68531-91-9Relevant academic research and scientific papers
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.]
Divergent Synthesis of Quinolones and Dihydroepindolidiones via Cu(I)-Catalyzed Cyclization of Anilines with Alkynes
Xu, Xuefeng,Sun, Ruzhong,Zhang, Sheng,Zhang, Xu,Yi, Wei
supporting information, p. 1893 - 1897 (2018/04/16)
A unique and efficient method for one-pot synthesis of diverse 4-quinolones from simple and readily available primary anilines and alkynes via Cu(I)-catalyzed direct cyclization has been developed. The (thio)phenols were also found to visible substrates for this reaction. Moreover, an unprecedented synthesis of dihydroepindolidiones has been demonstrated by using secondary anilines as the versatile substrates.
Iron-Catalyzed Ortho C-H Methylation of Aromatics Bearing a Simple Carbonyl Group with Methylaluminum and Tridentate Phosphine Ligand
Shang, Rui,Ilies, Laurean,Nakamura, Eiichi
supporting information, p. 10132 - 10135 (2016/08/31)
Iron-catalyzed C-H functionalization of aromatics has attracted widespread attention from chemists in recent years, while the requirement of an elaborate directing group on the substrate has so far hampered the use of simple aromatic carbonyl compounds such as benzoic acid and ketones, much reducing its synthetic utility. We describe here a combination of a mildly reactive methylaluminum reagent and a new tridentate phosphine ligand for metal catalysis, 4-(bis(2-(diphenylphosphanyl)phenyl)phosphanyl)-N,N-dimethylaniline (Me2N-TP), that allows us to convert an ortho C-H bond to a C-CH3 bond in aromatics and heteroaromatics bearing simple carbonyl groups under mild oxidative conditions. The reaction is powerful enough to methylate all four ortho C-H bonds in benzophenone. The reaction tolerates a variety of functional groups, such as boronic ester, halide, sulfide, heterocycles, and enolizable ketones.
Regioselective synthesis of flavone derivatives via DMAP-catalyzed cyclization of o-alkynoylphenols
Yoshida, Masahito,Fujino, Yuta,Saito, Koya,Doi, Takayuki
, p. 9993 - 9997 (2012/02/06)
A catalytic amount of DMAP promoted cyclization of o-alkynoylphenols via a 6-endo cyclization mode leading to flavone derivatives in high yields without forming 5-exo cyclized aurone derivatives. Utilizing this method, methoxy substituted flavone and alkyl substituted γ-benzopyranone derivatives were synthesized.
