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

Abstract

Transition‐metal catalyzed intermolecular 1,2‐diarylation 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 nickel‐catalyzed reductive 1,2‐diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2‐diarylation 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.

Ni- and Pd-Catalyzed Enantioselective 1,2-Dicarbofunctionalization of Alkenes

“…Recently, a reductive 1,2-homodiarylation of unactivated alkenes facilitated by an AQ directing group was reported by Chen and co-workers (Scheme 20 ). 45 This was achieved by using aryl iodides and alkenyl amides under Ni(ClO 4 ) 2 ·6H 2 O/ i -Pr-PHOX ( L17 ) or Ni(BF 4 ) 2 ·6H 2 O/ s -Bu-PHOX ( L18 ) catalysis. The authors did not propose a catalytic cycle, however, high syn -diastereoselectivity and enantioselectivity are observed with internal alkene substrates, indicating that migratory insertion is the enantioselective step.…”

“…Recently, a reductive 1,2-homodiarylation of unactivated alkenes facilitated by an AQ directing group was reported by Chen and co-workers (Scheme 20). 45 This was achieved by using aryl iodides and alkenyl amides under Ni(ClO 4 )…”

Direct and modular access to allylic amines via nickel-catalyzed three-component coupling

“…Over the past decades, transition metal-catalyzed MCRs have been widely explored to construct valuable functionalized molecules, largely extending the chemical sphere of MCRs. 41,42 Within our continuing interest in the synthesis of important scaffolds via nickel catalysis, [43][44][45][46] we herein disclose a Ni(0)catalyzed three-component reaction of commercially available aldehydes, amines, and alkenes (Fig. 1b).…”

Iodonium based regioselective double nucleophilic alkene functionalization of a hydrofluoroolefin scaffold

“…Moreover, they have short atmospheric lifetime, decreased Ozone Depleting Potential (ODP) and decreased Global Warming Potential (GWP) values compared to traditional HFCs and CFCs. 5 Although several methods were developed for the transformation of HFO-1234yf recently, 6–12 the utilization of an alkene difunctionalization strategy 13–16 would open further possibilities for the synthesis of novel fluoroalkyl linked nucleophilic heteroatom fragments from HFO-1234yf. This synthetic approach would offer important molecular motifs for pharmaceutical chemistry (Scheme 1).…”