Reinvestigation of Aminomethyltrifluoroborates and Their Application in Suzuki−Miyaura Cross-Coupling Reactions

Abstract

A reinvestigation into the chemical composition of potassium aminomethyltrifluoroborates is reported. These trifluoroborato salts have been reassigned as zwitterionic ammoniomethyltrifluoroborates. Minor adjustments to the previously disclosed reaction conditions are reported that permit a similar level of activity as nucleophiles in Suzuki–Miyaura cross-coupling reactions.

Nickel-Catalyzed Borylation of Halides and Pseudohalides with Tetrahydroxydiboron [B2(OH)4]

“…Furthermore, after addition of KHF 2 a mixture of potassium and internal salt was obtained for these substrates, and full conversion to the potassium salt required treatment of the crude mixture with K 2 CO 3 in acetonitrile. 21 To the best of our knowledge, the examples illustrated on Table 3 represent the largest and most diverse substrate scope for borylation of heteroaryl systems in the current literature. Unfortunately, heteroaryls such as pyrimidine, isoxazole and thiazole did not undergo borylation, and only halide starting material was recovered in these cases.…”

Aminomethylation of Aryl Halides Using α-Silylamines Enabled by Ni/Photoredox Dual Catalysis

“…This approach has been realized previously via the efforts of Molander, Tanaka, and Dumas. 5 This catalytic approach nicely complements existing “go-to” approaches for aminomethylation (e.g., reductive amination or alkylation of amines) because the electrophilic partners are aryl halides or sulfonate esters as opposed to aromatic aldehydes or benzylic halides. Indeed, the latter are not as stable to long term storage, and furthermore, there are easily thousands more commercially available aryl- and heteroaryl halides than aryl/heteroaryl aldehydes or benzylic halides.…”

“…5 The harsh nature of aminomethylation via cross-coupling is due, in part, to the inherent thermodynamic penalty paid to transmetalation when attempting to forge C sp 2 –C sp 3 bonds. As a general resolution to this mechanistic impediment, an odd-electron activation mode involving the concerted action of a Ni complex and visible light activated photocatalyst was conceived and simultaneously realized by our group and the groups of Mac-Millan and Doyle.…”

Suzuki–Miyaura Cross-Coupling of Potassium Trifluoro(N-methylheteroaryl)borates with Aryl and Heteroaryl Halides

“…15 After removal of the solvent in vacuo, the reaction mixture was suspended in hot acetone and filtered to remove the insoluble KCl. Crystallizing the products was difficult as oiling out was often observed, especially with the indole system ( 1c ).…”