Phosphonium Ions asActivating Groups for the SelectiveAlkylation of Pyridines and Polyazines

The Minisci reaction is a broadly applicable method for coupling carbon-bearing groups to pyridines but suffers from poor regio- and site-selectivity, particularly in complex structures. Here, we show that C4-phosphonium salts serve as activating groups in Minisci alkylation processes. In this way, radicals add selectively to pyridines bearing phosphonium salts rather than to those without phosphonium salts in polypyridine structures. Furthermore, the phosphonium salt serves as a blocking group, ensuring regioselective alkylation at the 2-position. The C-P bond is easily cleavable in a simple workup procedure or can be used as a versatile functional handle to construct 2,4-disubstituted pyridines. We also show that site-selective switching reactions are possible by controlling the site of C-P bond formation in drug-like structures.