Copper-Catalyzed Synthesis of Tetrasubstituted Alkenes via Regio- and anti-Selective Addition of Silylboronates to Internal Alkynes

As a new and complementary method for the synthesis of structurally defined tetrasubstituted alkenes, a copper-catalyzed regio- and anti-selective addition of silylboronates to unsymmetric internal alkynes has been developed. A variety of unactivated alkynes can be employed with high selectivity under simple and mild conditions, and the resulting products have been further functionalized by utilizing silyl and boryl groups on the alkene.     

Catalytic activity of gold nanoclusters in intramolecular hydroamination of alkenes and alkynes with toluenesulfonamide under aerobic and basic conditions

Gold nanoclusters stabilized by a hydrophilic polymer, poly(N-vinyl-2-pyrrolidone) (Au:PVP), catalyzed the intramolecular hydroamination of toluenesulfonamides to unactivated alkenes/alkynes in EtOH under aerobic and basic conditions. The reaction proceeds via anti-addition of toluenesulfonamide to the alkenes assisted by π-activation of the gold clusters.     

Copper-catalyzed Z-selective semihydrogenation of alkynes with hydrosilane: a convenient approach to cis-alkenes

A copper catalyst generated in situ from widely available copper salt and imidazolium salt in the presence of t-BuOK showed high efficiency for the semihydrogenation of a wide range of internal and terminal alkynes to their corresponding alkenes without obvious over-reduction. Functional groups, such as hydroxyl, nitro, halides, and amino, etc. were tolerated. The Z/E ratios of the obtained alkenes were generally >99%. Finally, semireduction of bulky alkynes also went smoothly.     

Hydrocarboxylation of unactivated internal alkynes with carboxylic acids catalyzed by dinuclear palladium complexes

Dinuclear palladium complexes catalyzed addition reactions of carboxylic acid O-H bond to unactivated internal alkynes. The reaction afforded a trans-adduct selectively.     

“On water” cascade synthesis of benzopyranopyrazoles and their macrocycles

Reported herein is an intramolecular 1,3-dipolar cycloaddition strategy for rapid entry into benzopyranopyrazoles (BPP) on water medium as “open flask chemistry” approach. The in situ generation of diazo functionality in two-step sequence from the appropriate alkylated salicylaldehydes undergoes smooth [3?+?2]-cycloaddition with unactivated alkynes/alkenes furnishing benzopyranopyrazoles in good yield. This methodology was also extended for the synthesis of pyrazole incorporated macrocycles. This cascade protocol involving water medium provides an atom-economical and environment friendly approach.     

Atroposelective Synthesis of Axially Chiral Styrenes by Platinum- Catalyzed Stereoselective Hydrosilylation of Internal Alkynes

Hydrofunctionalization of alkynes is one of the most efficient ways to access axially chiral styrenes with open-chained olefins. While great advances have been achieved for 1-alkynylnaphthalen-2-ols and analogues, atroposelective hydrofunctionalization of unactivated internal alkynes lags. Herein we reported a platinum-catalyzed atroposelective hydrosilylation of unactivated internal alkynes for the first time. With monodentate TADDOL-derived phosphonite L1 used as a chiral ligand, various axially chiral styrenes were achieved in excellent enantioselectivities with high E-selectivities. Control experiments showed that the NH-arylamide groups have significant effects on both the yields and enantioselectivities and could act as directing groups. The potential utilities of the products were shown by the transformations of the amide motifs of the products.     

Regioselective and Enantioselective Copper-Catalyzed Hydroaminocarbonylation of Unactivated Alkenes and Alkynes

Given the prevalence of amide backbones in marketed pharmaceuticals and their ubiquity as critical binding units in natural peptides and proteins, it remains important to develop novel methods to construct amide bonds. We report here a general method for the anti-Markovnikov hydroaminocarbonylation of unactivated alkenes under mild conditions, using copper catalysis in combination with hydroxylamine electrophile reagents and poly(methylhydrosiloxane) (PMHS) as a cheap and environmentally friendly hydride source. The reaction tolerates a variety of functional groups and efficiently converts unactivated terminal alkenes, 1,1-disubstituted alkenes, and cyclic alkenes to the corresponding amides with exclusive anti-Markovnikov selectivity (and high enantioselectivities/diastereoselectivities). Additionally, with minimal modification of the reaction conditions, alkynes can also undergo tandem hydrogenation-hydroaminocarbonylation to alkyl amides.     

Directed Asymmetric Nickel-Catalyzed Reductive 1,2-Diarylation of Electronically Unactivated Alkenes

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.     

Air-initiated hydrosilylation of unactivated alkynes and alkenes and dehalogenation of halohydrocarbons by tris(trimethylsilyl)silane under solvent-free conditions

A highly efficient air-initiated hydrosilylation of unactivated alkynes and alkenes and dehalogenation of halohydrocarbons with tris(trimethylsilyl)silane ((TMS)₃SiH) as a reducing agent has been established under solvent-free conditions. These observations demonstrate that the potential and versatility of air to function as a competent initiator for Si-H bond activations. It can rival organic initiators and metal catalysts in its efficiency and is a superior initiating system from economic, environmentally sound and practical perspectives.     

Rhodium‐Catalyzed Intermolecular trans‐Disilylation of Alkynones with Unactivated Disilanes

Disilylation of alkynes could provide rapid entry to synthetically useful 1,2‐bissilyl‐alkenes, but is currently limited to activated disilanes reacting in an intramolecular fashion. Reported herein is an efficient rhodium(I)‐catalyzed intermolecular disilylation of a wide array of alkynones with unactivated disilanes. Importantly, this reaction produces exclusively trans‐disilylation products, selectivity that has been rarely reported. These disilylation products were transformed into interesting pentacyclic vinyl silane ethers, among other additional synthetic manipulations. Mechanistic studies uncovered that the unactivated disilanes underwent facile Si?Si activation and crossover under the reaction conditions.     

Asymmetric Enzymatic Hydration of Unactivated,Aliphatic Alkenes

The direct enantioselective addition of water to unactivated alkenes could simplify the synthesis of chiral alcohols and solve a long‐standing challenge in catalysis. Here we report that an engineered fatty acid hydratase can catalyze the asymmetric hydration of various terminal and internal alkenes. In the presence of a carboxylic acid decoy molecule for activation of the oleate hydratase from E. meningoseptica, asymmetric hydration of unactivated alkenes was achieved with up to 93 % conversion, excellent selectivity (>99 % ee, >95 % regioselectivity), and on a preparative scale.     

Asymmetric Enzymatic Hydration of Unactivated,Aliphatic Alkenes

The direct enantioselective addition of water to unactivated alkenes could simplify the synthesis of chiral alcohols and solve a long‐standing challenge in catalysis. Here we report that an engineered fatty acid hydratase can catalyze the asymmetric hydration of various terminal and internal alkenes. In the presence of a carboxylic acid decoy molecule for activation of the oleate hydratase from E. meningoseptica, asymmetric hydration of unactivated alkenes was achieved with up to 93 % conversion, excellent selectivity (>99 % ee, >95 % regioselectivity), and on a preparative scale.     

Umsetzungen von ω-alkenylsubstituierten Zirconocendichloridkomplexen mit n-Alkyllithiumverbindungen in Gegenwart von Alkenen bzw. Alkinen

The reaction of ω-alkenyl substituted zirconocene dichloride complexes with two equivalents of n-butyllithium is strongly influenced in the presence of alkenes and alkynes. Metallacyclic zirconocene complexes of novel structures are obtained. The additives alkenes and alkynes compete with the ω-alkenyl substituents and the intermediate 1-butene for the formation of a metallacyclic structure. The reaction of ω-alkenyl substituted zirconocene dichloride complexes with two equivalents of ethyllithium and n-hexyllithium gives analogous reactions and metallacycles as with n-butyllithium.     

Highly efficient gold(III)-catalyzed intermolecular hydroarylation of unactivated alkenes with arenes under mild conditions

A simple and efficient method for functionalization of electron-rich arenes and heteroarenes with unactivated alkenes by Au(III)-catalyzed intermolecular hydroarylation under mild reaction conditions was developed. This method features a short reaction time (5 h) under mild conditions and has a broad substrate scope, including electron-rich arenes and heteroarenes, terminal and internal substituted aryl alkenes, and unactivated aliphatic alkenes.     

Synthesis and equilibrium binding studies of cationic, two-coordinate gold(I) π-alkyne complexes

Reaction of a 1:1 mixture of (L)AuCl [L = P(t-Bu)₂o-biphenyl or IPr] and AgSbF₆ with internal alkynes led to isolation of the corresponding cationic, two-coordinate gold π-alkyne complexes in ≥ 90% yield. Equilibrium binding studies show that the binding affinities of alkynes to gold(I) are strongly affected by the electron density of the alkyne and to a lesser extent on the steric bulk of the alkyne. These substituent effects on alkyne binding affinity are greater than are the differences between the inherent binding affinities of alkynes and alkenes to gold(I).     

Radical Monofluoroalkylative Alkynylation of Olefins by a Docking–Migration Strategy

A radical‐mediated monofluoroalkylative alkynylation of alkenes is disclosed for the first time. The reaction demonstrates a remarkably broad substrate scope in which both activated and unactivated alkenes are suitable starting materials. The concurrent addition of an alkynyl and a monofluoroalkyl group onto an alkene proceeds through a docking–migration sequence, affording a vast array of valuable fluoroalkyl‐substituted alkynes. Many complex natural products and drug derivatives are readily functionalized, demonstrating that this method can be used for late‐stage alkynylation.     

Dichloroborane-dioxane: an exceptional reagent for the preparation of alkenyl- and alkylboronic acids

Terminal alkynes and alkenes were conveniently hydroborated to the corresponding alkenyl- and alkyldichloroboranes using dichloroborane-dioxane in dichloromethane. These dichloroboranes were hydrolyzed by water to the corresponding alkenyl- and alkylboronic acids in moderate to good yields. With terminal alkenes and alkynes boron was predominantly attached to terminal carbon. Alkynes gave exclusively trans-vinylboronic acids.     

Intermolecular Photocatalyzed Heck‐like Coupling of Unactivated Alkyl Bromides by a Dinuclear Gold Complex

A practical protocol for a photocatalyzed alkyl‐Heck‐like reaction of unactivated alkyl bromides and different alkenes promoted by dinuclear gold photoredox catalysis in the presence of an inorganic base is reported. Primary, secondary, and tertiary unactivated alkyl bromides with β‐hydrogen can be applied. Esters, aldehydes, ketones, nitriles, alcohols, heterocycles, alkynes, alkenes, ethers, and halogen moieties are all well tolerated. In addition to 1,1‐diarylalkenes, silylenolethers and enamides can also be applied, which further increases the synthetic potential of the reaction. The mild reaction conditions, broad substrate scope, and an excellent functional‐group tolerance deliver an ideal tool for synthetic chemists that can even be used for challenging late‐stage modifications of complex natural products.     

X=Y-ZH Systems as potential 1,3-dipoles : Part 13. Prototropic generation of azomethine imines from hydrazones

Hydrazones of aldehydes and ketones undergo intermolecular cycloaddition to electronegative olefins via azomethine imines, formed by a formal 1,2-prototropic shift, in low to moderate yield on heating in xylene or ethanol. In some instances the reaction is diverted to give products derived (at least formally) from an ene reaction. Similar intramolecular cycloadditions occur with unactivated terminal alkenes and alkynes.     

Brønsted acid-promoted cyclizations of siloxy alkynes with unactivated arenes, alkenes, and alkynes

In this article, we describe the development of a general concept for the development of new carbon-carbon bond-forming processes, which is based on Brønsted acid-mediated activation of a siloxy alkyne, followed by efficient interception of the resulting highly reactive ketenium ion by unactivated arenes, alkenes or alkynes. We found that trifluoromethane sulfonimide (HNTf₂) proved to be a superior promoter of these reactions compared to a range of other Brønsted acids. This finding could be attributed to a high acidity of HNTf₂ in aprotic organic solvents combined with a low nucleophilicity of the NTf₂⁻ anion. Depending on the nature of the nucleophile, the carbocyclizations proceeded either via 6-endo-dig or 5-endo-dig manifolds. In the case of 1-siloxy-1,5-diynes, the cyclizations occurred with a concomitant halide abstraction or arylation.