Directed Asymmetric Nickel‐Catalyzed Reductive 1,2‐Diarylation of Electronically Unactivated Alkenes

Abstract

Transition-metal catalyzed intermolecular 1,2diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickelcatalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

Recent Advances in the 1,2‐Diarylation of Alkenes

“…Later in 2023, Dong et al [33] . reported Ni‐catalyzed intermolecular 1,2‐DIAR of electronically unactivated alkenes bearing an amide‐linked aminoquinoline (AQ) directing group.…”

“…Later in 2023, Dong et al [33] reported Ni-catalyzed intermolecular 1,2-DIAR of electronically unactivated alkenes bearing an amide-linked aminoquinoline (AQ) directing group. The diastereoselective 1,2-DIAR of unactivated internal alkenes with aryl iodides was carried out using Ni(OTf) 2 as the catalyst in the presence of Mn as the reductant in DMF solvent at 50 °C for 48 hours (Scheme 15).…”

Enantioselective Directed Nickel-Catalyzed Three-Component Reductive Arylalkylation of Alkenes via the Carbometalation/Radical Cross-Coupling Sequence

“…Recently, asymmetric nickel-catalyzed reductive two-component 1,2-homodiarylation , and redox-neutral three-component diarylation of alkenes via stereoselective Heck migratory insertion have been reported. As a continuation of our interest in this area, we herein disclose the first enantioselective nickel-catalyzed reductive three-component arylalkylation between terminal or internal alkenes, aryl halides, and alkyl halides through carbonickelation/Csp 3 –Csp 3 cross-coupling sequence (Figure d). This reductive asymmetric arylalkylation of alkenes makes it reasonable to proceed with the chiral aryl–[Ni] complex in situ catalytically generated from aryl halides performing stereoselective carbonickelation of alkene ,,,− to afford the chiral α-branched Csp 3 –Ni intermediate with opposite regioselectivity to those radical relay strategies. − A coordinating-group-based chelation strategy is employed to stabilize the enantiomerically enriched Csp 3 –Ni intermediate as a transient nickelacycle followed by radical cross-coupling with alkyl halides to deliver aryl/alkyl difunctionalized products with exquisite control of regio-, chemo-, and enantioselectivity.…”

“…To corroborate the approach, we began our initial optimization study of the model reaction of alkene 1 bearing 8-aminoquinoline (AQ) as a directing group, p -MePhI, and EtI (Table ). To achieve this three-component arylalkylation, varieties of competing reactions, including diarylation, , dialkylation, hydroalkylation, and hydroarylation, needed to be prohibited. Besides, it should be stressed that the reaction also functioned smoothly without a chiral ligand, affording the racemic product 2 in 74% yield (entry 1).…”

“…Recently, asymmetric nickel-catalyzed reductive two-component 1,2-homodiarylation 41,55 and redoxneutral three-component diarylation 56 of alkenes via stereoselective Heck migratory insertion have been reported. As a continuation of our interest in this area, 55 we herein disclose the first enantioselective nickel-catalyzed reductive threecomponent arylalkylation between terminal or internal alkenes, aryl halides, and alkyl halides through carbonickelation/Csp 3 − Csp 3 cross-coupling sequence (Figure 1d). This reductive asymmetric arylalkylation of alkenes makes it reasonable to proceed with the chiral aryl−[Ni] complex in situ catalytically generated from aryl halides performing stereoselective carbonickelation of alkene 36,37,41,55−59 Reaction Optimization.…”