Nickel‐Catalyzed 1,2‐Diarylation of Alkenyl Carboxylates: A Gateway to 1,2,3‐Trifunctionalized Building Blocks

Abstract

A nickel‐catalyzed conjunctive cross‐coupling of alkenyl carboxylic acids, aryl iodides, and aryl/alkenyl boronic esters is reported. The reaction delivers the desired 1,2‐diarylated and 1,2‐arylalkenylated products with excellent regiocontrol. To demonstrate the synthetic utility of the method, a representative product is prepared on gram scale and then diversified to eight 1,2,3‐trifunctionalized building blocks using two‐electron and one‐electron logic. Using this method, three routes toward bioactive molecules are improved in terms of yield and/or step count. This method represents the first example of catalytic 1,2‐diarylation of an alkene directed by a native carboxylate group.

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.…”

A free-radical design featuring an intramolecular migration for a synthetically versatile alkyl–(hetero)arylation of simple olefins

“…Intermolecular difunctionalizations forming two C-C bonds have thus received signicant interest over the past 10-15 years. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Given the importance of aromatic moieties in bioactive compounds and the continued underrepresentation of sp 3 content in pharmaceuticals, 33,34 alkyl-arylations of olens are critical tools in the synthetic arsenal. Transition-metalcatalyzed conjunctive couplings between an olen, an aromatic partner, and an aliphatic partner have received the most attention to this end.…”

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

“…Drawing inspiration from the coordinating directing strategy, [6d–n] we envisioned taking advantage of a coordinating group‐based chelation control strategy not only to favor the Heck migratory insertion of aryl‐M species into unactivated internal alkenes but also to stabilize the in situ generated chiral C(sp 3 )−M intermediates by the favorable formation of transient metallacycle. Recently, reductive alkene dicarbofunctionalization has garnered widespread interest as a powerful tool for installing two carbon electrophiles [1g, k] .…”