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Chemistry, An Asian Journal Jun 2022Alkene amino(hetero)arylation presents a highly efficient and straightforward strategy for direct installation of amino groups and heteroaryl rings across a double bond... (Review)
Review
Alkene amino(hetero)arylation presents a highly efficient and straightforward strategy for direct installation of amino groups and heteroaryl rings across a double bond simultaneously. An extensive array of practical transformations has been developed via alkene difunctionalization approach to access a broad range of medicinally valuable (hetero)arylethylamine motifs. This review presents recent progress in 1,2-amino(hetero)arylation of alkenes organized in three different modes. First, intramolecular transformations employing C, N-tethered alkenes will be introduced. Next, two-component reactions will be discussed with different combination of precursors, N-tethered alkenes and external aryl precursor, C-tethered alkenes and external amine precursor, or C, N-tethered reagents, and alkenes. Last, three-component intermolecular amino(hetero)arylation reactions will be covered.
Topics: Alkenes; Amination; Amines; Catalysis
PubMed: 35460596
DOI: 10.1002/asia.202200215 -
Angewandte Chemie (International Ed. in... Dec 2022A direct strategy for the difunctionalization of alkenes, with acylation occurring at the more substituted alkene position, would be attractive for complex ketone...
A direct strategy for the difunctionalization of alkenes, with acylation occurring at the more substituted alkene position, would be attractive for complex ketone synthesis. We report herein a reaction driven by a single photocatalyst that enables α-acylation in this way with the introduction of a fluoromethyl, alkyl, sulfonyl or thioether group at the β-position of the alkene with high chemo- and regioselectivity under extremely mild conditions. Crucial to the success of this method are rate differences in the kinetics of radical generation through single-electron transfer (SET) between different radical precursors and the excited photocatalyst (PC*). Thus, the β-position of the alkene is first occupied by the group derived from the radical precursor that can be generated most readily, and α-keto acids could be used as an electrophilic reagent for the α-acylation of alkenes.
Topics: Alkenes; Catalysis; Acylation; Indicators and Reagents
PubMed: 36202761
DOI: 10.1002/anie.202208831 -
Molecules (Basel, Switzerland) Dec 2020Popular and readily available alkenes and alkynes are good substrates for the preparation of functionalized molecules through radical and/or ionic addition reactions.... (Review)
Review
Popular and readily available alkenes and alkynes are good substrates for the preparation of functionalized molecules through radical and/or ionic addition reactions. Difunctionalization is a topic of current interest due to its high efficiency, substrate versatility, and operational simplicity. Presented in this article are radical addition followed by oxidation and nucleophilic addition reactions for difunctionalization of alkenes or alkynes. The difunctionalization could be accomplished through 1,2-addition (vicinal) and 1,n-addition (distal or remote) if H-atom or group-transfer is involved in the reaction process. A wide range of moieties, such as alkyl (R), perfluoroalkyl (R), aryl (Ar), hydroxy (OH), alkoxy (OR), acetatic (OCR), halogenic (X), amino (NR), azido (N), cyano (CN), as well as sulfur- and phosphorous-containing groups can be incorporated through the difunctionalization reactions. Radicals generated from peroxides or single electron transfer (SET) agents, under photoredox or electrochemical reactions are employed for the reactions.
Topics: Alkenes; Alkynes; Free Radicals; Oxidation-Reduction; Peroxides
PubMed: 33379397
DOI: 10.3390/molecules26010105 -
Chemistry (Weinheim An Der Bergstrasse,... Nov 2022Fluorine incorporation into organic molecules is often beneficial to their absorption, distribution, metabolism, and excretion (ADME) properties or bioactivity. As a... (Review)
Review
Fluorine incorporation into organic molecules is often beneficial to their absorption, distribution, metabolism, and excretion (ADME) properties or bioactivity. As a consequence, organofluorine compounds have become quite common amongst drugs and agrochemicals, and their preparation is a highly important topic in both synthetic organic chemistry and pharmaceutical chemistry. One of the newly developed methods for accessing organofluorine compounds is Pd-catalyzed arylfluorination of alkenes. It is an olefin difunctionalization process that simultaneously introduces an aryl group and a fluorine atom into an alkene framework. This review provides a concise overview of this powerful and versatile method.
Topics: Palladium; Alkenes; Fluorine; Catalysis
PubMed: 35943039
DOI: 10.1002/chem.202202076 -
Angewandte Chemie (International Ed. in... Dec 2015Although recent years have witnessed significant advances in the development of catalytic, enantioselective halofunctionalizations of alkenes, the related dihalogenation... (Review)
Review
Although recent years have witnessed significant advances in the development of catalytic, enantioselective halofunctionalizations of alkenes, the related dihalogenation of olefins to afford enantioenriched vicinal dihalide products remains comparatively underdeveloped. However, the growing number of complex natural products bearing halogen atoms at stereogenic centers has underscored this critical gap in the synthetic chemist's arsenal. This Review highlights the selectivity challenges inherent in the design of enantioselective dihalogenation processes, and formulates a mechanism-based classification of alkene dihalogenations, including those that may circumvent the "classical" haliranium (or alkene-dihalogen π-complex) intermediates. A variety of metal and main group halide reagents that have been used for the dichlorination or dibromination of alkenes are discussed, and the proposed mechanisms of these transformations are critically evaluated.
Topics: Alkenes; Catalysis; Halogens; Stereoisomerism
PubMed: 26630449
DOI: 10.1002/anie.201507152 -
Chemical Reviews Jan 2022Geometrical → alkene isomerization is intimately entwined in the historical fabric of organic photochemistry and is enjoying a renaissance (Roth et al. ,... (Review)
Review
Geometrical → alkene isomerization is intimately entwined in the historical fabric of organic photochemistry and is enjoying a renaissance (Roth et al. , 1193-1207). This is a consequence of the fundamental stereochemical importance of -alkenes, juxtaposed with frustrations in thermal reactivity that are rooted in microscopic reversibility. Accessing excited state reactivity paradigms allow this latter obstacle to be circumnavigated by exploiting subtle differences in the photophysical behavior of the substrate and product chromophores: this provides a molecular basis for directionality. While direct irradiation is operationally simple, photosensitization via selective energy transfer enables augmentation of the alkene repertoire to include substrates that are not directly excited by photons. Through sustained innovation, an impressive portfolio of tailored small molecule catalysts with a range of triplet energies are now widely available to facilitate -thermodynamic and thermo-neutral isomerization reactions to generate -alkene fragments. This review is intended to serve as a practical guide covering the geometric isomerization of alkenes enabled by energy transfer catalysis from 2000 to 2020, and as a logical sequel to the excellent treatment by Dugave and Demange (. , 2475-2532). The mechanistic foundations underpinning isomerization selectivity are discussed together with induction models and rationales to explain the counterintuitive directionality of these processes in which very small energy differences distinguish substrate from product. Implications for subsequent stereospecific transformations, application in total synthesis, regioselective polyene isomerization, and spatiotemporal control of pre-existing alkene configuration in a broader sense are discussed.
Topics: Alkenes; Catalysis; Energy Transfer; Isomerism; Photochemistry
PubMed: 34449198
DOI: 10.1021/acs.chemrev.1c00324 -
Journal of the American Chemical Society Jun 2022A visible-light-mediated, enantioselective approach to axially chiral alkenes is described. Starting from a racemic mixture, a major alkene enantiomer is formed due to...
A visible-light-mediated, enantioselective approach to axially chiral alkenes is described. Starting from a racemic mixture, a major alkene enantiomer is formed due to selective triplet energy transfer from a catalytically active chiral sensitizer. A catalyst loading of 2 mol % was sufficient to guarantee consistently high enantioselectivities and yields (16 examples, 51%-quant., 81-96% ). NMR studies and DFT computations revealed that triplet energy transfer is more rapid within the substrate-catalyst complex of the minor alkene enantiomer. Since this enantiomer is continuously racemized, the major enantiomer is enriched in the photostationary state.
Topics: Alkenes; Catalysis; Energy Transfer; Light; Stereoisomerism
PubMed: 35658423
DOI: 10.1021/jacs.2c02511 -
Nature Chemistry Feb 2022In the absence of directing auxiliaries, the catalytic addition of carbogenic groups to unactivated alkenes with control of regioselectivity remains an ongoing challenge...
In the absence of directing auxiliaries, the catalytic addition of carbogenic groups to unactivated alkenes with control of regioselectivity remains an ongoing challenge in organic chemistry. Here we describe a directing-group-free, nickel-catalysed strategy that couples a broad array of unactivated and activated olefins with aryl-substituted triflates and organometallic nucleophiles to afford diarylation adducts in either regioisomeric form, in up to 93% yield and >98% site selectivity. By switching the reagents involved, the present strategy may be extended to other classes of dicarbofunctionalization reactions. Mechanistic and computational investigations offer insights into the origin of the observed regiochemical outcome and the utility of the method is highlighted through the concise syntheses of biologically active molecules. The catalyst control principles reported are expected to advance efforts towards the development of general site-selective alkene functionalizations, removing the requirement for neighbouring activating groups.
Topics: Alkenes; Catalysis; Indicators and Reagents; Nickel
PubMed: 34903858
DOI: 10.1038/s41557-021-00836-6 -
Organic Letters Nov 2022A series of novel trifluoromethylative thiolations of alkene are realized by using visible light as a driving force and iron salts as a catalyst, and...
A series of novel trifluoromethylative thiolations of alkene are realized by using visible light as a driving force and iron salts as a catalyst, and 1,2-bis(trifluoromethylated) compounds could be obtained in moderate to good yields. These multicomponent protocols proceed in an atom-economical way with a broad substrate scope. Biologically active chemicals can also be tolerated to provide desired products, suggesting that the catalytic protocol could be viable for late-stage modification in pharmaceutical discovery. At last, flow-setup synthesis of the desired product is successfully applied on a gram scale, indicating the synthetic power of these reactions in industrial applications.
Topics: Alkenes; Iron; Catalysis; Light
PubMed: 36286580
DOI: 10.1021/acs.orglett.2c03348 -
Chemistry (Weinheim An Der Bergstrasse,... 2008Silylmetalation of alkenes is challenging due to the low reactivity of the substrates. In contrast, carbometalation of alkenes has been realized through several...
Silylmetalation of alkenes is challenging due to the low reactivity of the substrates. In contrast, carbometalation of alkenes has been realized through several innovative methods, including activation of the reagent and the substrate. A similar approach could be applicable to silylmetalation of alkenes, and we have recently developed a bimetal activation method using zincate complexes for this purpose. Here, we describe how the silylzincation of alkenes was achieved. First, the strategies for carbometalation of alkenes will be summarized. Secondly, the history and development of silylzincation chemistry are briefly described. Then the details of our findings related to two types of silylzincation of alkenes, as well as recent progress in mechanistic studies, are discussed. The key point in the silylzincation of alkenes proved to be the bimetal activation of the substrate. One metal (copper or titanium) strongly coordinates and activates the alkene moiety, and the other metal (zinc) acts as the electron acceptor from the silyl group by way of the alkene moiety. This dual activation concept is expected to be applicable to other combinations of metals, as well as to new types of reactions.
Topics: Alkenes; Catalysis; Copper; Organometallic Compounds; Styrene; Zinc
PubMed: 18034443
DOI: 10.1002/chem.200701118