Selectivity of hydrogenations. Part 3. N-methylquinolinium, N-methylisoquinolinium, and 4-(3-phenylpropyl)pyridinium salts

Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment

“…In this way it is possible to access the (un)protected tetrahydroquinoline in a concise fashion from an indole, a “skeletal edit” that involves not only ring expansion, but also a valuable increase in 3D character. Finally, hydrogenation with Adam's catalyst in TFA promotes complete reduction of all the benzenoid rings while leaving the azinium core untouched (pathway f) [61] …”

“…Finally, hydrogenation with Adam's catalyst in TFA promotes complete reduction of all the benzenoid rings while leaving the azinium core untouched (pathway f). [61]…”

Switchable and Chemoselective Arene Hydrogenation for Efficient Late Stage Applications

“…Therefore, the development of switchable-ring-selective hydrogenation of arenes stands as a pivotal goal − and remains challenging (Figure d). Most of the time, the hydrogenation reaction preferably reduces the heteroaromatic ring when both a benzene and a heteroaromatic ring are present. ,, Some instances of chemoselective hydrogenation of aromatic rings have been documented both with homogeneous and heterogeneous catalysis. ,,− The primary focus has been directed toward achieving selectivity among different heteroaromatic rings or selectively saturating the carbocyclic portion in fused bicyclic rings, such as quinoline. − This is attributed to the relatively lower aromatic stability of such aromatic rings. − Reports on the preferred hydrogenation of more challenging independent carbon aromatic rings before pyridine rings remain underdeveloped. ,,− Additionally, the co-occurrence of the partially saturated analogues, such as molecules containing piperidine and benzene motifs or molecules with cyclohexane and pyridine, is relatively low as compared to drugs bearing both benzene and pyridine rings (Figure b). This accentuates the importance of developing methodologies that enable the introduction of sp 3 motifs into drug scaffolds.…”

“…Notably, by controlling the reaction time, sequential reduction of the two benzene rings in the naphthalene system was achieved. Subsequently, when benzene was connected by a nitrogen atom to the pyridine ring, the reduction exhibited remarkable selectivity for the benzene ring (24), while the reduction of pyridine proved unsuccessful (more negative data can be found in SI). However, switchable saturation was achieved by introducing a propionyl group to the nitrogen atom, leading to the precursor of fentanyl with high yield and selectivity (25).…”