Copper(II)-catalyzed cascade functionalization of 2-(trimethylsilyl)thiazole with two α-aryl diazoesters: Synthesis of highly substituted pyrrolo[2,1- <i>b</i> ]thiazol-6(5 <i>H</i> )-ones

Thiazole heterocycles possess electronic characteristics that render them valuable scaffolds in medicinal chemistry. A copper(I)-catalyzed cascade reaction employing two equivalents of α‑aryl diazoesters has previously been shown to convert thiazoles into densely functionalized 4‑thiazolines. In the present study, we demonstrate that utilization of a trimethylsilyl (TMS)‑protected substrate—2‑TMS thiazole—diverts this reaction pathway and furnishes highly substituted pyrrolo[2,1‑b]thiazol‑6(5H)-ones under Cu(hfacac)2 catalysis. Mechanistic investigations indicate that the catalytic cycle proceeds via an in situ copper carbene intermediate intercepted by the nitrogen atom of the thiazole ring. A subsequent [1,2]-Stevens rearrangement coupled with a directed migration of the TMS group enforces exclusive E‑configuration of a key alkenyl intermediate; this stereochemical bias governs downstream transformations and culminates in the stereoselective synthesis of functionalized pyrrolo[2,1‑b]thiazol‑6(5H)-ones. These results illustrate how stereoelectronic effects can be exploited to steer a catalytic sequence toward divergent product manifolds.