Cobalt‐Catalyzed Hydrogen‐Atom Transfer Induces Bicyclizations that Tolerate Electron‐Rich and Electron‐Deficient Intermediate Alkenes

Abstract

A novel CoII‐catalyzed polyene cyclization was developed that is uniquely effective when performed in hexafluoroisopropanol as the solvent. The process is presumably initiated by metal‐catalyzed hydrogen‐atom transfer (MHAT) to 1,1‐disubstituted or monosubstituted alkenes, and the reaction is remarkable for its tolerance of internal alkenes bearing either electron‐rich methyl or electron‐deficient nitrile substituents. Electron‐rich aromatic terminators are required in both cases. Terpenoid scaffolds with different substitution patterns are obtained with excellent diastereoselectivities, and the bioactive C20‐oxidized abietane diterpenoid carnosaldehyde was made to showcase the utility of the nitrile‐bearing products. Also provided are the results of several mechanistic experiments that suggest the process features an MHAT‐induced radical bicyclization with late‐stage oxidation to regenerate the aromatic terminator.

Catalytic hydrogen atom transfer to alkenes: a roadmap for metal hydrides and radicals

“…More recently, an exploration of cobalt-catalyzed polyene cyclization identified effects of the catalyst structure on the diastereomeric ratios of cyclization products with trans or cis ring junctions depending on the salen ligand backbone. This effect was attributed to the likely formation of secondary organocobalt( iii ) complexes, 109 effectively increasing F c by introducing a kinetically competitive cage collapse pathway. Substrate arene deuteration did not result in product alkane deuteration, which one would expect from M–D formation and engagement of another alkene.…”

Cycloisomerization of Olefins in Water

“…We thought this tolerance might be useful for the synthesis of partially saturated heterocycles. Such cycloisomers benefit from fewer rotatable bonds and a higher fraction of sp 3 ‐hybridized atoms (Fsp 3 ) compared to their linear, sp 2 ‐rich precursors . We were interested to explore whether this reaction could be rendered biocompatible, and thus open olefin hydrofunctionalization as a bioorthogonal tool (Figure ).…”

Asymmetric Total Synthesis of Dankasterones A and B and Periconiastone A Through Radical Cyclization

“…On the other hand, the efficiency of the diastereocontrol was a concern. Of note, in comparison, a very recent work from the Vanderwal group revealed trans ‐decalins could be formed via MHAT‐induced polyene cyclization [8r] …”