Markovnikov-Selective Addition of Fluorous Solvents to Unactivated Olefins Using a Co Catalyst

Shigehisa, Hiroki; Kikuchi, Harue; Hiroya, Kou

doi:10.1248/cpb.c15-01024

Cited by 26 publications

(12 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…36 Critically, our desired hydrocyanation reaction is an overall oxidative transformation, which requires the turnover of both catalysts via a pair of single-electron oxidation events to return the resultant Co II and Cu I species We note that the attributes of electrochemistry render it uniquely capable of facilitating the merger of the two aforementioned catalytic processes into a broadly useful hydrocyanation protocol. Co-catalyzed hydrofunctionalization can encounter chemoselectivity issues with styrenetype substrates (vide infra), particularly in the presence of an oxidant, likely because the benzylic radical formed upon HAT is susceptible to over-oxidation to the benzyl cation 37 (except when the reaction between the benzylic radical and oxidant is desirable). Cu-catalyzed cyanation requires a potent chemical oxidant, 34,35 which can also limit the reaction scope to substrates lacking oxidatively labile functional groups.…”

Section: Resultsmentioning

confidence: 99%

Dual electrocatalysis enables enantioselective hydrocyanation of conjugated alkenes

et al. 2020

View full text Add to dashboard Cite

Chiral nitriles and their derivatives are prevalent in pharmaceuticals and bioactive compounds. Enantioselective alkene hydrocyanation represents a convenient and efficient approach for synthesizing these molecules. However, a generally applicable method featuring a broad substrate scope and high functional group tolerance remains elusive. Here, we address this long-standing synthetic problem using an electrocatalytic strategy. Electrochemistry allows for the seamless combination of two classic radical reactions-cobalt-mediated hydrogen-atom transfer and copper-promoted radical cyanation-to accomplish highly enantioselective hydrocyanation without the need for stoichiometric oxidant. We harness electrochemistry's unique feature of precise potential control to optimize the chemoselectivity of challenging substrates. Computational analysis sheds light on the origin of enantioinduction, for which the chiral catalyst imparts a combination of attractive and repulsive non-covalent interactions that direct the enantio-determining C-CN bond formation. This discovery demonstrates the power of electrochemistry in accessing new chemical space and providing solutions to pertinent challenges in synthetic chemistry. File list (2) download file view on ChemRxiv 01_Lin_MS.pdf (1.70 MiB) download file view on ChemRxiv 00_Lin_TOC.png (333.52 KiB)

show abstract

Section: Resultsmentioning

confidence: 99%

Dual electrocatalysis enables enantioselective hydrocyanation of conjugated alkenes

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Although we considered that this result might be due to adventitious oxygen, replacing the N ‐fluoropyridinium oxidant with an atmosphere of molecular oxygen led to a complex mixture, containing only traces of 6 a (entry 12). In the context of the optimal solvent for this transformation, it is noteworthy that Shigehisa has reported a method for hydrofunctionalization of alkenes employing fluorinated alcohols as nucleophiles using the same catalytic system . Other conditions evaluated (not shown) but found to be ineffective included: a) Shenvi's Co‐catalyzed conditions for alkene isomerization, which can also lead to cyclization and hydroarylation; b) Shenvi's Mn‐mediated conditions for intramolecular radical hydroarylation; and c) Baran's Fe‐catalyzed system, which is excellent at promoting Giese‐type reactions that strongly resemble the first ring formation in the transformation of 5 a into 6 a .…”

Section: Resultsmentioning

confidence: 99%

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

Vrubliauskas

Vanderwal

2020

Angew Chem Int Ed

View full text Add to dashboard Cite

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.

show abstract

“…158 A variety of styrenes and phenyl propanoids are competent substrates in this reaction. Other substrates failed to give the desired product, and the authors surmise that this is due to lack of carbocation stabilization.…”

Section: C-o Bondsmentioning

confidence: 99%

Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

et al. 2016

View full text Add to dashboard Cite

Cofactor-mimetic aerobic oxidation has conceptually merged with catalysis of syngas reactions to form a wide range of Markovnikov-selective olefin radical hydrofunctionalizations. We cover the development of the field and review contributions to reaction invention, mechanism and application to complex molecule synthesis. We also provide a mechanistic framework for understanding this compendium of radical reactions.

show abstract

Markovnikov-Selective Addition of Fluorous Solvents to Unactivated Olefins Using a Co Catalyst

Cited by 26 publications

References 15 publications

Dual electrocatalysis enables enantioselective hydrocyanation of conjugated alkenes

Dual electrocatalysis enables enantioselective hydrocyanation of conjugated alkenes

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

Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

Contact Info

Product

Resources

About