Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume -, Issue -, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202313848
Keywords
Cobalt Catalysis; Cross-Coupling Reactions; High-Throughput Experimentation; N,O Ligands; Phenoxythiazoline
Categories
Ask authors/readers for more resources
The relative rates of the cobalt-catalyzed C(sp(2))-C(sp(3)) Suzuki-Miyaura cross-coupling were evaluated, and it was found that smaller N-alkyl substituents on the phenoxyimine ligand accelerated the reaction. This inspired the design of optimal cobalt catalysts with phenoxyoxazoline and phenoxythiazoline ligands. The catalyst lifetime was improved by adding excess KOMe•B(O-iPr)3, which attenuated alkoxide basicity and prevented demetallation of the ligand.
Evaluation of the relative rates of the cobalt-catalyzed C(sp(2) )-C(sp(3) ) Suzuki-Miyaura cross-coupling between the neopentylglycol ester of 4-fluorophenylboronic acid and N-Boc-4-bromopiperidine established that smaller N-alkyl substituents on the phenoxyimine (FI) supporting ligand accelerated the overall rate of the reaction. This trend inspired the design of optimal cobalt catalysts with phenoxyoxazoline (FOx) and phenoxythiazoline (FTz) ligands. An air-stable cobalt(II) precatalyst, (FTz)CoBr(py)(3) was synthesized and applied to the cross-coupling of an indole-5-boronic ester nucleophile with a piperidine-4-bromide electrophile that is relevant to the synthesis of reported toll-like receptor (TLR) 7/8 antagonist molecules including afimetoran. Addition of excess KOMe & sdot;B(O-i Pr)(3) improved catalyst lifetime due to attenuation of alkoxide basicity that otherwise resulted in demetallation of the FI chelate. A first-order dependence on the cobalt precatalyst and a saturation regime in nucleophile were observed, supporting turnover-limiting transmetalation and the origin of the observed trends in N-imine substitution.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available