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.     

A domino ring-closing metathesis as a key-step in the synthesis of chiral lactones from d-mannitol

Chiral lactones were synthesized in six steps from d-mannitol. The key-step was a domino ring-closing metathesis reaction leading to the symmetric cleavage of a d-mannitol triene derivative and to the formation of two molecules of the desired lactone.     

Synthesis of cyclic hydrazines by ring-closing metathesis of dienes and enynes tethered by an N-N bond

Ring-closing metathesis of dienes and enynes tethered by an N-N bond produced 6- to 10-membered cyclic 1,2-diaza compounds. The enyne RCM adducts were further transformed by Diels-Alder reaction into aromatic compounds.     

Substituent-controlled domino-Knoevenagel-hetero Diels-Alder reaction—a one-pot synthesis of polycyclic heterocycles

The reaction of 2-(N-alkenyl-N-aryl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde with dimedone/Meldrum’s acid/4-hydroxycoumarin by heating in ethanol in the presence of pyridine produces polycyclic heterocycles bearing pyridine and pyran rings in a one-pot reaction. The effect of substituents on N-atom of the amino function controls the mode of reaction. Terminal alkenes prefer intramolecular Michael type reaction, but non-terminal alkenes favour Diels-Alder reaction, whereas, under similar condition, 2-(N-alkyl-N-allyl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde undergoes domino-Knoevenagel-hetero Diels-Alder reaction.     

Organocatalytic domino reactions: synthesis of densely functionalized cyclohexene derivatives

A highly enantioselective domino reaction of α,β-unsaturated aldehydes and 4-acetyl-5-oxohexanal catalyzed by a chiral secondary amine catalyst has been developed, providing an efficient synthetic approach for the synthesis of densely functionalized chiral cyclohexene derivatives with high yields (up to 96%) and enantioselectivities (up to 97% ee) under mild conditions.     

Synthetic approach to cis and trans-decalins via Diels—Alder reaction and ring-closing metathesis as key steps: further extension to dioxapropellane derivative by ring-closing metathesis

9,10-Substituted cis and trans-decalins were synthesized by a simple route using the Diels-Alder reaction and ring-closing metathesis (RCM) as key steps. Later, the cis-decalin system has been extended to 3,8-dioxa[8.4.4]propellane derivative by RCM sequence as a key step.     

Three-component domino reaction synthesis of highly functionalized bicyclic pyrrole derivatives

An efficient one-pot synthesis of highly functionalized bicyclic pyrrole derivatives by a three-component domino reaction of heterocyclic ketene aminals (HKAs), arylglyoxal monohydrate, and indoles in ethanol medium catalyzed by acetic acid is described. In this procedure, three sigma bonds were formed simultaneously. The present synthesis features excellent regio-selectivity, easy purification as well as simple starting materials.     

Model synthetic studies toward the central 7/8/5 tricarbocyclic core of complex Schisanartane-type nortriterpenoids

A short, flexible approach to a functionally embellished 7/8/5 fused tricyclic scaffold corresponding to the CDEF segment of Schisanartane nortriterpenoids, from commercially available 1,5-cyclooctadiene, is delineated.     

Ring-closing metathesis of fluoroalkenes toward the synthesis of fluorinated heterocycles containing an oxaza bond

This study reports the ring-closing metathesis reaction of bisolefins, including a reluctant fluoroalkenes, linked with oxaza moiety. The resulting heterocycles were produced in high yields under high diluting conditions disfavoring the homodimerization side reaction of nonfluorinated double bond. The use of a mixture of solvents proved to be a good strategy to obtain the fluorinated heterocycles in fair to excellent yields.     

Domino intramolecular enyne metathesis/cross metathesis approach to the xanthanolides. Enantioselective synthesis of (+)-8-epi-xanthatin

The first total synthesis of (+)-8-epi-xanthatin (1) has been achieved in 14 steps starting from the commercially available ester 24, which was converted into aldehyde 23 in six steps. An enantioselective aldol reaction of 23 gave 30, which was transformed into triflate 22 in four steps, setting the stage for a palladium-catalyzed carbonylation reaction to form acrylate 34. Compound 34 was then subjected to a deprotection/lactonization sequence to furnish enyne 21, which underwent a domino enyne ring-closing metathesis/cross metathesis process to form a seven-membered carbocycle and (E)-conjugated dienone, thereby completing the synthesis of 1. This domino ruthenium-catalyzed metathesis reaction thus serves as an efficient method to construct the core of xanthanolide and other sesquiterpene lactones.     

Intramolecular diels-alder reactions of diester-tethered trienes. synthesis of medium ring-containing carbocycles and heterocycles

Intramolecular Diels-Alder reactions of cyclohexane-1,2-dicarboxylic anhydride-derived diester-tethered trienes are described. The stereoselectivities of most of the cycloaddition processes studied may be rationalised in terms of an preferred ‘inside’-oriented diene giving rise to an endo-transition state.     

Synthesis of diversely functionalized pyrrolizidines and indolizidines using olefin ring-closing metathesis

Various nitrogen-fused tricyclic compounds, having benzoindolizidine and benzopyrrolizidines ring systems were synthesized via ene-ene metathesis using the first and second-generation Grubbs catalyst. The ene-ene metathesis proceeded smoothly in refluxing CH₂Cl₂ with 3.0 mol % of G₁, giving good yields (78-86%) of the benzoindolizidine products 12a,b. The benzopyrrolizidine 6 was prepared after optimization in 64% yield by using 5.0+5.0 mol % of G₂. The resulting olefin moiety of the indolizidine framework is a suitable precursor for polyhydroxy structures via the Sharpless process. The structures of the polyhydroxylated adducts were determined by ¹H NMR spectra and single-crystal X-ray analysis.     

Generation and reaction of heteroaromatic zirconocene: synthetic application to polycyclic heterocycles

Heteroaromatic zirconocene intermediates were generated by the reaction of ‘Cp₂Zr’ with alkoxymethyl-(TMS-ethynyl)-indole, -benzofuran or -benzothiophene derivatives under mild conditions in moderate to good yields. Copper-catalyzed C-C bond formation of the zirconocene intermediate with allylic halides gave allylation products, which were transformed into heterocyclic dienes through enyne metathesis. Preliminary Diels-Alder reaction of the dienes with DMAD showed notable site selectivity.     

Synthesis of trans,trans,cis-fused tetracyclic skeleton via radical domino cyclization

Limonoids are characterized by a polycyclic structure and show a wide variety of bioactivities. In particular, mesendanin L, 12-hydroxyamoorastatone, and meliatoosenin F have unique structures containing a trans-A/B/C and cis-C/D-fused tetracyclic skeleton. We synthesized the core structure of these limonoids via Mn(OAc)₃ and Cu(OAc)₂-mediated radical domino cyclization of an acyclic tetraene precursor having a terminal β-keto ester. To the best of our knowledge, this is the first example of the radical-mediated construction of a 6/6/6/5-membered tetracyclic skeleton.     

Efficient microwave-assisted formation of functionalized 2,5-dihydropyrroles using ruthenium-catalyzed ring-closing metathesis

A rapid method for the formation of functionalized 2,5-dihydropyrroles using ruthenium-catalyzed ring-closing metathesis under microwave irradiation is presented. The diene substrates were efficiently prepared from aza-Baylis-Hillman adducts.     

Cross‐metathesis functionalized exo‐olefin derivatives of lactide

Poly(lactic acid) is at the forefront of research into alternative replacements to fossil fuel derived polymers, yet preparation of derivatives of this key biodegradable polymer remain challenging. This article explores the use of two derivatives of lactide, each of which features an exocyclic olefin, and their pre‐polymerization modification by olefin cross‐metathesis. Methylenation of lactide with Tebbe's reagent generates a novel 5‐methylenated lactide monomer, (3S,6S)‐3,6‐dimethyl‐5‐methylene‐1,4‐dioxan‐2‐one, complementing the previously reported 3‐methylenated (6S)‐3‐methylene‐6‐methyl‐1,4‐dioxan‐2,5‐dione. While ring‐opening of each monomer is not productive, olefin cross‐metathesis can be used to functionalize each of the exocyclic olefins to produce a family of monomers. The ring‐opening polymerization of these new monomers, and their hydrogenated congeners, is facilitated by organo‐ and Lewis‐acid catalysts. Together, they offer a new strategy for derivatizing and altering the properties of poly(lactic acid). © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 741–748     

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.     

Synthesis of (+)-7a-epi-7-deoxycasuarine via cross metathesis

Olefin cross metathesis of vinyl pyrrolidine derivatives has been explored, culminating in a concise synthesis of (+)-7a-epi-7-deoxycasuarine in nine steps, from commercially available starting materials.