Ligand-Enabled Ni-Catalyzed Enantioselective Hydroarylation of Styrenes and 1,3-Dienes with Arylboronic Acids

Abstract

We report an enantioselective hydroarylation reaction of styrenes and 1,3-dienes with arylboronic acids catalyzed by nickel complexes bearing chiral spiro aminophosphine ligands. The reaction serves as an efficient, straightforward, and mild method for the preparation of enantioenriched 1,1-diarylalkanes, which are important building blocks for the synthesis of many biologically active molecules. This redox neutral reaction uses only catalytic amounts of the reagents and is, therefore, atom economical and environmentally benign. R Ar (HO) 2 B + R = aryl, alkenyl Ni(COD) 2 (2.5 mol %) (S )-SpiroAP (3.0 mol %) t BuOK (5 mol %) n PrOH, 40°C, 24 h R Ar up to 99% yield up to 93% ee P(Ph) 2 NH 2

Enantio‐ and Regioselective NiH‐Catalyzed Reductive Hydroarylation of Vinylarenes with Aryl Iodides

“…Transition‐metal‐catalyzed enantioselective hydroarylation, an efficient process to form an aryl‐substituted stereogenic center from alkenes, has attracted considerable interest recently [5, 6b,d,g,h] . Starting from an aryl nucleophile and styrene, and using alcohol as a hydride source, Sigman [6b] developed an enantioselective Pd II H‐catalyzed hydroarylation system while Zhou [5b] and Mei [5a] independently demonstrated a robust Ni II H system achieving the same goal (i in Figure 1 b). In these reactions however, the alkene scope is limited to β‐unsubstituted vinylarenes.…”

Enantioselective Synthesis of Functionalized Arenes by Nickel‐Catalyzed Site‐Selective Hydroarylation of 1,3‐Dienes with Aryl Boronates

“…In 2019, Zhou and co‐workers reported a strategy for the catalytic hydroarylation of alkenyl arenes that involves reaction between an olefin, aryl boronic acid, and an alcohol in the presence of a phosphine–nickel complex . Subsequently, the Mei and Zhou groups independently disclosed enantioselective versions based on the development and application of chiral N,N and P,N bidentate ligands. Included in both of these studies, 1,3‐dienes provide low levels of enantioselectivity (Scheme B).…”

“…In the case of the bis‐oxazoline–Ni catalyst system, a single example of a symmetric 1,3‐diene is described (77:23 er) . In the closely related report by Zhou and co‐workers, several examples of 1,3‐dienes promoted by a spiro‐N,P–Ni complex are reported, with products formed in 88.5:11.5–92:8 er . In the case of the nickel‐catalyzed processes, substrate scope is very limited, with methods relying on relatively unfunctionalized or symmetric 1,3‐dienes, and enantioselectivity values lower than synthetically desirable (>95:5 er).…”

Ligand‐Enabled Nickel‐Catalyzed Redox‐Relay Migratory Hydroarylation of Alkenes with Arylborons

“…However, the scope of the arylation is limited to only trifluoromethylarenes or heteroarenes with low p K a values. To address these shortcomings, we speculated that oxidative addition of a ligated nickel(0) with an alcohol followed by transmetalation with commercial available arylboronic acids would provide rapid access to a broad range of aryl‐nickel(II)‐hydride species, which could also serve as a platform for remote hydroarylation of alkenes (Figure b). Specifically, if the aryl‐nickel(II)‐hydride generated in situ is active enough to insert into an isomer or mixture of isomers of the olefin substrate and promote a fast and reversible chain‐walking process along the hydrocarbon chain prior to a selective reductive elimination, then a convergent and regioselective migratory arylation instead of hydroarylation at the ipso position would be achieved.…”