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Nature Communications Dec 2022Vicinal diamines are privileged synthetic motifs in chemistry due to their prevalence and powerful applications in bioactive molecules, pharmaceuticals, and ligand...
Vicinal diamines are privileged synthetic motifs in chemistry due to their prevalence and powerful applications in bioactive molecules, pharmaceuticals, and ligand design for transition metals. With organic diazides being regarded as modular precursors to vicinal diamines, enormous efforts have been devoted to developing efficient strategies to access organic diazide generated from olefins, themselves common feedstock chemicals. However, state-of-the-art methods for alkene diazidation rely on the usage of corrosive and expensive oxidants or complicated electrochemical setups, significantly limiting the substrate tolerance and practicality of these methods on large scale. Toward overcoming these limitations, here we show a photochemical diazidation of alkenes via iron-mediated ligand-to-metal charge transfer (LMCT) and radical ligand transfer (RLT). Leveraging the merger of these two reaction manifolds, we utilize a stable, earth abundant, and inexpensive iron salt to function as both radical initiator and terminator. Mild conditions, broad alkene scope and amenability to continuous-flow chemistry rendering the transformation photocatalytic were demonstrated. Preliminary mechanistic studies support the radical nature of the cooperative process in the photochemical diazidation, revealing this approach to be a powerful means of olefin difunctionalization.
Topics: Alkenes; Ligands; Catalysis; Iron; Diamines
PubMed: 36564375
DOI: 10.1038/s41467-022-35560-3 -
Angewandte Chemie (International Ed. in... Apr 2022We herein report the preparation of solid and salt-stabilized silylzinc pivalates from the corresponding silyllithium reagents via transmetalation with Zn(OPiv) . These...
We herein report the preparation of solid and salt-stabilized silylzinc pivalates from the corresponding silyllithium reagents via transmetalation with Zn(OPiv) . These resulting organosilylzinc pivalates show enhanced air and moisture stability and unique reactivity in the silylative difunctionalization of alkenes. Thus, a practical chelation-assisted nickel-catalyzed regioselective alkyl and benzylsilylation of alkenes has been developed, which provides an easy method to access alkyl silanes with broad substrate scope and wide functional group compatibility. Kinetic experiments highlight that the OPiv-coordination is crucial to improve the reactivity of silylzinc pivalates. Furthermore, late-stage functionalizations of druglike molecules and versatile modifications of the products illustrate the synthetical utility of this protocol.
Topics: Alkenes; Catalysis; Nickel
PubMed: 35179292
DOI: 10.1002/anie.202202379 -
Journal of the American Chemical Society Dec 2022The amide is one of the most prevalent functional groups in all of pharmaceuticals, and for this reason, reactions that introduce the amide moiety are of particular...
The amide is one of the most prevalent functional groups in all of pharmaceuticals, and for this reason, reactions that introduce the amide moiety are of particular value. Intermolecular hydroamidation of alkenes remains an underexplored method for the synthesis of amide-containing compounds. The majority of hydroamidation procedures exhibit Markovnikov regioselectivity, while current methods for anti-Markovnikov hydroamidation are somewhat limited to activated alkene substrates or radical processes. Herein, we report a general method for the intermolecular anti-Markovnikov hydroamidation of unactivated alkenes under mild conditions, utilizing Rh(III) catalysis in conjunction with dioxazolone amidating reagents and isopropanol as an environmentally friendly hydride source. The reaction tolerates a wide range of functional groups and efficiently converts electron-deficient alkenes, styrenes, and 1,1-disubstituted alkenes, in addition to unactivated alkenes, to their corresponding linear amides. Mechanistic studies reveal a reversible rhodium hydride migratory insertion step, leading to exquisite selectivity for the anti-Markovnikov product.
Topics: Rhodium; Alkenes; Indicators and Reagents; Molecular Structure; Catalysis; Amides
PubMed: 36453859
DOI: 10.1021/jacs.2c10552 -
Journal of the American Chemical Society Aug 2022The concurrent installation of C-C and C-N bonds across alkene frameworks represents a powerful tool to prepare motifs that are ubiquitous in pharmaceuticals and...
The concurrent installation of C-C and C-N bonds across alkene frameworks represents a powerful tool to prepare motifs that are ubiquitous in pharmaceuticals and bioactive compounds. To construct such prevalent bonds, most alkene difunctionalization methods demand the use of precious metals or activated alkenes. We report a metal-free, photochemically mediated imino-alkylation of electronically diverse alkenes to install both alkyl and iminyl groups in a highly efficient manner. The exceptionally mild reaction conditions, broad substrate scope, excellent functional group tolerance, and facile one-pot reaction protocol highlight the utility of this method to prepare privileged motifs from readily available alkene and acid feedstocks. One key and striking feature of this transformation is that an electrophilic trifluoromethyl radical is equally efficient with both electron-deficient and electron-rich alkenes. Additionally, dispersion-corrected density functional theory (DFT) and empirical investigations provide detailed mechanistic insight into this reaction.
Topics: Alkenes; Alkylation; Catalysis; Esters; Oximes
PubMed: 35984388
DOI: 10.1021/jacs.2c07170 -
Angewandte Chemie (International Ed. in... Feb 2019Pd -catalyzed Mizoroki-Heck reactions traditionally exhibit poor reactivity with polysubstituted, unbiased alkenes. Intermolecular reactions with simple, all-carbon...
Pd -catalyzed Mizoroki-Heck reactions traditionally exhibit poor reactivity with polysubstituted, unbiased alkenes. Intermolecular reactions with simple, all-carbon tetrasubstituted alkenes are unprecedented. Herein we report that pendant carboxylic acids, combined with bulky monophospine ligands on palladium, can direct the arylation of tri- and tetrasubstituted olefins. Quaternary carbons are established at high Fsp attached-ring junctures and the carboxylate directing group can be removed after coupling. Carboxylate directivity prevents over-arylation of the new, less substituted alkene, which can be diversified in subsequent reactions.
Topics: Alkenes; Carboxylic Acids; Catalysis; Molecular Structure; Palladium; Potassium
PubMed: 30602064
DOI: 10.1002/anie.201813233 -
Journal of the American Chemical Society Dec 2020Electrochemistry grants direct access to reactive intermediates (radicals and ions) in a controlled fashion toward selective organic transformations. This feature has...
Electrochemistry grants direct access to reactive intermediates (radicals and ions) in a controlled fashion toward selective organic transformations. This feature has been demonstrated in a variety of alkene functionalization reactions, most of which proceed via an anodic oxidation pathway. In this report, we further expand the scope of electrochemistry to the reductive functionalization of alkenes. In particular, the strategic choice of reagents and reaction conditions enabled a radical-polar crossover pathway wherein two distinct electrophiles can be added across an alkene in a highly chemo- and regioselective fashion. Specifically, we used this strategy in the intermolecular carboformylation, -Markovnikov hydroalkylation, and carbocarboxylation of alkenes-reactions with rare precedents in the literature-by means of the electroreductive generation of alkyl radical and carbanion intermediates. These reactions employ readily available starting materials (alkyl halides, alkenes, etc.) and simple, transition-metal-free conditions and display broad substrate scope and good tolerance of functional groups. A uniform protocol can be used to achieve all three transformations by simply altering the reaction medium. This development provides a new avenue for constructing Csp-Csp bonds.
Topics: Alkenes; Bromides; Electrochemical Techniques; Oxidation-Reduction; Quantum Theory; Stereoisomerism
PubMed: 33231074
DOI: 10.1021/jacs.0c08532 -
Angewandte Chemie (International Ed. in... Apr 2022Catalytic enantioselective functionalization of unactivated 1,1-disubstituted alkenes is challenging due to the difficulty to discriminate the enantiotopic faces....
Catalytic enantioselective functionalization of unactivated 1,1-disubstituted alkenes is challenging due to the difficulty to discriminate the enantiotopic faces. Enantioselective hydrofunctionalization of unactivated 1,1-disubstituted alkenes with tunable Markovnikov and anti-Markovnikov selectivity remains elusive. We report here an amide-directed, regiodivergent and enantioselective hydroalkynylation of unactivated alkenes. The regioselectivity can be readily tuned by the choice of a proper ligand. Catalytic alkynylations occurred with tunable Markovnikov and anti-Markovnikov selectivity to afford products containing acyclic tertiary or quaternary stereocenters β to an amide. Combining a sequence of alkene isomerization and regioselective hydroalkynylation, we further realized an iridium-catalyzed formal asymmetric conjugated alkynylation of β,β-disubstituted α,β-unsaturated amides. Computational studies suggest that the regioselectivity is dictated by the ligand structures.
Topics: Alkenes; Amides; Catalysis; Iridium; Ligands; Stereoisomerism
PubMed: 35178846
DOI: 10.1002/anie.202201099 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2003The pi complexes first formed as essential intermediates from alkenes, alkynes, and allenes with bromine have been investigated in different solvents by UV-spectroscopy... (Review)
Review
The pi complexes first formed as essential intermediates from alkenes, alkynes, and allenes with bromine have been investigated in different solvents by UV-spectroscopy in combination with stopped-flow techniques allowing the determination of the equilibrium constants, K(f). Using alkenes with sterically protected double bonds, such as di-tert-butylstilbene and tetraneopentylethylene, the reaction stops at the stage of the 1:1 and 1:2 pi complex of the alkene with bromine as persistent species in 1,2-dichlorethane as solvent. Calculations by state-of-art ab initio and DFT methods reproduces the experimentally determined thermodynamic values quite well, and reveal the preferred structures and nature of both complexes for ethene, ethyne, and allene. Consideration of the entropy term reveals that complexes are stabilized in solution owing to reduction of the entropy loss by restricted translations and rotation. According to calculations these species are Mulliken-outer-type complexes with no or little charge transfer from bromine to the double or triple bond, respectively. The 1:2 complex has a close structural relationship to the bromonium- or bromirenium ion, which is the subsequent intermediate on the reaction coordinate. Steric influences show a strong effect on the K(f) value, which can be explained by the polarizibility of the parent system. Addition-elimination often occurs. In bromination of adamantylidenadamantane and its derivatives the reaction stops at the stage of the bromonium ion. The effect of various polar groups situated in equatorial homoallyl positions on the stability of corresponding pi complex and bromonium ion has been studied in this series.
Topics: Alkadienes; Alkenes; Alkynes; Halogens; Hydrocarbons, Acyclic; Isomerism; Models, Molecular
PubMed: 12596140
DOI: 10.1002/chem.200390097 -
Angewandte Chemie (International Ed. in... Jun 2020Metal-coordinating directing groups have seen extensive use in the field of transition-metal-catalyzed alkene functionalization; however, their waste-generating...
Metal-coordinating directing groups have seen extensive use in the field of transition-metal-catalyzed alkene functionalization; however, their waste-generating installation and removal steps limit the efficiency and practicality of reactions that rely on their use. Inspired by developments in asymmetric organocatalysis, where reactions rely on reversible covalent interactions between an organic substrate and a chiral mediator, we have developed a transient-directing-group approach to reductive Heck hydroarylation of alkenyl benzaldehyde substrates that proceeds under mild conditions. Highly stereoselective migratory insertion is facilitated by in situ formation of an imine from catalytic amounts of a commercially available amino acid additive. Computational studies reveal an unusual mode of enantioinduction by the remote chiral center in the transient directing group.
Topics: Alkenes; Benzaldehydes; Catalysis; Stereoisomerism; Temperature; Transition Elements
PubMed: 32196876
DOI: 10.1002/anie.202001069 -
Chemistry (Weinheim An Der Bergstrasse,... Feb 2022Catalytic transfer hydrodeuteration of unactivated alkenes is challenging because of the requirement that chemically similar hydrogen and deuterium undergo selective...
Catalytic transfer hydrodeuteration of unactivated alkenes is challenging because of the requirement that chemically similar hydrogen and deuterium undergo selective insertion across a π-bond. We now report a highly regioselective catalytic transfer hydrodeuteration of unactivated terminal alkenes across a variety of heteroatom- or heterocycle-containing substrates. The base-metal-catalyzed reaction is also demonstrated on two complex natural products. Reaction studies indicate modular conditions that can also be extended to perform either an alkene transfer hydrogenation or transfer deuteration.
Topics: Alkenes; Catalysis; Copper; Hydrogenation; Molecular Structure
PubMed: 34882859
DOI: 10.1002/chem.202104340