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

Abstract

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

Ring‐Opening Intramolecular Arylation of 1,2‐Disubtituted Epoxides with Tuneable Stereoselectivity

“…[17] After the emergence of titanocene-catalyzed ring-opening conversion of epoxides via β-titanoxy radicals intermediate, [18][19][20][21][22][23][24] most of the advances on titanocene-catalyzed methylamine-tethered epoxide ringopening transformation was related to achieving remarkable regiodivergent selectivity (Figure 1a). [25][26][27][28][29] Among these advances, the titanocene-catalyzed ring-opening arylation of epoxides offer an unique approach to multi-substituted benzo-fused Nheterocycles. [23,30,31] The titanocene-catalyzed ring-opening arylation of 1,1-disusbtutited and 1,2-trans-disubstituted epoxides can respectively produce 3,3-disubstituted (aza) indolines and trans-3,4-disubstituted tetrahydroquinolines in good regiose-lectivity (eq.…”

Dinuclear Titanium(III)-Catalyzed Radical-Type Kinetic Resolution of Epoxides for the Enantioselective Synthesis of cis-Glycidic Esters

“…However, while the intriguing bimetallic catalytic mechanism therein ensures sufficient stereochemical communications to afford excellent enantioselectivities, it concurrently introduces considerable steric sensitivity toward epoxides, restricting its effectiveness primarily to terminal epoxides. , In addressing the above challenges, an enantio-differentiated radical-type ring-opening through a stepwise process devoid of concerted attack by nucleophiles can be ideal to address the steric hindrance issue. Nonetheless, KR of epoxides via a radical approach remains largely untapped and presents itself as a formidable challenge in current scientific exploration (Scheme c). , …”

Insights into the Mechanism of Metal-Catalyzed Transformation of Oxime Esters: Metal-Bound Radical Pathway vs Free Radical Pathway

“…It has been shown recently that by binding radicals to a transition metal, highly chemo-, regio-, diastereo-, and even enantioselective redox-neutral radical reactions have become feasible. , Gansäuer et al developed a titanocence­(III)/(IV) redox couple to catalyze a series of reactions using epoxides, including the excellent work of asymmetric synthesis (Scheme a) . Lin and his co-workers achieved elegant Ti-catalyzed [3 + 2] cycloaddition reactions of N -acylaziridines/cyclopropyl ketones with alkenes (Scheme b) achieving asymmetric synthesis by chiral ligands, and the concept of “radical redox-relay” was introduced .…”