitutional isomer of ap roduct is formed from an enantiomerically pure substrate by the action of one enantiomer of acatalyst and the other isomer by the action of the other enantiomer of the catalyst. In our case,t wo points are critical:F irst, the highly regioselective generation of either R-2 or R-3 from 1 by an electron transfer (ET) from titanium to the epoxide needs to be controlled by the absolute configuration of the titanocene catalyst (Scheme 1).

We describe a formal total synthesis of the racemic natural product rhazinal by a rapid elaboration of a recently reported tetrahydroindolizine intermediate into the cyclization precursor reported by Trauner. The synthesis focuses on the early and convergent introduction of functional groups while the synthetic challenges encountered by this approach are described.