Difunctionalization Of Alkenes Research Articles

Synthesis of Biindene Derivatives via Pd-Catalyzed Alkene Difunctionalization Reactions.

The palladium-catalyzed cross-coupling of 2-allylphenyl triflate and related electrophiles with substituted indenes affords biindene derivatives in moderate to good yields with high selectivity for thermodynamically preferred alkene isomers. The transformations involve alkene nucleopalladation with indenyl anions, and we also demonstrate that 2-allylphenyl triflates can be transformed to indenes under similar conditions. The scope of this transformation, along with the mechanism of formation of both indene and biindene products, is described.

Copper-Catalyzed Asymmetric Aminative Difunctionalization of Alkenes with Azodicarboxylates

Copper-Catalyzed Asymmetric Aminative Difunctionalization of Alkenes with Azodicarboxylates

Visible‐Light‐Induced Three‐Component Alkylpyridylation of Alkenes Enabled by Electron Donor‐Acceptor Complex

Visible‐light‐induced difunctionalization of alkenes is a powerful strategy for constructing complex molecules. Herein, we disclose a three‐component 1,2‐alkylpyridylation of alkenes under mild and photosensitizers‐free conditions. UV‐vis absorption spectroscopy studies and NMR titration experiments indicate that the formation of an EDA complex between 4‐alkyl‐DHPs and 4‐cyanopyridines. Primary, secondary, and tertiary C(sp3)‐centered radicals were formed by homolytic cleavage of 4‐alkyl‐DHPs. Gram‐scale synthesis and late‐stage functionalization of medicinally relevant molecules showed the synthetic potential of our methodology.

Construction of β-Oximino Phosphorodithioates via (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl-Promoted Difunctionalization of Alkenes with tert-Butyl Nitrite, P4S10, and Alcohols.

A (2,2,6,6-tetramethylpiperidin-1-yl)oxyl-mediated difunctionalization of alkenes with tert-butyl nitrite, P4S10, and alcohols has been developed for the synthesis of β-oximino phosphorodithioates. The reaction goes through a radical pathway with the successive installation of phosphorodithioate and an oxime group. This four-component protocol offers a practical approach to constructing a variety of β-oximino phosphorodithioates in moderate to good yields with favorable functional group tolerance.

Nickel-catalysed enantioselective alkene dicarbofunctionalization enabled by photochemical aliphatic C–H bond activation

AbstractThe development of novel strategies to rapidly construct complex chiral molecules from readily available feedstocks is a long-term pursuit in the chemistry community. Radical-mediated alkene difunctionalizations represent an excellent platform towards this goal. However, asymmetric versions remain highly challenging, and more importantly, examples featuring simple hydrocarbons as reaction partners are elusive. Here we report an asymmetric three-component alkene dicarbofunctionalization capitalizing on the direct activation of C(sp3)–H bonds through the combination of photocatalysed hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for installing two vicinal carbon–carbon bonds across alkenes in an atom-economic fashion, providing a wide array of high-value chiral α-aryl/alkenyl carbonyls and phosphonates, as well as 1,1-diarylalkanes from ubiquitous alkane, ether and alcohol feedstocks. This method exhibits operational simplicity, broad substrate scope and excellent regioselectivity, chemoselectivity and enantioselectivity. The compatibility with bioactive motifs and expedient synthesis of pharmaceutically relevant molecules highlight the synthetic potential of this protocol.

Copper-Catalyzed 1,2-Sulfonyletherification of 1,3-Dienes.

A selective three-component 1,2-sulfonyl etherification of aryl 1,3-dienes enabled by copper catalysis to afford biologically interesting alkenyl 1,2-sulfone ether derivatives through C-S and C-O bond formation is described. The protocol proceeds with the sulfonyl chloride and alcohols under simple, mild, and base-free conditions, providing a straightforward route to sulfonylated allyl ether compounds with broad functional group tolerance and excellent chemo- and regioselectivity. Mechanistic studies indicate that the selective alkene difunctionalization includes a key copper-mediated single-electron transfer process.

Photoredox-Catalyzed Acylchlorination of α-CF3 Alkenes with Acyl Chloride and Application as Masked Access to β-CF3-enones.

We disclose a photocatalytic strategy that simultaneously addresses the construction of trifluoromethylated quaternary carbon centers and the preparation of β-CF3-enones through radical difunctionalization of α-CF3 alkenes with acyl chlorides. This method is characterized by its broad functional group compatibility, high efficiency, and atom economy. The versatility of this transformation is poised to broaden the applications of α-CF3 alkenes, providing new pathways for the rapid assembly of structurally diverse fluorinated compounds.

Copper‐Catalyzed Cyanoalkylation and Trifluoromethylthiolation of Styrene Derivatives via a Visible‐Light‐Promoted Cross‐Coupling

Transition‐metal catalyzed difunctionalization of olefins has attracted considerable attention as a method to construct carbon‐carbon and carbon‐hetero bonds. Herein, the copper‐catalyzed three‐component radical cross‐coupling of oxime esters, styrenes, and AgSCF3 through a visible‐light‐promoted iminyl radical‐mediated carbon‐carbon bond cleavage strategy has been described. Utilizing low‐cost copper salt as both photosensitizers and cross‐couplers, this protocol delivers diverse target products, providing a supplementary approach for cyanoalkylation and trifluoromethylthiolation of drug molecules.

The Difunctionalization of Alkenes Completed by DMTSM and CF3SO2Na without Metal Catalysts

AbstractThe electrophilic thiolation of alkenes initiated by DMTSM and the addition of CF3SO2Na in one pot has been developed. This reaction also can be extended to ArSO2Na. This protocol features a good substrate scope, simple procedures, and mild reaction conditions and affords the desired products in moderate yields without metal catalysts.

Confinement Effect in Metal-Organic Framework Cu3(BTC)2 for Enhancing Shape Selectivity of Radical Difunctionalization of Alkenes.

The radical difunctionalization of alkenes plays a vital role in pharmacy, but the conventional homogeneous catalytic systems are challenging in selectivity and sustainability to afford the target molecules. Herein, the famous readily available metal-organic framework (MOF), Cu3(BTC)2, has been applied to cyano-trifluoromethylation of alkenes as a high-performance and recyclable heterogeneous catalyst, which possesses copper(II) active sites residing in funnel-like cavities. Under mild conditions, styrene derivatives and various unactivated olefins could be smoothly transformed into the corresponding cyano-trifluoromethylation products. Moreover, the transformation brought about by the active copper center in confined environments achieved regio- and shape selectivity. To understand the enhanced selectivity, the activation manner of the MOF catalyst was studied with control catalytic experiments such as FT-IR and UV-vis absorption spectroscopy of substrate-incorporated Cu3(BTC)2, which elucidated that the catalyst underwent a radical transformation with the intermediates confined in the MOF cavity, and the confinement effect endowed the method with pronounced selectivities.

Catalytic Enantioselective Aminative Difunctionalization of Alkenes.

Enantioselective difunctionalization of alkenes offers a straightforward means for the rapid construction of enantioenriched complex molecules. Despite the tremendous efforts devoted to this field, enantioselective aminative difunctionalization remains a challenge, particularly through an electrophilic addition fashion. Herein, we report an unprecedented approach for the enantioselective aminative difunctionalization of alkenes via copper-catalyzed electrophilic addition with external azo compounds as nitrogen sources. A series of valuable cyclic hydrazine derivatives via either [3 + 2] cycloaddition or intramolecular cyclization have been achieved in high chemo-, regio-, enantio-, and diastereoselectivities. In this transformation, a wide range of functional groups, such as carboxylic acid, hydroxy, amide, sulfonamide, and aryl groups, could serve as nucleophiles. Importantly, a new cyano oxazoline chiral ligand was found to play a crucial role in the control of enantioselectivity.

Harnessing charge relocation: A novel approach for the remote difunctionalization of alkenes

Harnessing charge relocation: A novel approach for the remote difunctionalization of alkenes

Photocatalytic Keto- and Amino-Trifluoromethylation of Alkenes.

Efforts to develop alternatives to triflic anhydride (Tf2O) as a trifluoromethylation reagent continue due to its limitations, including volatility, corrosiveness, and moisture sensitivity. Described herein is the use of a trifluoromethylsulfonylpyridinium salt (TFSP), easily obtained by a one-step reaction of Tf2O with 4-dimethylaminopyridine, as a reagent for the trifluoromethylative difunctionalization of alkenes by photoredox catalysis. DMSO and CH3CN are suitable solvents for achieving keto- and amino-trifluoromethylation of alkenes, respectively, with good functional group tolerance.

Arylthianthrenium Salts as the Aryl Sources: Visible Light/Copper Catalysis-Enabled Intermolecular Azidosulfonylation of Alkenes.

The difunctionalization of alkenes using aryl thianthrenium salts as the aryl sources has been reported sporadically. However, the four-component difunctionalization of alkenes on the basis of aryl thianthrenium salts has not been reported thus far and still remains a challenge. Herein, a visible light/copper catalysis-enabled four-component reaction of aryl thianthrenium salts, DABCO·(SO2)2, alkenes, and TMSN3 is presented, which affords a facile approach to β-azidosulfones in good yields with broad substrate scope and excellent functional group tolerance. This strategy indirectly realizes the method for the synthesis of β-azidosulfones through site-selective aryl C-H bond functionalization and alkene difunctionalization. This developed method is an important complement to thianthrenium salts chemistry.

Iron-catalyzed fluoroalkylative alkylsulfonylation of alkenes via radical-anion relay

Transition metal-catalyzed reductive difunctionalization of alkenes with alkyl halides is a powerful method for upgrading commodity chemicals into densely functionalized molecules. However, super stoichiometric amounts of metal reductant and the requirement of installing a directing group into alkenes to suppress the inherent β-H elimination bring great limitations to this type of reaction. We demonstrate herein that the difunctionalization of alkenes with two different alkyl halides is accessible via a radical-anion relay with Na2S2O4 as both reductant and sulfone-source. The Na2S2O4 together with the electron-shuttle catalyst is crucial to divert the mechanistic pathway toward the formation of alkyl sulfone anion instead of the previously reported alkylmetal intermediates. Mechanistic studies allow the identification of carbon-centered alkyl radical and sulfur-centered alkyl sulfone radical, which are in equilibrium via capture or extrusion of SO2 and could be converted to alkyl sulfone anion accelerated by iron electron-shuttle catalysis, leading to the observed high chemoselectivity.

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis.

Monofluoromethyl (CH2F) motifs exhibit unique bioactivities and are considered privileged units in drug discovery. The radical monofluoromethylative difunctionalization of alkenes stands out as an appealing approach to access CH2F-containing compounds. However, this strategy remains largely underdeveloped, particularly under metal-free conditions. In this study, we report on visible light-mediated three-component monofluoromethylation/acylation of styrene derivatives employing NHC and organic photocatalyst dual catalysis. A diverse array of α-aryl-β-monofluoromethyl ketones was successfully synthesized with excellent functional group tolerance and selectivity. The mild and metal-free CH2F radical generation strategy from NaSO2CFH2 holds potential for further applications in fluoroalkyl radical chemistry.

Difluoromethylated Difunctionalization of Alkenes under Visible Light.

Difluoromethylated compounds usually act as bioisosteres for alcohol functional groups and show unique physicochemical and biological properties. The cyano-difluoromethylation of alkenes using 5-((difluoromethyl)sulfonyl)-1-phenyl-1H-tetrazole as a CF2H radical difluoromethyl precursor was developed to afford nitriles including a CF2H group. A low-cost, stable, easily handled 5-((difluoromethyl)sulfonyl)-1-methyl-1H-tetrazole (DFSMT) was synthesized and applied as the radical CF2H reagent. Using DFSMT as the radical CF2H precursor, the oxyl-difluoromethylation of alkenes was developed to obtain difluoromethylated ether products. All of the reactions showed good functional group tolerability. Initial mechanistic experiments indicated that the CF2H radical was involved as the key active intermediate.

Visible-Light-Driven Multicomponent Diamination and Oxyamination of Alkene.

Herein, we describe an effective method for the synthesis of 2-alkoxyamides and 1,2-diamines through visible-light-mediated difunctionalization of alkenes. N-Aminopyridinium salts were employed as appropriate precursors to generate key amidyl radical intermediates via a photoinduced single-electron transfer (SET) process. The amidyl radicals would react with alkenes, followed by oxidation and nucleophilic addition. Excellent functional group tolerance and good yields demonstrate the synthetic potential of this transformation.

Chiral arylsulfinylamides as reagents for visible light-mediated asymmetric alkene aminoarylations.

Two- or one-electron-mediated difunctionalizations of internal alkenes represent straightforward approaches to assemble molecular complexity by the simultaneous formation of two contiguous Csp3 stereocentres. Although racemic versions have been extensively explored, asymmetric variants, especially those involving open-shell C-centred radical species, are much more limited both in number and scope. Here we describe enantioenriched arylsulfinylamides as all-in-one reagents for the efficient asymmetric, intermolecular aminoarylation of alkenes. Under mild photoredox conditions, nitrogen addition of the arylsulfinylamide onto the double bond, followed by 1,4-translocation of the aromatic ring, produce, in a single operation, the corresponding aminoarylation adducts in enantiomerically enriched form. The sulfinyl group acts here as a traceless chiral auxiliary, as it is eliminated in situ under the mild reaction conditions. Optically pure β,β-diarylethylamines, aryl-α,β-ethylenediamines and α-aryl-β-aminoalcohols, prominent motifs in pharmaceuticals, bioactive natural products and ligands for transition metals, are thereby accessible with excellent levels of regio-, relative and absolute stereocontrol.

Decarboxylative Difunctionalization of Alkenes Enabled by Nickel/Photoredox Catalysis

Decarboxylative Difunctionalization of Alkenes Enabled by Nickel/Photoredox Catalysis