High E-selectivity Research Articles

The Assembly of Cerium(III)-Containing Silicotungstate with Lewis Acid-Base Sites Enables the Selective C3-Alkenylation of Oxindole.

A cerium(III)-containing silicotungstate, [H2N(CH3)2]10NaK[KCe(SiW11O39)2(H2O)]·18.5H2O (CeSiW), was successfully synthesized and characterized. Structure analysis reveals that CeSiW is composed of two {SiW11O39} units connected by one cerium(III) cation to form a typical 1:2 sandwich structure, which is further expanding into a 1D chain linked by K+ ions. The oxygen-enriched surfaces of {SiW11O39} units and open cerium sites provide abundant Lewis base and acid sites in CeSiW. As a result, CeSiW efficiently catalyzed the C3-alkenylation of oxindoles with aldehydes through the simultaneous activation of both reaction substrates on its crystal framework. Various 3-benzylidene-oxindoles are synthesized with excellent yields and high E-selectivity under solvent-free conditions.

Hypervalent-Iodine-Mediated Base-Free Oxidative Olefination of Benzylic Amines to Access α,β-Unsaturated Ketones

AbstractWe report a one-pot base-free protocol for the oxidative olefination of benzylic amines promoted by a hypervalent iodine reagent for the synthesis of α,β-unsaturated ketones. Mechanistically, (diacetoxyiodo)benzene oxidizes the benzylic amine to the corresponding imine, which, on reaction with a phenacyl(triphenyl)phosphonium bromide salt and an in situ generated acetoxy anion leads to an α,β-unsaturated ketone. A wide range of α,β-unsaturated ketones were easily accessed through direct oxidative olefination of substituted benzylic amines in good to excellent yields and with high E-selectivity.

Electrochemical E-Selective Semireductive Dicarboxylation of Aryl Alkynes with CO2.

Herein, we report an electrochemical protocol for the dicarboxylation of aryl alkynes using CO2. With a graphite rod as the cathode and Al as the sacrificial anode, a series of valuable butenedioic acids are obtained in moderate to excellent yields with an E/Z ratio up to 50:1. This method features high E-selectivity, high step and atom economy, easy scalability, and a nice substrate scope, which renders it appealing for promising applications in organic synthesis and materials chemistry.

Uracil-Cu(i) catalyst: allylation of cyclopropanols with Morita-Baylis-Hillman alcohols under water-tolerant conditions.

Inspired by the high affinity of copper with DNA and RNA, a uracil-copper catalytic system was developed to promote ring-opening allylation of cyclopropanols with allylic alcohols under water-tolerant conditions. A new C-OH bond-breaking model can well resolve the trade-off between the need for acidic activators for C(allyl)-OH bond cleavage and the demand for strong basic conditions for generating homoenolates. Therefore, Morita-Baylis-Hillman alcohols, rather than their pre-activated versions, could be incorporated directly into dehydrative cross-coupling with cyclopropanols delivering water as the only by-product. A variety of functionalized δ,ε-unsaturated ketones were obtained in good-to-high yield with high E-selectivity.

Nickel-catalysed chelation-assisted reductive defluorinative sulfenylation of trifluoropropionic acid derivatives.

Herein we reported a directing-group assisted strategy for nickel-catalysed reductive defluorinative sulfenylation of trifluoropropionic acid derivatives with disulfides in the presence of Zn, involving triple C-F bond cleavage. This process yielded a diverse array of carbonyl-sulfide di-substituted alkenes in moderate to good yields with good functional group tolerance. Specifically, the reactions exhibited high E-selectivity with E/Z ratio up to >99 : 1.

Stereoselective Copper-Catalyzed Olefination of Imines.

Alkenes are an important class of organic molecules found among synthetic intermediates and bioactive compounds. They are commonly synthesized through stoichiometric Wittig-type olefination of carbonyls and imines, using ylides or their equivalents. Despite the importance of Wittig-type olefination reactions, their catalytic variants remain underdeveloped. We explored the use of transition metal catalysis to form ylide equivalents from readily available starting materials. Our investigation led to a new copper-catalyzed olefination of imines with alkenyl boronate esters as coupling partners. We identified a heterobimetallic complex, obtained by hydrocupration of the alkenyl boronate esters, as the key catalytic intermediate that serves as an ylide equivalent. The high E-selectivity observed in the reaction is due to the stereoselective addition of this intermediate to an imine, followed by stereospecific anti-elimination.

Atroposelective Synthesis of Axially Chiral Styrenes by Platinum- Catalyzed Stereoselective Hydrosilylation of Internal Alkynes.

Hydrofunctionalization of alkynes is one of the most efficient ways to access axially chiral styrenes with open-chained olefins. While great advances have been achieved for 1-alkynylnaphthalen-2-ols and analogues, atroposelective hydrofunctionalization of unactivated internal alkynes lags. Herein we reported a platinum-catalyzed atroposelective hydrosilylation of unactivated internal alkynes for the first time. With monodentate TADDOL-derived phosphonite L1 used as a chiral ligand, various axially chiral styrenes were achieved in excellent enantioselectivities with high E-selectivities. Control experiments showed that the NH-arylamide groups have significant effects on both the yields and enantioselectivities and could act as directing groups. The potential utilities of the products were shown by the transformations of the amide motifs of the products.

Aminative annulation of cyano-enynyl esters leading to functionalized cyclopentenones.

A base-mediated unexpected aminative carbo-cyclization of cyano-enynyl esters, generated from Morita-Baylis-Hillman (MBH) acetates of propiolaldehydes, with secondary-amines is described. This metal-free reaction allows the synthesis of a unique cyclopentenone bearing an exocyclic double bond (cyano-olefin) with high E-selectivity in good yields. The synthetic potential of this annulation was further exemplified by the derivatization of bioactive molecules, a scale-up synthesis and synthetic transformations of the obtained cyclopentenone.

Regio- and stereoselective synthesis of bromoalkenes by homolytic hydrobromination of alkynes with hydrogen bromide

Homolytic hydrobromination of terminal and internal alkynes with a commercially available solution of hydrogen bromide in acetic acid has been investigated for regio- and stereoselective synthesis of bromoalkenes. Under an aerobic atmosphere at room temperature, the reaction of ethynylarenes with a small excess of HBr efficiently gave (2-bromoethenyl)arenes with good to high E-selectivity. (Alk-1-ynyl)arenes, or internal alkynes bearing both phenyl and alkyl groups at the sp-carbons also underwent the air-initiated hydrobromination to exhibit high Z-selectivity under kinetic conditions using a half equivalent of HBr.

E-Selective Ring-Closing Metathesis in α-Helical Stapled Peptides Using Carbocyclic α,α-Disubstituted α-Amino Acids.

We present an E-selective ring-closing metathesis reaction in α-helical stapled peptides at positions i and i + 4. The use of two chiral carbocyclic α,α-disubstituted α-amino acids, (1S,3S)-Ac5c3OAll and (1R,3S)-Ac5c3OAll, provides a high E-selectivity of a ≤59:1 E:Z ratio, while mixtures with E:Z ratios of 2.1-0.5:1 were produced with standard acyclic (S)-(4-pentenyl)alanine amino acids. A stapled octapeptide composed of (1S,3S)- and (1R,3S)-Ac5c3OAll amino acids showed a right-handed α-helical crystal structure.

Stereochemical Control via Chirality Pairing: Stereodivergent Syntheses of Enantioenriched Homoallylic Alcohols

We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α-CH2 Bpin-substituted crotylboronate. Chiral phosphoric acid (S)-A-catalyzed asymmetric allyl addition with the reagent gave Z-anti-homoallylic alcohols with excellent enantioselectivities and Z-selectivities. When the enantiomeric acid catalyst (R)-A was utilized, the stereoselectivity was completely reversed and E-anti-homoallylic alcohols were obtained with high E-selectivities and excellent enantioselectivities. By pairing the chirality of the boron reagent with the catalyst, two complementary stereoisomers of chiral homoallylic alcohols can be obtained selectively from the same boron reagent. DFT computational studies were conducted to probe the origins of the observed stereoselectivity. These reactions generate highly enantioenriched homoallylic alcohol products that are valuable for rapid construction of polyketide structural frameworks.

Asymmetric Syntheses of (E)-δ-Hydroxymethyl-anti-homoallylic Alcohols via Highly Enantio- and Stereoselective Aldehyde Allylation with α-Borylmethyl-(E)-crotylboronate.

Highly stereo- and enantioselective synthesis of (E)-δ-hydroxymethyl-anti-homoallylic alcohols is reported. Under the developed conditions, reactions between aldehydes and chiral nonracemic α-borylmethyl-(E)-crotylboronate upon oxidative workup gave δ-hydroxymethyl-anti-homoallylic alcohols with high E-selectivities and enantioselectivities.

Toward E-selective Olefin Metathesis: Computational Design and Experimental Realization of Ruthenium Thio-Indolate Catalysts

The selective transformation of 1-alkenes into E-olefins is a long-standing challenge in olefin metathesis. Density functional theory (DFT) calculations predict high E-selectivity for catalysts incorporating a bidentate, dianionic thio-indolate ligand within a RuXX’(NHC)(py)(= CHR) platform (NHC = N-heterocyclic carbene; py = pyridine). Such complexes are predicted to yield E-olefins by favoring anti-disposed substituents in the transition state expected to be rate-determining: specifically, that for cycloreversion of the metallacyclobutane intermediate. Three pyridine-stabilized catalysts Ru21a-c were synthesized, in which the thio-indolate ligand bears a H, Me, or Ph substituent at the C2 position, and the NHC ligand is the unsaturated imidazoline-2-ylidene Me2IMes (which bears N-mesityl groups and methyl groups on the C4,5 backbone). Single-crystal X-ray diffraction analysis of Ru21c confirms the ligand orientation required for E-selective metathesis, with the thio-indolate sulfur atom binding cis to the NHC, and the indolate nitrogen atom trans to the NHC. However, whereas the new complexes mediated metathetic exchange of their 2-thienylmethylidene ligand in the presence of the common metathesis substrates styrene and allylbenzene, no corresponding self-metathesis products were obtained. Only small amounts of 2-butene (73% (Z)-2-butene) were obtained in self-metathesis of propene using Ru21a. Detailed DFT analysis of this process revealed that product release is surprisingly slow, limiting the reaction rate and explaining the low metathesis activity. With the barrier to dissociation of (Z)-2-butene being lower than that of (E)-2-butene, the calculations also account for the observed Z-selectivity of Ru21a. These findings provide guidelines for catalyst redesign in pursuit of the ambitious goal of E-selective 1-alkene metathesis.Graphic abstract

Cu-Catalyzed Highly Stereoselective Syntheses of (E)-δ-Vinyl-homoallylic Alcohols.

Stereoselective synthesis of (E)-δ-vinyl-homoallylic alcohols was developed. Starting from α-vinyl allylboronate, Cu-catalyzed allylation of aldehydes or ketones forms secondary or tertiary δ-vinyl-homoallylic alcohols with high E-selectivities. It is proposed that the reaction operates under the Curtin-Hammett principle via the intermediacy of α-vinyl allylic copper species to give the alcohol products with high E-selectivities.

Organocatalyzed [2+2] Cycloaddition Reactions between Quinone Imine Ketals and Allenoates

AbstractA new cycloaddition reaction of quinone imine ketals (QIKs), which could be utilized to the construction of functionalized azaspirocyclics under mild conditions, is described. This transformation involved a [2+2] cycloaddition reaction between QIKs and allenoates catalyzed by DABCO, and then treatment with 1 N HCl in one-pot. The strategy could provide a practical route to access azetidine-fused spirohexadienones in good to excellent yields and with high E-selectivity.

Fluorine Effects for Tunable C–C and C–S Bond Cleavage in Fluoro-Julia–Kocienski Intermediates

Classical Julia–Kocienski fluoroolefination represents an indispensable platform for the construction of monofluoroalkenes. Nevertheless, its complex multistep mechanistic manifold along with the u...

Efficient synthetic method of β-fluorocinnamate by arylboronic acids and ethyl 3,3,3-trifluoropropionate under palladium-catalyzed conditions

A convenient and efficient method for synthesizing β-fluorocinnamate and derivatives is reported. Palladium (II) catalysis was employed in β-F elimination and coupling reaction of phenylboronic acid and ethyl 3,3,3-trifluoropropionate with a high yield and E-selectivity. The reaction was conducted under mild conditions and could be widely adapted to boronic acid substrates.

The regioselective annulation of alkylidenecyclopropanes by Rh(iii)-catalyzed C-H/C-C activation to access spirocyclic benzosultams.

Functionalized benzosultams are an essential class of structural motif found in various biologically active molecules. The synthesis of spirocyclic benzosultams from N-sulfonyl ketimine and alkylidenecyclopropanes (ACPs) under the catalysis of Rh(iii) has been developed. This transformation enables the formation of two C-C bonds and a double bond with high E-selectivity through C-H and C-C bond activation. This reaction proceeded smoothly with excellent regioselectivity, high efficiency, and tolerance for various functional groups.

Stereoselective Syntheses of γ,δ-Bifunctionalized Homoallylic Alcohols and Ethers via Chemoselective Allyl Addition to Aldehydes.

Stereoselective synthesis of γ,δ-bifunctionalized homoallylic alcohols and ethers via chemoselective allylation is reported. Pd-catalyzed 1,2-diboration of allenylsilane provided a novel 1,1,2-trifunctional allylation reagent. Allylboration of aldehydes with the reagent followed by in situ protection gave TES-protected homoallylic alcohols with excellent Z-selectivities. Chemoselective allylsilation with the same reagent delivered γ,δ-bifunctionalized homoallylic ethers with high E-selectivities. The bifunctionalized alkene group in the products underwent various transformations without erosion of the olefin geometry.

Nickel-Catalyzed Defluorinative Reductive Cross-Coupling Reaction of gem-Difluoroalkenes with Thiosulfonate or Selenium Sulfonate.

A nickel-catalyzed defluorinative reductive cross-coupling of gem-difluoroalkenes with thiosulfonate or selenosulfonates is described. The reaction involves the formation of thiolated or selenylated monofluoroolefins via regioselective C-F bond cleavage and C-S or C-Se bond formation and features easily available substrates, mild reaction conditions, and high E-selectivity. One of the derivatives by further cross coupling with PhMgBr exhibited an aggregation-induced emission enhancement effect.