Recent Developments in Copper(I)‐Catalyzed Enantioselective Alkynylation Reactions via a Radical Process

Abstract

Alkynes are one of the most significant functional groups in organic chemistry and great efforts have been made to explore efficient approach for the construction of chiral alkynes. The asymmetric C(sp 3 )-C(sp) cross-coupling provides a significant complementary strategy through radical-initiated process. However, the stereocontrol of highly reactive and unstable radical intermediate has been a challenge for decades. To address this problem, a variety of chiral ligands are developed for initiating the reaction and achieving enantiocontrol of alkyl radicals. This review summarizes recent developments in copper-catalyzed enantioselective alkynylation of prochiral alkyl radicals and their brief mechanistic studies.www.cjc.wiley-vch. de

Diversified Synthesis of All-Carbon Quaternary gem-Difluorinated Cyclopropanes via Copper-Catalyzed Cross-Coupling

“…Indeed, DFCs have been found to participate in a variety of ring-opening cross-coupling reactions through transition-metal catalyzed two-electron processes. , Taking this into account as well as the stabilizing effect of a fluoroalkyl group on its α-radical, we hypothesized that the use of a radical coupling strategy in the presence of a transition metal might be a solution to overcome the challenge . Herein, a new type of synthon, gem -difluorocyclopropyl bromides (DFCBs), was developed and used for coupling with a wide range of nucleophiles under copper catalysis via a radical process. ,, This approach provides a general method for synthesizing diverse quaternary carbon-containing DFCs (Scheme D).…”

Photoinduced Copper-Catalyzed Enantioconvergent Remote Alkynylation via 1,4-Heteroaryl Migration

“…Particularly, the feedstock terminal alkynes can serve as facile, convenient, and general alkynylating reagents, which are widely used in numerous asymmetric alkynylation reactions. 3 Early reports in this area focused on the asymmetric Shono-type coupling between terminal alkynes and C(sp 3 )−H of N-heterocycles. 4 More recently, great efforts have been made to achieve catalytic asymmetric hydroalkynylation and carboalkynylation of olefins with terminal alkynes.…”

“…Additionally, they are also recognized as versatile synthons for the construction of diverse building blocks. , Therefore, the catalytic asymmetric alkynylation has become one of the hot spots in organic synthesis for many years. Particularly, the feedstock terminal alkynes can serve as facile, convenient, and general alkynylating reagents, which are widely used in numerous asymmetric alkynylation reactions . Early reports in this area focused on the asymmetric Shono-type coupling between terminal alkynes and C­(sp 3 )–H of N -heterocycles .…”

“…4 More recently, great efforts have been made to achieve catalytic asymmetric hydroalkynylation and carboalkynylation of olefins with terminal alkynes. 5,6 Notably, Liu and co-workers reported their pioneering work of enantioconvergent radical Sonogashira cross-coupling between racemic secondary alkyl halides and terminal alkynes, 7 which led a following booming development in Cu-catalyzed asymmetric C(sp 3 )−C(sp) coupling with diverse organohalides. 8 Later on, a photoinduced Cu-catalyzed asymmetric decarboxylative alkynylation of N-hydroxyphthalimide (NHPI) esters has also been established by the same group (Scheme 1b).…”

“…To date, achievements in this area have rarely been reported. The enantioselective remote C(sp 3 )−H alkynylations with terminal alkynes via the intramolecular 1,5-hydrogen atom transfer (HAT) strategy have been developed by Liu and Zhang, respectively. 10 Very recently, Tu and Jiang have realized Cucatalyzed asymmetric remote alkynylation via the ring opening of cycloketone oxime esters.…”