We also wanted to expand the library of reacted ketones, so we selected acetophenone next and combined it with azuliporphyrin (Scheme 4), which gives the most stable and symmetric derivatives. The reaction was conducted at an elevated temperature, and despite limiting the number of reactive α-carbon sites, we obtained two substitution products (9 and 10) this time. Both products possess a 1 H NMR signal around -100 ppm, but 10 also has another signal at -41.2 ppm (Fig. ), unexpected for acetophenone substitution (aryl protons are too distant from the Co II centre to be highly shielded). HRMS analysis indicated that deoxygenation of a substrate occurs during the reaction, leading effectively to a styrene substitution. The E-styryl substitution was confirmed through single-crystal X-ray crystallography (Fig ). Prolonged reaction times enrich the mixture in 10, suggesting that the Scheme 4. The scope of tested ketones and the final substituents. The next question was if the increased steric hindrance at αcarbon, namely the presence of CH2R instead of CH3, also allows the substitution reaction. To test this, we used 3-pentanone (Scheme 4). The 1 H NMR spectrum of obtained product 11 (Fig. ) is complicated by the fact that the α-C substitution leads to an inherently asymmetric, chiral molecule. There is virtually one set of paramagnetic signals, meaning that the crowding does not inhibit the reaction nor directs it into β-carbon activation. DFT calculations support the thermodynamic character of the occurring pathway as long as dispersion interactions are included (Fig. ). The yield is further decreased not only by 21-oxoazuliporphyrin generation but also by seven-membered ring substitution products identified during a mixture separation (Fig. ), as 1 and its derivatives are prone to undergo such nucleophilic attacks. In the end, we were interested in seeing the selectivity between activating CH3 and CH2R. Thus, we took 2-butanone for the reaction (Scheme 4), which, when conducted at reflux (bp 80 °C) for ca. 1 h, leads to one product with a set of expected chemical shifts for symmetric species 12a. Nonetheless, when we tested the reaction at 60 °C in time, two sets of substitution product signals were present (Fig. ), including an asymmetric one, coming clearly from chiral 12b. After 1 h, the estimated ratio was 2.4:1 (12a:12b), but after 28 h, only 20.5:1, suggesting 12b is either less stable and decomposing or somehow a kinetic product. The total yield of 12 was dropping with prolonged or more intensive heating. Also in this case, seven-membered ring substitutions were observed as additional byproducts.