Coupling Products Research Articles

Reversible Radical Addition Guides Selective Photocatalytic Intermolecular Thiol‐Yne‐Ene Molecular Assembly

AbstractIn modern organic chemistry, harnessing the power of multicomponent radical reactions presents both significant challenges and extraordinary potential. This article delves into this scientific frontier by addressing the critical issue of controlling selectivity in such complex processes. We introduce a novel approach that revolves around the reversible addition of thiyl radicals to multiple bonds, reshaping the landscape of multicomponent radical reactions. The key to selectivity lies in the intricate interplay between reversibility and the energy landscapes governing C−C bond formation in thiol‐yne‐ene reactions. The developed approach not only allows to prioritize the thiol‐yne‐ene cascade, dominating over alternative reactions, but also extends the scope of coupling products obtained from alkenes and alkynes of various structures and electron density distributions, regardless of their relative polarity difference, opening doors to more versatile synthetic possibilities. In the present study, we provide a powerful tool for atom‐economical C−S and C−C bond formation, paving the way for the efficient synthesis of complex molecules. Carrying out our experimental and computational studies, we elucidated the fundamental mechanisms underlying radical cascades, a knowledge that can be broadly applied in the field of organic chemistry.

C–C bond coupling differences between β-O-4 and 4-O-5 ether bonds over hydrophobic mesoporous Ru/MY-O catalysts: from lignin model compounds to polycyclic alkanes

MY zeolites with mesopores were prepared by hydrothermal method using functionalized SiO2 (F-SiO2) as a silica source, and hydrophobic bifunctional Ru/MY-O catalysts were obtained by deposition precipitation method and silylation treatment. This work aims at obtaining polycyclic alkane (PCA) based high-density hydrocarbon fuels (HDHFs). We focused on the catalytic hydroconversion (CHC) of 2-phenoxy-1-phenylethanol (PP-ol) and oxydibenzene (ODB), two typical lignin-related model compounds (LRMCs), over Ru/MY-O. The effects of different reaction conditions and catalysts on the product distribution in PP-ol and ODB were investigated. The partial hydrogenation of ODB was found to be a necessary step before achieving C-O ether bond cleavage and C-C bond coupling. The balance of metal/acidic sites is critical for maximizing PCA yields. Changes in the metal/acid ratio had a greater effect on PCA yield in PP-ol than in ODB. Poor stability of cycloalkyl cations and partial hydrogenation of ODB hinder the generation of C-C coupling products. The incorporation of mesopores and hydrophobic treatment were found to weaken the negative effects of C-C bond coupling products and water on the catalyst. The conversion of Ru3/MY-O was improved by nearly 10% compared to Ru3/Y in the fifth cycle reaction. This work provided a theoretical basis for the generation of HDHFs from lignin.

Tert‐ Butyl nitrite promoted visible light induced steric‐hindrance‐regulated concurrent cross‐coupling and regioselective nitration of 3‐alkylidene‐2‐ oxindoles

tert‐ butylnitrite (TBN) promoted visible‐light‐induced one‐pot C‐N cross coupling reaction of 3‐alkylidene‐2‐oxindoles with benzene‐1,2‐diamine has been explored. Simultaneously, the indoline motif of 3‐alkylidene‐2‐oxindoles as well as 3‐ylidene oxindoles are regioselectively nitrated at C‐6 position by in‐situ formed NO2 radical. (E)‐3‐(2‐(aryl)‐2‐oxoethylidene)oxindole and (E)‐3‐ylidene oxindole, produce distinct nitrated diastereomeric coupling products, a phenomenon influenced by the steric bulk of the functional group. The experimental findings suggest the potential involvement of a radical pathway in this reaction.

Copper Catalyzed Enantioconvergent Nucleophilic Substitutions†

Comprehensive SummaryAs a versatile earth‐abundant transition metal, Cu has long been widely applied in the C—C and C—X bond forming reactions. As for now, low‐valent Cu(I) is known to reduce the redox active electrophiles via an SET pathway to give the corresponding radical and Cu(II) species. The resulting Cu(II) species can interact with the radical via the out‐sphere pathway, affording the coupling product. Alternatively, Cu(II) can trap the radical through the inner‐sphere process to generate Cu(III) species and then realize challenging bond formations due to the facile reductive elimination of Cu(III) intermediate. Although copper catalysis has been widely applied in arylations of various nucleophiles, copper‐catalyzed enantioconvergent nucleophilic substitutions of racemic alkyl electrophiles have been less explored, likely due to the difficulties in overcoming the reduction potential of alkyl electrophiles, elimination of side reactions, and enantiomeric control. In order to overcome the high reduction potential of alkyl electrophiles, the photo‐induced strategy has been developed under mild conditions. An alternative strategy with new anionic tridentate ligands has also been reported in this regard. This review summarizes recent developments in copper‐catalyzed enantioconvergent nucleophilic substitutions of alkyl electrophiles by various nucleophiles to realize C—N, C—C, C—B, C—P and C—O bond formations and their brief mechanistic studies. Key ScientistsIn 2016, Fu and Peters et al. reported the first photo‐induced Cu‐catalyzed enantiocovergent C—N bond formations of tertiary alkyl halides with N‐hetereocycles, opening the door for the Cu‐catalyzed enantiocovergent nucleophilic substitutions. The photo‐induced strategy has been developed that greatly enhances the reducing power of Cu(I). The Cu‐catalyzed enantioconvergent cyanation (decarboxylative) and borylation were then successively presented by Liu and Ito in 2017 and 2018, respectively. Other than the photo‐induced strategy, Liu et al. in 2019 demonstrated that anionic ligands can also significantly enhance the reducing ability of Cu(I). The cinchona‐based chiral anionic tridentate ligands have been utilized for a series of Cu‐catalyzed enantiocovergent nucleophilic substitutions. Zhang et al. also developed chiral anionic tridentate ligands containing the oxazoline binding sites in 2020. In 2020, Xiao and Lu et al. reported the Cu‐catalyzed enantiocovergent deoxygenative cyanation. Later in 2022, Feng and Liu et al. developed the new guanidine hybrid ligands. This review focuses on the Cu‐catalyzed enantioconvergent nucleophilic substitutions that emerged in recent years.

Gas‐phase Smiles rearrangement of ortho‐nitro‐substituted diaryliodonium cations and their mechanistic insights

RationaleDiaryliodonium salts are useful electrophilic reagents in organic chemistry, finding extensive applications in arylations and photo‐induced polymerizations. However, comprehensive mechanistic investigations, particularly concerning the mass spectrometric behaviors of diaryliodonium salts, are relatively scarce in the literature.MethodsDiaryliodonium salts could be readily ionized using electrospray ionization mass spectrometry (ESI‐MS) to give [Ar1‐I+‐Ar2], and high‐resolution ESI‐tandem mass spectrometry (MS/MS) experiments were conducted to investigate their gas‐phase chemical reactions.ResultsInvestigations on ESI‐MS/MS of [Ar1‐I+‐Ar2] revealed two major fragmentation patterns: (1) reductive elimination resulting in the diaryl coupling product ion [Ar1‐Ar2]+• by the loss of I; (2) generation of aryl cations [Ar1]+ or [Ar2]+ through cleavage of the C–I bonds. We revealed that the introduction of NO2 into Ar2 of [Ar1‐I+‐Ar2] could lead to an unexpected fragmentation ion [Ar1O]+ in MS/MS, arising from an O‐atom transfer process from NO2 to Ar1. Particularly, when NO2 was ortho‐positioned to the iodine in Ar2, the [Ar1O]+ sometimes exhibited dominant behavior.ConclusionsComprehensive ESI‐MS/MS studies and theoretical calculations provided strong support for the O‐atom transfer mechanistic pathway: [Ar1‐I+‐(o‐NO2‐Ar2)] initially underwent a Smiles rearrangement to the intermediate [Ar1‐O‐(o‐NO‐Ar2I)]+, which subsequently dissociated to [Ar1O]+ or [o‐NO‐Ar2I]+•. Herein, we proposed an unexpected “ortho effect” in the gas‐phase fragmentation reaction of [Ar1‐I+‐(o‐NO2‐Ar2)], in which the crucial determinant factor for the aryl migration was identified as the Smiles rearrangement reaction.

Quantitative Determination of Active Species Transforming the R-NHC Coupling Process under Catalytic Conditions.

Palladium complexes with N-heterocyclic carbenes (Pd/NHC) serve as prominent precatalysts in numerous Pd-catalyzed organic reactions. While the evolution of Pd/NHC complexes, which involves the cleavage of the Pd-C(NHC) bond via reductive elimination and dissociation, is acknowledged to influence the catalysis mechanism and the performance of the catalytic systems, conventional analytic techniques [such as NMR, IR, UV-vis, gas chromatography-mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC)] frequently fail to quantitatively monitor the transformations of Pd/NHC complexes at catalyst concentrations typical of real-world conditions (below approximately 1 mol %). In this study, for the first time, we show the viability of using electrospray ionization mass spectrometry (ESI-MS). This approach was combined with the use of selectively deuterated H-NHC, Ph-NHC, and O-NHC coupling products as internal standards, allowing for an in-depth quantitative analysis of the evolution of Pd/NHC catalysts within actual catalytic systems. The reliability of this approach was affirmed by aligning the ESI-MS results with the NMR spectroscopy data obtained at greater Pd/NHC precatalyst concentrations (2-5 mol %) in the Mizoroki-Heck, Sonogashira, and alkyne transfer hydrogenation reactions. The efficacy of the ESI-MS methodology was further demonstrated through its application in the Mizoroki-Heck reaction at Pd/NHC loadings of 5, 0.5, 0.05, and 0.005 mol %. In this work, for the first time, we present a methodology for the quantitative characterization of pivotal catalyst transformation processes commonly observed in M/NHC systems.

Thioarylation of 6-Amino-2,3,6-trideoxy-d-manno-oct-2-ulosonic Acid (IminoKdo): Access to 3,6-Disubstituted Picolinates and Mechanistic Insights.

In this work, we present a metal-free coupling protocol for the regio- and stereoselective C3-thioarylation of 6-amino-2,3,6-trideoxy-d-manno-oct-2-ulosonic acid (iminoKdo). The developed procedure enables the coupling of electron-rich, electron-deficient, and hindered arylthiols, providing a series of C3-modified iminoKdo derivatives in moderate to good yields. Elucidation of active species through controlled experimental studies and time-lapse 31 P NMR analysis provides insights into the reaction mechanism. We demonstrate that, following a tandem Staudinger/aza-Wittig reaction of an azido-containing keto ester, an inseparable equimolar mixture of imine/enamine is formed. The enamine then undergoes a Stork-like nucleophilic attack with the in situ-formed disulfide reagent, resulting in the formation of the coupling products. Additionally, we describe a rarely reported acid-promoted aromatization of the C3-thioarylated iminoKdo skeleton into 3,6-disubstituted picolinates, which are reminiscent of dichotomines.

Copper-promoted ortho-directed C-H amination of 2-arylpyridines with NH-heterocycles.

Copper-mediated C-N coupling of azaheterocycles with aryl C-H bonds has been realized for the synthesis of N-(hetero)arylated heteroarenes. This method is characterized by high regioselectivity, atom economy and a wide substrate scope of 2-arylazines and azaheterocycles. The corresponding C-N coupling products were shown to undergo further transformation to synthesize more complex molecules.

Oxidation of N-trifluoromethylthio sulfoximines using NaOCl·5H2O.

N-Trifluoromethylthio sulfoximines are biologically interesting compounds, but their potential is still poorly understood. The oxidation of N-trifluoromethylthio sulfoximines led to their corresponding sulfoxide derivatives as a new class of compounds, when using sodium hypochlorite pentahydrate (NaOCl·5H2O) as a green and relatively unexplored reagent. The reactions took place with a small excess of oxidant under environmentally friendly conditions in EtOAc for 16 h at room temperature. Noteworthy distinctions of this transformation are the simplicity, high selectivity, energy and cost efficiency, minimal amounts of non-hazardous waste, isolation of most of the products without the additional need for chromatographic purification, and simple scalability to gram reactions without deterioration of the yield. The reaction exhibited excellent green chemistry metrics with high atom economy (82.0%), actual atom economy (79.5%), reaction mass efficiency (79.7%), E-factor (16.48) and a very high EcoScale score (84.5). Competitive experiments demonstrated that electron-rich substrates are more reactive than their electron-poor counterparts. Furthermore, the Suzuki-Miyaura functionalization of N-trifluoromethylsulfaneylidene sulfoximine could be achieved depending on the conditions, resulting in coupling products with or without an introduced sulfoxide moiety. Sonogashira coupling of N-trifluoromethylsulfaneylidene sulfoximine furnished the expected acetylene derivative in high yield, and the reaction conditions are compatible with the newly introduced sulfaneylidene functionality. Bromine and nickel catalysts were also shown to be deprotecting agents of the sulfoxide group. A selected N-trifluoromethylsulfaneylidene sulfoximine demonstrated its stability in water in the presence of air and in dilute hydrochloric acid, while it converted back to the parent sulfoximine under basic conditions.

An assay for aryl radicals using BHAS coupling.

Aryl radicals are intermediates in many reactions, but determining their presence unambiguously is often challenging. As we recently reported, reaction of 2-iodo-1,3-dimethylbenzene (7) in benzene with KOtBu and a suitable organic additive, leads to a base-induced homolytic aromatic substitution (BHAS) coupling reaction giving 2,6-dimethylbiphenyl (12) and biphenyl (3) as coupled products, together with xylene (13). In this case, biphenyl arises from a radical translocation and is the major coupling product. This paper now quantitatively investigates that reaction, which shows a very similar ratio for 3 : 12 [ca. 4 : 1] when using different sources of radical initiation. Deuterium isotope studies provide detailed mechanistic support for the proposed mechanism; when carried out in C6D6vs. C6H6, the reaction is characterised by a strong isotope effect for formation of 3-d10vs. 3, but not for formation of 12-d5vs. 12. These distinctive properties mean that the transformation can act as an assay for aryl radicals. An advantage of such a BHAS process is its sensitivity, since it involves a chain reaction that can amplify radical activity.

Recent research progress on building C-N bonds via electrochemical NOx reduction.

The release of NOx species (such as nitrate, nitrite and nitric oxide) into water and the atmosphere due to human being's agricultural and industrial activities has caused a series of environmental problems, including accumulation of toxic pollutants that are dangerous to humans and animals, acid rain, the greenhouse effect and disturbance of the global nitrogen cycle balance. Electrosynthesis of organonitrogen compounds with NOx species as the nitrogen source offers a sustainable strategy to upgrade the waste NOx into value-added organic products under ambient conditions. The electrochemical reduction of NOx species can generate surface-adsorbed intermediates such as hydroxylamine, which are usually strong nucleophiles and can undergo nucleophilic attack to carbonyl groups to build C-N bonds and generate organonitrogen compounds such as amine, oxime, amide and amino acid. This mini-review summarizes the most recent progress in building C-N bonds via the in situ generation of nucleophilic intermediates from electrochemical NOx reduction, and highlights some important strategies in facilitating the reaction rates and selectivities towards the C-N coupling products. In particular, the preparation of high-performance electrocatalysts (e.g., nano-/atomic-scale catalysts, single-atom catalysts, alloy catalysts), selection of nucleophilic intermediates, novel design of reactors and understanding the surface adsorption process are highlighted. A few key challenges and knowledge gaps are discussed, and some promising research directions are also proposed for future advances in electrochemical C-N coupling.

Reaction of aromatic carboxylic acids with phenylacetylene with the participation of a zinc catalyst

The reaction of benzoic, 4-methylbenzoic, 2-bromobenzoic and 4-bromobenzoic acids with phenylacetylene was carried out in a toluene solution at a temperature of 110 0C in the presence of a catalyst - 1 mol % [Zn(C4H7S2)4](NO3)2. In the coupling reaction of carboxylic acids with phenylacetylene a mixture of coupling products is formed according to the Markovnikov and anti-Markovnikov rules. A reaction mechanism was proposed and it was found that the yield of vinyl esters increased in the serie 4-CH3-C6H4COOH< C6H5COOH< 4-Br-C6H4COOH< 2-Br-C6H4COOH. It was found that with an increasing acidity of the carboxylic acids, the product formed by Markovnikov rule has been formed in a larger amount. On the contrary, as the acidity of the starting compounds decreased, the amount of the anti-Markovnikov coupling product has increased. The total yield of reaction products of phenylacetylene with carboxylic acid is 44% (65/35) in 4-methylbenzoic acid, 67% (80/20) in benzoic acid, 78% (82/18) in 4-bromobenzoic acid, 82% (85 /15) in 2-bromobenzoic acid. The structure of the synthesized vinyl esters was proved on the base of the analysis of IR, 1H, 13C NMR and Mass spectrums.

Coupling between magnetism and topology: From fundamental physics to topological magneto-electronics

Magnetism and topological physics are both well-developed disciplines, and their combination is a demand and foundation for the development of next-generation magneto-electronics. Magnetic topological materials are important products of coupling between magnetic order and topological physics, providing material carrier and regulatory degrees of freedom for novel topological physics. Magnetic Weyl semimetals realize Weyl fermion states under time-reversal symmetry breaking, leading to a host of novel magnetic, electric, thermal, and optical effects through enhanced Berry curvature originating from topology. The interaction between Weyl electrons and magnetic order also establishes topological electronic physics as a new principle and driving force for magneto-electronic applications. At present, the primary task and characteristic of the first development stage of magnetic topological materials is to discover new states and effects, while the understanding of interaction between topologically nontrivial electrons in momentum space and magnetic order in real space has received attention of researchers. The comprehensive advances of these two stages will accumulate the physical foundation and application explorations for topological magneto-electronics. This paper focuses on the two development stages of magnetic topological materials and discusses three aspects: (i) proposal and realization of strategy for magnetic topological materials; (ii) exploration of electronic states with nontrivial topology under uniform magnetic order and their associated novel physical properties; (iii) the interaction between localized magnetic states and topological electrons. It provides an in-depth discussion on current hot topics and development trends in the field, and future development in topological magneto-electronics, thereby assisting in the future development of topological spin quantum devices.

Alkylphenols disrupt estrogen homeostasis via diradical cross-coupling reactions: A novel pathway of endocrine disruption

Estrogen, being an essential class of sex hormone, is an important target of endocrine disruption chemicals. It is well known that environmental disruptors could activate or inhibit estrogen receptors, acting as agonists or antagonists, and thus affect the circulating estrogen concentrations. Here, we report enzyme-mediated diradical cross-coupling reactions between alkylphenols (e.g., 2,4-di-tert-butylphenol [DBP], 4-nonylphenol [4-NP], and 4-tert-octylphenol [4-t-OP]) and estrogens (e.g., estradiol [E2]) that generate coupling metabolites and disrupt estrogen homeostasis. Among the phenolic xenobiotics, the screening of metabolic products revealed that alkylphenols had the highest reaction activities and generated coupling metabolites with high abundances (DBP-O-E2, 4-t-OP-O-E2, and 4-NP-O-E2). The coupling reactions were catalyzed by cytochrome P450 3A4 (CYP3A4) and verified by the detection of the coupling products in general populations. In vitro and in vivo exposures together with CYP3A4 inhibition demonstrated that cross-coupling reactions of phenols and E2 significantly reduced the normal levels of E2. We further established a unique spin-trapping-based high-throughput screening method to show the existence of diradicals in the coupling reaction. Density functional theory calculations revealed that spin aromatic delocalization was the fundamental cause of the high rebound barrier and sufficient lifetime of phenoxy radicals that enabled phenolic cross-coupling triggered by cytochrome P450. The identified mechanistic details for diradical cross-coupling reactions provide a novel pathway for phenolic chemicals to disrupt estrogen homeostasis.

Performance evaluation of multi-stage manufacturing systems operating under feedback and feedforward quality control loops

In manufacturing, the essential product characteristics are often created through multiple stages. Coupling product data obtained through inspection and controllers based on decision models with prediction capabilities enables quality control loops, enhancing both feedback and feedforward mechanisms. This paper proposes a methodology to merge the formulation of feedback and feedforward quality control loops into a performance evaluation model for multi-stage manufacturing systems. This approach evaluates quality control loop impacts system-wide, aiding in configuring and reconfiguring quality gates. A case study illustrates how allocating inspection technologies and efficient decision models improves overall system performance through effective feedback and feedforward control loops.

Directed copper-catalyzed C-H functionalization of unactivated olefins with azodicarbonamide compounds.

The copper-catalyzed strategy employing the 8-aminoquinoline directing group has proven to be a highly advantageous approach for functionalizing C-H bonds. In this study, we present the successful application of this strategy to accomplish Heck-type coupling reactions and construct β-lactam skeletons, simultaneously introducing a unique cyano functional group. The resulting Heck-type coupling products demonstrate good stereo- and region-selectivity. Initial mechanistic investigations indicate that the reaction proceeds via a radical coupling mechanism, exhibiting a wide substrate scope and delivering good yields.

Glycosylation of n-pentenyl glycosides using bromodiethylsulfonium salt as an activator: interception of the glycosyl intermediate by chloride ion transfer.

Utilization of n-pentenyl glycosides (NPGs) in modern carbohydrate synthesis may be hindered by their sluggish activation, which results from reversible halogenation and cyclization processes. Bromodiethylsulfonium bromopentachloroantimonate (BDSB) has been previously shown to be a powerful brominating agent for the cation-π polyene cyclization of less reactive and electron-poor polyenes. This study demonstrates the activation of NPGs using BDSB as a powerful brominating agent. BDSB effectively activates the terminal olefins of NPGs and the reaction proceeds through 5-exo-tet cyclization, offering a rapid and mild approach for glycosylation with a wide range of glycosyl donors, including n-pentenyl mannoside, n-pentenyl galactoside, and n-pentenyl glucoside. The success of this approach derives from the chloride ion transfer from the nonnucleophilic SbCl5Br anion to the glycosyl intermediate, which disrupts the equilibrium and produces a glycosyl chloride intermediate that is smoothly converted to 22 coupling products, with yields ranging from moderate to excellent (49-100%). The β-selective glycosylation is accomplished when employing NPGs equipped with a neighboring participating group. The practicality of the BDSB-activated glycosylation is demonstrated by a gram-scale synthesis. This study showcases BDSB as a potent activator for NPG glycosylation through the interception of a glycosyl intermediate that diminishes the equilibration during halogenation and 5-exo-tet cyclization.

Pd-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction in Glycerol Using KOH as Base and Glycerol-Triethanolamine Deep Eutectic Solvent under Inorganic Base‑Free Conditions

Glycerol and glycerol-triethanolamine deep eutectic solvent are both environmentally benign, cost-effective, and practical solvents for the Pd-catalyzed Suzuki-Miyaura cross-coupling of aryl halides with arylboronic acids. Utilizing KOH as base, the reaction in glycerol proceeded smoothly with low catalyst loadings (up to 0.5 mol% of PdCl2(PPh3)2) providing excellent yields (up to 99%) of the cross-coupling products, which can be readily extracted with hexane. However, the recyclability of the glycerol medium containing the catalyst is limited to a few cycles. Furthermore, it was explored the use of chlorodiphenylphosphine as a pre-ligand. Although glycerol phosphinite was not generated in situ, PPh2Cl proved to be an excellent pre-ligand, yielding the coupling product with a 98% yield. Compared to glycerol, glycerol-triethanolamine deep eutectic solvent (TEOA:G DES) proves to be a superior solvent for the cross-coupling reaction. In addition, the presence of amine group in the solvent allowed to obtain an inorganic base-free cross-coupling protocol. Aryl bromides and aryl boronic acids containing both electron releasing and attracting functional groups can be coupled without requiring the addition of any further base, affording the biphenyl products in moderate to good yields. The cross-coupling products can be easily isolated by extraction with hexane. Moreover, we observed the formation of triethanolamine phenylboronate during the reaction. The triethanolamine boronate was subsequently synthesized through the condensation of phenylboronic acid with triethanolamine and fully characterized. 11B nuclear magnetic resonance (NMR) spectroscopy confirmed the coordination of the nitrogen to the boron atom of the triethanolamine boronate.

Asymmetric Synthesis of Chiral 1,2-Bis(Boronic) Esters Featuring Acyclic, Non-Adjacent 1,3-Stereocenters.

The construction of acyclic, non-adjacent 1,3-stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long-standing synthetic challenge due to acyclic nucleophiles being distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2-bis(boronic) esters featuring acyclic and nonadjacent 1,3-stereocenters. Notably, this reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct allylation byproducts. This approach introduces a new activation mode for selective transformations of gem-diborylmethane in asymmetric catalysis. Additionally, we found that other gem-diborylalkanes, previously challenging due to steric hindrance, also successfully participated in this reaction. The incorporation of 1,2-bis(boryl)alkenes facilitated the diversification of the alkenyl and two boron moieties in our target compounds, thereby enabling access to a broad array of versatile molecules. DFT calculations were performed to elucidate the reaction mechanism and shed light on the factors responsible for the observed excellent enantioselectivity and diastereoselectivity. These were determined to arise from ligand-substrate steric repulsions in the syn-addition transition state.

Asymmetric Synthesis of Chiral 1,2‐Bis(Boronic) Esters Featuring Acyclic, Non‐Adjacent 1,3‐Stereocenters

AbstractThe construction of acyclic, non‐adjacent 1,3‐stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long‐standing synthetic challenge due to acyclic nucleophiles being distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2‐bis(boronic) esters featuring acyclic and nonadjacent 1,3‐stereocenters. Notably, this reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct allylation byproducts. This approach introduces a new activation mode for selective transformations of gem‐diborylmethane in asymmetric catalysis. Additionally, we found that other gem‐diborylalkanes, previously challenging due to steric hindrance, also successfully participated in this reaction. The incorporation of 1,2‐bis(boryl)alkenes facilitated the diversification of the alkenyl and two boron moieties in our target compounds, thereby enabling access to a broad array of versatile molecules. DFT calculations were performed to elucidate the reaction mechanism and shed light on the factors responsible for the observed excellent enantioselectivity and diastereoselectivity. These were determined to arise from ligand‐substrate steric repulsions in the syn‐addition transition state.