Vinyl Halides Research Articles

Nickel‐Catalyzed Reductive Protocol to Access Silacyclobutanes with Unprecedented Functional Group Tolerance

AbstractWhile significant progress has been made in the area of transition metal‐catalyzed ring‐opening and formal cycloaddition reactions of 1,1‐disubstituted silacyclobutanes (SCBs), synthesizing these SCBs—particularly those bearing additional functional groups—continues to present synthetic challenges. In this context, we present a novel Ni‐catalyzed reductive coupling reaction that combines 1‐chloro‐substituted silacyclobutanes with aryl or vinyl halides and pseudohalides, thereby obviating the need for organometallic reagents. This method facilitates the generation of 1,1‐disubstituted silacyclobutanes with a remarkable tolerance for various functional groups. This approach serves as a complementary and more step‐economical alternative to the commonly used yet moisture‐ and air‐sensitive nucleophilic substitution reactions involving Grignard or lithium reagents. Our initial mechanistic studies indicate that this reaction is initiated by oxidative cleavage of the Si−Cl bond in 1‐chlorosilacyclobutanes, which represents a distinct mechanism from the previously documented reductive coupling processes involving carbon electrophiles and chlorosilanes.

Nickel-Catalyzed Reductive Protocol to Access Silacyclobutanes with Unprecedented Functional Group Tolerance.

While significant progress has been made in the area of transition metal-catalyzed ring-opening and formal cycloaddition reactions of 1,1-disubstituted silacyclobutanes (SCBs), synthesizing these SCBs-particularly those bearing additional functional groups-continues to present synthetic challenges. In this context, we present a novel Ni-catalyzed reductive coupling reaction that combines 1-chloro-substituted silacyclobutanes with aryl or vinyl halides and pseudohalides, thereby obviating the need for organometallic reagents. This method facilitates the generation of 1,1-disubstituted silacyclobutanes with a remarkable tolerance for various functional groups. This approach serves as a complementary and more step-economical alternative to the commonly used yet moisture- and air-sensitive nucleophilic substitution reactions involving Grignard or lithium reagents. Our initial mechanistic studies indicate that this reaction is initiated by oxidative cleavage of the Si-Cl bond in 1-chlorosilacyclobutanes, which represents a distinct mechanism from the previously documented reductive coupling processes involving carbon electrophiles and chlorosilanes.

Isolable Si=B Analogue of a Vinyl Halide: A Building Block for Facile Access toward Silicon‐Boron Multiple Bonded Species

AbstractCompared to the outstanding development in the synthesis of Si−B single bonded species, borylsilanes and their application to organic synthesis, the chemistry of Si=B double bonded species, borasilenes and boratasilenes have only made little progress, first of all, due to the difficulties in accessing such double bonds. Herein we report the synthesis of the first Si=B analogue of a vinyl halide, a bromoboratasilene, via formal borylene insertion to the coordination sphere of a monoatomic Si(0) complex, using a dihaloborane as the borylene source. The treatment of bromoboratasilene toward neutral or anionic Lewis bases gives access to new boratasilenes, all of which were proved to possess significant Si=B double bond character by XRD analysis and DFT calculations. These results demonstrate exciting strategies to synthesize new types of Si=B double bonded species which should further progress the chemistry of boron, silicon‐containing molecules.

Isolable Si=B Analogue of a Vinyl Halide: A Building Block for Facile Access toward Silicon-Boron Multiple Bonded Species.

Compared to the outstanding development in the synthesis of Si-B single bonded species, borylsilanes and their application to organic synthesis, the chemistry of Si=B double bonded species, borasilenes and boratasilenes have only made little progress, first of all, due to the difficulties in accessing such double bonds. Herein we report the synthesis of the first Si=B analogue of a vinyl halide, a bromoboratasilene, via formal borylene insertion to the coordination sphere of a monoatomic Si(0) complex, using a dihaloborane as the borylene source. The treatment of bromoboratasilene toward neutral or anionic Lewis bases gives access to new boratasilenes, all of which were proved to possess significant Si=B double bond character by XRD analysis and DFT calculations. These results demonstrate exciting strategies to synthesize new types of Si=B double bonded species which should further progress the chemistry of boron, silicon-containing molecules.

Visible-Light-Mediated Ni-Catalyzed Gas-Free Carboxylation: Stereodivergent Synthesis of E- and Z-Acrylic Acids.

Stereodivergent syntheses of different scaffolds from identical starting materials by switching the fewest parameters are among the most appealing synthetic technologies. Herein, a visible-light mediated Ni-catalyzed carboxylation of vinyl halides with formates has been developed, affording acrylic acids in both Z- and E-configurations from identical vinyl halides. The reaction features Ni-catalyzed gas-free carboxylation of vinyl halides by utilizing formates as a surrogate of carbon dioxide.

Formate-Mediated Reductive Cross-Coupling of Vinyl Halides and Aryl Iodides: cine-Substitution via Palladium(I) Catalysis.

Formate-mediated reductive cross-couplings of vinyl halides with aryl iodides via palladium(I) catalysis occur with highly uncommon cine-substitution. The active dianionic palladium(I) catalyst, [Pd2I4][NBu4]2, is generated in situ from Pd(OAc)2, Bu4NI, and formate. Oxidative addition of aryl iodide followed by dissociation of the dimer provides the monomeric anionic T-shaped arylpalladium(II) species, [Pd(Ar)(I)2(NBu4)], which, upon vinyl halide carbopalladation, forms products of cine-substitution by way of palladium(IV) carbenes, as corroborated by deuterium-labeling experiments.

Pd-Catalyzed Stereospecific Glycosyl Cross-Coupling of Reversed Anomeric Stannanes for Modular Synthesis of Nonclassical C-Glycosides.

Nonclassical C-glycosides, distinguished by their unique glycosidic bond connection mode, represent a promising avenue for the development of carbohydrate-based drugs. However, the accessibility of nonclassical C-glycosides hinders broader investigations into their structural features and modes of action. Herein, we present the first example of Pd-catalyzed stereospecific glycosylation of nonclassical anomeric stannanes with aryl or vinyl halides. This method furnishes desired nonclassical aryl and vinyl C-glycosides in good to excellent yields, while allowing for exclusive control of nonclassical anomeric configuration. Of significant note is the demonstration of the generality and practicality of this nonclassical C-glycosylation approach across more than 50 examples, encompassing various protected and unprotected saccharides, deoxy sugars, oligopeptides, and complex molecules. Furthermore, biological evaluation indicates that nonclassical C-glycosylation modifications of drug molecules can positively impact their biological activity. Additionally, extensive computational studies are conducted to elucidate the rationale behind differences in reaction reactivity, unveiling a transmetalation transition state containing silver (Ag) within a six-membered ring. Given its remarkable controllability, predictability, and consistently high chemical selectivity and stereospecificity regarding nonclassical anomeric carbon and Z/E configuration, the method outlined in this study offers a unique solution to the longstanding challenge of accessing nonclassical C-glycosides with exclusive stereocontrol.

Merging Photoredox and Nickel Catalysis: A Ligand-Free Cross-Coupling of Vinyl Halides and α-Silylamines toward Tertiary Allylic Alkylamines

Merging Photoredox and Nickel Catalysis: A Ligand-Free Cross-Coupling of Vinyl Halides and α-Silylamines toward Tertiary Allylic Alkylamines

Palladium-Catalyzed Asymmetric Intramolecular Addition of Vinyl Halides to Carbonyl Groups

Palladium-Catalyzed Asymmetric Intramolecular Addition of Vinyl Halides to Carbonyl Groups

Air Induced Phosphoryl Radical Mediated Stereoselective Hydrosulfonylation of Alkynes via Halogen Atom Transfer: Ingress of Z-Vinyl Sulfones.

The phosphoryl radical is well-known to participate in addition reactions with alkenes/alkynes. Here, we report a novel reaction mode of the phosphoryl radical where it participates in halogen atom transfer (XAT) with electron deficient vinyl halides instead of a facile addition reaction. Nevertheless, in comparison with aryl and alkyl halides, the exploitation of vinyl halides into a carbon radical via XAT is quite rare. This protocol provides an opportunity for direct hydrosulfonylation of numerous internal as well as terminal alkynes to get various Z-vinyl sulfones under environmentally benign conditions. Generation of the phosphoryl radical in the open air, water as a solvent, excellent functional group compatibility, and exceptional chemoselectivity are the attractive features of the present methodology.

The Murahashi Reaction: Palladium-Catalyzed Cross-Coupling of Vinyl Halides with Organolithium Reagents

The Murahashi Reaction: Palladium-Catalyzed Cross-Coupling of Vinyl Halides with Organolithium Reagents

Direct Heterocycle C-H Alkenylation via Dual Catalysis Using a Palladacycle Precatalyst: Multifactor Optimization and Scope Exploration Enabled by High-Throughput Experimentation.

One of the major challenges in developing catalytic methods for C-C bond formation is the identification of generally applicable reaction conditions, particularly if multiple substrate structural classes are involved. Pd-catalyzed direct arylation reactions are powerful transformations that enable direct functionalization of C-H bonds; however, the corresponding direct alkenylation reactions, using vinyl (pseudo) halide electrophiles, are less well developed. Inspired by process development efforts toward GSK3368715, an investigational active pharmaceutical ingredient, we report that a Pd(II) palladacycle derived from tri-tert-butylphosphine and Pd(OAc)2 is an effective single-component precatalyst for a variety of direct alkenylation reactions. High-throughput experimentation identified optimal solvent/base combinations for a variety of HetAr-H substrate classes undergoing C-H activation without the need for cocatalysts or stoichiometric silver bases (e.g., Ag2CO3). We propose this reaction proceeds via a dual cooperative catalytic mechanism, where in situ-generated Pd(0) supports a canonical Pd(0)/(II) cross-coupling cycle and the palladacycle effects C-H activation via CMD in a redox-neutral cycle. In all, 192 substrate combinations were tested with a hit rate of approximately 40% and 24 isolated examples. Importantly, this method was applied to prepare a key intermediate in the synthesis of GSK3368715 on multigram scale.

Dual Transition Metal Electrocatalysis: Direct Decarboxylative Alkenylation of Aliphatic Carboxylic Acids.

Direct decarboxylative alkenylation of widely available aliphatic carboxylic acids with vinyl halides for the synthesis of alkenes with all substitution patterns has been accomplished by means of Ce/Ni dual transition metal electrocatalysis. The reactions employ alkyl acids as the limiting reagents and exhibit a broad scope with respect to both coupling partners. Notably, simple primary alkyl carboxylic acids could be readily engaged as carbon-centered radical precursors in the reaction. This new alkenylation protocol has been successfully demonstrated in direct modification of naturally occurring complex acids and is amenable to the enantioselective decarboxylative alkenylation of arylacetic acid. Mechanistic studies, including a series of controlled experiments and cyclic voltammetry data, allow us to probe the key intermediates and the pathway of the reaction.

Alkynyl Halo-Aza-Prins Annulative Couplings.

This article is a comprehensive report describing our studies in the field of aza-alkynyl Prins chemistry, comparing and contrasting the different reaction partners and reactivities observed during method development. The synthetic strategies combine an alkynyl aza-Prins coupling with an annulation, enabling the preparation of different nitrogen-containing heterocycles. Different iminium ions are explored as viable electrophiles for an alkynyl Prins cyclization, terminated by capture with a halogen nucleophile to form a vinyl halide. The synthetic utility of this functional handle is exploited through a number of Suzuki cross-couplings, allowing for the preparation of a modest library of compounds. In most cases, the Prins couplings are highly selective for the vinyl halides with E geometry, resulting from anti-addition across the alkyne.

Photocatalytic Cross-Coupling of Tetrafluoropyridine Sulfides with Vinyl Halides for the Synthesis of β,γ-Unsaturated Carbonyl Compounds.

β,γ-Unsaturated carbonyl compounds serve as versatile building blocks in organic synthesis and medicinal chemistry. Herein we reported the synthesis of β,γ-unsaturated carbonyl compounds from tetrafluoropyridine sulfides with vinyl halides. This cross-coupling reaction takes the advantage of photocatalysis, as well as zinc catalysis, which is preferred due to its less-toxic, earth abundant, and cost-effective nature.

Nickel/Copper Co‐catalyzed Enantioselective Reductive Coupling of Oxabenzonorbornadienes with Vinyl Bromides

AbstractThe enantioselective reductive coupling of oxabenzonorbornadiene with vinyl bromide is developed with earth‐abundant nickel catalyst with copper as Lewis acid co‐catalyst. The asymmetric reductive coupling is applicable with a wide range of azabenzonorbornadienes and vinyl bromides under nickel/copper co‐catalytic system, affording the cis ring‐opening vinylation products in good yields with high optical purities. The present study has enabled straightforward stereoselective preparation of chiral 2‐vinyl‐tetrahydronaphthalens from vinyl halides.

Access to Aryl and Vinyl Halides Enabled by Nickel-Catalyzed Halogenation of Thianthrenium Salts

Access to Aryl and Vinyl Halides Enabled by Nickel-Catalyzed Halogenation of Thianthrenium Salts

Stereospecific Cu(I)-Catalyzed C-O Cross-Coupling Synthesis of Acyclic 1,2-Di- and Trisubstituted Vinylic Ethers from Alcohols and Vinylic Halides.

CuI and trans-N,N'-dimethylcyclohexyldiamine catalyze the single-step C-O bond cross-coupling between 1,2-di- and trisubstituted vinylic halides with functionalized alcohols, producing acyclic vinylic ethers. This stereospecific transformation selectively gives each of the (E)- and (Z)-vinylic ether products from the corresponding vinyl halide precursors. This method is compatible with carbohydrate-derived primary and secondary alcohols and several other functional groups. The conditions are mild enough to reliably generate vinylic allylic ethers without promoting Claisen rearrangements.

Synthesis of linear and branched poly(phenylacetylene)s through Mizoroki-Heck coupling reaction of vinyl bromides

Polyacetylene and its derivatives are a class of traditional conjugated polymers that started the era of conducting plastics. In this paper, we develop a new approach of synthesizing substituted poly(phenylacetylene)s through Mizoroki-Heck coupling of vinyl bromides. A series of α-bromostyrene derivatives are synthesized and used as the monomers for the polycoupling reaction. It is found that K2CO3 is the effective base while Et3N shows almost no catalytic reactivity. Gel permeation chromatography (GPC) results indicate that the molecular weight distribution is broad, which is typical for step growth polymerization. A kinetic study shows that electron withdrawing group on the phenyl ring increase the polymerization rate of the corresponding monomer. Furthermore, incorporating both aryl and vinyl halides into a single vinyl monomer allows the synthesis of branched polyacetylene possessing oligo(phenylene vinylene) at the branch points. The current approach may serve as a new tool for the molecular engineering of substituted polyacetylene materials.

1,3-Difunctionalization of Propargyl Silanes with Concomitant 1,2-Silyl Shift: Synthesis of Allyl Functionalized Vinyl Silanes

Terminal alkynes with a silyl group at the propargylic position upon activation with electrophiles such as N-bromosuccinimide undergo (E)-selective 1,2-silyl group migration. Subsequently, an allyl cation is formed that is intercepted by an external nucleophile. This approach provides allyl ethers and esters with stereochemically defined vinyl halide and silane handles for further functionalization. The scope of propargyl silanes and electrophile–nucleophile pairs are investigated, and various trisubstituted olefins are prepared in up to 78% yield. The obtained products have been demonstrated to serve as building blocks for transition-metal-catalyzed cross-couplings of vinyl halides, silicon-halogen exchange, and allyl acetate functionalization reactions.