金属复分解闭环反应合成C=C键的研究进展

金属复分解反应是合成C=C键的有效方法,被广泛地用于合成各种类型的化合物,特别是碳环、杂环化合物以及天然产物的合成。本文综述了近年来金属复分解反应合成C=C键的最新研究进展。参考文献31篇。     

Thorpe-Ingold效应及其在有机成环反应中的应用

本文首先介绍了Thorpe-Ingold效应及其相关理论和实验研究进展,然后综述了近年来Thorpe-Ingold效应在形成三、四、五和六元环产物的环化反应中的应用。Thorpe-Ingold效应可以有效地促进分子内和分子间环化,提高环化的产率和速率。该效应主要通过空间效应、电子效应或者两者协同起作用,在某些情况下,该效应还会受催化剂和溶剂等影响。利用该效应可以促使一些难以发生的环化反应顺利进行,并能获得较好的产率。     

Synthesis of Berkeleylactone A by Ring-Closing Alkyne Metathesis

A new route to the macrolactone antibiotic berkeleylactone A was developed. As a key step, a ring-closing alkyne metathesis (RCAM) of an ester substrate featuring 1-propynyl termini was used. The carboxylic part of the substrate was easily assembled using alkyne chemistry, like carboxylation of a diyne followed by isomerization of the ynoate section to a dienoate and dihydroxylation of the 4,5-double bond. The synthesis of the alcohol part of the ester started with opening of (R)-propylene oxide with an acetylide and was followed by two triple bond migrations. After successful RCAM which formed the C8−C9 bond, the triple bond was selectively hydrogenated to the corresponding alkene before the 4,5-diol was oxidized to the 5-hydroxy-4-oxo derivative. At this stage, the thioether was formed and the 8,9-double bond reduced. We also prepared the 8,9-didehydro analog of berkeleylactone A. However, it turned out that its antimicrobial activity was slightly reduced.     

Ring-Closing Olefin Metathesis Catalyzed by Well-Defined Vanadium Alkylidene Complexes

Vanadium-based catalysts have shown activity and selectivity in ring-opening metathesis polymerization of strained cyclic olefins comparable to those of Ru, Mo, and W catalysts. However, the application of V alkylidenes in routine organic synthesis is limited. Here, we present the first example of ring-closing olefin metathesis catalyzed by well-defined V chloride alkylidene phosphine complexes. The developed catalysts exhibit tolerance to various functional groups, such as an ether, an ester, a tertiary amide, a tertiary amine, and a sulfonamide. The size and electron-donating properties of the imido group and the phosphine play a crucial role in the stability of active intermediates. Reactions with ethylene and olefins suggest that both β-hydride elimination of the metallacyclobutene and bimolecular decomposition are responsible for catalyst degradation.     

Selective formation of dihydropyran derivatives by a tandem domino ring-closing metathesis/cross-metathesis

A ring-closing metathesis (RCM)/cross-metathesis (CM) domino reaction has been applied to esters and unsymmetrical ether prepared from 1,5-hexadien-3-ol. For the first time, dihydropyran derivatives have been obtained via a regioselective cyclization. This reaction was performed in high yield and E stereoselectivity.     

Ring-Closing Metathesis of Ene-Ynamide: Application to the Synthesis of Medium-Sized Cyclic Dienamide

Summary: Ring-closing metathesis (RCM) of ene-ynamide, which could be applied to the synthesis of various heterocycles containing 7- and 8-membered rings, was investigated. Ene-ynamides are easily synthesized by the known method. When a toluene solution of ene-ynamide was stirred in the presence of a catalytic amount of second-generation ruthenium carbene complex 1 under an ethylene atmosphere, RCM proceeded smoothly to provide a heterocyclic compound having a diene moiety in good to high yield. A substituent of the ynamide moiety affected the yield of the cyclized product.     

Tandem Claisen rearrangement and ruthenium catalyzed enyne bond reorganization as a route to the synthesis of tricyclic 1,8-naphthyridinones

A novel procedure for the synthesis of substituted 1,8-naphthyridinones via tandem Claisen rearrangement and ring-closing enyne metathesis is reported.     

Synthesis of oxepine-, oxocine- and azepine-annulated carbazole derivatives by combined Claisen rearrangement and diene/enyne metathesis

A new route to various medium ring heterocycle-annulated tetra-, penta- and hexacyclic carbazole derivatives has been developed using successive applications of three atom economic processes, viz. Claisen rearrangement, olefin metathesis and Diels-Alder reactions.     

Metathesis of a novel dienediyne system: A unique example involving the usage of in situ generated ethylene as cross-enyne metathesis partner

A unique example of sequential ring-closing metathesis and cross-enyne metathesis is reported. Here, the in situ generated ethylene by product from ring-closing metathesis is trapped by alkyne moiety. No metathesis product formation was observed with more reactive second generation catalyst in the absence of ethylene. Differential chemoselectivity with the first and second generation Grubbs’ catalyst has been observed when the reaction was performed in presence of the external source of ethylene.     

胺基膦钌卡宾化合物的合成及催化烯烃复分解反应

合成并表征了一类含新型胺基膦配体的Grubbs二代型钌卡宾烯烃复分解催化剂[RuCl₂(H₂IMes)·(R¹HNPR²₂)(=CHPh)], 采用核磁共振波谱和单晶X射线衍射确定了催化剂的结构. 在室温条件下, 以N,N-二烯丙基-对甲苯磺酰胺的关环复分解反应(RCM)为模型, 考察了不同胺基膦配体对钌卡宾催化反应速率的影响. 结果表明, G2?1表现出最佳的催化活性. 通过底物研究发现, G2?1催化剂(摩尔分数, 1%)对双端烯及多端烯的RCM反应具有较好的活性和官能团适应性, 产物收率均>95%; G2?1催化剂同样适用于同(异)端烯底物的交叉复分解反应(CM), 其催化苯乙烯与3-苯氧基丙烯的CM反应时产物收率高达92%.     

Stereoselective Synthesis of (+)-Nephrosteranic Acid by Ring-Closing Metathesis and Its Biological Evaluation

A simple and efficient approach to (+)-nephrosteranic acid from dodecanol as a starting material is described, employing Sharpless asymmetric epoxidation, ring-closing metathesis, and Gilman addition of a vinyl group as key steps. These key reactions allow fast access to trisubstituted γ-butyrolactone. The molecule synthesized exhibits potent antifungal, antibacterial, and cytotoxic activities against all the tested strains.     

Thorpe-Ingold effect in the reaction of vicinal amino primary alcohol hydrogen sulfates and carbon disulfide

The Thorpe-Ingold effect is a key factor that affects the ring-closure rates and efficiency, as well as the structure of products in some ring-closure reactions. The reaction of vicinal amino primary alcohol hydrogen sulfates and carbon disulfide in the presence of potassium hydroxide produces the desired 4,4-disubstituted thiazolidine-2-thiones, and their isomers 5,5-disubstituted derivatives companying with their oxygen analogues 4,4-disubstituted oxazolidine-2-thiones. The formation of 5,5-disubstituted thiazolidine-2-thiones was rationalized via 2,2-disubstituted aziridine-1-carbodithioate intermediates, which were generated due to the Thorpe-Ingold effect. 4,4-Disubstituted oxazolidine-2-thiones were generated from carbon disulfide and free amino alcohols yielded via basic hydrolysis of active amino alcohol hydrogen sulfates in the reaction system.     

Simultaneous Enantiodivergent Synthesis of Diverse Lactones and Lactams via Sequential One-Pot Enzymatic Kinetic Resolution–Ring-Closing Metathesis Reactions

One of the goals of diversity-oriented synthesis is to achieve the structural diversity of obtained compounds. As most biologically active compounds are chiral, it is important to develop enantioselective methods of their synthesis. The application of kinetic resolution in DOS is problematic because of low efficiency (max. 50% yield) and many purification steps. The further derivatization of kinetic resolution products in DOS leads to the formation of a narrow library of compounds of the same stereochemistry. To overcome these limitations, we present a new concept in which the kinetic resolution is combined, the subsequent reaction of which in a one-pot protocol leads to the simultaneous formation of two skeletally and enantiomerically diverse platform molecules for DOS. Their further derivatization can gain access to a double-sized library of products in respect to a classical approach. The validity of our concept was evidenced in enzymatic kinetic resolution followed by a ring-closing metathesis cascade. From racemic carboxylic acid ester, a simultaneous formation of enantiopure lactones and lactams was achieved. These compounds are important building blocks in organic and medicinal chemistry and until now were synthesized in separate procedures.     

Directed ring-closing metathesis of trienes by silyl substitution

A synthetic strategy for ‘disarming’ a terminal alkene by substitution with a bulky silyl blocking group has been developed. In a series of model studies, sequential selective ring-closing metathesis of trienes followed by selective mono-hydrogenation of the resulting diene is described. The bulky silylated alkene is activated for a subsequent cross-metathesis reaction with a range of diverse alkenes by protodesilylation.     

Generation of Stoichiometric Ethylene and Isotopic Derivatives and Application in Transition‐Metal‐Catalyzed Vinylation and Enyne Metathesis

Ethylene is one of the most important building blocks in industry for the production of polymers and commodity chemicals. ¹³C‐ and D‐isotope‐labeled ethylenes are also valuable reagents with applications ranging from polymer‐structure determination, reaction‐mechanism elucidation to the preparation of more complex isotopically labeled compounds. However, these isotopic derivatives are expensive, and are flammable gases, which are difficult to handle. We have developed a method for the controlled generation of ethylene and its isotopic variants including, for the first time, fully isotopically labeled ethylene, from simple alkene precursors by using Ru catalysis. Applying a two‐chamber reactor allows both the synthesis of ethylene and its immediate consumption in a chemical transformation permitting reactions to be performed with only stoichiometric amounts of this two carbon olefin. This was demonstrated in the Ni‐catalyzed Heck reaction with aryl triflates and benzyl chlorides, as well as Ru‐mediated enyne metathesis.     

Synthesis of fused imidazo azepine derivatives by sequential van Leusen/enyne metathesis reactions

A facile synthesis of fused imidazo azepine derivatives by a van Leusen/intramolecular enyne metathesis synthetic sequence is reported. The two-step reaction sequence generates compounds of significant molecular complexity from simple starting materials in an expedient fashion with good overall yields.