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Chemical Reviews Aug 2021This Review describes the development of strategies for carbonyl-olefin metathesis reactions relying on stepwise, stoichiometric, or catalytic approaches. A... (Review)
Review
This Review describes the development of strategies for carbonyl-olefin metathesis reactions relying on stepwise, stoichiometric, or catalytic approaches. A comprehensive overview of currently available methods is provided starting with Paternò-Büchi cycloadditions between carbonyls and alkenes, followed by fragmentation of the resulting oxetanes, metal alkylidene-mediated strategies, [3 + 2]-cycloaddition approaches with strained hydrazines as organocatalysts, Lewis acid-mediated and Lewis acid-catalyzed strategies relying on the formation of intermediate oxetanes, and protocols based on initial carbon-carbon bond formation between carbonyls and alkenes and subsequent Grob-fragmentations. The Review concludes with an overview of applications of these currently available methods for carbonyl-olefin metathesis in complex molecule synthesis. Over the past eight years, the field of carbonyl-olefin metathesis has grown significantly and expanded from stoichiometric reaction protocols to efficient catalytic strategies for ring-closing, ring-opening, and cross carbonyl-olefin metathesis. The aim of this Review is to capture the status quo of the field and is expected to contribute to further advancements in carbonyl-olefin metathesis in the coming years.
Topics: Alkenes; Carbon; Catalysis; Cycloaddition Reaction; Lewis Acids
PubMed: 34133136
DOI: 10.1021/acs.chemrev.0c01096 -
Angewandte Chemie (International Ed. in... Aug 2022The asymmetric hydroaminocarbonylation of olefins represents a straightforward approach for the synthesis of enantioenriched amides, but is hampered by the necessity to...
The asymmetric hydroaminocarbonylation of olefins represents a straightforward approach for the synthesis of enantioenriched amides, but is hampered by the necessity to employ CO gas, often at elevated pressures. We herein describe, as an alternative, an enantioselective hydrocarbamoylation of alkenes leveraging dual copper hydride and palladium catalysis to enable the use of readily available carbamoyl chlorides as a practical carbamoylating reagent. The protocol is applicable to various types of olefins, including alkenyl arenes, terminal alkenes, and 1,1-disubstituted alkenes. Substrates containing a diverse range of functional groups as well as heterocyclic substructures undergo functionalization to provide α- and β-chiral amides in good yields and with excellent enantioselectivities.
Topics: Alkenes; Amides; Catalysis; Molecular Structure; Palladium; Stereoisomerism
PubMed: 35657208
DOI: 10.1002/anie.202206692 -
Chemistry (Weinheim An Der Bergstrasse,... Oct 2022Herein we report a photo-mediated formal addition of carboxylic acids to activated alkenes catalyzed by a pyrimidopteridine photoredox catalyst. The decarboxylation of...
Herein we report a photo-mediated formal addition of carboxylic acids to activated alkenes catalyzed by a pyrimidopteridine photoredox catalyst. The decarboxylation of aliphatic carboxylic acids upon single-electron oxidation is countered in the presence of electron-rich alkenes and a hydroacetoxylation is observed. Mechanistic proposals have been made based on CV measurements, competitive Stern-Volmer quenching and EPR experiments. Evidence that tetra-N-substituted pyrimidopteridines function as dual photoredox and hydrogen atom transfer catalyst was supported by spectroscopic means.
Topics: Alkenes; Carboxylic Acids; Catalysis; Hydrogen; Oxidation-Reduction
PubMed: 35916156
DOI: 10.1002/chem.202201761 -
Angewandte Chemie (International Ed. in... Oct 2022Molecular machines are at the frontier of biology and chemistry. The ability to control molecular motion and emulating the movement of biological systems are major steps... (Review)
Review
Molecular machines are at the frontier of biology and chemistry. The ability to control molecular motion and emulating the movement of biological systems are major steps towards the development of responsive and adaptive materials. Amazing progress has been seen for the design of molecular machines including light-induced unidirectional rotation of overcrowded alkenes. However, the feasibility of inducing unidirectional rotation about a single bond as a result of chemical conversion has been a challenging task. In this Review, an overview of approaches towards the design, synthesis, and dynamic properties of different classes of atropisomers which can undergo controlled switching or rotation under the influence of a chemical stimulus is presented. They are categorized as molecular switches, rotors, motors, and autonomous motors according to their type of response. Furthermore, we provide a future perspective and challenges focusing on building sophisticated molecular machines.
Topics: Alkenes; Rotation; Smart Materials
PubMed: 35852813
DOI: 10.1002/anie.202206631 -
Molecules (Basel, Switzerland) Aug 2022Among the variety of sulfonamides, triflamides (CFSONHR, TfNHR) occupy a special position in organic chemistry. Triflamides are widely used as reagents, efficient... (Review)
Review
Among the variety of sulfonamides, triflamides (CFSONHR, TfNHR) occupy a special position in organic chemistry. Triflamides are widely used as reagents, efficient catalysts or additives in numerous reactions. The reasons for the widespread use of these compounds are their high NH-acidity, lipophilicity, catalytic activity and specific chemical properties. Their strong electron-withdrawing properties and low nucleophilicity, combined with their high NH-acidity, makes it possible to use triflamides in a vast variety of organic reactions. This review is devoted to the synthesis and use of -trifluoromethanesulfonyl derivatives in organic chemistry, medicine, biochemistry, catalysis and agriculture. Part of the work is a review of areas and examples of the use of bis(trifluoromethanesulfonyl)imide (triflimide, (CFSO)NH, TfNH). Being one of the strongest NH-acids, triflimide, and especially its salts, are widely used as catalysts in cycloaddition reactions, Friedel-Crafts reactions, condensation reactions, heterocyclization and many others. Triflamides act as a source of nitrogen in C-amination (sulfonamidation) reactions, the products of which are useful building blocks in organic synthesis, catalysts and ligands in metal complex catalysis, and have found applications in medicine. The addition reactions of triflamide in the presence of oxidizing agents to alkenes and dienes are considered separately.
Topics: Alkenes; Catalysis; Cyclohexanones; Molecular Structure
PubMed: 36014447
DOI: 10.3390/molecules27165201 -
Journal of the American Chemical Society Sep 2022Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled...
Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled intermolecular -cycloadditions are rare. Herein, a method to achieve photochemical cycloaddition of quinolines and alkenes is shown. Emphasis is placed on generating sterically congested products and reaction of highly substituted alkenes and allenes. In addition, the mechanistic details of the process are studied, which revealed a reversible radical addition and a selectivity-determining radical recombination. The regio- and stereochemical outcome of the reaction is also rationalized.
Topics: Alkenes; Catalysis; Cycloaddition Reaction; Molecular Structure; Quinolines
PubMed: 36106902
DOI: 10.1021/jacs.2c07726 -
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 -
Journal of the American Chemical Society Dec 2020A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the...
A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI (which cannot accomplish the same reaction).
Topics: Alkenes; Catalysis; Electron Transport; Ketones
PubMed: 33259715
DOI: 10.1021/jacs.0c11214 -
Journal of the American Chemical Society Jun 2022We report a total synthesis of the alkaloid myrioneurinol enabled by the recognition of hidden symmetry within its polycyclic structure. Our approach traces...
We report a total synthesis of the alkaloid myrioneurinol enabled by the recognition of hidden symmetry within its polycyclic structure. Our approach traces myrioneurinol's complex framework back to a symmetrical diketone precursor, a double reductive amination of which forges its central piperidine unit. By employing an inexpensive chiral amine in this key desymmetrizing event, four stereocenters of the natural product including the core quaternary stereocenter are set in an absolute sense, providing the first asymmetric entry to this target. Other noteworthy strategic maneuvers include utilizing a bicyclic alkene as a latent -1,3-bis(hydroxymethyl) synthon and a topologically controlled alkene hydrogenation. Overall, our synthesis proceeds in 18 steps and ∼1% yield from commercial materials.
Topics: Alkaloids; Alkenes; Amination; Heterocyclic Compounds, 4 or More Rings; Stereoisomerism
PubMed: 35699935
DOI: 10.1021/jacs.2c04487 -
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