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

Abstract

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), β‐dicarbonyl compounds, and α‐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.

Regio- and Stereoselective Hydroiodination of Internal Alkynes with Ex Situ-Generated HI

“…Vinyl iodides are important building blocks used in many organic transformations such as transition-metal-catalyzed coupling, halogen–metal exchange, and radical reactions . Therefore, the straightforward synthesis of these compounds is highly desirable.…”

α-Tertiary Dialkyl Ether Synthesis via Reductive Photocatalytic α-Functionalization of Alkyl Enol Ethers

“…Similar findings were are also observed when analogous experiments were conducted using benzyl methacrylate as the alkene substrate (see Supporting Information for more details). Taken together, these results point to an alternative termination process, whereby an intramolecular HAT event, , prior to intermolecular termination with a Hantzsch ester species, leads to the α-tertiary dialkyl ether product . Calculated electrophilicity indices reveal that the positions where deuterium has been incorporated all provide a more nucleophilic radical species, which in turn would lead to a more favorable HAT with the Hantzsch radical cation. , Furthermore, kinetic effects in the termination of primary vs tertiary radicals cannot be ruled out …”

Four‐Step Synthesis of (−)‐4‐epi‐Presilphiperfolan‐8α‐ol by Intramolecular Iron Hydride Atom Transfer‐Mediated Ketone‐Alkene Coupling and Studies to Accesstrans‐Hydrindanols with a Botryane Scaffold

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