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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 -
Nature Chemistry Jun 2022Many therapeutic agents are macrocyclic trisubstituted alkenes but preparation of these structures is typically inefficient and non-selective. A possible solution would...
Many therapeutic agents are macrocyclic trisubstituted alkenes but preparation of these structures is typically inefficient and non-selective. A possible solution would entail catalytic macrocyclic ring-closing metathesis, but these transformations require high catalyst loading, conformationally rigid precursors and are often low yielding and/or non-stereoselective. Here we introduce a ring-closing metathesis strategy for synthesis of trisubstituted macrocyclic olefins in either stereoisomeric form, regardless of the level of entropic assistance. The goal was achieved by addressing several unexpected difficulties, including complications arising from pre-ring-closing metathesis alkene isomerization. The power of the method is highlighted by two examples. The first is the near-complete reversal of substrate-controlled selectivity in the formation of a macrolactam related to an antifungal natural product. The other is a late-stage stereoselective generation of an E-trisubstituted alkene in a 24-membered ring, en route to the cytotoxic natural product dolabelide C.
Topics: Alkenes; Biological Products; Catalysis; Cyclization; Stereoisomerism
PubMed: 35577918
DOI: 10.1038/s41557-022-00935-y -
Molecules (Basel, Switzerland) Apr 2020The interest of organoboron chemistry in organic synthesis is growing, together with the development of new and versatile polyborated reagents. Here, the preparation of... (Review)
Review
The interest of organoboron chemistry in organic synthesis is growing, together with the development of new and versatile polyborated reagents. Here, the preparation of 1,1,1-tri(boryl)alkanes, 1,2,3-tri(boryl)alkanes, 1,1,2-tri(boryl)alkanes, as well as 1,1,2-tri(boryl)alkenes as suitable and accessible polyborated systems is demonstrated as being easily applied in the construction of new carbon-carbon and carbon-heteroatom bonds. Synthetic procedures and limitations have been collected to demonstrate the powerful strategies to construct selective molecules, taking advantages of the easy transformation of carbon-boron bond in multiple functionalities, under the total control of chemo- and stereoselectivity.
Topics: Alkenes; Chemistry Techniques, Synthetic; Models, Chemical; Stereoisomerism
PubMed: 32290330
DOI: 10.3390/molecules25071758 -
Chemical Reviews Dec 2021Asymmetric hydroalkoxylation of alkenes constitutes a redox-neutral and 100% atom-economical strategy toward enantioenriched oxygenated building blocks from readily... (Review)
Review
Asymmetric hydroalkoxylation of alkenes constitutes a redox-neutral and 100% atom-economical strategy toward enantioenriched oxygenated building blocks from readily available starting materials. Despite their great potential, catalytic enantioselective additions of alcohols across a C-C multiple bond are particularly underdeveloped, especially compared to other hydrofunctionalization methods such as hydroamination. However, driven by some recent innovations, e.g., asymmetric MHAT methods, asymmetric photocatalytic methods, and the development of extremely strong chiral Brønsted acids, there has been a gratifying surge of reports in this burgeoning field. The goal of this review is to survey the growing landscape of asymmetric hydroalkoxylation by highlighting exciting new advances, deconstructing mechanistic underpinnings, and drawing insight from related asymmetric hydroacyloxylation and hydration. A deep appreciation of the underlying principles informs an understanding of the various selectivity parameters and activation modes in the realm of asymmetric alkene hydrofunctionalization while simultaneously evoking the outstanding challenges to the field moving forward. Overall, we aim to lay a foundation for cross-fertilization among various catalytic fields and spur further innovation in asymmetric hydroalkoxylations of C-C multiple bonds.
Topics: Acids; Alkenes; Catalysis; Oxidation-Reduction; Stereoisomerism
PubMed: 34860509
DOI: 10.1021/acs.chemrev.1c00620 -
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 -
Angewandte Chemie (International Ed. in... Jan 2023A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized...
A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized products. The process allows E,Z-mixed dienes to be processed to a single E-alkene isomer, and leverages an inexpensive and operationally convenient I(I)/I(III) catalysis platform. The first example of catalytic 1,4-difluorination is disclosed and subsequently evolved to enable 1,4-hetero-difunctionalization, which allows δ-fluoro-alcohol and amine derivatives to be forged in a single operation. The protocol is compatible with a variety of nucleophiles including fluoride, nitriles, carboxylic acids, alcohols and even water thereby allowing highly functionalized products, with a stereocenter bearing both C(sp )-F and C(sp )-CF groups, to be generated rapidly. Scalability (up to 3 mmol), and facile post-reaction modifications are demonstrated to underscore the utility of the method in expanding organofluorine chemical space.
Topics: Polyenes; Isomerism; Alkenes; Catalysis; Alcohols
PubMed: 36345795
DOI: 10.1002/anie.202214906 -
Molecules (Basel, Switzerland) Dec 2018Diboron reagents have been traditionally regarded as "Lewis acids", which can react with simple Lewis base to create a significant nucleophilic character in one of boryl... (Review)
Review
Diboron reagents have been traditionally regarded as "Lewis acids", which can react with simple Lewis base to create a significant nucleophilic character in one of boryl moieties. In particular, bis(pinacolato)diboron (B₂pin₂) reacts with simple Lewis bases, such as -heterocyclic carbenes (NHCs), phosphines and alkoxides. This review focuses on the application of trivalent nucleophilic boryl synthon in the selective preparation of organoboron compounds, mainly through metal-free catalytic diboration and the β-boration reactions of alkynes and alkenes.
Topics: Alkenes; Alkynes; Boron Compounds; Catalysis; Hydrocarbons; Metals
PubMed: 30597884
DOI: 10.3390/molecules24010101 -
Nature Aug 2021Aziridines-three-membered nitrogen-containing cyclic molecules-are important synthetic targets. Their substantial ring strain and resultant proclivity towards...
Aziridines-three-membered nitrogen-containing cyclic molecules-are important synthetic targets. Their substantial ring strain and resultant proclivity towards ring-opening reactions makes them versatile precursors of diverse amine products, and, in some cases, the aziridine functional group itself imbues important biological (for example, anti-tumour) activity. Transformation of ubiquitous alkenes into aziridines is an attractive synthetic strategy, but is typically accomplished using electrophilic nitrogen sources rather than widely available amine nucleophiles. Here we show that unactivated alkenes can be electrochemically transformed into a metastable, dicationic intermediate that undergoes aziridination with primary amines under basic conditions. This new approach expands the scope of readily accessible N-alkyl aziridine products relative to those obtained through existing state-of-the-art methods. A key strategic advantage of this approach is that oxidative alkene activation is decoupled from the aziridination step, enabling a wide range of commercially available but oxidatively sensitive amines to act as coupling partners for this strain-inducing transformation. More broadly, our work lays the foundations for a diverse array of difunctionalization reactions using this dication pool approach.
Topics: Alkenes; Amines; Aziridines; Chemistry Techniques, Synthetic; Electrochemistry; Oxidation-Reduction; Thermodynamics
PubMed: 34157720
DOI: 10.1038/s41586-021-03717-7 -
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 -
Nature Chemistry Jun 2022The controlled isomerization and functionalization of alkenes is a cornerstone achievement in organometallic catalysis that is now widely used throughout industry. In...
The controlled isomerization and functionalization of alkenes is a cornerstone achievement in organometallic catalysis that is now widely used throughout industry. In particular, the addition of CO and H to an alkene, also known as the oxo-process, is used in the production of linear aldehydes from crude alkene feedstocks. In these catalytic reactions, isomerization is governed by thermodynamics, giving rise to functionalization at the most stable alkylmetal species. Despite the ubiquitous industrial applications of tandem alkene isomerization/functionalization reactions, selective functionalization at internal positions has remained largely unexplored. Here we report that the simple W(0) precatalyst W(CO) catalyses the isomerization of alkenes to unactivated internal positions and subsequent hydrocarbonylation with CO. The six- to seven-coordinate geometry changes that are characteristic of the W(0)/W(II) redox cycle and the conformationally flexible directing group are key factors in allowing isomerization to take place over multiple positions and stop at a defined unactivated internal site that is primed for in situ functionalization.
Topics: Alkenes; Catalysis; Isomerism; Oxidation-Reduction; Tungsten
PubMed: 35655006
DOI: 10.1038/s41557-022-00951-y