There is growing interest in the preparation of compounds that possess branched (secondary) alkyl side chains directly connected to aromatic moieties. In fact, a numbering of promising lead compounds in the pharmaceutical and materials science sectors contain this molecular arrangement.<br/>A series of new N-heterocyclic carbene (NHC) based Pd complexes has been created and evaluated in the Negishi cross-coupling of aryl- and heteroaryl chlorides and bromides with a variety of secondary alkylzinc reagents. Pd-PEPPPSI-IHept-Chloro couples secondary alkylzinc reagents to 6-membered-ring heterocycles with essential zero migratory insertion, which leads to undesired isomeric cross-coupled products. This same catalyst has demonstrated remarkable selectivity as well with 5-membered-ring heterocycles that invariably couple with extensive isomerization using other known catalysts. Discussion will include substrate scope with this, and other new Pd-NHC catalysts for the coupling of secondary alkylzinc reagents. Further, in depth analysis will be provided for how these catalysts have demonstrated such high levels of cross-coupling selectivity where almost all other catalysts have struggled.

Selective Negishi coupling of secondary alkylzinc reagents to aromatics: Solving the 5-membered ring heterocycle problem

249th National Meeting (2015)

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