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Journal of the American Chemical Society Aug 2022The mechanism of chiral hydrogen-bond donor (HBD) and hydrogen chloride (HCl) co-catalyzed Prins cyclizations was analyzed through a combination of experimental and...
The mechanism of chiral hydrogen-bond donor (HBD) and hydrogen chloride (HCl) co-catalyzed Prins cyclizations was analyzed through a combination of experimental and computational methods and revealed to involve an unexpected and previously unrecognized mode of alkene activation. Kinetic and spectroscopic studies support the participation of a catalytically active HCl·HBD complex that displays reduced Brønsted acidity relative to HCl alone. Nevertheless, rate acceleration relative to the HCl-catalyzed background reaction as well as high levels of enantioselectivity are achieved. This inverse Brønsted correlation is ascribed to chloride-mediated substrate activation in the rate-limiting and enantiodetermining cyclization transition state. Density functional theory (DFT) calculations, distortion-interaction analysis, and quasiclassical dynamics simulations support a stepwise mechanism in which rate acceleration and enantioselectivity are achieved through the precise positioning of the chloride anion within the active site of the chiral thiourea to enhance the nucleophilicity of the alkene and provide transition-state stabilization through local electric field effects. This mode of selective catalysis through anion positioning likely has general implications for the design of enantioselective Brønsted acid-catalyzed reactions involving π-nucleophiles.
Topics: Alkenes; Anions; Catalysis; Chlorides; Cyclization; Halogens; Hydrochloric Acid; Stereoisomerism; Thiourea
PubMed: 35994741
DOI: 10.1021/jacs.2c06688 -
Chemistry (Weinheim An Der Bergstrasse,... Jan 2023Recently, it was shown that the double Ca-H-Ca bridged calcium hydride cation dimer complex [LCaH CaL] (macrocyclic ligand L=NNNN-tetradentate Me TACD) exhibited...
Recently, it was shown that the double Ca-H-Ca bridged calcium hydride cation dimer complex [LCaH CaL] (macrocyclic ligand L=NNNN-tetradentate Me TACD) exhibited remarkable activity in catalyzing the hydrogenation of unactivated 1-alkenes as well as the H isotope exchange under mild conditions, tentatively via the terminal Ca-H bond of cation monomer LCaH . In this DFT mechanistic work, a novel substrate-dependent catalytic mechanism is disclosed involving cooperative Ca-H-Ca bridges for H isotope exchange, competitive Ca-H-Ca bridges and terminal Ca-H bonds for anti-Markovnikov addition of unactivated 1-alkenes, and terminal Ca-H bonds for Markovnikov addition of conjugation-activated styrene. THF-coordination plays a key role in favoring the anti-Markovnikov addition while strong cation-π interactions direct the Markovnikov addition to terminal Ca-H bonds.
Topics: Hydrogenation; Calcium; Alkenes; Catalysis; Cations
PubMed: 36214655
DOI: 10.1002/chem.202202602 -
Nature Chemistry Aug 2020Chiral nitriles and their derivatives are prevalent in pharmaceuticals and bioactive compounds. Enantioselective alkene hydrocyanation represents a convenient and...
Chiral nitriles and their derivatives are prevalent in pharmaceuticals and bioactive compounds. Enantioselective alkene hydrocyanation represents a convenient and efficient approach for synthesizing these molecules. However, a generally applicable method featuring a broad substrate scope and high functional group tolerance remains elusive. Here, we address this long-standing synthetic problem using dual electrocatalysis. Using this strategy, we leverage electrochemistry to seamlessly combine two canonical radical reactions-cobalt-mediated hydrogen-atom transfer and copper-promoted radical cyanation-to accomplish highly enantioselective hydrocyanation without the need for stoichiometric oxidants. We also harness electrochemistry's unique feature of precise potential control to optimize the chemoselectivity of challenging substrates. Computational analysis uncovers the origin of enantio-induction, for which the chiral catalyst imparts a combination of attractive and repulsive non-covalent interactions to direct the enantio-determining C-CN bond formation. This work demonstrates the power of electrochemistry in accessing new chemical space and providing solutions to pertinent challenges in synthetic chemistry.
Topics: Alkenes; Carbon; Catalysis; Cobalt; Copper; Density Functional Theory; Electrochemical Techniques; Hydrogen; Nitriles; Stereoisomerism
PubMed: 32601407
DOI: 10.1038/s41557-020-0469-5 -
Journal of the American Chemical Society Jan 2021Hydroamination of alkenes catalyzed by transition-metal complexes is an atom-economical method for the synthesis of amines, but reactions of unactivated alkenes remain...
Hydroamination of alkenes catalyzed by transition-metal complexes is an atom-economical method for the synthesis of amines, but reactions of unactivated alkenes remain inefficient. Additions of N-H bonds to such alkenes catalyzed by iridium, gold, and lanthanide catalysts are known, but they have required a large excess of the alkene. New mechanisms for such processes involving metals rarely used previously for hydroamination could enable these reactions to occur with greater efficiency. We report ruthenium-catalyzed intermolecular hydroaminations of a variety of unactivated terminal alkenes without the need for an excess of alkene and with 2-aminopyridine as an ammonia surrogate to give the Markovnikov addition product. Ruthenium complexes have rarely been used for hydroaminations and have not previously catalyzed such reactions with unactivated alkenes. Identification of the catalyst resting state, kinetic measurements, deuterium labeling studies, and DFT computations were conducted and, together, strongly suggest that this process occurs by a new mechanism for hydroamination occurring by oxidative amination in concert with reduction of the resulting imine.
Topics: Alkenes; Amination; Aminopyridines; Catalysis; Coordination Complexes; Density Functional Theory; Models, Chemical; Oxidation-Reduction; Ruthenium
PubMed: 33356181
DOI: 10.1021/jacs.0c11043 -
Yakugaku Zasshi : Journal of the... 2011The cycloaddition and cycloisomerization of the allene with an alkyne, alkene, or an additional allene for construction of various monocyclic and bicyclic ring systems... (Review)
Review
The cycloaddition and cycloisomerization of the allene with an alkyne, alkene, or an additional allene for construction of various monocyclic and bicyclic ring systems has been developed. The characteristic features of these methods using allene functionality instead of a simple alkene or alkyne include the reaction mode that originated from the double function as well as the high efficiency for the constructions of medium-sized rings. Furthermore, asymmetric formal synthesis of (+)-nakadomarin A and total synthesis of (+)-fawcettimine and (+)-lycoposerramine-B based on highly stereoselective Pauson-Khand reaction of alkene-alkynes were completed.
Topics: Alkadienes; Alkaloids; Alkenes; Alkynes; Carbolines; Cyclization; Heterocyclic Compounds, 3-Ring; Organic Chemistry Phenomena; Oximes; Stereoisomerism
PubMed: 21963970
DOI: 10.1248/yakushi.131.1437 -
The Journal of Organic Chemistry Nov 2017This Perspective describes the development of a family of copper(II)-catalyzed alkene difunctionalization reactions that enable stereoselective addition of amine...
This Perspective describes the development of a family of copper(II)-catalyzed alkene difunctionalization reactions that enable stereoselective addition of amine derivatives and alcohols onto pendant unactivated alkenes to provide a range of valuable saturated nitrogen and oxygen heterocycles. 2-Vinylanilines and related substrates undergo alternative oxidative amination or allylic amination pathways, and these reactions will also be discussed. The involvement of both polar and radical steps in the reaction mechanisms have been implicated. Major product formation is a function of the lowest energy pathway, which in turn is a function of structural aspects of the various reaction components.
Topics: Alcohols; Alkenes; Amines; Catalysis; Copper; Heterocyclic Compounds; Molecular Structure; Stereoisomerism
PubMed: 28910106
DOI: 10.1021/acs.joc.7b02072 -
Journal of the American Chemical Society Sep 2016The lasonolides are novel polyketides that have displayed remarkable biological activity in vitro against a variety of cancer cell lines. Herein we describe our...
The lasonolides are novel polyketides that have displayed remarkable biological activity in vitro against a variety of cancer cell lines. Herein we describe our first-generation approach to the formal synthesis of lasonolide A. The key findings from these studies ultimately allowed us to go on and complete a total synthesis of lasonolide A. The convergent approach unites two highly complex fragments utilizing a Ru-catalyzed alkene-alkyne coupling. This type of coupling typically generates branched products; however, through a detailed investigation, we are now able to demonstrate that subtle structural changes to the substrates can alter the selectivity to favor the formation of the linear product. The synthesis of the fragments features a number of atom-economical transformations which are highlighted by the discovery of an engineered enzyme to perform a dynamic kinetic reduction of a β-ketoester to establish the absolute stereochemistry of the southern tetrahydropyran ring with high levels of enantioselectivity.
Topics: Alkenes; Alkynes; Antineoplastic Agents; Catalysis; Chemistry Techniques, Synthetic; Kinetics; Macrolides; Ruthenium; Stereoisomerism
PubMed: 27548113
DOI: 10.1021/jacs.6b05127 -
Accounts of Chemical Research Sep 2021Recently, alkene dicarbofunctionalization, i.e., the powerful organic synthesis method of alkene difunctionalization with two carbon sources, emerged as a formidable...
Recently, alkene dicarbofunctionalization, i.e., the powerful organic synthesis method of alkene difunctionalization with two carbon sources, emerged as a formidable reaction with immense promise to synthesize complex molecules expeditiously from simple chemicals. This reaction is generally achieved with transition metals (TMs) through interception by carbon sources of an alkylmetal [β-H-C(sp)-[M]] species, a key intermediate prone to undergo rapid β-H elimination. Related prior reports, since Paolo Chiusoli and Catellani's work in 1982 [ 1982, 23, 4517], have used bicyclic and disubstituted terminal alkenes, wherein β-H elimination is avoided by geometric restriction or complete lack of β-H's. With reasoning that β-H-C(sp)-[M] intermediates could be rendered amenable to interception with the use of first row late TMs and formation of coordination-assisted transient metallacycles, these two strategies were implemented to address the β-H elimination problem in alkene dicarbofunctionalization reactions.Because first row late TMs catalyze C(sp)-C(sp) coupling, Cu and Ni were anticipated to impart sufficient stability to β-H-C(sp)-[M] intermediates, generated catalytically upon alkene carbometalation, for their subsequent interception by carbon electrophiles/nucleophiles in three-component reactions. Additionally, such an innate property could enable alkene difunctionalization with carbon coupling partners through entropically driven cyclization/coupling reactions. The cyclometalation concept to stabilize intractable β-H-C(sp)-[M] intermediates was hypothesized when three-component reactions were performed. The idea of cyclometalation to curtail β-H elimination is founded upon Whitesides's [ 1976, 98, 6521] observation that metallacycles undergo β-H elimination much slower than acyclic alkylmetals.In this Account, examples of alkene dicarbofunctionalization reactions demonstrate that Cu and Ni catalysts could enable cyclization/coupling of alkenylzinc reagents, alkyl halides, and aryl halides to afford complex carbo- and heterocycles. In addition, forming coordination-assisted transient nickellacycles enabled regioselective performance of three-component dicarbofunctionalization of various alkenyl compounds. In situ reaction of [M]-H with alkenes generated after β-H elimination induced an unprecedented metallacycle contraction process, in which six-membered metal-containing rings shrank to five-membered cycles, allowing creation of new carbon-carbon bonds at allylic (1,3) positions. Applications of these regioselective alkene dicarbofunctionalization reactions are discussed.
Topics: Alkenes; Catalysis; Copper; Electrochemical Techniques; Nickel; Palladium; Polycyclic Aromatic Hydrocarbons
PubMed: 34383469
DOI: 10.1021/acs.accounts.1c00329 -
Journal of the American Chemical Society Jul 2022Catalytic semihydrogenation of internal alkynes using H is an attractive atom-economical route to various alkenes, and its stereocontrol has received widespread...
Catalytic semihydrogenation of internal alkynes using H is an attractive atom-economical route to various alkenes, and its stereocontrol has received widespread attention, both in homogeneous and heterogeneous catalyses. Herein, a novel strategy is introduced, whereby a poisoning catalytic thiol is employed as a reversible inhibitor of a ruthenium catalyst, resulting in a controllable H-based semihydrogenation of internal alkynes. Both ()- and ()-alkenes were obtained efficiently and highly selectively, under very mild conditions, using a single homogeneous acridine-based ruthenium pincer catalyst. Mechanistic studies indicate that the ()-alkene is the reaction intermediate leading to the ()-alkene and that the addition of a catalytic amount of bidentate thiol impedes the / isomerization step by forming stable ruthenium thiol(ate) complexes, while still allowing the main hydrogenation reaction to proceed. Thus, the absence or presence of catalytic thiol controls the stereoselectivity of this alkyne semihydrogenation, affording either the ()-isomer as the final product or halting the reaction at the ()-intermediate. The developed system, which is also applied to the controllable isomerization of a terminal alkene, demonstrates how metal catalysis with switchable selectivity can be achieved by reversible inhibition of the catalyst with a simple auxiliary additive.
Topics: Alkenes; Alkynes; Catalysis; Molecular Structure; Ruthenium; Sulfhydryl Compounds
PubMed: 35839274
DOI: 10.1021/jacs.2c04233 -
Applied and Environmental Microbiology Feb 2010Aliphatic hydrocarbons are highly appealing targets for advanced cellulosic biofuels, as they are already predominant components of petroleum-based gasoline and diesel...
Aliphatic hydrocarbons are highly appealing targets for advanced cellulosic biofuels, as they are already predominant components of petroleum-based gasoline and diesel fuels. We have studied alkene biosynthesis in Micrococcus luteus ATCC 4698, a close relative of Sarcina lutea (now Kocuria rhizophila), which 4 decades ago was reported to biosynthesize iso- and anteiso-branched, long-chain alkenes. The underlying biochemistry and genetics of alkene biosynthesis were not elucidated in those studies. We show here that heterologous expression of a three-gene cluster from M. luteus (Mlut_13230-13250) in a fatty acid-overproducing Escherichia coli strain resulted in production of long-chain alkenes, predominantly 27:3 and 29:3 (no. carbon atoms: no. C=C bonds). Heterologous expression of Mlut_13230 (oleA) alone produced no long-chain alkenes but unsaturated aliphatic monoketones, predominantly 27:2, and in vitro studies with the purified Mlut_13230 protein and tetradecanoyl-coenzyme A (CoA) produced the same C(27) monoketone. Gas chromatography-time of flight mass spectrometry confirmed the elemental composition of all detected long-chain alkenes and monoketones (putative intermediates of alkene biosynthesis). Negative controls demonstrated that the M. luteus genes were responsible for production of these metabolites. Studies with wild-type M. luteus showed that the transcript copy number of Mlut_13230-13250 and the concentrations of 29:1 alkene isomers (the dominant alkenes produced by this strain) generally corresponded with bacterial population over time. We propose a metabolic pathway for alkene biosynthesis starting with acyl-CoA (or-ACP [acyl carrier protein]) thioesters and involving decarboxylative Claisen condensation as a key step, which we believe is catalyzed by OleA. Such activity is consistent with our data and with the homology (including the conserved Cys-His-Asn catalytic triad) of Mlut_13230 (OleA) to FabH (beta-ketoacyl-ACP synthase III), which catalyzes decarboxylative Claisen condensation during fatty acid biosynthesis.
Topics: Alkenes; Amino Acid Sequence; Bacterial Proteins; Base Sequence; Biofuels; DNA Primers; DNA, Bacterial; Escherichia coli; Fatty Acids; Gas Chromatography-Mass Spectrometry; Gene Expression; Genes, Bacterial; Metabolic Networks and Pathways; Micrococcus luteus; Models, Biological; Molecular Sequence Data; Multigene Family; Plasmids; Recombinant Proteins; Sequence Homology, Amino Acid; Spectrometry, Mass, Electrospray Ionization
PubMed: 20038703
DOI: 10.1128/AEM.02312-09