Organozinc Research Articles

Enantioconvergent Negishi Cross-Couplings of Racemic Secondary Organozinc Reagents to Access Privileged Scaffolds: A Combined Experimental and Theoretical Study.

An enantioconvergent palladium-catalyzed Negishi cross-coupling with racemic secondary organozinc reagents has been developed, enabling access to enantioenriched 1,1-diarylalkane motifs in high yields and enantioselectivities. Computational data indicates that the racemization of organozinc compounds most likely occurs through a bridged bimolecular mechanism.

Ferromagnetic ZnO nanostructures from an organo zinc complex formulated via Piper Longum L-assisted green synthesis: Multifaceted prospects in photocatalysis, antimicrobial activity, and cell viability studies

Transition metal oxides like ZnO nanostructures are pivotal in various scientific and technological fields due to their chemical stability, high electrochemical coupling efficiency, and broad radiation absorption spectrum. This study offers an in-depth examination of ZnO nanostructures synthesized via the green route using Piper Longum L, emphasizing their photocatalytic efficacy in degrading organic pollutants such as Sulphanilamide and Chromium. The ZnO nanostructures with a rod-like morphology exhibited an average crystallite size of 26 nm and an optical bandgap of 2.8 eV. Solid state structure of ZnO was investigated by Fourier Transform Infrared spectroscopy (FTIR) and X-Ray Diffraction (XRD). Zinc in the synthesized organo zinc complex and zinc oxide was estimated to 324.325 and 133.02 ppm, respectively. The saturation magnetization obtained from Superconducting Quantum Interference Device-Vibrating Sample Magnetometer (SQUID-VSM) for organo zinc complex and ZnO is 2.1 × 10−3 and 1.7 × 10−3 emu/g, respectively. These nanostructures achieved 99 and 93 % degradation of chromium (VI) ions present in solutions of two different concentrations in about 30 and 80 min, respectively, under UV and visible radiation, a remarkable achievement. Almost the same efficiency was maintained during three consecutive runs and then deactivation of the catalyst was observed. Additionally, a rapid 84 % degradation of Sulphanilamide was observed in 42 min, underscoring the potential of ZnO nanostructures as efficient photocatalysts for environmental remediation.

Continuous Scalable Synthesis and Concentration Variation of Organozinc Compounds

Continuous Scalable Synthesis and Concentration Variation of Organozinc Compounds

Preparation of a Key Intermediate En Route to the Anti-HIV Drug Lenacapavir.

A very efficient four-step synthesis of the main fragment of Gilead's anti-HIV drug lenacapavir is described. The route showcases a 1,2-addition to an intermediate aldehyde using an organozinc halide derived from a commercially available difluorobenzyl Grignard reagent. This sets the stage for the oxidation of the resulting secondary alcohol to the desired ketone, which relies solely on catalytic amounts of TEMPO together with NaClO as the terminal oxidant, affording the targeted ketone in 67% overall yield.

General alkyl fluoride functionalization via short-lived carbocation-organozincate ion pairs

Fluorinated organic compounds are frequently used across the chemical and life sciences. Although a large, structurally diverse pool of alkyl fluorides is nowadays available, synthetic applications trail behind the widely accepted utility of other halides. We envisioned that C(sp2)-C(sp3) cross-coupling reactions of alkyl fluorides with fluorophilic organozinc compounds should be possible through a heterolytic mechanism that involves short-lived ion pairs and uses the stability of the Zn-F bond as the thermodynamic driving force. This would be mechanistically different from previously reported radical reactions and overcome long-standing limitations of organometallic cross-coupling methodology, including competing β-hydride elimination, homodimerization and hydrodefluorination. Here, we show a practical Csp3-F bond functionalization method that expands the currently restricted synthetic space of unactivated primary, secondary and tertiary C(sp3)-F bonds but also uses benzylic, propargylic and acyl fluorides. Many functional groups and sterically demanding substrates are tolerated, which allows practical carbon-carbon bond formation and late-stage functionalization.

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides.

The use of alkylzinc bromides in the multicomponent Mannich reaction is described. Heteroleptic organozinc compounds were obtained in THF or 2-MeTHF by direct insertion of zinc dust into the C-Br bond of alkyl bromides. It was found that the presence of a stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines. A variety of primary, secondary, and tertiary organozinc reagents as well as secondary amines and aromatic aldehydes could be used for the straightforward preparation of α-branched amines. Interestingly, whereas previously reported work describing the preparation and reaction of organozinc iodides in acetonitrile showed higher reactivity of secondary organozinc reagents over primary ones, reactions in THF in the presence of LiCl led to opposite results, with higher reactivity of primary organozinc reagents.

SYNTHESIS OF 1,1′-(2,3,5,6-TETRAFLUORO-1,4-PHENYLENE)DIPROPAN-1-ONE

1-(Pentafluorophenyl)propan-1-one reacts with zinc in the presence of catalytic amounts of SnCl2 under heating in dimethyl formamide to give (2,3,5,6-tetrafluoro-4-propionylphenyl)zinc chloride and bis(2,3,5,6-tetrafluoro-4-propionylphenyl)zinc. 1,1¢-(2,3,5,6-Tetrafluoro-1,4-phenylene)dipropan-1-one was synthesized from these organozinc compounds and propionyl chloride in the presence of CuI. The reaction of organozinc compounds obtained from 3-bromo-1,2,4,5-tetrafluorobenzene leads to the formation of 1-(2,3,5,6-tetrafluorophenyl)propan-1-one

Bright and Stable ZnSeTe Core/Shell Quantum Dots Enabled by Surface Passivation with Organozinc Halide Ligands

Bright and Stable ZnSeTe Core/Shell Quantum Dots Enabled by Surface Passivation with Organozinc Halide Ligands

Quinolinamide-Enabled Nickel-Catalyzed Regio- and Diastereoselective γ,δ-Arylalkylation of Nonactivated Alkenes

AbstractA quinolinamide-enabled nickel-catalyzed γ,δ-arylalkylation of homoallylic amines with aryl iodides and organozinc compounds has been developed. The cleavable quinolinamide directing group facilitates the stabilization of a five-membered nickelacycle, and enables the dicarbofunctionalization of nonactivated alkenes with excellently regio-, chemo-, and diastereoselectivity. The reaction with internal alkenes proceeds stereospecifically to provide valuable γ-alkyl-δ-aryl-substituted amines with two vicinal stereocenters. The scope of substrates and the utility of the protocol have been thoroughly studied.

Catalytic Asymmetric Ring-Opening Reactions of Unstrained Heterocycles Using Cobalt Vinylidenes.

Cobalt catalysts promote highly enantioselective ring-opening reactions of 2,5-dihydrofurans using vinylidenes. The products are acyclic organozinc compounds that can be functionalized with an electrophile. The proposed mechanism involves the generation of a cobalt vinylidene species that adds to the alkene by a [2+2]-cycloaddition pathway. Ring-opening then occurs via outer-sphere β-O elimination assisted by coordination of a ZnX2 Lewis acid to the alkoxide leaving group. DFT models reveal that competing inner-sphere syn β-H and β-O elimination pathways are suppressed by the geometric constraints of the metallacycle intermediate. These models rationalize the observed stereochemical outcome of the reaction.

Catalytic Asymmetric Ring‐Opening Reactions of Unstrained Heterocycles Using Cobalt Vinylidenes

AbstractCobalt catalysts promote highly enantioselective ring‐opening reactions of 2,5‐dihydrofurans using vinylidenes. The products are acyclic organozinc compounds that can be functionalized with an electrophile. The proposed mechanism involves the generation of a cobalt vinylidene species that adds to the alkene by a [2+2]‐cycloaddition pathway. Ring‐opening then occurs via outer‐sphere β‐O elimination assisted by coordination of a ZnX2 Lewis acid to the alkoxide leaving group. DFT models reveal that competing inner‐sphere syn β‐H and β‐O elimination pathways are suppressed by the geometric constraints of the metallacycle intermediate. These models rationalize the observed stereochemical outcome of the reaction.

Multicomponent Reaction of Aliphatic Organozinc Reagents, Acrylates and Acyl chlorides: Synthesis of α‐Substituted β‐Ketoesters

AbstractAn uncatalyzed three‐component reaction employing aliphatic organozinc reagents for the preparation of α‐substituted β‐ketoesters is described. This modular procedure, which relies on a formal conjugate addition/crossed‐Claisen domino reaction between an organozinc, an acrylate and an acyl chloride, allows the straightforward synthesis of the reaction products under mild conditions. The three‐component coupling can also be conducted from alkyl iodides, in an even more simple procedure. Experimental findings account for a probable polar concerted mechanism involving at least two organozinc compounds at the stage of the transition state.

Zinc Chelate Complexes of N‐Acyl Hydrazones as Substrates for Addition of Alkyl and Fluorinated Radicals

AbstractZinc chelate complexes can be generated in situ from N‐acyl hydrazones by treatment with isopropyl zinc iodide. These complexes couple with alkyl and fluorinated radicals under photoredox conditions. Alkyl radicals were generated from organozinc halides using an organic photocatalyst and afford hydrazines as a result of reductive mode of addition. Fluorinated radicals were formed from perfluorinated alkyl iodides under photoredox conditions leading to fluoroalkylated hydrazones via neutral reaction pathway.

Stereospecific Transformations of Alkylboronic Esters Enabled by Direct Boron-to-Zinc Transmetalation.

Chiral secondary organoboronic esters, when activated with t-butyllithium, are shown to undergo efficient stereoretentive transmetalation with either zinc acetate or zinc chloride. This reaction provides chiral secondary alkylzinc reagents that are configurationally stable under practical experimental conditions. The organozinc compounds were found to engage in stereospecific reactions with difluorocarbene, catalytic cross-couplings with palladium-based catalysts, and trifluoromethylation with a copper(III) complex. Mechanistic and computational studies shed light on the inner workings of the transmetalation event.

Synthesis, Characterization, and Reactivity Studies of Bis(β‐diketiminate) Zinc(II) Complexes

AbstractZinc(II) complexes bearing bis(β‐diketiminate) ligands with various linker groups and terminal substituents have been synthesized by deprotonation of the related bis(β‐diketimine)s with zinc(II) bis[bis(trimethylsilylamide)] and diethyl zinc, respectively. One mononuclear and seven dinuclear zinc(II) complexes could be isolated and fully characterized; their solid‐state structures have been determined by means of single‐crystal X‐ray diffraction analysis. Oxygenation experiments of selected dinuclear ethyl zinc bis(β‐diketiminate) complexes afforded a series of novel heteroleptic zinc alkoxide, hydroxide, carbonate, and carboxylate complexes. These findings do not only illustrate the complexity of both the oxygenation of organozinc compounds and the transformation pathways of the thus formed compounds but highlight also the impact of the reaction conditions and variations in the ligand framework.

Redox Behavior of Cobalt-Phosphine Complexes vs Their Catalytic Activity in Organozinc Compound Formation: Background for Mechanistic Investigations.

Catalytic activity in arylzinc compound formation was studied for eight Co complexes with phosphines along with their redox properties for implementing the idea of rational design. It was found that Co(XantPhos)Cl2 and Co(N-XantPhos)Cl2 demonstrated distinct reversible CoII/CoI redox processes and acted as efficient catalysts of arylzinc compound formation. Meanwhile, for Co(DPEphos)Cl2, Co(dppf)Cl2, Co(dppb)Cl2, Co(PPh3)2Cl2, and Co(XantPhos)(Piv)2 (the latter one without the addition of LiCl), reversible redox processes were not observed. These catalysts did not act efficiently for the model process of organozinc compound formation. Co4(dppe)5Cl8 was the only exception, explained by a completely different structure (CoP4Cl and CoPCl3) of donor sets instead of CoP2X2 (X = Cl or O). The stability of complexes in tetrahydrofuran (THF) and N,N-dimethylformamide (DMF) solutions was studied by UV-vis spectroscopy. Previously unknown X-ray structures for Co(XantPhos)(Piv)2, Co(N-XantPhos)Cl2, and {Co(DMF)6}{(CoCl3)2(dppb)} were determined. The use of pivalate counterions instead of chloride for Co(XantPhos)2+ led to a significant (ca. 20 times) increase of the kinetic solubility in THF compared to Co(XantPhos)Cl2, preserving high catalytic productivity upon the addition of LiCl. This allowed the latter to be efficiently used in combination with LiCl as the catalyst for arylzinc compound formation on a 2 g scale. The data obtained in this work can be regarded as experimental confirmation of the first and last stages of the plausible reaction pathway of arylzinc compound formation, involving CoII → CoI and CoI → CoII transformations, which could be a significant framework for further mechanistic investigations.

Catalyst-Free Formal Conjugate Addition/Aldol or Mannich Multicomponent Reactions of Mixed Aliphatic Organozinc Reagents, π-Electrophiles and Michael Acceptors.

Catalyst-free multicomponent reactions of mixed alkylzinc reagents with Michael acceptors and aldehydes, ketones or activated imines are described. Primary, secondary and tertiary alkylzinc reagents, pre-generated in acetonitrile from the corresponding iodoalkanes, were used in the process, leading to the very efficient formation of a variety of β-hydroxycarbonyl compounds. The imines showed more contrasting results, due to the direct addition of the organozinc compound to the C=N bond. Mechanistic assays involving TEMPO account for a polar instead of a radical character of the reaction.

New Catalysts Derived from Natural Products as Highly Stereoselective Chiral Inductors for Diethylzinc Addition to Aromatic Aldehydes

Asymmetric addition of organozinc compounds to carbonyl groups is one of the most useful methods for the synthesis of alcohols with high enantioselectivity. There is a wide range of chiral catalysts, although their synthesis requires more than one step and not often readily available starting materials. In this work, chiral β-hydroxy oxazolines derived from (+)-camphor and (−)-fenchone were easily synthesized through a one-step method, with good yields. Both ligands were evaluated as catalysts for the stereoselective addition of diethylzinc to aromatic aldehydes. All ligands showed good catalytic activity, leading both to the preparation of the R enantiomer of chiral secondary alcohols. As ligand 2 provided slightly better enantioselectivities, it was used as chiral inductor for the addition of diethylzinc for a larger number of aldehydes, resulting in good to excellent yields (88-98%) and enantiomeric excess up to 96%.

P‐12.5: Synthesis of Quaterphenyl Liquid Crystalline Isothiocyanates by Successive Alternating Cross‐linking

Due to their high dielectric anisotropy, nematic thioisocyanate quaterphenyl liquid crystals have found application in a wide GHz range. This article proposes a method for obtaining a sequential combination of quaterphenyl derivatives of thioiocyanates containing a methyl group lateral substitute on benzene structure. First, the reaction of pentylphenyl boric acid with diazobromotoluene tetrafluoroborates gives the corresponding biphenyl bromo derivatives, which are converted into organozinc derivatives through the Grignard reagent. Terphenyl bromo derivatives were obtained by the Negishi reaction of organozinc compounds with p‐iodobromobenzene. Terphenyl derivatives after transformation into boric acids were further combined according to the classical scheme.

Well-Defined Ni(0) and Ni(II) Complexes of Bicyclic (Alkyl)(Amino)Carbene (Me BICAAC): Catalytic Activity and Mechanistic Insights in Negishi Cross-Coupling Reaction.

Negishi cross-coupling reaction of organozinc compounds as nucleophiles with aryl halides has drawn immense focus for C-C bond formation reactions. In comparison to the well-established library of Pd complexes, the C-C cross-coupling of this particular approach is largely primitive with nickel-complexes. Herein, we describe the syntheses of Ni(II) complexes, [(Me BICAAC)2 NiX2 ] (X=Cl (1), Br (2), and I (3)) by employing the bicyclic (alkyl)(amino)carbene (Me BICAAC) ligand. The reduction of complexes 1-3 using KC8 afforded the two coordinate low valent, Ni(0) complex, [(Me BICAAC)2 Ni(0)] (4). Complexes 1-4 have been characterized by spectroscopic techniques and their solid-state structures were also confirmed by X-ray crystallography. Furthermore, complexes 1-4 have been applied in a direct and convenient method to catalyze the Negishi cross-coupling reaction of various aryl halides with 2,6-difluorophenylzinc bromide or phenylzinc bromide as the coupling partner in the presence of 3 mol % catalyst. Comparatively, among all-pristine complexes, 1 exhibit high catalytic potential to afford value-added C-C coupled products without the use of any additive. The UV-vis studies and HRMS measurements of controlled stochiometric reactions vindicate the involvement of Ni(I)-NI(III) cycle featured with a penta-coordinated Ni(III)-aryl species as the key intermediate for 1 whereas Ni(0)/Ni(II) species are potentially involved in the catalytic cycle of 4.