Recent Advances in Transition Metal‐Catalyzed Asymmetric Radical Reactions

Abstract

Control of enantioselectivity in radical reactions was a formidable challenge for organic chemists for decades. Thanks to the key role of transition metal complexes both in promoting and highly enantioselectively controlling sophisticated synthetic routes, great improvements in this filed have been achieved by merging transition‐metal asymmetric catalysis with radical chemistry. Herein we provide a perspective of some of the most significant contributions in the field during the past decades. Accordingly, the major advances are classified based on different strategies for controlling stereoselectivity including: (1) chiral metal complex chelation, (2) chiral metal complex combined with radical species and reductive elimination, (3) chiral metal complex outer‐sphere substitution by radical intermediate. Brief discussion of mechanism is presented whenever relevant.

Copper-catalyzed radical relay in C(sp3)–H functionalization

“…17,18 Thus, TM-catalyzed radical relay offers substantial opportunities to expand the regime of radical-mediated C(sp 3 )–H bond functionalization, and significant progress has been achieved in recent decades. 19–21 More importantly, the asymmetrical version of radical C–H functionalization could be achieved by introducing appropriate chiral ligands.…”

Nickel-Catalyzed Enantioselective Desymmetrizing Aza-Heck Cyclization of Oxime Esters

“…[20][21][22][23][24][25][26][27][28][29][30] Nickel (Ni) has numerous advantages as a catalyst, including natural abundance, affordability, and chemical sustainability. 31 Recent years also witnessed a surge of interest in Ni-catalyzed asymmetric tranformations, [32][33][34][35][36][37][38] but Ni-catalyzed enantioselective Heck reactions still remain underdeveloped among them. The first enantioselective Ni-catalyzed Heck cyclization generating oxindoles with quaternary stereogenic centers was reported by Desrosiers et al 39 A Ni-catalyzed intermolecular enantioselective Heck reaction of cycloalkenes with aryl triflates, mesylates, and tosylates was also described by Zhou et al 40 However, a Ni-catalyzed enantioselective aza-Heck cyclization, which can support a sustainable synthesis of chiral nitrogen-containing heterocycles, has not yet been reported, presumably because the Ni promotes the cleavage of the N-O bond likely through a single-electron transfer (SET) mechanism, making the conditions less suitable for adaption to enantioselective cyclizations (Scheme 1b).…”

Recent Advances in Asymmetric Catalytic Electrosynthesis

“…Traditionally, asymmetric catalysis has focused on two-electron transformations [1,2]. However, the toolbox of the organic chemist has been expanded tremendously in the last decade with the introduction of methods for asymmetric transformations with open-shell radical intermediate species using chemical, photochemical and electrochemical strategies [3][4][5][6][7][8][9][10].…”