Synthesis of enantiomerically enriched propargylamines by copper-catalyzed addition of alkynes to enamines

The first copper(I) bromide/Quinap-catalyzed synthesis of enantiomerically enriched propargylamines by addition of alkynes to enamines is reported. Various functionalized terminal alkynes add smoothly to Nprotected enamines to afford the corresponding amines in good to high yields and moderate to good enantiomeric excesses. The influence of the metal salt, the ligand, and the protecting group on the conversion, the reaction rate, and the stereoselectivity of the reaction are investigated. The scope of the reaction and further transformations of the resulting propargylamines (deprotection, Pauson-Khand reaction) are also described.     

Metal Nanoparticles Supported on Biomass‐Derived Hierarchical Porous Heteroatom‐Doped Carbon from Bamboo Shoots: Design,Synthesis and Applications

Heteroatom‐doped porous carbon derived from biomass have recently received increasing attention due to their unique properties such as high electrical conductivity, large specific surface area, high porosity, and easy availability, which are appealing materials for versatile applications in catalysis, energy, separation and adsorption, and life sciences as well. On the basis of our previous work in this field, we summarized in this account our recent progress on design, synthesis of metal (e. g., Pd, Co) nanoparticles supported heteroatom‐doped hierarchical porous carbon material derived from bamboo shoots and their applications for important organic transformations, including chemoselective semihydrogenation of alkynes, hydrosilylation of alkynes, cascade synthesis of benzofurans from terminal alkynes and iodophenols, selective hydrogenation of functionalized nitroarenes to form anilines, imines, and formamides. Finally, the current state and future challenges in this field are discussed. We hope this account could shed light on the rational design of novel non‐noble metal based heterogeneous catalysts derived from biomass for efficient and sustainable organic transformations.     

Highly Regioselective Sequential 1,1‐Dihydrosilylation of Terminal Aliphatic Alkynes with Primary Silanes

A regioselective double 1,1‐hydrosilylation of terminal aliphatic alkynes with primary silanes catalyzed by one cobalt catalyst has been developed. gem‐Bis(dihydrosilyl)alkanes containing four silicon‐hydrogen bonds are efficiently constructed in an atom‐economical manner. Tolerated substrates include simplest alkyne‐ethyne, a complicated drug derivative and various functionalized terminal aliphatic alkynes. Asymmetric approach using two catalysts is achieved with excellent enantioselectivities to access corresponding chiral products. The transformations of Si—H bonds into Si—C, Si—O, and Si—F bonds and the synthesis of enantioriched α‐hydroxysilane show synthetic utility.     

Regioselectivity and enantioselectivity in nickel-catalysed reductive coupling reactions of alkynes

Nickel-catalysed reductive coupling reactions of alkynes have emerged as powerful synthetic tools for the selective preparation of functionalized alkenes. One of the greatest challenges associated with these transformations is control of regioselectivity. Recent work from our laboratory has provided an improved understanding of several of the factors governing regioselectivity in these reactions, and related studies have revealed that the reaction mechanism can differ substantially depending on the ligand employed. A discussion of stereoselective transformations and novel applications of nickel catalysis in coupling reactions of alkynes is also included.     

Organic transformations on sigma-aryl organometallic complexes

This work reviews recent developments in the field of organic transformations on sigma-aryl organometallic complexes. The general notion that M--C sigma bonds are kinetically labile, highly reactive, and incompatible with typical reaction conditions met in organic synthesis has limited the use of these synthetic strategies thus far. However, organic transformations on metal-bound sigma-aryl fragments are being used more and more by chemists in both industry and academia. In this Review, emphasis is put on the synthetic methods applied in this field up to now. The simplicity and generally good yields of these methods are very attractive for the construction of functionalized organometallic building blocks that are potentially useful as photochemical molecular devices, biosensors and -conjugates, or molecular switches. Thus, this Review has been tailored for a broader audience with the aim of encouraging the application of these strategies.     

Silver(I)‐Catalyzed Hydroazidation of Ethynyl Carbinols: Synthesis of 2‐Azidoallyl Alcohols

The hydroazidation of alkynes is the most straightforward pathway to synthetically useful vinyl azides. However, a general hydroazidation of alkynes remains elusive. Herein, a chemo‐ and regioselective transformation of ethynyl carbinols into vinyl azides is described. This reaction produces a wide variety of 2‐azidoallyl alcohols with high efficiency and in good to excellent yields. These compounds constitute a new class of densely functionalized synthetic intermediates. Their synthetic potential has been demonstrated by further transformations into NH aziridines. The mechanistic aspects of the reaction will attract the attention of chemists working on alkyne chemistry and silver catalysis. The findings that are described in this paper represent significant advances in the regioselective hydroelementation of alkynes and open a new reaction manifold for exploitation.     

Synthesis of 1,1‐Diborylalkenes through a Brønsted Base Catalyzed Reaction between Terminal Alkynes and Bis(pinacolato)diboron

A method for the synthesis of 1,1‐diborylalkenes through a Brønsted base catalyzed reaction between terminal alkynes and bis(pinacolato)diboron has been developed. The procedure allows direct synthesis of functionalized 1,1‐diborylalkenes from various terminal alkynes including propiolates, propiolamides, and 2‐ethynylazoles.     

Copper catalyzed regioselective coupling of allylic halides and alkynes promoted by weak inorganic bases

Allylic halides and terminal alkynes couple under CuI catalysis in DMSO or DMF solution. In most cases, sodium carbonate or bicarbonate is sufficient to promote the reaction; less reactive alkynes require catalytic amounts of DBU. Bifunctional alkynes and halides can be reacted selectively according to the stoichiometry used. Trimethylsilyl, hydroxyl, ester and halide groups are tolerated in the alkyne. Most halides react without allylic rearrangement. The method is suitable for the synthesis of functionalized enynes.     

Sonogashira cross-coupling in iodo-containing 2-aryloxazolines

Aryloxazolines represents potential building blocks in the synthesis of precursors of ESIPT-active sensors. Here we describe the Sonogashira cross-coupling reaction between iodo-containing 2-aryloxazolines and terminal alkynes. The reaction occurs under mild conditions and a range of alkynes was employed leading the formation of a small library of functionalized aryloxazolines.     

Ruthenium-Induced Cyclization of Heteroatom-Functionalized Alkynes: Progress,Challenges and Perspectives

Metal-induced cyclization of functionalized alkynes represents one of the most general approaches to prepare organic heterocycles. Although Ru^II centers are well-established to promote alkyne to vinylidene rearrangements and many Ru^II-mediated alkyne cyclizations have been rationalized to be the results of post-vinylidene transformations, recent discoveries indicate that Ru^II centers can serve as electrophiles and induce alkyne cyclizations without vinylidene intermediacy. In this Minireview, an overview of the Ru^II-induced cyclization of heteroatom-functionalized alkynes in the last decade is provided, with an emphasis on the discoveries and validations of the unconventional “non-vinylidene-involving” pathways.     

Annulation of internal alkynes through a hydroamination/aza-Heck reaction sequence for the regioselective synthesis of indoles

Highly regioselective annulation reactions of unsymmetrically substituted alkynes by primary 2-bromo or 2-chloroanilines are achieved with an efficient one-pot protocol, which relies on a regioselective TiCl₄-catalyzed intermolecular hydroamination and a subsequent palladium-catalyzed intramolecular aza-Heck reaction. The use of unsymmetrically substituted alkynes in this strategy enables the synthesis of diversely functionalized indoles, with a regioselectivity that is complementary to the one obtained when employing Larock's annulation reaction.     

Copper‐Catalyzed Borocarbonylative Coupling of Internal Alkynes with Unactivated Alkyl Halides: Modular Synthesis of Tetrasubstituted β‐Borylenones

Reported is a general procedure to synthesize tetrasubstituted enones, which are borylated in the β‐position, using a copper‐catalyzed four‐component coupling reaction of simple chemical feedstocks: internal alkynes, alkyl halides, bis(pinacolato)diboron (B₂pin₂), and CO. A broad scope of highly functionalized β‐borylated enones, a largely unknown class of organic compounds, can be accessed efficiently using this method. The synthesis of all‐carbon tetrasubstituted enones was realized by employing the β‐borylated enone unit, without purification, in a Suzuki–Miyaura coupling. The utility of the method was further demonstrated by various transformations, including halogenation, oxidation, and protodeboration, of the corresponding reduced oxaborole species to provide densely substituted allylic alcohol and ketone products.     

The [2+2] Cycloaddition‐Retroelectrocyclization (CA‐RE) Click Reaction: Facile Access to Molecular and Polymeric Push‐Pull Chromophores

The [2+2] cycloaddition‐retroelectrocyclization (CA‐RE) reaction between electron‐rich alkynes and electron‐deficient alkenes is an efficient procedure to create nonplanar donor–acceptor (D‐A) chromophores in both molecular and polymeric platforms. They feature attractive properties including intramolecular charge‐transfer (ICT) bands, nonlinear optical properties, and redox activities for use in next‐generation electronic and optoelectronic devices. This Review summarizes the development of the CA‐RE reaction, starting from the initial reports with organometallic compounds to the extension to purely organic systems. The structural requirements for rapid, high‐yielding transformations with true click chemistry character are illustrated by examples that include the broad alkyne and alkene substitution modes. The CA‐RE click reaction has been successfully applied to polymer synthesis, with the resulting polymeric push‐pull chromophores finding many interesting applications.     

Library-friendly synthesis of fluorinated ketones through functionalized hydration of alkynes and investigation of the reaction mechanism

A library-friendly synthesis of α-substituted-α-fluoroketones through functionalized hydration of alkynes in one pot under mild conditions is reported. The ready availability of alkynes and organoboronic acids makes this reaction quite attractive. We also studied the key intermediate—a fluorinated cationic gold species—using in situ NMR spectroscopy and ESI-high resolution mass spectrometry.     

A novel approach towards the preparation of functionalized alkyne derivatives via ArS-mediated AdE reaction of cobaltcarbonyl complexed conjugated enynes

A unified protocol of three-component coupling of arenesulfenyl chloride, dicobalthexacarbonyl complexed conjugated enynes, and nucleophiles of π-donor type is applied for the synthesis of functionalized alkynes.     

Synthesis of polyfunctional allenes by successive copper-mediated substitutions

Readily available 1,1-dichloro-2-alkynes are versatile starting materials for the synthesis of polyfunctionalized allenes. They can be prepared from commercially available terminal alkynes in a two-step procedure. The Cu-mediated reaction of several 1,1-propargylic derivatives with functionalized alkyl, benzylic, or allylic zinc reagents proceeds exclusively with S(N)2' selectivity and allows a rapid and efficient synthesis of functionalized chloroallenes. These chloroallenes undergo a novel Cu(I) -catalyzed substitution reaction with functionalized arylmagnesium reagents with excellent S(N)2 selectivity to give trisubstituted polyfunctionalized allenes. The functional group tolerance is excellent and functionalities, such as cyano, keto, ester, phosphate, trifluoromethyl, and halogens, are well tolerated.     

Ring-Opening Lithiation–Borylation of 2-Trifluoromethyl Oxirane: A Route to Versatile Tertiary Trifluoromethyl Boronic Esters

Stereogenic trifluoromethyl-substituted carbon centers are highly sought-after moieties in pharmaceutical and agrochemical discovery. Here, we show that lithiation–borylation reactions of 2-trifluoromethyl oxirane give densely functionalized and highly versatile trifluoromethyl-substituted α-tertiary boronic esters. The intermediate boronate complexes undergo the desired 1,2-rearrangement of the carbon-based group with complete retentive stereospecificity, a process that was only observed in non-polar solvents in the presence of TESOTf. Although the trifluoromethyl group adversely affects subsequent transformations of the α-boryl group, Zweifel olefinations provide trifluoromethyl-bearing quaternary stereocenters substituted with alkenes, alkynes and ketones.     

Synthesis of new quinuclidine derivatives via Pd-mediated cross-coupling and cross-benzannulation reactions

New functionalized quinuclidines were prepared via palladium-catalyzed addition reactions of terminal alkynes (donors) to internal alkynes (acceptors). The enantiopure terminal alkynes were derivatives of quincoridine and quincorine, two semi-natural Cinchona alkaloids. The processes exhibited high chemoselectivity and excellent diastereoselectivity, the E-enynes being obtained as single products in almost all cases. The synthesis of new tetra and pentasubstituted benzene derivatives in good yields by [2+2+2] benzannulation of the diynes, obtained by the palladium-catalyzed homodimerization of 10,11-didehydro quincoridine and 10,11-didehydro quincorine, with terminal alkynes and in fair yield by [4+2] benzannulation of an enyne derivative of 10,11-didehydro quincoridine with 2,4-hexane-diyne are reported.     

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.     

Cyclic Hypervalent Iodine Reagents for Atom‐Transfer Reactions: Beyond Trifluoromethylation

Hypervalent iodine compounds are privileged reagents in organic synthesis because of their exceptional reactivity. Among these compounds, cyclic derivatives stand apart because of their enhanced stability. They have been widely used as oxidants, but their potential for functional‐group transfer has only begun to be investigated recently. The use of benziodoxol(on)es for trifluoromethylation (Togni's reagents) is already widely recognized, but other transformations have also attracted strong interest recently. In this Review, the development in the area since 2011 will be presented. After a short summary of synthetic methods to prepare benziodoxol(on)e reagents, their use to construct carbon–heteroatom and carbon–carbon bonds will be presented. In particular, the introduction of alkynes by using ethynylbenziodoxol(on)e (EBX) reagents has been highly successful. Breakthroughs in the introduction of alkoxy, azido, difluoromethyl, and cyano groups will also be described.