Nickel-Catalyzed 1,2-Diarylation of Simple Alkenyl Amides

Abstract

A nickel-catalyzed conjunctive cross-coupling of simple alkenyl amides with aryl iodides and aryl boronic esters is reported. The reaction is enabled by an electron-deficient olefin (EDO) ligand, dimethyl fumarate, and delivers the desired 1,2-diarylated products with excellent regiocontrol. Under optimized conditions, a wide range of amides derived from 3-butenoic acid, 4-pentenoic acid, and allyl amine are compatible substrates. This methodology represents the first example of regiocontrolled 1,2-diarylation directed by a native amide functional group. Computational analysis sheds light on potential substrate binding mode and the role of EDO ligand in the reductive elimination step.

Nickel‐CatalyzedDicarbofunctionalization of Alkenes†

“…The same group also reported that a native carboxylic acid group could be used for nickel‐catalyzed 1,2‐diarylation under similar conditions without the ancillary ligand (Scheme 23). [ 75 ] Practically speaking, the use of versatile carboxylic acids as the starting materials complemented the previous works involving more inert amide compounds, [ 74 ] although the substrate scope was limited to β,γ‐unsaturated carboxylic acids.…”

“…In addition to arylzinc reagents, aryl boronic esters were also suitable aryl nucleophiles in the nickel‐catalyzed diarylation of alkenes as demonstrated by Engle in 2018 (Scheme 22). [ 74 ] It is noted that the amides could also proceed well under optimal reaction conditions, affording a wide range of β,γ‐ and γ,δ‐diaryl substituted carbonyl compounds. In contrast, benzyl‐protected allyl amine was not applicable to the reaction, suggesting that a carbonyl coordination rather than a nitrogen atom coordination was involved in this nickel‐catalyzed process.…”

Mechanisms of Nickel-Catalyzed Cross-Coupling Reactions

“…Other nucleophiles include Mg reagents [74] and boron reagents [75]. The olefin scope has been primarily limited to vinylarenes [76] and Michael acceptors [54] until the recent development of directing-group (DG) strategies, which have expanded the scope to include terminal aliphatic alkenes [77]. Computational analysis reveals that the reaction goes through a two-electron redox pathway mediated by Ni(0) 49 and Ni(II) 50 intermediates [77].…”

Integrating Allyl Electrophiles into Nickel-Catalyzed Conjunctive Cross-Coupling

“…[20][21] Reactivity and selectivity in these reactions can be controlled through use of conjugated substrates (e.g., styrenes, acrylates, or related activated alkenes), which react to form a stabilized allyl-metal intermediate or a metal enolate intermediate. [22][23][24][25] As a complementary strategy our lab [26][27][28] and others 23,24,[29][30][31][32][33] [20][21][22][23][24][25][26][27][28][29][30][31][32][33] use of allyl electrophiles remains rare. Notably, Semba and Nakao have described a palladium/copper dual catalytic system for carboallylation of conjugated, electron-deficient alkenes; however, the reaction required doubly activated substrates, such as benzalmalononitrile, thereby limiting the types of product structures that can be accessed.…”

“…Indeed, early studies from the 1970s on nickel-mediated 1,2-allylfunctionalization of alkenes were limited to carbonylation reactions or resulted in undesired rearrangements leading to mixtures of products. [36][37][38][39] With these considerations in mind and based on our lab's experience in developing substrate-directed nickel-catalyzed 1,2-difunctionalization reactions, [26][27][28]40 we sought to develop a three-component 1,2allylalkylation reaction. Given that alkene ligands have been previously found to promote challenging C(sp 3 )-C reductive eliminations (as required in our design), 28,[41][42][43][44][45][46][47] we reasoned that the reaction could be facilitated by a weakly coordinating, monodentate directing group capable of dissociating to allow the allyl group to serve as an alkene ligand.…”