Sequences Intercepted by Cyclizations

Alkynones [62] and 1,3-diaryl propenones (chalcones) [63] are reactive three-carbon building blocks that can be transformed into five-, six-, and seven-membered heterocycles with bifunctional nucleophiles in the sense of Michael addition and cyclocondensation. Therefore, a catalytic access to ynones [64] and enones [65] by Sonogashira alkynylation turned out to be a versatile entry to consecutive multicomponent syntheses of heterocycles. This reactivity-based concept has been considerably developed by the Muller group in the past decade. In several reviews, the major advancements of this one-pot methodology have been summarized [66]. Therefore, only very recent conceptual achievements with respect to sequentially Pd-catalyzed processes [7] will be considered here. 

Indeed, by virtue of the in situ generated 4-halo pyrazole 36 and the presence of the catalytic metal complexes, a sequentially Pd-catalyzed Suzuki coupling was conceived. Upon addition of catalytic amounts of triphenylphosphane, the proper 

R = aryi, (hetero)aryi, cyciopropyi, 1 -adamantyi (11 exampies, 61-75%) 

Since JV-Boc-protected 4-iodo pyrroles 38 are highly useful synthetic building blocks that can be transformed in the sense of a sequential Pd/Cu-catalyzed process, assuming that the catalyst system is still active after the coupling-addition-cyclocondensation sequence. Upon addition of another 

Sequential transition-metal-catalyzed processes based upon cycloisomerization and cyclization are receiving increasing attention because they combine the increase of structural complexity (cyclizing reactions) with an atom economically benign use of the employed catalyst sources (sequential catalysis). This reactivity-based concept has been predominantly illustrated for sequentially Pd-, Rh-, and Ru-catalyzed processes, and currently the literature is dominated by the three transition metals. However, many other metal complexes can be envisioned to be equally fruitful in further developments and, without any doubt, even more unusual sequences are waiting to be discovered. Inevitably, only the opening chapter of this never-ending story has been told. 

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