Catalytic methods play a central role in pharmaceutical synthesis, including C–H functionalization and asymmetric catalysis. However, the structural complexity of drug molecules often poses challenges for the safety, efficiency, and scalability of state-of-the-art catalysts. This presentation describes two catalytic solutions designed with practical application in mind.

First, we present a dual-catalyst approach that combines an organophotoredox catalyst with Wilkinson’s catalyst to enable the hydrogen isotope exchange (HIE) of aliphatic C(sp3)–H bonds in pharmaceuticals. Using preferred T2 gas as the isotopic feedstock, this protocol provides a safe and efficient method to the tritium labeling of pharmaceuticals under mild conditions. Second, we report a homogeneous, asymmetric cyclopropanation method that merges chiral pyridine bis-oxazoline (PyBox)–cobalt catalysts with readily accessible zinc carbenoids. The method furnishes chiral cyclopropanes bearing pyridyl, pyrimidyl, and other nitrogen-containing heteroaryl substituents with high enantioselectivity. Mechanistic studies support direct transmetallation of the zinc carbenoid to cobalt and a redox-neutral Co^(II) catalytic cycle for cyclopropanation. The catalyst’s homogeneity, high enantioselectivity, and compatibility with a range of green solvents enable straightforward scale-up and broad application across diverse heteroaryl substrates.

Together, these case studies demonstrate practical and scalable catalytic strategies for isotope labeling and for the construction of chiral heteroaryl cyclopropanes relevant to pharmaceutical synthesis.

Dan Lehnherr

Merck & Co Inc

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