Bidentate Phosphine Ligand Impacts on Previously Inaccessible Five-Membered N-Heteroaryne Formation and Functionalization

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Five-membered N-heteroarynes have long been considered synthetically inaccessible; however, we recently reported the use of a bisphosphine-ligated nickel center to stabilize and enable the formation of these otherwise unobtainable intermediates. Motivated by this success, we were compelled to study the role of the ancillary phosphine in aryne formation and reactivity. Herein, a set of four bidentate phosphine ligands with altered phosphine substituents and backbone length are interrogated for their competence as ancillary ligands for five-membered N-heteroaryne formation. We determined that ligands with phenylphosphine substituents or linker lengths longer than three carbons were unsuitable for this purpose, while ligands having alkylphosphine substituents and one-, two-, or three-carbon linkers allowed for successful aryne formation. Reactivity studies using 2-PyZnBr as a nucleophilic coupling partner revealed intriguing regioselectivity enhancement (up to >20:1 r.r.) when utilizing ligands with altered linker lengths. We hypothesize that regioselectivity can be traced back to structural differences between these Ni–aryne complexes, as evidenced by crystallographic characterization.