Cycloisomerization of Olefins in Water

Abstract

Preparative reactions that occur efficiently under dilute, buffered, aqueous conditions in the presence of biomolecules find application in ligation, peptide synthesis, and polynucleotide synthesis and sequencing. However, the identification of functional groups or reagents that are mutually reactive with one another, but unreactive with biopolymers and water, is challenging. Shown here are cobalt catalysts that react with alkenes under dilute, aqueous, buffered conditions and promote efficient cycloisomerization and formal Friedel–Crafts reactions. The constraining conditions of bioorthogonal chemistry are beneficial for reaction efficiency as superior conversion at low catalyst concentration is obtained and competent rates in dilute conditions are maintained. Efficiency at high dilution in the presence of buffer and nucleobases suggests that these reaction conditions may find broad application.

Cobalt‐Catalyzed Chemoselective Isomerization of 2‐Substituted Allyl Ethers Induced by Hydrogen Atom Transfer

“…In the following HAT process, the hydrogen atom is transferred to the alkene moiety on allyl ethers, furnishing the Co‐alkyl intermediate A . Then intermediate A achieves dynamic equilibrium with intermediate B through cage escape and cage reentry [15h–i] . The possible O ‐coordination [16] between Co II and β ‐alkoxy alkyl radical shifts the equilibrium to intermediate C , which then undergoes β ‐H atom abstraction to obtain the isomerization product and regenerate the active Co III −H complex for the next catalytic cycle.…”