Synthesis and cross-coupling reactions of imidomethyltrifluoroborates with aryl chlorides

Abstract

Potassium imidomethyltrifluoroborate salts were efficiently synthesized. Potassium phthalimidomethyl-trifluoroborate was successfully used in Suzuki–Miyaura-like cross-coupling reactions with a variety of aryl chlorides.

Palladium-Catalyzed Cross-Coupling Reactions of Potassium N-Methyltrifluoroborate Isoindolin-1-one with Aryl and Heteroaryl Chlorides

“…t-BuOH=H 2 O (4:1) was superior to other solvents used. In contrast to our previous experiences with different coupling substrates, and much to our surprise, the optimum conditions for this coupling reaction were found to be the same as those published [16] for potassium phthalimidomethyltrifluoroborate coupling reactions. Potassium N-methyltrifluoroborate isoindolin-1-one (6) and 7a were found to optimally couple with the use of PdCl 2 (CH 3 CN) 2 (7.5 mol%), X-Phos (15 mol%), and K 2 CO 3 (3 equiv.)…”

“…Preparation of substituted N-benzyl phthalimides 4. [16] bromomethyltrifluoroborate led to the desired potassium N-methyltriflouro-borate isoindolin-1-one salt (6) as a white crystalline stable salt in 65% yield.…”

“…[15] In particular, a new and complementary synthetic strategy for the preparation of substituted N-benzyl phthalimides (4) (Scheme 1) was recently reported. [16] In this study, the authors prepared substituted N-benzyl phthalimides by palladium-catalyzed Suzuki-Miyaura cross-coupling between potassium phthalimidomethyltrifluoroborate (2) and aryl chlorides (3). [16] The authors noted that a key difference is the dissonant carbon-carbon bond-forming reaction that couples an N-methyl nucleophile with aryl chloride electrophiles, rather than the traditional nitrogen-carbon bond formation between the nucleophilic nitrogen of deprotonated phthalimide and benzyl halide electrophiles.…”

“…[16] In this study, the authors prepared substituted N-benzyl phthalimides by palladium-catalyzed Suzuki-Miyaura cross-coupling between potassium phthalimidomethyltrifluoroborate (2) and aryl chlorides (3). [16] The authors noted that a key difference is the dissonant carbon-carbon bond-forming reaction that couples an N-methyl nucleophile with aryl chloride electrophiles, rather than the traditional nitrogen-carbon bond formation between the nucleophilic nitrogen of deprotonated phthalimide and benzyl halide electrophiles. A significant benefit of this approach is that there are many more commercially available aryl chlorides than benzyl chlorides, thereby supporting easier access to large libraries of compounds.…”

“…These methylaminotrifluoroborate nucleophiles have proven to be effective coupling partners in variety of Suzuki-Miyaura coupling reactions. [16][17][18][19][20][21][22][23][24] One drawback of methylaminotrifluoroborates is that coupling reaction conditions are usually not general in nature and typically need to be developed for each unique application. Because there are numerous reaction variables (e.g., substrate, solvent mixture, catalyst, ligand, base, temperature, time) screening for reaction protocols often benefits from the use of high-throughput facilities.…”