Radical Reactions in Alkaloid Synthesis: A Perspective from Carbon Radical Precursors

The usefulness of radical reactions in alkaloid synthesis is reviewed from the perspective of the functional groups embedded in the molecular structure of synthetic intermediates, that act as precursors of carbon-centered radicals in the construction of new C-C bonds. The functional groups featured are alkenes, alkynes, halides (alkyl, vinyl, aryl), xanthates, sulfides, selenides, aldehydes, ketones, carboxylic acid derivatives (selenoesters, haloacetamides), beta-dicarbonyl compounds, and alpha-heterosubstituted nitrogen-compounds. The use of nitrogen-centered radicals for C-N bond formation is also covered. Among the variety of radical processes applied, the most predominant are the hydride reductive method (Sn, Si), atom transfer radical reactions (Cu, Ru, B), and single-electron transfer radical reactions promoted by Sm, Ni, Fe, Mn, Ti, and Ag. This review showcases the role radical reactions have played in the recent development of new strategies in alkaloid synthesis, as well as the implementation of new radical procedures in demanding substrates.