A Highly Efficient Dimeric Manganese-Catalyzed Selective Hydroarylation of Internal Alkynes

We have developed a general and site-predictable manganese-catalyzed hydroarylation of internal alkynes in the presence of water, under an air atmosphere without the involvement of ligand. The unique catalytic feature of this reaction is highlighted by comparison with other widely used transition metal catalysts including palladium, rhodium, nickel, or copper. The simple operation, high efficiency and excellent functional group compatibility make this protocol practical for more than 90 structurally diverse internal alkynes, overcoming the influence of both electronic and steric effect of alkynes. Its exclusive regio- and chemoselectivity originates from the unique reactivity of the manganese-based catalyst towards an inherent double controlled strategy of sterically hindered propargyl alcohols without the installing of external directing groups. Its synthetic robustness and practicality have been illustrated by the concise synthesis of bervastatin, a hypolipidemic drug, and late-stage modification of complex alkynes with precise regioselectivity.     

Highly Selective Manganese(I)/Lewis Acid Cocatalyzed Direct C−H Propargylation Using Bromoallenes

A manganese(I)/Lewis acid cocatalyzed direct C?H propargylation with high selectivity has been developed. BPh₃ was discovered to not only promote the reactivity, but also enhance the selectivity. Secondary, tertiary, and even quaternary carbon centers at the propargylic position could be directly constructed. Both internal and terminal alkynes are easily accessible. The chirality was successfully transferred from an axially chiral allene to central chirality. The reactivity of the manganese catalyst in this reaction was found to be unique among transition metal catalysts.     

Cationic Cobalt(III) Catalyzed Indole Synthesis: The Regioselective Intermolecular Cyclization of N‐Nitrosoanilines and Alkynes

The unique regioselectivity and reactivity of cobalt(III) in the direct cyclization of N‐nitrosoanilines with alkynes for the expedient synthesis of N‐substituted indoles is demonstrated. In the presence of a cobalt(III) catalyst, high regioselectivity was observed when using unsymmetrical meta‐substituted N‐nitrosoanilines. Moreover, internal alkynes bearing electron‐deficient groups, which are almost unreactive in the [Cp*Rh^III]‐catalyzed system, display good reactivity in this transformation.     

Rhenium‐ and Manganese‐Catalyzed Insertion of Alkynes into a Carbon–Carbon Single Bond of Cyclic and Acyclic 1,3‐Dicarbonyl Compounds

Treatment of alkynes with cyclic and acyclic 1,3‐dicarbonyl compounds in the presence of a catalytic amount of a rhenium or manganese complex gives ring‐expanded and carbon‐chain extension products, respectively. In these reactions, alkynes insert into a non‐strained carbon–carbon single bond of 1,3‐dicarbonyl compounds. The ring‐expansion reaction is also promoted by the addition of 4‐Å molecular sieves instead of a catalytic amount of an isocyanide.     

Synergistic Manganese(I) C−H Activation Catalysis in Continuous Flow: Chemoselective Hydroarylation

Chemoselective hydroarylations were accomplished by a novel synergistic Brønsted acid/manganese(I)‐catalyzed C−H activation manifold. Thus, alkynes bearing O‐leaving groups could, for the first time, be employed for C−H alkenylations without concurrent β‐O elimination, thereby setting the stage for versatile late‐stage diversifications. Also described is the first manganese‐catalyzed C−H activation in continuous flow, thus enabling efficient hydroarylations within only 20 minutes.     

Reaction between Azidyl Radicals and Alkynes: A Straightforward Approach to NH‐1,2,3‐Triazoles

Reaction between nitrogen‐centered radicals and unsaturated C?C bonds is an effective synthetic strategy for the construction of nitrogen‐containing molecules. Although the reactions between nitrogen‐centered radicals and alkenes have been studied extensively, their counterpart reactions with alkynes are extremely rare. Herein, the first example of reactions between azidyl radicals and alkynes is described. This reaction initiated an efficient cascade reaction involving inter‐/intramolecular radical homolytic addition toward a C?C triple bond and a hydrogen‐atom transfer step to offer a straightforward approach to NH‐1,2,3‐triazoles under mild reaction conditions. Both the internal and terminal alkynes work well for this transformation and some heterocyclic substituents on alkynes are compatible. This mechanistically distinct strategy overcomes the inherent limitations associated with azide anion chemistry and represents a rare example of reactions between a nitrogen‐centered radicals and alkynes.     

Gold‐Catalyzed C(sp3)?H/C(sp)?H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans

In sharp contrast to the gold‐catalyzed reactions of alkynes/allenes with nucleophiles, gold‐catalyzed oxidative cross‐couplings and especially C H/C H cross‐coupling have been under represented. By taking advantage of the unique redox property and carbophilic π acidity of gold, this work realizes the first gold‐catalyzed direct C(sp³) H alkynylation of 1,3‐dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region‐defined approach to 3‐alkynyl polysubstituted furans.     

Organomagnesium‐Catalyzed Isomerization of Terminal Alkynes to Allenes and Internal Alkynes

Organomagnesium complexes 2 were synthesized from N,N‐dialkylamineimine ligands 1 and dibenzylmagnesium by benzylation of the imine moiety. 3‐Aryl‐1‐propynes reacted with 2 to form the corresponding tetraalkynyl complexes, which acted as catalysts for the transformation of these terminal alkynes into allenes and further to internal alkynes under mild conditions. To the best of our knowledge, this example is the first of an organomagnesium‐catalyzed isomerization of alkynes. Notably, the reactions proceeded through temporally separated autotandem catalysis, thus allowing the isolation of the allene or internal alkyne species in good yields. Mechanistic experiments suggested that the catalytically active tetraalkynyl complexes consist of a tautomeric mixture of alkynyl‐, allenyl‐, and propargylmagnesium species.     

Silver(I)‐Catalyzed Tandem 1,3‐Acyloxy Migration/Mannich‐type Addition/Elimination of the Sulfonyl Group of N‐Sulfonylhydrazone‐propargylic Esters to 5,6‐Dihydropyridazin‐4‐one Derivatives

The addition of nucleophiles to C?N bonds offers a highly efficient synthetic strategy for accessing nitrogen‐containing molecules. 1 Among the well‐developed addition reactions, such as the highly efficient Mannich reaction, various C? H bond‐activated compounds including carboxylic acid derivatives, nitroalkanes, and terminal alkynes have been applied as nucleophiles to achieve different classes of amines. 2 However, employing new nucleophiles without activated C? H bonds, such as internal alkynes and allenic esters are limited when using metal catalysts. 3 Herein, we wish to report a new addition of allenic esters to C?N bonds initiated by a silver‐catalyzed 1,3‐migration of propargylic esters.     

3 d Transition Metal‐Catalyzed Hydrogenation of Nitriles and Alkynes

Selective hydrogenation of nitriles and alkynes is crucial considering the vast applications of reduced products in industries and in the synthesis of bioactive compounds. Particularly, the late 3d transition metal catalysts (manganese, iron, cobalt, nickel and copper) have shown promising activity for the hydrogenation of nitriles to primary amines, secondary amines and imines. Similarly, semihydrogenation of alkynes to E‐ and Z‐alkenes by 3d metals is adequately successful both via the transfer hydrogenation and by using molecular hydrogen. The emergence of 3d transition metals in the selective synthesis of industrially relevant amines, imines and alkenes makes this protocol more attractive. Herein, we provide a concise overview on the late 3d transition metal‐catalyzed hydrogenation of nitriles to amines and imines as well as semihydrogenation of alkynes to alkenes.     

Gold‐Catalyzed C(sp3)H/C(sp)H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans

In sharp contrast to the gold‐catalyzed reactions of alkynes/allenes with nucleophiles, gold‐catalyzed oxidative cross‐couplings and especially C? H/C? H cross‐coupling have been under represented. By taking advantage of the unique redox property and carbophilic π acidity of gold, this work realizes the first gold‐catalyzed direct C(sp³)? H alkynylation of 1,3‐dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region‐defined approach to 3‐alkynyl polysubstituted furans.     

Regioconvergent and Enantioselective Rhodium‐Catalyzed Hydroamination of Internal and Terminal Alkynes: A Highly Flexible Access to Chiral Pyrazoles

The rhodium‐catalyzed asymmetric N‐selective coupling of pyrazole derivatives with internal and terminal alkynes features an utmost chemo‐, regio‐, and enantioselective access to enantiopure allylic pyrazoles, readily available for incorporation in small‐molecule pharmaceuticals. This methodology is distinguished by a broad substrate scope, resulting in a remarkable compatability with a variety of different functional groups. It furthermore exhibits an intriguing case of regio‐, position‐, and enantioselectivity in just one step, underscoring the sole synthesis of just one out of up to six possible products in a highly flexible approach to allylated pyrazoles by emanating from various internal and terminal alkynes.     

Cobalt‐Catalyzed Annulation of Salicylaldehydes and Alkynes to Form Chromones and 4‐Chromanones

A unique cobalt(I)–diphosphine catalytic system has been identified for the coupling of salicylaldehyde (SA) and an internal alkyne affording a dehydrogenative annulation product (chromone) or a reductive annulation product (4‐chromanone) depending on the alkyne substituents. Distinct from related rhodium(I)‐ and rhodium(III)‐catalyzed reactions of SA and alkynes, these annulation reactions feature aldehyde C?H oxidative addition of SA and subsequent hydrometalation of the C=O bond of another SA molecule as common key steps. The reductive annulation to 4‐chromanones also involves the action of Zn as a stoichiometric reductant. In addition to these mechanistic features, the Co^I catalysis described herein is complementary to the Rh^I‐ and Rh^III‐catalyzed reactions of SA and internal alkynes, particularly in the context of chromone synthesis.     

Regioselective Formation of (E)‐β‐Vinylstannanes with a Topologically Controlled Molybdenum‐Based Alkyne Hydrostannation Catalyst

The regioselective formation of (E)‐β‐vinylstannanes has been a long‐standing challenge in transition‐metal‐catalyzed alkyne hydrostannation. Herein, we report a well‐defined molybdenum‐based system featuring two encumbering m‐terphenyl isocyanides that reliably and efficiently delivers (E)‐β‐vinylstannanes from a range of terminal and internal alkynes with high regioselectivity. The system is particularly effective for aryl alkynes and can discriminate between alkyl chains of low steric hindrance in unsymmetrically substituted dialkyl alkynes. Catalytic hydrostannation with this system is also characterized by an electronic effect that leads to a decrease in regioselectivity when electron‐withdrawing groups are present on the alkyne substrate.     

Alkyne Cycloaddition to a Titanocene Oxide as a Route to Cyclopentadienyl Modification

Addition of terminal or internal alkynes to a base‐free titanocene oxide results in synthesis of the corresponding oxometallocyclobutene. With appropriate cyclopentadienyl substitution, these compounds undergo reversible C? C reductive elimination offering a unique approach to cyclopentadienyl modification.     

Trimethylsilyl‐Protected Alkynes as Selective Cross‐Coupling Partners in Titanium‐Catalyzed [2+2+1] Pyrrole Synthesis

Trimethylsilyl (TMS)‐protected alkynes served as selective alkyne cross‐coupling partners in titanium‐catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS‐protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido complexes yielded pentasubstituted 2‐TMS‐pyrroles with greater than 90 % selectivity over the other nine possible pyrrole products. The steric and electronic effects of the TMS group were both identified to play key roles in this highly selective pyrrole synthesis. This strategy provides a convenient method to synthesize multisubstituted pyrroles as well as an entry point for further pyrrole diversification through facile modification of the resulting 2‐silyl pyrrole products, as demonstrated through a short formal synthesis of the marine natural product lamellarin R.     

The Mechanism of Gold(I)‐Catalyzed Hydroalkoxylation of Alkynes: An Extensive Experimental Study

An extensive experimental study of the mechanism of gold(I)‐catalyzed hydroalkoxylation of internal alkynes has been conducted by using NMR spectroscopy. This study was focused on the organogold intermediates, observations of actual catalytic intermediates in situ, and the reaction kinetics that are involved in this reaction. Based on the experimental results, a complete mechanistic picture was established, including on‐ and off‐cycle processes that explain the role of diaurated species. We have shown that gold‐catalyzed hydroalkoxylation of internal alkynes is a reaction that requires only one gold atom for the catalytic cycle, disproving a recent hypothesis regarding the involvement of cooperative gold catalysis.     

Syngas‐Free Highly Regioselective Rhodium‐Catalyzed Transfer Hydroformylation of Alkynes to α,β‐Unsaturated Aldehydes

The hydroformylation of alkynes is a fundamental and important reaction in both academic research and industry. Conventional methods focus on the conversion of alkynes, CO, and H₂ into α,β‐unsaturated aldehydes, but they often suffer from problems associated with operation, regioselectivity, and chemoselectivity. Herein, we disclose an operationally simple, mild, and syngas‐free rhodium‐catalyzed reaction for the hydroformylation of alkynes via formyl and hydride transfer from an alkyl aldehyde. This synthetic method uses inexpensive and easy‐to‐handle n‐butyraldehyde to overcome the challenge posed by the use of syngas in traditional approaches and employs a commercially available catalyst and ligand to transform a broad range of internal alkynes, especially alkynyl‐containing complex molecules, into versatile stereodefined α,β‐unsaturated aldehydes with excellent chemo‐, regio‐, and stereoselectivity.     

A Manganese Nanosheet: New Cluster Topology and Catalysis

While the coordination chemistry of monometallic complexes and the surface characteristics of larger metal particles are well understood, preparations of molecular metallic nanoclusters remain a great challenge. Discrete planar metal clusters constitute nanoscale snapshots of cluster growth but are especially rare owing to the strong preference for three‐dimensional structures and rapid aggregation or decomposition. A simple ligand‐exchange procedure has led to the formation of a novel heteroleptic Mn₆ nanocluster that crystallized in an unprecedented flat‐chair topology and exhibited unique magnetic and catalytic properties. Magnetic susceptibility studies documented strong electronic communication between the manganese ions. Reductive activation of the molecular Mn₆ cluster enabled catalytic hydrogenations of alkenes, alkynes, and imines.     

Iron‐Carbonyl‐Catalyzed Redox‐Neutral [4+2] Annulation of N−H Imines and Internal Alkynes by C−H Bond Activation

Stoichiometric C?H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C?H transformations have not been developed. Herein, an iron‐catalyzed annulation of N?H imines and internal alkynes to furnish cis‐3,4‐dihydroisoquinolines is described, and represents the first iron‐carbonyl‐catalyzed C?H activation reaction of arenes. Remarkablely, this is also the first redox‐neutral [4+2] annulation of imines and alkynes proceeding by C?H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C?H bond activation to afford a dinuclear ferracycle and a synergetic diiron‐promoted H‐transfer to the alkyne as the turnover‐determining step.