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 Hydride Oxidase Catalysis Enabled Hydroamination of Unactivated Olefins

“…Notably, cobalt hydride-catalyzed radical cyclizations have been shown to benefit from high dilution by Shenvi and coworkers. 36 However, the opposite trend was predicted here based on our mechanistic hypothesis for at least two reasons. First, the key oxidation involves two cobalt species and should be facilitated by high concentration, while dioxygen presumably stays at the saturation concentration; second, as the system gets more concentrated, a rise in viscosity would increase the cage efficiency and thereby increase S. Indeed, a boost in yield and S was observed as the reactions were carried out using less solvent and eventually in neat form (entries 9-10).…”

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

“…The related Co 3+ tetrauoroborate could be generated by oxidation of Co 2+ with silver(I) tetrauoroborate, which was shown to be catalytically competent. 18,33 The mechanism of hydride formation in this instance is less obvious but one possibility is hydride delivery from a pentavalent silicate intermediate formed by the association of triate, uoride, or solvent. 34 Both pathways would produce the previously mentioned Si-O or Si-F bond.…”

“…In another example, (salen)Co 3+ -H was shown to consume alkylsubstituted, unactivated alkenes within 30 minutes even at substrate concentrations of 1 Â 10 À3 M and a pre-catalyst concentration of 1 Â 10 À4 . 33 More information could in principle be gleaned from determination of rate laws, but kinetic analysis has proven challenging. For example, the cobaltcatalyzed hydrohydrazination and hydroazidation, as well as the iron-catalyzed alkene-alkene coupling, exhibited partialorder rate dependencies on metal, alkene and silane, 28 and apparent orders for alkene, radical acceptor, and silane that depended on the choice of alkene.…”

“…Increasing dilution with no changes to the catalyst structure favored cycloisomerization. 33 If isomerization took place exclusively from the primary geminate radical pair, then the ratio of isomerization to cycloisomerization would be expected to remain constant as both rates would depend only on the concentration of the primary geminate radical pair. To explain this result, isomerization and cycloisomerization products must be formed upon cage escape and re-entry.…”

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

“…It should be mentioned that both Fe‐mediated Giese‐type reaction and Co‐mediated cycloisomerization in this case gave exclusive desired cis ‐fused A/B ring. We speculated the radical intermediate 32 , which was produced through a direct hydrogen atom transfer from M‐H based on Shenvi's mechanistic insight about MHAT‐based reaction, [7e, 8a–g] may prefer to adopt a chair chair conformation wherein both the methyl at C10 and side chain at C5 are equatorial, thus leading to sole desired cis ‐fused A/B ring intermediate (Scheme 4). Another point that deserves discussion is terminator used in Co‐mediated HAT based cyclizations.…”