金催化1,6-二炔选择性构筑3-吡喃酮衍生物的研究

… In conclusion, a new gold-catalyzed cyclization reaction of disubstituted 1,6-diynes has been developed, providing Z-cyclopentylidene derivatives. Mono- and diterminal 1,6-diynes …

Summary Gold(I)-catalyzed highly enantioselective [4 + 2] cycloadditions of 1,6-enynes were achieved by utilizing chiral bifunctional P,N ligand. A wide range of 1,6-enynes were converted to enantioenriched 5-6-6-fused tricyclic compounds under mild reaction condition (up to 99% ee). This chiral gold(I) complex was also employed in the first desymmetric cycloadditions of 1,6-diynes bearing single ester group at the tether (up to 93% ee), where 5-exo-dig pathway predominates over 6-endo-dig pathway. DFT calculations and control experiments were performed to rationalize the origin of precise stereocontrol. It implies that hydrogen bonding interaction between the ester group of substrates and the secondary amine of the chiral P,N ligands plays a pivotal role in the control of enantioselectivity. The utilities of the current reaction were demonstrated by scale-up experiment and derivatizations.

… In summary, we developed an unprecedented gold-catalyzed cyclization/carbonylation cascade reaction of 1,6-diynes (Scheme 6), which provides straightforward access for the …

We disclose herein a Au(I)-catalyzed domino cyclization of 1,6-diynes incorporated with indole. This protocol enabled the diastereoselective buildup of indole-fused azabicyclo[3.3.1]nonanes from linear precursors. Density functional theory calculations showed that the reaction proceeded via an unprecedented cascade dearomatization/rearomatization/dearomatization process. Independent gradient model analysis revealed that a noncovalent attractive interaction between the distal alkyne and the Au/proximal complex was responsible for the chemoselectivity of the first spirocyclization step.

… reaction pattern for gold-catalyzed cycloisomerizations of 1,6-diynes containing an ynamide propargyl ester moiety that provides an attractive route to a diverse-substituted 3-acyloxy-1,4…

Transition‐metal‐catalyzed CH activation has emerged as a powerful tool for constructing diverse heterocycles and efficiently increasing molecular complexity in a single operation. Compared with the well‐studied diyne [2 + 2 + 2] cycloaddition, diyne‐involved CH functionalization represents a promising evolution of this field. The inherent reactivity of diynes enables sequential participation of both alkyne units in relay processes, a feature central to their utility. Recent years have witnessed remarkable progress in diyne‐based CH functionalization/cyclization with exquisite site ‐ and chemoselectivity, spanning substrate control strategies, catalysis design, reaction development, mechanistic insights, substrate scope, and practical applications. Organized by the type of diyne and reaction patterns, this review highlights recent advances in transition‐metal‐catalyzed tandem CH functionalization/cyclization reactions of 1,6‐diynes, 1,5‐diynes, 1,4‐diynes, and other tethered diyne substrates, with a focus on the assembly of 1,3‐dienes, polycyclic aromatic hydrocarbons, π ‐conjugated polymers, polyheterocycles, and related structures. Notably, this review focuses exclusively on reactions where both alkyne units participate in tandem processes, excluding cases where only one alkyne acts as a π ‐coupling reagent.

… Investigations on gold-catalyzed tandem cyclization reactions of 1,6-diynes, tethered to nucleophilic functionalities such as amine, carboxylic acid, amide, and sulfonamide, are reported…

Gold is currently one of the most used metals in organometallic catalysis. The ability of gold to activate unsaturated groups in different modes, together with its tolerance to a wide range of functional groups and reaction conditions, turns gold-based complexes into efficient and highly sought after catalysts. Natural products and relevant compounds with biological and pharmaceutical activity are often characterized by complex molecular structures. (Cyclo)isomerization reactions are often a useful strategy for the generation of this molecular complexity from synthetically accessible reactants. In this review, we collect the most recent contributions in which gold(I)- and/or gold(III)-catalysts mediate intramolecular (cyclo)isomerization transformations of unsaturated species, which commonly feature allene or alkyne motifs, and organize them depending on the substrate and the reaction type.

… We have recently developed hydrative cyclization of 1,6-diynes to produce 3,5-substituted conjugate cyclohexenone ring systems using (PPh 3 )AuMe/acid as a catalyst. However, the …

… six-membered heterocyclic compounds using 1,n-enynes and diynes … gold catalyzed cycloisomerization of 1,6-diynes. In addition, we will also disclose a novel silver catalyzed tandem 1,…

Abstract A novel gold‐catalyzed cycloisomerization of 1,6‐diynes was achieved, providing an atom‐economic approach to a diverse set of bicyclo[2.2.1]hept‐5‐en‐2‐ones in moderate to good yields. With unsymmetrical starting materials with two different internal alkynyl substituents, to some extent, the regioselectivity could be controlled by both electronic and steric factors. This unprecedented reactivity pattern may inspire new and unconventional strategies for the preparation of bridged ring systems.

The gold-catalyzed [3 + 2] cycloaddition of areneyne-yne functionalities represents one of the most efficient methodologies for the construction of tricyclic ring systems under mild conditions. In the current report, a detailed mechanistic understanding of the reaction was achieved by DFT calculations. It was found that under the catalysis of gold(i), the initial cyclization occurs more favorably between the two alkynyl moieties via the 6-exo-dig pathway other than the arene-yne addition, which is the selectivity-determining step of the whole reaction and leads eventually to the [3 + 2] cycloadduct irreversibly by following the steps of arene-cation cyclization and proton transfer. Electronic and geometric factors are analyzed to better understand the calculation results.

Compounds having cyclic molecular frameworks are highly regarded for their abundance and diverse utilities. In particular, medium-sized carbocycles and heterocycles exist in a broad spectrum of natural products, bioactive therapeutics, and medicinally significant synthetic molecules. Metal-mediated methods have been developed for the preparation of compounds containing a medium-sized ring (MSR) through cyclization of different classes of substrates and acyclic precursors. This review focuses on the methodologies for construction of MSRs via gold catalysis. Given the challenges in enabling the assembly of different ring sizes, we present here accounts on Au-mediated cyclization giving notable 7-membered and medium-sized (8-11-membered ring) structures. Emphasis on the pathway and mode of cyclization and the selection of precursors ranging from structurally biased compounds were outlined. Reactivity patterns and the choice of efficient Au catalysts for controlling reaction performance and selectivity in addition to mechanistic attributes are examined.

Abstract Research on gold catalysis has flourished over the last 20 years, and gold catalysts are now acknowledged as the “best choice” for a range of organic transformations. Gold complexes have emerged as promising candidates for this use in recent years because of their high reactivity, which enables them to induce a broad range of transformations under mild conditions. Extensive demonstrations have showcased the extraordinary efficiency of synthesizing complex organic compounds from the basic starting components. In addition to its traditional applications in catalysis, gold catalysis has expanded to include the total synthesis of natural compounds, which is a complex and demanding undertaking. The class of molecules known as carbo- and heterocycles, which is arguably the most important, has a significant impact on the synthesis of agrochemicals and pharmaceuticals among the numerous additional products made possible by the novel procedures pioneered. The main topic of this review is how to use Au salts in homogeneous catalysis to create cyclization processes for small heterocyclic and carbocyclic systems. This study gives an overview of most of the books and articles written after 2013 that discuss making three- and four-membered carbo- and heterocyclic rings with gold as a catalyst. We have made every effort to include all outstanding reports on this subject; nonetheless, we apologize for any omissions.

Three- and four-membered rings, widespread motifs in nature and medicinal chemistry, have fascinated chemists ever since their discovery. However, due to energetic considerations, small rings are often difficult to assemble. In this regard, homogeneous gold catalysis has emerged as a powerful tool to construct these highly strained carbocycles. This review aims to provide a comprehensive summary of all the major advances and discoveries made in the gold-catalyzed synthesis of cyclopropanes, cyclopropenes, cyclobutanes, cyclobutenes, and their corresponding heterocyclic or heterosubstituted analogs.

A synthetic method to prepare dispiroheterocycles containing two all-carbon quaternary centers efficiently that relies on the gold(I)-catalyzed double spirocyclization of 3-ene-1,7-diyne esters is described. The suggested mechanism delineates a rare example of a dispirocyclization featuring two 1,n-acyloxy shifts comprising a 1,3-acyloxy migration and an interrupted 1,5-acyl migration that was achieved with the assistance of residual water in the reaction media.

… oxidative cyclization of readily available 1,5- and 1,6-diynes. … 4-catalyzed oxidative diyne cyclization, and importantly, this … Gold-catalyzed selective oxidation of 4-oxahepta-1,6-diynes …

… et al. also reported31 a similar gold-catalyzed enantioselective synthesis of [3.2.1] … synthesized (–)-exo-isobrevicomin from a furan derivative 132. Transformation of 132 to 3-pyranone …

… catalyzed by chiral N-heterocyclic carbenes (NHCs) (Scheme 12).33 A variety of 6-substituted 3-pyranone … ,4-trifluorohexosides by a similar gold-catalyzed 6-endo cycloisomerization of …

… of gold catalysis, the 1,5-diynes and the 1,6-diynes are the … can undergo an intramolecular cyclisation with the remaining … the intramolecular reaction of azomethine ylides with 1,6-diynes …

In the last two decades, interest in reactions catalysed by gold complexes has tremendously increased due to their ability to tolerate a variety of functional groups and their capability to activate various unsaturated groups. In this review, gold-catalysed cycloisomerisation reactions of ynamides, diynes and 1,n-enynes have been summarized. These gold-catalysed cycloisomerisation reactions open new opportunities for synthesising a range of new complex polycyclic chemical moieties in one step. Gold-catalysed cycloisomerisation is a valuable way for synthesising fused spiro carbocycles, BODIPY cores, bicyclo[3.2.1]oct-2-ene, dihydro benzo[b]thiepine, disubstituted furans, spiroindolines, bridged [n.2.1] skeletons, etc.

1.1. General Reactivity of Alkyne-Gold(I) Complexes For centuries, gold had been considered a precious, purely decorative inert metal. It was not until 1986 that Ito and Hayashi described the first application of gold(I) in homogeneous catalysis.1 More than one decade later, the first examples of gold(I) activation of alkynes were reported by Teles2 and Tanaka,3 revealing the potential of gold(I) in organic synthesis. Now, gold(I) complexes are the most effective catalysts for the electrophilic activation of alkynes under homogeneous conditions, and a broad range of versatile synthetic tools have been developed for the construction of carbon–carbon or carbon–heteroatom bonds. Gold(I) complexes selectively activate π-bonds of alkynes in complex molecular settings,4−10 which has been attributed to relativistic effects.11−13 In general, no other electrophilic late transition metal shows the breadth of synthetic applications of homogeneous gold(I) catalysts, although in occasions less Lewis acidic Pt(II) or Ag(I) complexes can be used as an alternative,9,10,14,15 particularly in the context of the activation of alkenes.16,17 Highly electrophilic Ga(III)18−22 and In(III)23,24 salts can also be used as catalysts, although often higher catalyst loadings are required. In general, the nucleophilic Markovnikov attack to η2-[AuL]+-activated alkynes 1 forms trans-alkenyl-gold complexes 2 as intermediates (Scheme 1).4,5a,9,10,12,25−29 This activation mode also occurs in gold-catalyzed cycloisomerizations of 1,n-enynes and in hydroarylation reactions, in which the alkene or the arene act as the nucleophile. Scheme 1 Anti-Nucleophilic Attack to η2-[AuL]+-Activated Alkynes

Density functional theory (DFT) calculations reveal a distinct mechanism for the Au(I)-catalyzed synthesis of bicyclo-[2.2.1]heptanes through cycloisomerizations of 3-alkoxyl-1,6-diynes. The proposed mechanism highlights the crucial involvement of an allyl-gold species...

… cyclisation of 1,6-diynes. Scheme 6 Synthetic application of Ru-catalysed hydrative cyclisation of 1,6-diynes. … An eventual intramolecular carbocyclisation relies on a Brønsted acid in …