Difunctionalization Of Alkynes Research Articles

Photoredox-Catalyzed Synthesis of 3,3-Difluoro-γ-lactams via 1,5-Hydrogen Atom Transfer-Involved Alkyne Difunctionalization and C-N Cleavage.

This manuscript describes the application of a 1,5-hydrogen atom transfer strategy in photoredox-catalyzed hydrodifluoroalkylation of alkynes. The approach utilizes a sequential cascade process of difluoroalkylation, 1,5-hydrogen atom transfer, C(sp3)-N cleavage, and intramolecular condensation cyclization to accomplish efficient [3 + 2] cycloaddition of readily available propargylamines with halodifluoroacetates (or halodifluoroacetamides). The reaction allows for the selective construction of polysubstituted 3,3-difluoro-γ-lactams with good functional group tolerance, and further transformations of the resulting 3,3-difluoro-γ-lactams into different building blocks are also accomplished.

Visible-Light Photoredox-Catalyzed Difunctionalization of Alkynes with Quinoxalin-2(1H)-Ones, P4S10, and Alcohols.

Visible-light photoredox-catalyzed method has been developed for the synthesis of quinoxalin-2(1H)-one-containing vinyl phosphorodithioates via direct difunctionalization of alkynes with quinoxalin-2(1H)-ones, P4S10 and alcohols. This four-component reaction could be carried out under metal-free and mild conditions, affording a number of quinoxalin-2(1H)-one-containing vinyl phosphorodithioates in moderate to good yields with Z-isomers as the major products. Photocatalytic radical mechanism is proposed based on the results of radical trapping and fluorescence quenching experiments.

Electrophotocatalytic Tellurosulfonylation of Alkynes for the Synthesis of β-(Telluro)vinyl Sulfones.

Difunctionalization of alkynes has gained a lot of interest in current organic chemistry. Herein, we developed an electrophotocatalytic multicomponent cascade reaction of alkynes and indoles with sulfinic acid sodium salts using elemental tellurium as the tellurium source. Using synergistic anodic oxidation and visible-light irradiation, various β-(telluro)vinyl sulfones have been prepared. This strategy features mild reaction conditions, excellent substrate scope, readily available starting materials, and great functional group tolerance.

E-Selective Radical Difunctionalization of Unactivated Alkynes: Preparation of Functionalized Allyl Alcohols from Aliphatic Alkynes.

Radical difunctionalization of aliphatic alkynes provides direct access to valuable multi-substituted alkenes, but achieving a high level of chemo- and stereo-control remains a formidable challenge. Herein a novel photoredox neutral alkyne di-functionalization is reported through functional group migration followed by a radical-polar crossover and energy transfer-enabled stereoconvergent isomerization of alkenes. In this sequence, a hydroxyalkyl and an aryl group are incorporated concomitantly into an alkyne, leading to diversely functionalized E-allyl alcohols. The scope of alkynes is noteworthy, and the reaction tolerates aliphatic alkynes containing hydrogen donating C─H bonds that are prone to intramolecular hydrogen atom transfer. The protocol features broad functional group compatibility, high product diversity, and exclusive chemo- and stereoselectivity, thus providing a practical strategy for the elusive radical di-functionalization of unactivated alkynes.

Ni‐Catalyzed Enantioselective Difunctionalization of Alkynes to Azepine Derivatives Bearing a Quaternary Center and an Unprotected Imine†

Comprehensive SummaryThe azepine ring is a prominent structural scaffold in biologically significant molecules. In this study, we present a Ni(II)‐catalyzed asymmetric difunctionalization of alkynes, involving intermolecular regioselective arylation and intramolecular nitrile addition, enabling the synthesis of enantioenriched azepine derivatives. This reaction simultaneously installs an all‐carbon quaternary stereocenter and introduces an unprotected imine functionality, showing great promise for subsequent transformations. The reaction exhibits good tolerance toward various functional groups, resulting in high yields and enantioselectivities. The synthetic utility of this methodology is further demonstrated through gram‐scale synthesis and product derivatization. This research offers an efficient approach to the synthesis of seven‐membered nitrogen heterocycles.

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.

Photocatalytic aerobic thiocyanation/sulfonylation of alkynes by D-A type COFs: Enhanced generation of superoxide and sulfur-based radicals via building units adjusted band structures

Photocatalytic radical-mediated aerobic thiocyanation/sulfonylation of alkynes represents the most straightforward and atom-economic method to synthesize α-thiocyanate/sulfonyl ketones. The core issue is the generation of desired thiocyanate/sulfonyl radicals and their subsequent conversion into target products. In this work, three polyimide-based donor–acceptor COFs, named TAPB-PMDA, TTA-PMDA, and TTA-NDA, respectively, have been prepared for the photosynthesis of α-thiocyanate/sulfonyl ketones. Based on efficient adjusting electron donor-accept capacity of building units, TTA-NDA possesses broader visible absorption, richer redox properties, faster carrier separation efficiency and shows higher photocatalytic activity in thiocyanation/sulfonylation of alkynes under blue LED light illumination. Control experiments and EPR tests provide insight into the tandem radical addition/cross-coupling mechanism, in which the thiocyanate/sulfonyl radicals generation via h+ oxidation and the reactive oxygen species (ROS, e.g. •OH, H2O2, 1O2, O2•−) production by e− reduction carry out simultaneously, avoiding the employing of electron sacrificial agents or extra additives as precursors of singe electron transfer reagents. This operable strategy opens up a door for the difunctionalization of alkynes in photosynthetic manner.

Iterative Dual-Metal and Energy Transfer Catalysis Enables Stereodivergence in Alkyne Difunctionalization: Carboboration as Case Study.

Stereochemically defined tetrasubstituted olefins are widespread structural elements of organic molecules and key intermediates in organic synthesis. However, flexible methods enabling stereodivergent access to E and Z isomers of fully substituted alkenes from a common precursor represent a significant challenge and are actively sought after in catalysis, especially those amenable to complex multifunctional molecules. Herein, we demonstrate that iterative dual-metal and energy transfer catalysis constitutes a unique platform for achieving stereodivergence in the difunctionalization of internal alkynes. The utility of this approach is showcased by the stereodivergent synthesis of both stereoisomers of tetrasubstituted β-boryl acrylates from internal alkynoates with excellent stereocontrol via sequential carboboration and photoisomerization. The reluctance of electron-deficient internal alkynes to undergo catalytic carboboration has been overcome through cooperative Cu/Pd-catalysis, whereas an Ir complex was identified as a versatile sensitizer that is able to photoisomerize the resulting sterically crowded alkenes. Mechanistic studies by means of quantum-chemical calculations, quenching experiments, and transient absorption spectroscopy have been applied to unveil the mechanism of both steps.

Regio- and Stereoselective Intermolecular Oxysulfonylation of Alkynes with 1,3-Diketones to Access (Z)-β-Sulfonated Enethers.

The first multicomponent regio- and stereoselective difunctionalization of alkynes via concomitant C-O and C-S bond formation using 1,3-diketones and sodium sulfinate has been developed for the synthesis of various sulfonated enethers. The viability of this strategy is unveiled by gram-scale, various synthetic modifications and late-stage functionalization. This transformation does not require any prefunctionalization, metal catalysts, and oxidants. The present operationally simple, efficient, and sustainable approach provides various functionalized olefins in a one-pot protocol with high Z-selectivity.

Ru(OAc)3-Catalyzed Regioselective Difunctionalization of Alkynes: Access to (E)-2-Bromo-1-alkenyl Sulfonates.

A new approach is proposed for the divergent and regioselective synthesis of (E)-2-bromo-1-phenylvinyl trifluoromethanesulfonates through alkyne difunctionalization by employing a compatible system of abundantly available alkynes, N-bromosuccinimide (NBS), and trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed by ruthenium(III) acetate [Ru(OAc)3]. It is a novel method for the preparation of vinyl triflate and it offers a fundamental basis for the development of advanced functional compounds, including drugs and organic functional materials. Unlike previously reported methods, the proposed protocol can tolerate a broad range of functional groups. Alkynes derived from bioactive molecules, such as l(-)-borneol, demonstrate the potential value of this new reaction in organic synthesis.

Base‐Promoted Difunctionalization of Alkynes: One‐Pot Synthesis of Polysubstituted Chromones

AbstractA transition‐metal‐free one‐pot procedure for the difunctionalization of alkynes by C−C triple bond oxidation and transformation towards chromone derivatives has been developed. It involves cascade reactions for carbonylation of alkynes, base‐promoted C−C σ‐bond cleavage, and intramolecular cyclization. This procedure provides an efficient protocol for the synthesis of polysubstituted chromones from readily available starting materials.

Group 14 Element Hetero-Difunctionalizations via Ni-Catalyzed Electroreductive Cross-Coupling.

The difunctionalization of unsaturated bonds plays a vital role in the enrichment of molecular complexity. While various catalytic methods for alkene and alkyne difunctionalization have been developed in recent years, hetero-functionalization the introduction of two different atoms has been less explored. This is mainly due to the challenges associated with achieving high chemo-, regio-, and stereoselectivity, especially when adding two similar atoms from the same group across unsaturated bonds. In this study, we describe a nickel-catalyzed, three-component reductive protocol for group 14 element hetero-difunctionalization of 1,3-enynes using electrochemistry. This new method is mild, selective, and general, allowing for the silyl-, germanyl-, and stannyl-alkylation of enynes. Various chlorosilanes as well as chlorogermans, and chlorostannanes can be successfully used in combination with aryl/alkyl-substituted 1, 3-enynes and primary, secondary, and tertiary alkyl bromides in the electroreductive coupling.

Group 14 Elements Hetero‐Difunctionalizations via Nickel‐Catalyzed Electroreductive Cross‐Coupling

AbstractThe difunctionalization of unsaturated bonds plays a vital role in the enrichment of molecular complexity. While various catalytic methods for alkene and alkyne difunctionalization have been developed in recent years, hetero‐functionalization the introduction of two different atoms has been less explored. This is mainly due to the challenges associated with achieving high chemo‐, regio‐, and stereoselectivity, especially when adding two similar atoms from the same group across unsaturated bonds. In this study, we describe a nickel‐catalyzed, three‐component reductive protocol for group 14 element hetero‐difunctionalization of 1,3‐enynes using electrochemistry. This new method is mild, selective, and general, allowing for the silyl‐, germanyl‐, and stannyl‐alkylation of enynes. Various chlorosilanes as well as chlorogermans, and chlorostannanes can be successfully used in combination with aryl/alkyl‐substituted 1,3‐enynes and primary, secondary, and tertiary alkyl bromides in the electroreductive coupling.

SO42- ions as a nucleophilic reagent: straightforward electrochemical access to organosulfates.

An electrooxidation direct difunctionalization of alkynes with sulfonyl hydrazides has been developed for the construction of sulfonyl alkenyl sulfates in the absence of metal catalysts and a stoichiometric amount of oxidants. Notably, it is the first example to verify that SO42- ions can act as a nucleophilic reagent for the preparation of organosulfates.

Ni-catalyzed, enantioselective three-component radical relayed reductive coupling of alkynes: Synthesis of axially chiral styrenes

Axially chiral styrenes are of great interest because they could serve as a class of novel chiral ligands in enantioselective synthesis. However, only recently have strategies been developed for their enantioselective preparation. Herein, we have developed a Ni-catalyzed, enantioselective, three-component radical relayed reductive coupling to rapidly construct axially chiral styrene. This three-component radical relayed reductive coupling strategy utilizes a chiral nickel/pyridine-oxazoline system to facilitate the challenging three-component, enantioselective difunctionalization of alkynes with high efficiency and excellent enantioselectivity. The mild conditions allow for broad substrate scopes as well as good functional-group toleration. We performed computational mechanistic studies to gain insights into the mechanism and origin of the chemo- and enantioselectivity. Furthermore, the reaction could be scaled up, and the resulting axially chiral styrenes could be easily transformed into 1-(1-phenylvinyl)naphthalene phosphine ( ( s )-SJTU-PHOS-1 ) with high stereoselectivities, which showed great promise as a new type of styrene ligand. • Three-component radical relayed reductive coupling to construct axial chiral styrene • Broad substrate scope with excellent enantioselectivity and regioselectivity • Axially chiral styrenes transformed into chiral ligand • Computational studies to gain insights into the chemo- and enantioselectivity Axially chiral styrene has recently attracted considerable attention from chemists because of its widespread use in biological active compounds, chiral catalysts, and ligands. In this article, we develop a radical relayed reductive coupling to construct axially chiral styrene with high efficiency and excellent enantioselectivity via highly active sp 2 center radicals. The resulting axially chiral styrenes could be easily transformed into a new type of potential styrene ligand. Mechanistically, we conducted detailed computational mechanistic studies to understand the chemo- and enantioselectivity of this reaction. We anticipate that this enantioselective three-component radical relayed reductive coupling protocol will have important implications for the construction of axially chiral styrene. Zhang and co-workers have developed a novel radical relayed reductive coupling to construct axial chiral styrene with high efficiency. A weak coordination effect, found to be crucial in nickel-catalyzed three-component cross-coupling reactions, is not required in this system. The authors performed computational studies to gain insights into the chemo- and enantioselectivity. Furthermore, the reaction could be scaled up, and the resulting axially chiral styrenes could be transformed into chiral ligand ( s )-SJTU-PHOS-1 , which showed great promise as a new styrene ligand.

Stereodivergent Synthesis of (Z)-/(E)-β-Sulfonylacrylamides via Tandem Difunctionalization of Alkynes with Sulfinates and Isocyanides.

Stereoselective difunctionalizations of the terminal and internal alkynes with various sulfinates and isocyanides have been achieved to prepare (Z)-/(E)-β-sulfonylacrylamides. The (Z)-β-sulfonylacrylamides were generated via a one-pot process that involves the reaction of terminal alkynes with sulfinates and isocyanides in the presence of iodine in sequential manner. The (E)-β-sulfonylacrylamides were prepared in a two-step synthesis via palladium(II)-catalyzed addition of isocyanide to (E)-β-iodovinylsulfones synthesized from alkynes.

Palladium-Catalyzed Chemo- and Regiocontrolled Tandem Cyclization/Cross-Coupling of 2-Benzyl-3-alkynyl Chromones with Aryl Iodides for the Synthesis of 4H-Furo[3,2-c]chromenes and Xanthones

A novel Pd-catalyzed chemo- and regiocontrolled tandem cyclization/cross-coupling reaction of 3-alkynyl chromone with aryl iodide was developed for the synthesis of 4H-furo[3,2-c]chromenes and xanthones. The difunctionalization of alkynes through O-attack/5-exo-dig and C-attack/6-endo-dig cyclization was reported by this rare approach, which was selectively controlled by the addition of KF or a bidentate phosphine ligand. A one-pot tandem process was demonstrated directly from γ-alkynyl-1,3-diketone for this method.

Nickel-Catalyzed Alkyne Difunctionalization Using Two Distinct sp3-Hybridized Electrophiles

Key words nickel catalysis - multicomponent reaction - cross-electrophiles - fluoromethylation

Widely applicable (radio)dihalogenation of alkynes and alkenes using two different nucleophilic alkali metal halides

A hydrogen bond donor solvent-assisted highly regio- and stereoselective difunctionalization of alkynes and alkenes using two nucleophilic alkali metal salts as halogenation reagents.

Origins of regio- and stereoselectivity in Cu-catalyzed alkyne difunctionalization with CO2 and organoboranes

The anti-to-Cu 1,2-migration of alkynyl boronates is critical for the 1,1-E-selective difunctionalization of terminal alkynes with CO2 and organoboranes.