Letter to the Editor pubs.acs.org/OPRD
Letter to the Editor concerning: “Carbon−Heteroatom Coupling Using Pd−PEPPSI Complexes” by Valente et al.
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hundred ppm of palladium with heating and lower temperatures are desired, an approximate estimate of the required loading at lower temperatures to effect complete conversion within the same time frame can be made. It should be appreciated that the requirements of a given reaction will vary considerably: if milligrams of a highly sensitive compound are required, then high (i.e., > 1 mol %) loadings of palladium at low temperature are most appropriate; for the synthesis of multikilogram batches of less sensitive materials, ppm loadings of palladium at higher temperatures may well be more economical. Detailed screening of catalysts under a huge number of conditions is impractical and unnecessary for the initial evaluation of new palladium complexes; we typically choose to minimise the palladium loading, but other researchers may have different priorities. (ii) Our second point is somewhat related to the above. Organ makes the point that a direct comparison is almost always not possible, due to differing reaction conditions: e.g. “Aryl amination reaction conditions employing soluble, highly aggressive tert-butoxide and its derivatives cannot be drawn into comparisons with reactions performed using a mild, insoluble carbonate base”. Only one direct comparison is reported (for which no reference is given)3 in which [PdCl2(IPent)(3-Clpy)] significantly outperforms [PdCl2(IPr*)(3-Cl-py)] in the sulfination of 2,6-dimethylchlorobenzene with benzenethiol to yield compound 27 (NB: compounds 21 and 27 are the same structure). Yet, the authors present Figure 4 in which the reactivity order is presented as “IPentCl > IPent > IPr* > IPr/ SIPr”; IPentCl is labelled as ‘ultrahigh activity’, IPent as ‘high activity’ and IPr*, IPr, and SIPr as ‘moderate activity’. Such an assertively presented reactivity order is clearly inconsistent with a lamented lack of direct comparisons! The criteria for selecting this reactivity order are, we feel, very weak and subject to interpretation. Again, we would strongly emphasise that the choice of conditions will depend entirely on the chemistry one wishes to achieve. Organ chooses to focus on mild conditions (using expensive carbonate bases) with high (often 2−4 mol %) catalyst loadings, in order to couple the widest range of substrates; we choose slightly more forcing conditions (alkoxide bases, although we would refute that these are as ‘aggressive’ as Organ implies) in order to achieve low (
