Progress in Enantioselective Radical Cyclizations

Abstract

The control of stereoselectivity in radical reactions is of great importance to organic synthesis. Hence, new concepts and strategies for controlling stereochemistry of radical reactions are emerging continuously. This Review highlights the recent remarkable progress in enantioselective radical cyclization reactions. Initially, the chiral Lewis acid-catalyzed method became a field of central importance for enantioselective radical cyclizations. In recent years, significant progress has been made in enantioselective organocatalysis. In contrast to intermolecular reactions, the successful examples for enantioselective radical cyclizations are still limited. In this Review, the radical cyclizations controlled by chiral Lewis acids, chiral metallic reagents, chiral imidazolidinone catalysts, chiral non-covalent organocatalysts, and chiral thiols are summarized.

Asymmetric Radical Bicyclization of Allyl Azidoformates via Cobalt(II)-Based Metalloradical Catalysis

“…Radical chemistry has been increasingly explored for the development of new synthetic tools to construct molecular structures. , Despite tremendous advances, formidable challenges, such as control of enantioselectivity, remain largely unaddressed for many radical reactions. Among recent strategies, metalloradical catalysis (MRC) presents a conceptually new approach in that metal-centered radicals are exploited as open-shell catalysts for initiating as well as controlling homolytic radical processes. , As stable 15e-metalloradicals, Co­(II) porphyrin complexes have recently been demonstrated with the unusual ability in activating diazo compounds and organic azides to generate the unprecedented α-Co­(III)-alkyl radicals (also known as Co­(III)-carbene radicals) and α-Co­(III)-aminyl radicals (also known as Co­(III)-nitrene radicals), respectively. These metal-stabilized organic radicals are competent for both H atom abstraction and radical addition, leading to new catalytic radical processes for C–H amination, C–H alkylation, CC aziridination, and CC cyclopropanation .…”

Origin of Stereocontrol in Photoredox Organocatalysis of Asymmetric α-Functionalizations of Aldehydes

“…An enantiocontrol model based on the pseudo C 2 -symmetric arrangement of the methyl and tert -butyl moieties on the catalyst rationalizes the stereoselective outcome of these reactions and may serve as a good model for the MacMillan imidazolidinone/photoredox dual catalysis. Given that the dual photoredox organocatalysis strategy offers an exciting opportunity in developing highly enantioselective radical reactions, , this study has important implications for the future development of new enantioselective catalytic radical reaction, a type of reaction that has daunted organic chemists for decades. , …”

5‐exo versus 6‐endo Thiyl‐Radical Cyclizations in Organic Synthesis

“…It has long been established that for intramolecular radical cyclizations the kinetics are the most favored for the unsaturated moiety δ to the radical . Furthermore, 5‐ exo cyclizations are favored over 6‐ endo , due to faster kinetics of the 5‐ exo process, even in cases in which the radical resulting from the 5‐ exo cyclization is less thermodynamically stable than that resulting from the 6‐ endo process.…”