Intramolecular, Stoichiometric (Li, Mg, Zn) and Catalytic (Ni, Pd, Pt) Metallo‐Ene Reactions in Organic Synthesis New Synthetic Methods (75)

Abstract Metallo‐ene reactions, hardly recognized until very recently, have experienced a breathtaking development when applied in an intramolecular sense. Efficient regio‐ and stereoselective magnesium‐ene cyclizations have served as a cornerstone for numerous syntheses of structurally diverse natural products (e.g., sesquiterpenes of marine or plant origin, alkaloids, fragrances, insect defense compounds, and a fungitoxin). A brilliant example is the synthesis of the elusive odorant (+)‐khusimone which outshines 20 years of work in the field of tricyclovetivane synthesis. Palladium‐, platinum‐, and nickel‐catalyzed versions of the metallo‐ene reaction are in a comparatively early stage of exploration, but, nevertheless, reveal intriguing potential. Hence an almost 100% stereospecific CO→C;Pd‐→ CC chirality transfer permits simple and selective, cis ‐ or trans ‐annelation processes. The mild cyclization conditions are compatible with various functional groups, such as nitrogen moieties, which offer interesting perspectives for the preparation of heterocycles (e.g., alkaloids) difficult to obtain by other methods. Carbon monoxide insertion reactions of the cyclized σ‐metal intermediates were shown to afford annelated cyclopentanones and cyclopentenones with concomitant stereocontrolled formation of four carbon–carbon bonds. These and other observations, highlighted in this article, provide a platform for further extensions and applications of this powerful method in organic synthesis.