Modeling transformation of C-H bonds to C-F bonds is of high practical importance because such reactions may extend our abilities to optimize potency; absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physico-chemical properties of drug candidates. Prediction of the rate and stereoselectivity of fluorination of various substrates in such reactions under various conditions could significantly speed up rational drug design and manufacturing optimization. Unfortunately, the current understanding of such reactions leave multiple questions unanswered, including the reasons why the recently discovered and very promising aliphatic C-H bonds fluorination catalyzed by Mn-containing porphyrins may be not applicable to drug-like molecules. In this work, we attempt to start filling out this gap in the knowledge.