Pyrazoles are heterocycles commonly found as key substructures in agrochemicals and medicinally active compounds alike.1,2 Despite their pervasiveness, established methods fall notably short in delivering complex pyrazoles selectively due to issues of differentiation during either assembly or _N_\-functionalization.3 This is a direct consequence of a dominant synthetic strategy that attempts to control selectivity-determining bonds between poorly differentiated starting materials. To overcome this longstanding challenge, we here describe a prototypical example of an alternative conceptual approach, “Strategic Atom Replacement”, in which we synthesize _N_\-alkyl pyrazoles from isothiazoles. The net forward transformation is a “swap” of the isothiazole sulfur atom with a nitrogen atom and its associated alkyl fragment to deliver the alkylated pyrazole.4,5 Linking the two azoles is an orphaned heterocycle class, 1,2,3-Thiadiazine-_S_\-Oxides, whose synthetic potential has yet to be tapped.6 By proceeding _via_ these unusual heterocycles, the typical selectivity and separation challenges associated with exclusively bond-based pyrazole preparations are circumvented, and even minimally differentiated peripheral substituents can be discriminated to afford isomerically pure products.
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Supplementary Sections 1–25, including Supplementary Figs 1–31 and Supplementary Tables 1–9 – see Table of Contents for details.