Difunctionalization Of Alkenes Research Articles

A general photocatalytic strategy for the synthesis of β-hydroxy acid derivatives from alkenes

We report a general and concise strategy to realize the photo-induced difunctionalization of alkenes for the synthesis of β-hydroxy acid derivatives. The reaction proceeds through an alkoxycarbonyl radical-induced process, and...

Photocatalytic, modular difunctionalization of alkenes enabled by ligand-to-metal charge transfer and radical ligand transfer.

Ligand-to-metal charge transfer (LMCT) is a mechanistic strategy that provides a powerful tool to access diverse open-shell species using earth abundant elements and has seen tremendous growth in recent years. However, among many reaction manifolds driven by LMCT reactivity, a general and catalytic protocol for modular difunctionalization of alkenes remains unknown. Leveraging the synergistic cooperation of iron-catalyzed ligand-to-metal charge transfer and radical ligand transfer (RLT), here we report a photocatalytic, modular difunctionalization of alkenes using inexpensive iron salts catalytically to function as both radical initiator and terminator. Additionally, strategic use of a fluorine atom transfer reagent allows for general fluorochlorination of alkenes, providing the first example of interhalogen compound formation using earth abundant element photocatalysis. Broad scope, mild conditions and versatility in converting orthogonal nucleophiles (TMSN3 and NaCl) directly into corresponding open-shell radical species are demonstrated in this study, providing a robust means towards accessing vicinal diazides and homo-/hetero-dihalides motifs catalytically. These functionalities are important precursors/intermediates in medicinal and material chemistry. Preliminary mechanistic studies support the radical nature of these transformations, disclosing the tandem LMCT/RLT as a powerful reaction manifold in catalytic olefin difunctionalization.

Divergent functionalization of alkenes enabled by photoredox activation of CDFA and α-halo carboxylic acids.

Herein we present our studies on the solvent-controlled difunctionalization of alkenes utilizing chlorodifluoroacetic acid (CDFA) and α-halo carboxylic acids for the synthesis of γ-lactones, γ-lactams and α,α-difluoroesters. Mechanistic insights revealed that photocatalytic reductive mesolytic cleavage of the C-X bond delivers elusive α-carboxyl alkyl radicals. In the presence of an olefin molecule, this species acts as a unique bifunctional intermediate allowing for stipulated formation of C-O, C-N and C-H bonds on Giese-type adducts via single electron transfer (SET) or hydrogen atom transfer (HAT) events. These protocols exhibit great efficiency across a broad spectrum of readily available α-halo carboxylic acids and are amenable to scalability in both batch and flow. To demonstrate the versatility of this concept, the synthesis of (±)-boivinianin A, its fluorinated analog and eupomatilone-6 natural products was successfully accomplished.

Electrochemical difunctionalization of alkenes and alkynes for the synthesis of organochalcogens involving C–S/Se bond formation

This review highlights the recent progress in the electrochemical difunctionalization of alkenes and alkynes involving C–S/Se bond formation to access organochalcogen frameworks.

Visible light-driven and substrate-promoted alkenyltrifluoromethylation of alkenes to synthesize CF3-functionalized 1,4-naphthoquinones.

The first example of the visible light-driven and substrate-promoted three-component alkenyltrifluoromethylation of alkenes is developed. This approach uses easily available alkenes, 2-arylamino-1,4-naphthoquinones and Togni reagent as the reactants, and describes good functionality tolerance. The reaction offers a precise synthesis of valuable CF3-functionalized 1,4-naphthoquinones and can be applied in late-stage modification of natural products and pharmaceuticals. Experimental results imply that bifunctional 2-arylamino-1,4-naphthoquinones serve as both substrates and catalysts. In terms of this autocatalytic system, the protocol enables a straightforward intermolecular difunctionalization of alkenes under visible light irradiation without external catalysts.

Thianthrenation-promoted photoinduced alkene difunctionalization and aryl allylation with Morita-Baylis-Hillman adducts.

An organophotoredox-catalyzed alkoxyallylation of feed-stock olefins, through thianthrenation using a Morita-Baylis-Hillman adduct as an allylating agent, is described. Site-selective addition of MeOH to an alkene-thianthrenium salt and its subsequent conversion into a nucleophilic radical species forms the basis of this unique difunctionalization strategy. The scope is also expanded into radical aryl allylation.

Iodonium based regioselective double nucleophilic alkene functionalization of a hydrofluoroolefin scaffold.

Herein, we report a modular regioselective alkene difunctionalization strategy based on the use of hydrofluoroolefin (HFO) gas as fluorous feedstock material. The transformation of the HFO gas to iodonium salt creates vicinal electrophilic sites readily available for a broad range of nucleophiles.

Photocatalyst-free light-mediated three-component alkoxy-, hydroxy-, and azidotrifluoromethylation of alkenes

A photocatalyst-free method enables efficient alkene difunctionalization in CF3-rich organic environments using accessible starting materials. This protocol is applicable for the synthesis of alkoxy, hydroxy, and azido derivatives.

Radical Brook Rearrangement Mediated Olefin Difunctionalization Involving α-Fluoroalkyl-α-silyl Methanols

Radical Brook Rearrangement Mediated Olefin Difunctionalization Involving α-Fluoroalkyl-α-silyl Methanols

Electrochemical Azidocyanation of Alkenes

AbstractThe difunctionalization of alkenes—a process that installs two functional groups in a single operation and transforms chemical feedstocks into value‐added products—is one of the most appealing synthetic methods in contemporary chemistry. However, the introduction of two distinct functional groups via two readily accessible nucleophiles remains a formidable challenge. Existing intermolecular alkene azidocyanation methods, which primarily focus on aryl alkenes and rely on stoichiometric chemical oxidants. We report herein an unprecedented electrochemical strategy for alkene azidocyanation that is compatible with both alkyl and aryl alkenes. This is achieved by harnessing the finely‐tuned anodic electron transfer and the strategic selection of copper/ligand complexes. The reactions of aryl alkenes were rendered enantioselective by employing a chiral ligand. Crucially, the mild conditions and well‐regulated electrochemical process assure exceptional tolerance for various functional groups and substrate compatibility with both terminal and internal alkyl alkenes.

Strategies for Direct, Transition Metal‐Free Addition of Nitrogen Synthons to Alkenes

AbstractThe incorporation of nitrogen into small molecules is one of the highest‐demanded transformations in modern synthetic chemistry. Alkene difunctionalization and aziridination offer desirable approaches to the incorporation of these amino synthons from feedstock precursors. Although amino groups can be added to alkenes following alkene reaction with an initiation reagent, the most desirable approach involves direct addition of the nitrogen group to the alkene, allowing for a range of possible secondary functionalization outcomes. Although many of these strategies have been accomplished through the use of transition metals, the utility of a transition metal‐free approach is still at the forefront of synthetic chemistry, both in development and demand. This review aims to present a comprehensive review of the history and current state‐of‐the‐art in the transition metal‐free, direct addition of nitrogen to alkenes.

Recent Advances in Ni‐Catalyzed 1,1‐Difunctionalization of Unactivated Olefins

AbstractUnactivated olefins rank amongst the most important feedstocks in organic synthesis. Their availability makes them particularly useful synthons for subsequent functionalization, particularly in a catalytic manner. Driven by the popularity ascribed by nickel catalysis as a new tool to rapidly forge molecular architectures via one‐or two‐electron manifolds, the recent years have witnessed significant advances in Ni‐catalyzed olefin difunctionalization. While 1,2‐difunctionalization or remote functionalization via “chain‐walk” have become mature disciplines for repurposing the potential of olefins as building blocks, it was only recently that extensions of this chemistry to 1,1‐difunctionalization have been possible. This review summarizes the recent advances in Ni‐catalyzed olefin 1,1‐difunctionalization, holding considerable promise as a new powerful strategy for our ever‐growing synthetic repertoire.

Distal Functional Group Migration of Unactivated Alkenes with IMDN‐Tf Reagents

AbstractThe difunctionalization of alkenes involving 1,5‐functional group migration strategies for the conversion of versatile and readily available olefins into more structurally complex molecules has been greatly studied. However, the vast majority of the reported reactions rely on strongly oxidizing conditions and oxidizing fluoroalkyl radical reagents. In contrast, few reactions with reduced radical reagents have been reported. This work describes a photo / electroredox catalytic condition for difunctional modification of unactivated olefins via a radical process using IMDN‐Tf reagents with broad substrate scope and excellent tolerance.

Accessing gold p-acid reactivity under electrochemical anode oxidation (EAO) through oxidation relay

The gold π-acid activation under electrochemical conditions is achieved. While EAO allows easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far are limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications.

Photoinduced Single‐Electron Reduction of Alkenes.

AbstractAlkenes serve as versatile building blocks in organic synthesis. However, the challenge of achieving single‐electron reduction of alkenes persists. In recent years, photocatalysis has emerged as a promising and efficient tool for accomplishing the single‐electron reduction of alkenes. Given the potential benefits that can be derived from photoinduced single‐electron reduction of alkenes, including the development of potent catalytic systems to enable diverse alkene difunctionalization reactions, it is necessary to provide a conceptual understanding of this emerging field. Hence, we present an overview of current synthetic techniques for photoinduced single‐electron reduction of alkenes.

Mechanoredox Enabled the Difunctionalization of Unactivated Alkenes via Distal Functional Group Migration

Mechanoredox Enabled the Difunctionalization of Unactivated Alkenes via Distal Functional Group Migration

Nitrative Difunctionalization of Alkenes via Cobalt-Mediated Radical Ligand Transfer and Radical-Polar Crossover Photoredox Catalysis

Nitrative Difunctionalization of Alkenes via Cobalt-Mediated Radical Ligand Transfer and Radical-Polar Crossover Photoredox Catalysis

Merging photoinduced protic HAT and radical-polar crossover for olefin difunctionalization

Merging photoinduced protic HAT and radical-polar crossover for olefin difunctionalization

Imino‐Fluoroalkanesulfonylation of γ,δ‐Unsaturated Oxime Esters Enabled by Photoredox/Cu Dual Catalysis

AbstractSulfonyl‐tethered N‐containing heterocycles are valuable building blocks in synthetic and pharmaceutical chemistry. Recently, the installation of fluoroalkanesulfonyl groups into heterocycles via the difunctionalization of alkenes still remains challenging. Herein in this work, an imino‐fluoroalkanesulfonylation of γ,δ‐unsaturated oxime esters has been achieved via photoredox/Cu dual catalysis. A variety of fluoroalkanesulfonyl‐tethered pyrroline derivatives have been readily synthesized in moderate to good yields under mild conditions.

Advances in Difunctionalization of Olefins with Diorganyl Dichalcogenides.

Organochalcogen molecules have extensive applications in various fields. They serve as pharmaceuticals, ligands, organocatalysts, agrochemicals, and other functional materials. Difunctionalization of olefins, which belong to a class of multicomponent reactions, is a successful technique for introducing two functional moieties in a single-step reaction, both in terms of atom economy and step economy. The difunctionalization of olefins with diorganyl dichalcogenides may effectively increase the molecular complexity, which has achieved significant advancements in recent decades. This article describes recent advancements in the difunctionalization of olefins with diorganyl diselenides and diorganyl disulfides.