Reduction Of Alkynes Research Articles

Efforts toward the Total Synthesis of Thuggacin A.

Thuggacin A (1) is a 17-membered-ring-polyketide antibiotic compound with excellent antituberculosis activity. The total synthesis of thuggacin A has not yet been reported so far. Herein, we disclose our efforts toward the convergent total synthesis of thuggacin A. The key synthetic features include our own one-pot cascade thiazole formation, Evans syn-aldol, Mukaiyama asymmetric aldol reaction, organosilicon-promoted selective alkyne reduction, Shiina macrolactonization, and a nucleophilic ring-opening of epoxide with alkyne to assemble the main framework of thuggacin A. The enantioselective synthesis of trimethylsilyl ethoxymethyl (SEM) derived thuggacin A analogue 2 was achieved in 18 longest linear steps with 2.0% overall yield, and the bioassay of 2 exhibited moderate antituberculosis activity with minimum inhibitory concentration (MIC) of 320 μg/mL.

Inexpensive and mild hydrogenation condition: Raney Ni-catalyzed reduction of alkenes and alkynes using Et3SiH at ambient temperature

The Raney Ni-catalyzed hydrogenation of alkenes and alkynes has been developed. Et3SiH was chosen as the reductant. Substrates with various substituents were reduced at ambient temperature, affording good to excellent yields. No pressure reactor, heating, or inert atmosphere is required and the catalyst can be removed/recycled by simple filtration.

Electronic Delocalization and σ-Aromaticity in Heterometallic Cluster with Multiple Thorium-Palladium Bonds.

Research on metal-metal bonds involving f-block actinides, such as thorium, lags far behind the well-studied metal-metal bonds of d-block transition metals. The complexes with Th-TM bonds are extremely rare; all previously identified examples have only a single Th-TM bond with the Th center at an invariably +IV oxidation state. Herein, we report a series of Th2Pdn (n = 2, 3, and 6) clusters (complexes 3, 4, and 7) with multiple Th(III)-Pd bonds. Theoretical studies reveal that the Th2Pdn unit allows electronic delocalization and σ aromaticity, leading to unexpected closed-shell singlet structures for these Th(III) species. This electronic delocalization is evident in the highest occupied molecular orbital of Th(III) complexes and facilitates a 2e reduction of alkyne by complex 7, resulting in the formation of 8. Complexes 7 and 8 are distinctive in featuring a Th2Pd6 core with six and eight Th-Pd bonds, respectively, making them the largest known d-f heterometallic clusters exhibiting metal-metal bonding.

Mechanochemical Birch Reduction with Low Reactive Alkaline Earth Metals.

Birch reduction and similar dissolved metal-type transformations hold significant importance in the organic synthesis toolbox. Historically, the field has been dominated by alkali metal reductants. In this study, we report that largely neglected, low-reactive alkaline earth metals can become powerful and affordable reductants when used in a ball mill under essentially solvent-free conditions, in the presence of ethylenediamine and THF as liquid additives. Calcium can reduce both electron-deficient and electron-rich arenes, with yields of products similar to those obtained with lithium metal. Magnesium reveals enhanced reducing power, enabling the reduction of benzoic acids while keeping electron-rich aromatic moieties intact and allows for chemoselective transformations. The developed mechanochemical approach uses readily available and safer-to-handle metals, operates under air and ambient temperature conditions, and can be used for gram-scale preparations. Finally, we demonstrate that the developed conditions can be used for other dissolved metal-type reductive transformations, including reductive amination, deoxygenation, dehalogenation, alkene and alkyne reductions.

Mechanochemical Birch Reduction with Low Reactive Alkaline Earth Metals

AbstractBirch reduction and similar dissolved metal‐type transformations hold significant importance in the organic synthesis toolbox. Historically, the field has been dominated by alkali metal reductants. In this study, we report that largely neglected, low‐reactive alkaline earth metals can become powerful and affordable reductants when used in a ball mill under essentially solvent‐free conditions, in the presence of ethylenediamine and THF as liquid additives. Calcium can reduce both electron‐deficient and electron‐rich arenes, with yields of products similar to those obtained with lithium metal. Magnesium reveals enhanced reducing power, enabling the reduction of benzoic acids while keeping electron‐rich aromatic moieties intact and allows for chemoselective transformations. The developed mechanochemical approach uses readily available and safer‐to‐handle metals, operates under air and ambient temperature conditions, and can be used for gram‐scale preparations. Finally, we demonstrate that the developed conditions can be used for other dissolved metal‐type reductive transformations, including reductive amination, deoxygenation, dehalogenation, alkene and alkyne reductions.

Electrocatalytic Semihydrogenation of Terminal Alkynes Using Ligand-Based Transfer of Protons and Electrons.

Alkyne semihydrogenation is a broadly important transformation in chemical synthesis. Here, we introduce an electrochemical method for the selective semihydrogenation of terminal alkynes using a dihydrazonopyrrole Ni complex capable of storing an H2 equivalent (2H+ + 2e-) on the ligand backbone. This method is chemoselective for the semihydrogenation of terminal alkynes over internal alkynes or alkenes. Mechanistic studies reveal that the transformation is concerted and Z-selective. Calculations support a ligand-based hydrogen-atom transfer pathway instead of a hydride mechanism, which is commonly invoked for transition metal hydrogenation catalysts. The synthesis of the proposed intermediates demonstrates that the catalytic mechanism proceeds through a reduced formal Ni(I) species. The high yields for terminal alkene products without over-reduction or oligomerization are among the best reported for any homogeneous catalyst. Furthermore, the metal-ligand cooperative hydrogen transfer enabled with this system directs the efficient flow of H atom equivalents toward alkyne reduction rather than hydrogen evolution, providing a blueprint for applying similar strategies toward a wide range of electroreductive transformations.

Mild and Selective Hydrogenation of Unsaturated Compounds Using Mn/Water as a Hydrogen Gas Source.

A mild and highly selective reduction of alkenes and alkynes using Mn/water is described. The highly controlled generation of H2 allows the selective reduction of these compounds in the presence of labile functional groups under mild and environmentally acceptable conditions.

Cationic Rhodium Diphosphane Complexes as Efficient Catalysts for the Semi‐Hydrogenation of Dehydroisophytol

AbstractThe selective reduction of terminal alkynes to alkenes was investigated using common cationic diphosphane rhodium complexes of the type [Rh(PP)(diolefin)]X (PP=diphosphane, X=anion). The effectiveness of the catalyst was demonstrated in the semi‐hydrogenation of dehydroisophytol (DIP), an industrial produced intermediate of vitamin E. The present study highlights the high activity and good selectivity of this simple catalytic system. However, deactivation increases at higher DIP concentrations. Several strategies to circumvent the deactivation are presented.

EHydrogenation: Hydrogen‐free Electrochemical Hydrogenation

AbstractHydrogenation reactions are staple transformations commonly used across scientific fields to synthesise pharmaceuticals, natural products, and various functional materials. However, the vast majority of these reactions require the use of a toxic and costly catalyst leading to unpractical, hazardous and often functionally limited conditions. Herein, we report a new, general, practical, efficient, mild and high‐yielding hydrogen‐free electrochemical method for the reduction of alkene, alkyne, nitro and azido groups. Finally, this method has been applied to deuterium labelling.

EHydrogenation: Hydrogen-free Electrochemical Hydrogenation.

Hydrogenation reactions are staple transformations commonly used across scientific fields to synthesise pharmaceuticals, natural products, and various functional materials. However, the vast majority of these reactions require the use of a toxic and costly catalyst leading to unpractical, hazardous and often functionally limited conditions. Herein, we report a new, general, practical, efficient, mild and high-yielding hydrogen-free electrochemical method for the reduction of alkene, alkyne, nitro and azido groups. Finally, this method has been applied to deuterium labelling.

Reduction of disubstituted acetylenes under conditions of organotantalum and organoniobium synthesis

Reduction of disubstituted acetylenes under conditions of organotantalum and organoniobium synthesis

Synthesis of the sex pheromone components of fall armyworm (Spodoptera frugiperda)

Main components of the sex pheromone of fall armyworm (Spodoptera frugiperda) contain (Z)-7-dodecen-1-yl acetate (Z7-12:OAc), (Z)-9-tetradecen-1-yl acetate (Z9-14:OAc), and (Z)-11-hexadecen-1-yl acetate (Z11-16:OAc) were succesfully synthesized with a total yield over 48% via 5 steps. The starting materials for the synthesis of pheromones were diols (1,6-hexandiol; 1,8-octandiol; 10-decandiol) and 1-alkyne (1-hexyne and 1-octyne). This purpose of the study was the extension of the carbon chain by alkylation of a terminal alkyne using the n-BuLi agent and the reduction of alkyne to (Z)-alkene using the Pd(dba)2/KOH/DMF catalyst without using the molecular hydrogen. In this case, KOH/DMF was the hydrogen source system to eliminate an alkyne to (Z)-alkene and give over 90% yield with the (Z)-configuration selectivity (> 99%). The extension reaction of the carbon chain was carried out at -78oC for 30 min. and then at room temperature for 2 h., the alkyne was reduced to (Z)-alkene at 145oC for 6 hours. After the deprotection of the alcohol group by ultrasound without further purification, the acetylation was performed with an efficiency over 84%. The (Z)-alkene configuration of the obtained compounds, examined by 1H NMR spectra, showed that the coupling constants were Jcis = 11,0 Hz and Jcis = 10,5 Hz for Z11-16:OAc, respectively; but Jcis = 11,0 Hz for the Z7-12:OAc and Z9-14:OAc. This preparation process of the (Z)-alkene pheromones opened an opportunity to control fall armyworms without polluting the environment in Vietnam.

Stereo- and Regioselective Synthesis of (E,E)-Dienes: Evolution from the Transition-Metal-Catalyzed Cross-Coupling to Titanium Alkoxide-Based Alkyne–Alkyne Reductive Coupling

AbstractThe pursuit of step- and atom-economy in natural product and complex molecule syntheses continuously inspires the development of synthetic methodologies. In this context, to enable efficient synthesis of (E,E)-dienes as common structural subunits in natural products, our lab has established robust protocols based on modified Negishi cross-couplings and evolved them to more concise titanium-mediated alkyne–alkyne reductive coupling. In this review, we summarize the natural product synthesis driven methodology development and their applications in the total synthesis of complex molecules, focusing on the studies from our laboratory.1 Introduction2 Transition-Metal-Catalyzed Cross-Coupling in Natural Product Synthesis2.1 Synthesis of Branched Trisubstituted Conjugated Dienes by Negishi Coupling2.2 Stereo- and Regiocontrolled Synthesis of Branched Trisubstituted Conjugated Dienes by Modified Negishi Coupling2.3 Enantioselective Total Synthesis of Reveromycin B by Drouet & Theodorakis2.4 Enantioselective Synthesis of the Protein Phosphatase Inhibitor (–)-Motuporin by Hu & Panek2.5 Total Synthesis of (–)-Callystatin A by Langille & Panek2.6 Total Synthesis of Brevisamide by Lee & Panek3 Titanium Alkoxide-Mediated Reductive Coupling in Natural Product Synthesis3.1 Titanium Alkoxide-Mediated Alkyne–Alkyne Reductive Coupling3.2 Total Synthesis of Callystatin A by Reichard & Micalizio3.3 Total Synthesis of (–)-Virginiamycin M2 by Wu & Panek3.4 Total Synthesis of Nuclear Factor of Activated T-Cells-68 (NFAT-68) by Cai & Panek3.5 Titanium Alkoxide-Based Regioselective Alkyne–Alkyne Reductive Coupling Mediated by in situ Generated Arylamidate4 Summary

Temperature-Controlled Chemoselective Synthesis of Multisubstituted 4-Alkynyl/trans 4-Alkenyl Coumarins.

A temperature-controlled facile synthesis of multisubstituted 4-alkynyl/trans 4-alkenyl coumarins with a metal salt cascade approach is reported. H2O serves both as a nucleophile and hydrogen source. The presence of metal salt facilitates the reduction of alkyne. The present protocol bypasses the structural shortcomings of the existing Sonogashira and Heck coupling reactions. In addition, the obtained 2,3-disubstituted coumarins are readily transformed into 2,3-disubstituted dihydrocoumarins, which serve as important building blocks in organic transformations.

Stereoselective Reduction of Alkynes: Synthesis of 4-Organoselenyl Quinolines.

This study describes the reaction of 2-amino arylalkynyl ketones with organoselenolates to form (Z)-vinyl selenides, which lead to 4-organoselenyl quinolines via an intramolecular condensation. Using the optimized reaction conditions, the generality of this cyclization was studied with various arylalkynyl ketones and diorganyl diselenides. The study of the reaction mechanisms led to the isolation and identification of a vinyl selenide, which was the key intermediate for this cyclization. To expand the structural diversity and to demonstrate the applicability of the 4-organoselenyl quinolines prepared, we studied their application as substrates in the cleavage of the carbon-selenium bond using n-butyllithium followed by the capture of the lithium intermediate by electrophiles and Suzuki and Sonogashira cross-coupling reactions.

Distinct Reactivity Modes of a Copper Hydride Enabled by an Intramolecular Lewis Acid.

We disclose a 1,4,7-triazacyclononane (TACN) ligand featuring an appended boron Lewis acid. Metalation with Cu(I) affords a series of tetrahedral complexes including a boron-capped cuprous hydride. We demonstrate distinct reactivity modes as a function of chemical oxidation: hydride transfer to CO2 in the copper(I) state and oxidant-induced H2 evolution as well as alkyne reduction.

Unified Electrochemical Synthetic Strategy for [2 + 2 + 2] Cyclotrimerizations: Construction of 1,3,5- and 1,2,4-Trisubstituted Benzenes from Ni(I)-Mediated Reduction of Alkynes

Unified Electrochemical Synthetic Strategy for [2 + 2 + 2] Cyclotrimerizations: Construction of 1,3,5- and 1,2,4-Trisubstituted Benzenes from Ni(I)-Mediated Reduction of Alkynes

Rigidity-Activity Relationships of bisQPC Scaffolds against Pathogenic Bacteria.

Biscationic quaternary phosphonium compounds (bisQPCs) represent a promising class of antimicrobials, displaying potent activity against both Gram-negative and Gram-positive bacteria. In this study, we explored the effects of structural rigidity on the antimicrobial activity of QPC structures bearing a two-carbon linker between phosphonium groups, testing against a panel of six bacteria, including multiple strains harboring known disinfectant resistance mechanisms. Using simple alkylation reactions, 21 novel compounds were prepared, although alkene isomerization as well as an alkyne reduction were observed during the respective syntheses. The resulting bisQPC compounds showed strong biological activity, but were hampered by diminished solubility of their iodide salts. One compound (P2P-10,10 I) showed single-digit micromolar activity against the entire panel of bacteria. Overall, intriguing biological activity was observed, with less rigid structures displaying better efficacy against Gram-negative strains and more rigid structures demonstrating slightly increased efficacy against S. aureus strains.

Nano gold coupled black titania composites with enhanced surface plasma properties for efficient photocatalytic alkyne reduction

A nanocomposite design is proven for achieving efficient, selective, and robust alkyne semi-hydrogenation through photocatalytic process, which avoids the use of additional heat sources and traditional toxic Pb additives. The gold nanoparticles (Au NPs) coupled crystalline-core@amorphous-shell structured and wide-spectrum-responsive black titania (BT) with enhanced surface plasma properties holds the key to attaining high activity and selectivity. The hot electron injection from conductive BT to the surface of plasmonic Au NPs stimulated by solar light activates the alkynes and directly participates in the selective conversion to overcome the energy barriers. The engineered Au/BT gives a record turnover frequency of 1012 h−1 and excellent stability for phenylacetylene semi-hydrogenation under solar light irradiation and shows broad scope toward selective hydrogenation of alkynes containing various substituent groups of –CH3, –OH, and –Cl. The kinetic isotope effects and in situ infrared spectroscopy analysis for structure-activity relationship and reaction mechanism of phenylacetylene reduction were also demonstrated.

Application of bioorganometallic B12 in green organic synthesis.

Bioorganometallic structure found in coenzyme B12 is a key component in B12-dependent enzymatic reactions in natural enzymes. Cleavage of a cobalt-carbon bond in organometallic B12 compound provide reactive intermediate for molecular transformations. Application of the bioorganometallic B12 in organic synthesis have been developed using natural vitamin B12 as well as synthetic vitamin B12 derivatives as a bioinspired catalyst in organic solvent. Vitamin B12 derivatives composed of corrinoid structure should form stable organometallic compound having a cobalt-carbon bond. Using the unique property of the organometallic vitamin B12 derivatives, various catalytic reactions have been developed in synthetic organic chemistry. The dual catalytic system of vitamin B12 derivatives and photocatalyst, such as Ru(II) polypyridyl complex or titanium oxide, could construct light-driven molecular transformations. The B12-dependent enzymes mimic reactions, such as the dechlorination of organic halides and the radical mediated isomerization reactions, catalytically proceed in the dual catalyst system. Electroorganic syntheses mediated by the vitamin B12 derivatives have been developed as green molecular transformations. The redox active vitamin B12 derivatives shows a unique catalysis in the electroorganic synthesis, such as alkene and alkyne reductions.