Ligand Development for Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Racemic Alkyl Halides

Abstract

The enantioconvergent cross-coupling of racemic alkyl halides represents a powerful tool for the synthesis of enantioenriched molecules. In this regard, the first-row transition metal catalysis provides a suitable mechanism for stereoconvergence by converting racemic alkyl halides to prochiral radical intermediates owing to their good single-electron transfer ability. In contrast to the noble development of chiral nickel catalyst, copper-catalyzed enantioconvergent radical cross-coupling of alkyl halides is less studied. Besides the enantiocontrol issue, the major challenge arises from the weak reducing capability of copper that slows the reaction initiation. Recently, significant efforts have been dedicated to basic research aimed at developing chiral ligands for copper-catalyzed enantioconvergent radical cross-coupling of racemic alkyl halides. This perspective will discuss the advances in this burgeoning area with particular emphasis on the strategic chiral anionic ligand design to tune the reducing capability of copper for the reaction initiation under thermal conditions from our research group.

Photoactive Copper Complexes: Properties and Applications

“…A visible-light-promoted stereoselective C­(sp 3 )-H glycosylation of quinolinyl-8 glycinates with modified carbohydrates bearing a redox active ester has been moreover shown to be promoted by a combination of copper­(II) triflate and (S)-PHANEPhos . A perspective article on ligand development for photoinduced copper-catalyzed enantioconvergent cross-coupling involving racemic alkyl halides has been recently published . A novel development in cooperative catalysis involving photoactivatable copper complexes has been reported, expanding the scope of biphotonic dual photoredox catalysts, by designing a system combining [Cu­(dap) 2 ]Cl (Cu­( NN 33 ) 2 ]­Cl) and 9,10-dicyanoanthracene under irradiation at 623 nm .…”

Synthesis of α‐Quaternary β‐Lactams via Copper‐Catalyzed Enantioconvergent Radical C(sp3)−C(sp2) Cross‐Coupling with Organoboronate Esters

“…have accomplished a nickel‐catalyzed enantioconvergent radical C(sp 3 )−C(sp 3 ) cross‐coupling of tertiary α‐bromo‐β‐lactams with alkenes (Scheme 1B) [9a] . We have been focusing on developing the multidentate chiral ligand‐copper catalyst for realizing enantioconvergent radical cross‐coupling via a transmetalation/single‐electron reduction/bond formation sequence [7d, 11] . Very recently, we described an enantioconvergent C(sp 3 )−C(sp) cross‐coupling of the similar tertiary α‐bromo‐β‐lactams with alkynes utilizing the same mechanistic sequence (Scheme 1C) [12] .…”

“…As part of our ongoing endeavors in the enantioconvergent transformations, [7d, 11, 12] we herein report an enantioconvergent radical C(sp 3 )−C(sp 2 ) cross‐coupling of tertiary α‐bromo‐β‐lactams with aryl‐ and alkenylboronate esters. The key to the success is the utilization of a hemilabile N,N,N‐ligand to enhance the reducing capability of L* Cu(I) so that it could convert the highly reactive α‐bromo‐β‐lactam to a tertiary alkyl radical III via a single‐electron reduction process (Scheme 1D) [13] .…”

Fe-Catalyzed Alkylazidation of α-Trifluoromethylalkenes: An Access to Quaternary Stereocenters Containing CF3 and N3 Groups

“…Recent research revealed that the metal-catalyzed radical relay strategy exhibited great translational potential for radical transformations, especially asymmetric radical synthesis . In this field, Liu, Feng, and Bao et.…”