Metathesis Cascade Research Articles

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.

Ten-Step Total Synthesis of (-)-Andranginine.

The total synthesis of the indole alkaloid (-)-andranginine has been achieved in 10 steps. Key reactions of the synthesis include a nucleophilic addition of acetylenyl anion to chiral N-sulfinyl imine, an intramolecular N-alkylation reaction to close the C ring, and a dienyne metathesis cascade reaction to construct the DE rings. Meanwhile, 16-epi-(-)-andranginine was also obtained with the developed strategy.

Conversion of butanol to propene in flow: A triple dehydration, isomerisation and metathesis cascade

A combined three-step flow cascade conversion of n-butanol to propene is demonstrated. Zeolite H-ZSM-5 gives high conversion in the initial n-butanol dehydration step (98%). Subsequent isomerisation of terminal butenes to internal butenes over zeolite H-Fer takes place with good conversion (87%). Finally, cross-metathesis with ethene over a tungsten on acid-washed SiO2/Al2O3 catalyst affords propene with good selectivity (65%). Coupling these three steps into a single flow sheet gives an overall yield of 64% propene from n-BuOH. Ethene cross-metathesis catalyst performance was probed using 2-pentene as a model co-substrate giving good conversion (~90%) and moderate selectivity to butenes (67%).

Metathesis Cascade‐Triggered Depolymerization of Enyne Self‐Immolative Polymers**

AbstractA novel class of enyne self‐immolative polymers (SIPs) capable of metathesis cascade‐triggered depolymerization is reported. Studies on model compounds established 1,6‐enyne structures for efficient metathesis cascade reactions. SIPs incorporating the optimized 1,6‐enyne motif were prepared via both polycondensation and iterative exponential growth approaches. These SIPs demonstrated excellent stability in strong acid, base, nucleophiles, or at elevated temperatures, and can undergo efficient and complete depolymerization once triggered by a metathesis catalyst. Further studies revealed that introducing a terminal alkene to the chain end of the enyne SIPs improved the depolymerization efficiency, and established their potential as stimuli‐responsive materials.

Metathesis Cascade‐Triggered Depolymerization of Enyne Self‐Immolative Polymers**

A novel class of enyne self-immolative polymers (SIPs) capable of metathesis cascade-triggered depolymerization is reported. Studies on model compounds established 1,6-enyne structures for efficient metathesis cascade reactions. SIPs incorporating the optimized 1,6-enyne motif were prepared via both polycondensation and iterative exponential growth approaches. These SIPs demonstrated excellent stability in strong acid, base, nucleophiles, or at elevated temperatures, and can undergo efficient and complete depolymerization once triggered by a metathesis catalyst. Further studies revealed that introducing a terminal alkene to the chain end of the enyne SIPs improved the depolymerization efficiency, and established their potential as stimuli-responsive materials.

Sulfoxide Reduction/C(sp3)-S Metathesis Cascade in Ionic Liquid.

A sulfoxide reduction/C-S bond metathesis cascade between sulfoxides and alkyl bromides has been developed to access high-value sulfides without the use of any catalysts or bases. In this cascade, classical Kornblum oxidation is employed to reduce sulfoxides with alkyl bromides in ionic liquid. This protocol features high functional tolerance, mild conditions, promising scalability, and sustainable solvents.

Divergent Synthesis of Novel Cylindrocyclophanes that Inhibit Methicillin-Resistant Staphylococcus aureus (MRSA).

The cylindrocyclophanes are a family of macrocyclic natural products reported to exhibit antibacterial activity. Little is known about the structural basis of this activity due to the challenges associated with their synthesis or isolation. We hypothesised that structural modification of the cylindrocyclophane scaffold could streamline their synthesis without significant loss of activity. Herein, we report a divergent synthesis of the cylindrocyclophane core enabling access to symmetrical macrocycles by means of a catalytic, domino cross‐metathesis‐ring‐closing metathesis cascade, followed by late‐stage diversification. Phenotypic screening identified several novel inhibitors of methicillin‐resistant Staphylococcus aureus. The most potent inhibitor has a unique tetrabrominated [7,7]paracyclophane core with no known counterpart in nature. Together these illustrate the potential of divergent synthesis using catalysis and unbiased screening methods in modern antibacterial discovery.

Rh-Catalyzed nitrene alkyne metathesis/formal C–N bond insertion cascade: synthesis of 3-iminoindolines

A Rh-catalyzed nitrene/alkyne metathesis (NAM) cascade reaction terminated by a formal C–N bond insertion has been developed, which provides facile access to the tricyclic 3-iminoindolines in good yields with broad substrate scope.

Insights into C–O insertion in a carbene/alkyne metathesis cascade reaction catalyzed by Rh2(OAc)4: a DFT study

The mechanism and selectivities of C–O insertion in the carbene/alkyne metathesis of diazo compounds catalyzed by Rh2(OAc)4 are studied with DFT calculations.

Rapid Construction of the Scaffold of Quorumolide A Enabled by a Tandem ROM/RCM Strategy and a Tandem Oxidative Cyclization Strategy

A synthetically challenging framework in the plant-derived cembranoid quorumolide A was established in a seven-step sequence featuring a ring-opening/-closing metathesis cascade reaction to construct the fused butenolide ring and the 14-membered macroring in a single step. The utilization of a tandem oxidative cyclization strategy is the key to build the tetrahydro-2H-pyran moiety.

Rhodium-Catalyzed Nitrene/Alkyne Metathesis: An Enantioselective Process for the Synthesis of N-Heterocycles.

A chiral dirhodium-carboxylates-catalyzed asymmetric nitrene/alkyne metathesis (NAM) cascade reaction of alkyne-tethered sulfamates has been developed, which provides a general access to the synthesis of tricyclic N-heterocycles in good yields and excellent enantioselectivity. The chiral dirhodium catalyst not only promotes the nitrene/alkyne metathesis (NAM) to generate the key α-imino metal carbene intermediate but also is responsible for the observed asymmetric induction in the terminating [2,3]-sigmatropic rearrangement of oxonium ylide species.

Palladium-catalyzed carbene/alkyne metathesis with enynones as carbene precursors: synthesis of fused polyheterocycles.

An unprecedented palladium-catalyzed novel carbene/alkyne metathesis cascade reaction of alkyne-tethered enynones is described. This reaction affords fused polyheterocycles in moderate to good yields. The transformation begins with Pd-catalyzed 5-exo-dig cyclization of the enynone to form the donor/donor metal carbene, which then undergoes metathesis with the alkyne followed by electrophilic aromatic substitution.

Tetrahydropyrans by a Rhodium-Catalyzed Metathesis Cascade

Key words tetrahydropyrans - rhodium catalysis - asymmetric catalysis - carbene–alkyne metathesis - carbene–allene metathesis - cascade reaction

Ruthenium-Catalyzed Metathesis Cascade Reactions in Natural Products Synthesis.

In this account, we provide a brief summary of recent developments in ruthenium-catalyzed metathesis cascade reactions towards the total synthesis of natural products. We also highlight recent progress from our own laboratory regarding the synthesis of securinega alkaloids and humulanolides, which has resulted in the development of novel ruthenium-catalyzed metathesis cascade reactions. Inspired and guided by the pioneering and elegant research conducted in this area, we developed a regio-controlled relay dienyne metathesis cascade reaction and a cyclobutene-promoted RCM/ROM/RCM cascade reaction for the synthesis of securinega alkaloids and humulanolides, respectively.

Dual-Functionalization of Alkynes via Copper-Catalyzed Carbene/Alkyne Metathesis: A Direct Access to the 4-Carboxyl Quinolines

A copper-catalyzed novel carbene/alkyne metathesis cascade reaction with alkyne-tethered diazo compounds is described. The whole transformation features a dual-functionalization of alkyne to install one C═N and one C═C bond on each carbon with azide and diazo groups, respectively, in one reaction, which represents a practical synthetic alternative to the multisubstituted 4-carboxyl quinoline derivatives and with most of them in high to excellent yields.

ChemInform Abstract: Collective Synthesis of Natural Products by Using Metathesis Cascade Reactions

AbstractReview: [54 refs.

Collective Synthesis of Natural Products by Using Metathesis ­Cascade Reactions

This account describes our laboratory’s latest endeavors toward the collective synthesis of natural products. An overview of the general strategy is presented together with several total syntheses developed by our group. These examples demonstrate the power of metathesis cascade reactions and biomimetic strategies for the collective synthesis of securinega alkaloids and humulanolides. 1 Introduction 2 Collective Synthesis: A Historical Perspective 3 Collective Synthesis in Our Laboratory 3.1 Metathesis Cascade Reactions 3.2 Collective Synthesis of Securinega Alkaloids 3.3 Collective Synthesis of Humulanolides 3.3.1. Total Synthesis of Racemic Asteriscunolide D 3.3.2. Asymmetric Total Syntheses of Humulanolides 4 Conclusions and Outlook

ChemInform Abstract: Collective Synthesis of Humulanolides Using a Metathesis Cascade Reaction.

ChemInformVolume 46, Issue 14 Natural Products ChemInform Abstract: Collective Synthesis of Humulanolides Using a Metathesis Cascade Reaction. Jing-chun Han, Jing-chun Han Dep. Chem., South Univ. Sci Technol., Shenzhen 518055, Peop. Rep. ChinaSearch for more papers by this authorFuzhuo Li, Fuzhuo Li Dep. Chem., South Univ. Sci Technol., Shenzhen 518055, Peop. Rep. ChinaSearch for more papers by this authorChuang-chuang Li, Chuang-chuang Li Dep. Chem., South Univ. Sci Technol., Shenzhen 518055, Peop. Rep. ChinaSearch for more papers by this author Jing-chun Han, Jing-chun Han Dep. Chem., South Univ. Sci Technol., Shenzhen 518055, Peop. Rep. ChinaSearch for more papers by this authorFuzhuo Li, Fuzhuo Li Dep. Chem., South Univ. Sci Technol., Shenzhen 518055, Peop. Rep. ChinaSearch for more papers by this authorChuang-chuang Li, Chuang-chuang Li Dep. Chem., South Univ. Sci Technol., Shenzhen 518055, Peop. Rep. ChinaSearch for more papers by this author First published: 19 March 2015 https://doi.org/10.1002/chin.201514256Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume46, Issue14April, 2015 RelatedInformation

Collective Synthesis of Humulanolides Using a Metathesis Cascade

Collective Synthesis of Humulanolides Using a Metathesis Cascade

Collective synthesis of humulanolides using a metathesis cascade reaction.

A new method has been developed for the concise and asymmetric synthesis of seven humulanolides in 5-7 steps without the need for protecting groups. Notably, the challenging 11-membered ring and bridged butenolide moieties in asteriscunolide D and 6,7,9,10-tetrahydroasteriscunolide were introduced in one step using a ring-opening/ring-closing metathesis cascade reaction. Asteriscunolide D was used as a versatile synthetic precursor to prepare asteriscunolides A-C via a photoinduced isomerization reaction, asteriscanolide via a unique transannular Michael reaction, and 6,7,9,10-tetradehydroasteriscanolide via a transannular Morita-Baylis-Hillman-type reaction. The unique bicyclo[6.3.0]undecane core was introduced diastereoselectively.