A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

While a great number of C–H functionalization methods have been developed in recent years, new mechanistic paradigms to deconstruct such bonds have been comparatively rare. Amongst possible strategies for breaking a C<i>_sp³</i>–H bond are deprotonation, oxidative addition with a metal catalyst, direct insertion via a nitrene intermediate, hydrogen atom transfer (HAT) with both organic and metal-based abstractors, and lastly, hydride abstraction. The latter is a relatively unexplored approach due to the unfavorable thermodynamics of such an event, and thus has not been developed as a general way to target both activated and unactivated C<i>_sp³</i>–H bonds on hydrocarbon substrates. Herein, we report our successful efforts in establishing a catalytic C–H functionalization manifold for accessing an intermediate carbocation by formally abstracting hydride from unactivated C<i>_sp³</i>–H bonds. The novel catalytic design relies on a stepwise strategy driven by visible light photoredox catalysis and is demonstrated in the context of a C–H fluorination employing nucleophilic fluorine sources. Difluorination of methylene groups is also demonstrated, and represents the first C–H difluorination with nucleophilic fluoride. Additionally, the formal hydride abstraction is shown to be amenable to several other classes of nucleophiles, allowing for the construction of C–C or C–heteroatom bonds.

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable a General Csp3–H Fluorination with HF

While a great number of C–H functionalization methods have been developed in recent years, new mechanistic paradigms to deconstruct such bonds have been comparatively rare. Amongst possible strategies for breaking a C<i>_sp³</i>–H bond are deprotonation, oxidative addition with a metal catalyst, direct insertion via a nitrene intermediate, hydrogen atom transfer (HAT) with both organic and metal-based abstractors, and lastly, hydride abstraction. The latter is a relatively unexplored approach due to the unfavorable thermodynamics of such an event, and thus has not been developed as a general way to target both activated and unactivated C<i>_sp³</i>–H bonds on hydrocarbon substrates. Herein, we report our successful efforts in establishing a catalytic C–H functionalization manifold for accessing an intermediate carbocation by formally abstracting hydride from unactivated C<i>_sp³</i>–H bonds. The novel catalytic design relies on a stepwise strategy driven by visible light photoredox catalysis and is demonstrated in the context of a C–H fluorination employing nucleophilic fluorine sources. Difluorination of methylene groups is also demonstrated, and represents the first C–H difluorination with nucleophilic fluoride. Additionally, the formal hydride abstraction is shown to be amenable to several other classes of nucleophiles, allowing for the construction of C–C or C–heteroatom bonds.

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable a General Csp3–H Fluorination with HF

While a great number of C–H functionalization methods have been developed in recent years, new mechanistic paradigms to deconstruct such bonds have been comparatively rare. Amongst possible strategies for breaking a C<i>_sp³</i>–H bond are deprotonation, oxidative addition with a metal catalyst, direct insertion via a nitrene intermediate, hydrogen atom transfer (HAT) with both organic and metal-based abstractors, and lastly, hydride abstraction. The latter is a relatively unexplored approach due to the unfavorable thermodynamics of such an event, and thus has not been developed as a general way to target both activated and unactivated C<i>_sp³</i>–H bonds on hydrocarbon substrates. Herein, we report our successful efforts in establishing a catalytic C–H functionalization manifold for accessing an intermediate carbocation by formally abstracting hydride from unactivated C<i>_sp³</i>–H bonds. The novel catalytic design relies on a stepwise strategy driven by visible light photoredox catalysis and is demonstrated in the context of a C–H fluorination employing nucleophilic fluorine sources. Difluorination of methylene groups is also demonstrated, and represents the first C–H difluorination with nucleophilic fluoride. Additionally, the formal hydride abstraction is shown to be amenable to several other classes of nucleophiles, allowing for the construction of C–C or C–heteroatom bonds.

Tropylium Salt Promoted Hydroboration Reactions: Mechanistic Insights via Experimental and Computational Studies

Hydroboration reaction of alkynes is one of the most synthetically powerful tools to access organoboron compounds, versatile precursors for cross coupling chemistry. This type of reaction has traditionally been mediated by transition metal or main group catalysts. Herein, we report a novel method using tropylium salts, typically known as organic oxidants and Lewis acids, to efficiently promote the hydroboration reaction of alkynes. A broad range of vinylboranes can be easily accessed via this metal-free protocol. Similar hydroboration reactions of alkenes and epoxides can also be efficiently catalyzed by the same tropylium catalysts. Experimental studies and DFT calculations suggested that the reaction follows an uncommon mechanistic paradigm, which is triggered by a hydride abstraction of pinacolborane with tropylium ion. This is followed by a series of <i>in situ</i> counterion-activated substituent exchanges to generate boron intermediates that promote the hydroboration reaction.

Tropylium Salt Promoted Hydroboration Reactions: Mechanistic Insights via Experimental and Computational Studies

Hydroboration reaction of alkynes is one of the most synthetically powerful tools to access organoboron compounds, versatile precursors for cross coupling chemistry. This type of reaction has traditionally been mediated by transition metal or main group catalysts. Herein, we report a novel method using tropylium salts, typically known as organic oxidants and Lewis acids, to efficiently promote the hydroboration reaction of alkynes. A broad range of vinylboranes can be easily accessed via this metal-free protocol. Similar hydroboration reactions of alkenes and epoxides can also be efficiently catalyzed by the same tropylium catalysts. Experimental studies and DFT calculations suggested that the reaction follows an uncommon mechanistic paradigm, which is triggered by a hydride abstraction of pinacolborane with tropylium ion. This is followed by a series of <i>in situ</i> counterion-activated substituent exchanges to generate boron intermediates that promote the hydroboration reaction.

Electron deficient borane-mediated hydride abstraction in amines: stoichiometric and catalytic processes

Borane mediated hydride abstraction of amines efficiently generates useful iminium salts. This review explores this fascinating reactivity and discusses how the iminium intermediates are utilised in a variety of stoichiometric and catalytic processes.

Synthesis and structure of a phosphinoboronic ester in a fused bicyclic framework

The first phosphinoboronic ester bearing a fused bicyclic framework was synthesised by either deprotonation and hydride abstraction or Rh-catalysed dehydrogenation of a hydrophosphineboronic ester. The phosphinoboronic ester reacted as a...

Regioselective formation of fluorinated metallacycles from fluoroalkenes and an electron-rich Ni(0) difluorocarbene

The reactivity of an electron-rich Ni-difluorocarbene complex, Ni=CF2(dppe)[P(OMe)3] (1), with a variety of fluorinated alkenes was investigated (dppe = 1,2-bis(diphenylphosphino)ethane). Reactions of 1 with perfluoro(methyl vinyl ether) and chlorotrifluoroethylene (CTFE) give regiospecific formation of metallacyclobutanes, in which the carbene C attacks the most electron-rich carbon of the fluoroalkene. Further reaction of the CTFE-derived metallacycle in the presence of tetrahydrofuran affords a single isomer of NiCl(σ-CF2CF=CFH) (dppe), 8, proposed to be formed by Ni-mediated Cα-Cl activation followed by hydride abstraction and loss of HF. Although 1 also undergoes a cyclization reaction with trifluoroethylene (TrFE), instability of the presumed nickelacyclobutane affords the C3 fluoroalkene, F2C=CH(CF3), and subsequent formation of isomeric metallacyclopentanes from two additional TrFEs. Alternatively, reaction of 1 with hexafluoropropene forms an unexpected Ni–CF3 σ-perfluoroallyl complex.