5358-34-9Relevant academic research and scientific papers
Rhoda-Electrocatalyzed C?H Methylation and Paired Electrocatalyzed C?H Ethylation and Propylation
Kuciński, Krzysztof,Simon, Hendrik,Ackermann, Lutz
supporting information, (2021/11/16)
The use of electricity over traditional stoichiometric oxidants is a promising strategy for sustainable molecular assembly. Herein, we describe the rhoda-electrocatalyzed C?H activation/alkylation of several N-heteroarenes. This catalytic approach has been successfully applied to several arenes, including biologically relevant purines, diazepam, and amino acids. The versatile C?H alkylation featured water as a co-solvent and user-friendly trifluoroborates as alkylating agents. Finally, the rhoda-electrocatalysis with unsaturated organotrifluoroborates proceeded by paired electrolysis.
Cobalt-catalysed C–H methylation for late-stage drug diversification
Ackermann, Lutz,Friis, Stig D.,Johansson, Magnus J.
, p. 511 - 519 (2020/06/05)
The magic methyl effect is well acknowledged in medicinal chemistry, but despite its significance, accessing such analogues via derivatization at a late stage remains a pivotal challenge. In an effort to mitigate this major limitation, we here present a strategy for the cobalt-catalysed late-stage C–H methylation of structurally complex drug molecules. Enabling broad applicability, the transformation relies on a boron-based methyl source and takes advantage of inherently present functional groups to guide the C–H activation. The relative reactivity observed for distinct classes of functionalities were determined and the sensitivity of the transformation towards a panel of common functional motifs was tested under various reaction conditions. Without the need for prefunctionalization or postdeprotection, a diverse array of marketed drug molecules and natural products could be methylated in a predictable manner. Subsequent physicochemical and biological testing confirmed the magnitude with which this seemingly minor structural change can affect important drug properties. [Figure not available: see fulltext.]
