Complex Polyenes Research Articles

Stereoselective Synthesis of Complex Polyenes through Sequential α‐/β‐C−H Functionalization of trans‐Styrenes

AbstractSequential C−H functionalization of molecules containing multiple C−H bonds can efficiently lead to structural diversity. Herein we present the first chelation‐assisted sequential α‐/β‐C−H functionalization of E‐styrenes with simple alkenes and alkynes in excellent regio‐ and stereo‐selectivity. The process involves α C−H functionalization by six‐membered exo‐cyclopalladation to result in tri‐ and tetrasubstituted 1,3‐dienes and β C−H functionalization through seven‐membered endo‐cyclopalladation to produce tetra‐ and pentasubstituted 1,3,5‐trienes in up to 97 % yield with up to >99/1 E/Z selectivity, both enabled by the chelation assistance of pyrazinamide. The protocol is demonstrated to be widely applicable, tolerant to a wide range of functional groups and bioactive fragments, and suitable for gram‐scale synthesis as well as one‐pot and two step preparation of trienes. Mechanistic experiments and density functional theory (DFT) calculations were performed to elucidate the selectivity and reactivity.

Stereoselective Synthesis of Complex Polyenes through Sequential α-/β-C-H Functionalization of trans-Styrenes.

Sequential C-H functionalization of molecules containing multiple C-H bonds can efficiently lead to structural diversity. Herein we present the first chelation-assisted sequential α-/β-C-H functionalization of E-styrenes with simple alkenes and alkynes in excellent regio- and stereo-selectivity. The process involves α C-H functionalization by six-membered exo-cyclopalladation to result in tri- and tetrasubstituted 1,3-dienes and β C-H functionalization through seven-membered endo-cyclopalladation to produce tetra- and pentasubstituted 1,3,5-trienes in up to 97 % yield with up to >99/1 E/Z selectivity, both enabled by the chelation assistance of pyrazinamide. The protocol is demonstrated to be widely applicable, tolerant to a wide range of functional groups and bioactive fragments, and suitable for gram-scale synthesis as well as one-pot and two step preparation of trienes. Mechanistic experiments and density functional theory (DFT) calculations were performed to elucidate the selectivity and reactivity.

Trimerization of Acetylene and Alkene: Rapid Access to Polyenes

Open AccessCCS ChemistryCOMMUNICATIONS22 Dec 2022Trimerization of Acetylene and Alkene: Rapid Access to Polyenes Boxiang Liu, Zhicong Lin, Yu Wang, Tairan Cheng, Tongxiang Cao and Shifa Zhu Boxiang Liu Google Scholar More articles by this author , Zhicong Lin Google Scholar More articles by this author , Yu Wang Google Scholar More articles by this author , Tairan Cheng Google Scholar More articles by this author , Tongxiang Cao Google Scholar More articles by this author and Shifa Zhu Google Scholar More articles by this author https://doi.org/10.31635/ccschem.022.202202579 SectionsSupplemental MaterialAboutPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Conjugated polyene motifs are ubiquitous in various natural products and functional molecules, however their synthesis is very challenging because of the required lengthy and time-consuming processes. We herein report an efficient approach for the synthesis of (E, E)-trienes via cationic rhodium catalysis using acetylene and simple alkenes bearing diverse directing groups as the starting materials. The reaction features high step economy, excellent functional group compatibility and exclusive stereoselectivity. Various directing groups such as carbonyl, sulfone, phosphate, and even hydroxyl and amino are compatible. Furthermore, the triene products allow versatile elaborations, providing rapid and convenient access to several important bioactive molecules, such as Vitamin A, (+)-Roxaticin and other complex polyenes. The mechanistic experiments show that the directing group on the alkene plays a crucial role in the reaction. Download figure Download PowerPoint Previous articleNext article FiguresReferencesRelatedDetails Issue AssignmentVolume 0Issue jaPage: 1-22Supporting Information Copyright & Permissions© 2022 Chinese Chemical Society Downloaded 84 times PDF downloadLoading ...

Modular terpene synthesis enabled by mild electrochemical couplings.

The synthesis of terpenes is a large field of research that is woven deeply into the history of chemistry. Terpene biosynthesis is a case study of how the logic of a modular design can lead to diverse structures with unparalleled efficiency. This work leverages modern nickel-catalyzed electrochemical sp2-sp3 decarboxylative coupling reactions, enabled by silver nanoparticle-modified electrodes, to intuitively assemble terpene natural products and complex polyenes by using simple modular building blocks. The step change in efficiency of this approach is exemplified through the scalable preparation of 13 complex terpenes, which minimized protecting group manipulations, functional group interconversions, and redox fluctuations. The mechanistic aspects of the essential functionalized electrodes are studied in depth through a variety of spectroscopic and analytical techniques.

Regiocontrolled Reductive Vinylation of Aliphatic 1,3-Dienes with Vinyl Triflates by Nickel Catalysis.

The regiocontrolled functionalization of 1,3-dienes has become a powerful tool for divergent synthesis, yet it remains a long-standing challenge for aliphatic substrates. Herein, we report a reductive approach for a branch-selective 1,2-hydrovinylation of aliphatic 1,3-dienes with R-X electrophiles, which represents a new selectivity pattern for diene functionalization. Simple butadiene, aromatic 1,3-dienes, and highly conjugated polyene were also tolerated. The combination of Ni(0) and the phosphine-nitrile ligand generally resulted in >20:1 regioselectivity with the retention of the geometry of the C3-C4 double bonds. This reaction proceeds with a broad substrate scope, and it allows for the conjugation of two biologically active units to form more complex polyene molecules, such as tetraene and pentaene as well as heptaene.

ChemInform Abstract: A Simple and General Platform for Generating Stereochemically Complex Polyene Frameworks by Iterative Cross‐Coupling.

AbstractBoronates such as (IX) are employed to construct complex polyene frameworks, e.g. present in vacidin A.

Allylmalonate as an Activator Subunit for the Initiation of Relay Ring-Closing Metathesis Reactions

Passing the baton: The relay ring-closing metathesis (RRCM) reaction of complex polyenes 1 has been studied. Several relay subunits (T) were examined and many did not sufficiently activate the RRCM. An allylmalonate-containing relay subunit solved this problem, and efficiently lead to the diene 2. TIPS=triisopropylsilyl.

A Simple and General Platform for Generating Stereochemically Complex Polyene Frameworks by Iterative Cross‐Coupling

A Simple and General Platform for Generating Stereochemically Complex Polyene Frameworks by Iterative Cross‐Coupling

A Simple and General Platform for Generating Stereochemically Complex Polyene Frameworks by Iterative Cross‐Coupling

Gar nicht kompliziert: Eine neuartige iterative Kreuzkupplungsstrategie bietet Zugang zu nützlichen Synthesebausteinen, die die einfache Herstellung von komplexen Polyenmotiven in allen stereoisomeren Formen ermöglichen. Die Methode wurde zur Synthese des Polyen-Teils von Vacidin A (siehe Struktur) genutzt.

Stereocontrolled Synthesis of Z-Dienes via an Unexpected Pericyclic Cascade Rearrangement of 5-Amino-2,4-pentadienals

Donor-acceptor dienes known as Zincke aldehydes, which derive readily from the ring-opening reactions of pyridinium salts with secondary amines, undergo a fascinating thermal rearrangement reaction to afford Z-alpha,beta,gamma,delta-unsaturated amides with excellent stereoselectivity. Efficient, stereocontrolled access to Z-trisubstituted alkenes with two different substitution patterns is possible in three steps beginning with the appropriately substituted pyridine derivative. Preliminary studies have shown that both the amide and the monosubstituted alkene termini can be selectively functionalized. Ease of access, generality of scope, and facile product manipulation render this process attractive for the synthesis of complex polyenes.

The synthesis of deoxyfusapyrone. 2. Preparation of the bis-trisubstituted olefin fragment and its attachment to the pyrone moiety.

A convergent and modular synthesis has been devised to construct the eight diastereoisomers of deoxyfusapyrone (1). In this paper the synthesis of the complex polyene chain is reported as is its connection to the pyrone moiety that is in the middle of the structure of the final target molecule. This route has been fully worked out for one of the isomers and will now be applied in a parallel synthesis format to make all the stereoisomers of 1.

Effects of Four Components of the Polyene Antibiotic, Filipin, on Phospholipid Spherules (Liposomes) and Erythrocytes

Abstract Effects of a complex polyene antibiotic, filipin, and its four components were studied upon biological (erythrocyte) and artificial (liposome) membranes in order to test the hypothesis of polyene action. The hemolytic activity of filipin complex could be removed more effectively by liposomes which had cholesterol incorporated (phosphatidyl choline (7)-dicetylphosphate (2)-cholesterol (1)) than by cholesterol-lacking spherules (phosphatidyl choline (7)-dicetylphosphate (2)-cholesterol (0)). The order of hemolytic activity of filipin components was: filipin II ≅ filipin III >> filipin I g filipin IV and this order paralleled their biological action. Filipin III, which is the major (53%) component of the complex, preferentially disrupted liposomes prepared with cholesterol (judged by release of CrO4=); filipin II (25% of the complex) indiscriminately disrupted liposomes whether or not cholesterol was present. Filipin I and filipin IV were far less disruptive to the artificial structures. Other phospholipids (sphingomyelin g cardiolipin >> phosphatidyl ethanolamine) were also shown to interact with filipin components. The experiments resolve discrepancies reported with filipin complex, the interaction of which with artificial membranes prepared either with or without cholesterol depends upon the relative enrichment of the complex in one or another of its components and the subsequent polyene-lipid ratio. Consequently, although filipins clearly interact with phospholipids in model systems, no significant objections remain to the general sterol receptor hypothesis of polyene action upon biological membranes.