Enantioselective benzylic C–H arylation via photoredox and nickel dual catalysis

Abstract

The asymmetric cross-coupling reaction is developed as a straightforward strategy toward 1,1-diaryl alkanes, which are a key skeleton in a series of natural products and bioactive molecules in recent years. Here we report an enantioselective benzylic C(sp 3 )−H bond arylation via photoredox/nickel dual catalysis. Sterically hindered chiral biimidazoline ligands are designed for this asymmetric cross-coupling reaction. Readily available alkyl benzenes and aryl bromides with various functional groups tolerance can be easily and directly transferred to useful chiral 1,1-diaryl alkanes including pharmaceutical intermediates and bioactive molecules. This reaction proceeds smoothly under mild conditions without the use of external redox reagents.

Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions

“…For example, using synergistic photoredox/Ni catalysis for C-H functionalization is an exciting new direction; however, it has been challenging to render these reactions enantioselective. 66,67 Ultimately, the development of new methods of C(sp 3 ) radical generation will improve the accessibility and synthetic utility of enantioselective RCCs.…”

Ligand-promoted cobalt-catalyzed radical hydroamination of alkenes

“…Continuing our pursuit of efficient earth-abundant transition metal catalysis via ligand design [36][37][38][39][40][41][42][43][44][45] ; here, we report the use of unsymmetric NNN tridentate ligands to promote the cobaltcatalyzed radical hydroamination of alkenes via HAT ( Fig. 2d).…”

Recent developments in enantioselective photocatalysis

“…The first enantioselective example of this dual mode catalysis reported was a decarboxylative arylation of α-amino acids 363 with aryl bromides 364 bearing electronwithdrawing groups, developed by Fu and MacMillan using NiCl 2 , chiral ligand L14, and a heteroleptic iridium-based Following this report, a large array of reactions has been developed using chiral ligands with nickel/photoredox catalysis [144][145][146]. For example, Rovis and Doyle developed a desymmetrisation of cyclic meso-anhydrides 368 using benzyl trifluoroborate salts 369, chiral ligand L15, Ni(COD) 2 , and the photocatalyst 4CzIPN (Scheme 62a) [147].…”

“…Following this report, a large array of reactions has been developed using chiral ligands with nickel/photoredox catalysis [ 144 – 146 ]. For example, Rovis and Doyle developed a desymmetrisation of cyclic meso -anhydrides 368 using benzyl trifluoroborate salts 369 , chiral ligand L15 , Ni(COD) 2 , and the photocatalyst 4CzIPN ( Scheme 62 ) [ 147 ].…”