Redox-Neutral Propargylic C–H Functionalization by Using Iron Catalysis

Abstract

In spite of their rich stoichiometric chemistry, cyclopentadienyliron(II) dicarbonyl complexes are rarely used as catalysts in organic synthesis. Inspired by precedents in the chemistry of cationic olefin complexes and neutral allylmetal species, our group has developed a coupling of alkynes or alkenes with aldehydes and other carbonyl electrophiles to give homopropargylic and homoallylic alcohols, respectively, by using a substituted cyclopentadienyliron(II) dicarbonyl complex as the catalyst. In this article, we first contextualize this development within the conceptual background of C–H functionalization chemistry and relative to key stoichiometric precedents. We then give an account of our group’s discovery and development of the catalytic α-functionalization of alkenes and alkynes with electrophilic reagents.Introduction Preliminary Stoichiometric WorkHydroxyalkylation Development and ScopeConclusions and Future Directions

Ene Reactivity of an Fe═NR Bond Enables the Catalytic α-Deuteration of Nitriles and Alkynes

“…Complexes 2 – 5 are unique examples of open-shell metal allenyl complexes. While allenyl complexes are typically synthesized by oxidative addition of propargyl halides at low-valent metal centers, − they can also be accessed through the deprotonation of coordinated alkyne and allene ligands by an external base. − The synthesis of 2 – 5 is conceptually similar to the latter route, except that the imido ligand acts as an internal base.…”

Iron-Catalyzed Coupling of Alkenes and Enones: Sakurai–Michael-type Conjugate Addition of Catalytic Allyliron Nucleophiles

“…Our group has previously demonstrated that cyclo­penta­dienyl­iron­(II) dicarbonyl complexes are capable of coordinating to and enhancing the C–H acidity of a range of unsaturated substrates, to facilitate the removal of protons at the allylic, propargylic, or allenic positions . As a result, functional group-tolerant amine and pyridine bases could be used for abstraction of the α-proton to deliver a nucleophilic organoiron species that could undergo subsequent electrophilic functionalization with predictable S E 2′ selectivity.…”

Synthesis of 1,3-Enynes by Iron-Catalyzed Propargylic C–H Functionalization: An Alkyne Analogue for the Eschenmoser Methenylation

“…Previously our group developed a catalytic method for the C–H functionalization of unsaturated hydrocarbons by employing cationic iron complexes for π-activation to increase the acidity of the propargylic, allylic, or allenic C–H bonds and enable their deprotonation by weak amine or pyridine bases to generate nucleophilic organoiron species. These organometallic nucleophiles undergo subsequent functionalization with carbonyl and iminium electrophiles to generate α-C–H functionalization products . We hypothesized that allenyliron intermediates generated from alkyne substrates could react with an Eschenmosher salt to give homopropargylic amine products.…”

“…These organometallic nucleophiles undergo subsequent functionalization with carbonyl and iminium electrophiles to generate α-C–H functionalization products. 18 We hypothesized that allenyliron intermediates generated from alkyne substrates could react with an Eschenmosher salt to give homopropargylic amine products. These adducts could then undergo elimination of the pendent dialkylamino group to afford 1,3-enynes, allowing for the development of a protocol that is formally and mechanistically analogous to the Eschenmoser methenylation ( Scheme 1 E).…”