Double Ring-closing Metathesis Research Articles

Asymmetric Total Synthesis of (+)-Mannolide C.

(+)-Mannolide C is a complex hexacyclic C20 cephalotane-type diterpenoid featuring a highly strained 7/6/6/5 tetracyclic core containing eight consecutive stereocenters and two bridging lactones. The first asymmetric total synthesis of (+)-mannolide C has been accomplished by lipase-mediated resolution, Ru-complex-catalyzed double ring-closing metathesis (RCM) reactions, NiII -catalyzed diastereoselective Michael addition, and MnIII -catalyzed allylic oxidation as the key transformations.

Bidirectional Synthesis of the IJK Fragment of Ciguatoxin CTX3C by Sequential Double Ring-Closing Metathesis and Tsuji-Trost Allylation.

A novel four-step bidirectional strategy has been used to synthesize the IJK fragment of the marine polyether natural product CTX3C from a simple monocyclic precursor in a concise and efficient manner. The four-step bidirectional sequence involves ring-closing metathesis, alcohol oxidation, enol carbonate formation, and palladium-mediated Tsuji–Trost allylation.

Applications of ring closing metathesis. Total synthesis of (±)-pseudotabersonine

A novel approach to the Aspidosperma family of alkaloids was developed and applied to a concise total synthesis of (±)-pseudotabersonine that was accomplished in 11 steps. Key transformations include a stepwise variant of a Mannich-like multicomponent assembly process, a double ring-closing metathesis sequence, and a one-pot deprotection/cyclization reaction.

ChemInform Abstract: Diversity‐Oriented Approach to Cyclophanes via Claisen Rearrangement and Ring‐Closing Metathesis as Key Steps

Abstract5 examples

Novel Strategy for the Bis-Butenolide Synthesis via Ring-Closing Metathesis

A new synthesis to bis-butenolide derivatives from inexpensive divinylglycol is described, employing a sequential double acylation followed by a double ring-closing metathesis. The selectivity is affected by the choice of catalyst.

Novel Approach to the Lundurine Alkaloids: Synthesis of the Tetracyclic Core

The tetracyclic core of the lundurine family of alkaloids has been synthesized by a novel approach that features a double ring-closing olefin metathesis to form the five-and eight-membered rings.

Concise Total Synthesis of (±)-Pseudotabersonine via Double Ring-Closing Metathesis Strategy

A concise synthesis of (+/-)-pseudotabersonine from commercially available 1-(phenylsulfonyl)-3-indolecarboxaldehyde has been accomplished. This synthesis features the convergent assembly of a key intermediate via a stepwise variant of a Mannich-type multicomponent coupling process, a double ring-closing metathesis, and a one-pot deprotection/cyclization reaction.

ChemInform Abstract: Synthesis of Polycyclic Ethers by Two-Directional Double Ring-Closing Metathesis.

trans-Fused tricyclic ethers containing combinations of six-, seven-, eight-, and nine-membered rings are constructed using two-directional double ring-closing metathesis reactions (see scheme). Such double cyclizations of precursors bearing alkenes, allylic ethers, enol ethers, or alkynyl ethers offer a new strategy for the synthesis of brevetoxins and ciguatoxins. PMB=(p-MeOC(6)H(4)CH(2)).

Bismacrocyclic Inhibitors of Hepatitis C NS3/4a Protease

Double time: The bismacrocycle 2 was prepared from 1 by a selective double ring-closing metathesis (RCM) reaction to form the 18- and 15-membered rings simultaneously. Derivative 3 shows excellent potency against NS3/4a protease. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ATRP-RCM Synthesis of 8-Shaped Poly(methyl acrylate) Using a 4-Armed Star Telechelics

Cyclic and multicyclic polymers have drawn increasing attention due to their unique architectures, i.e., free of chain ends. A number of protocols including, in particular, the ringexpansion polymerization and the end-to-end polymer cyclization, have now been developed for the selective and effective synthesis of single cyclic polymers to realize novel properties and functions unattainable by conventional linear or branched counterparts. We have also proposed a metathesis polymer cyclization (MPC) process, i.e., a ring-closing metathesis (RCM) reaction with a linear telechelic precursor having olefinic end groups under dilution. And the effective and selective synthesis of cyclic polyacrylate has been achieved through atom transfer radical polymerization (ATRP)-Keck allylation and the subsequent RCM reaction. In this process, the key telechelic prepolymer was produced by the ATRP using a difunctional initiator and the terminal bromide group was quantitatively converted to allyl group by the reaction with allyltributyltin. The subsequent intramolecular RCM reaction proceeded even under dilution in the presence of Grubbs catalyst to give a cyclic polymer in high efficiency. On the other hand, such a dicyclic as 8-shaped polymer has yet been an ongoing challenge in the synthetic polymer chemistry. We have shown that 8-shaped polymers are obtainable through an electrostatic self-assembly formed by two units of telechelic precursor having moderately strained cyclic ammonium salt end groups carrying one unit of tetracarboxylate counter anion. Alternatively, interand intramolecular metathesis condensation process have been applied between two units of a cyclic prepolymer having an allyloxy group (Scheme 1-a), and with a twin-tailed tadpole polymer precursor (Scheme 1-b), as well as with a cyclic polymer precursor having two allyloxy groups at the opposite positions (Scheme 1-c), respectively. The intramolecular metathesis condensation has also been applied with an H-shaped precursor having allyloxy end groups at each chain ends, to produce other types of dicyclic polymers having and manacle topologies (Scheme 1-d). As an extension of the preceding studies, we report in this paper on the synthesis of an 8-shaped polymer through the double ring-closing metathesis reaction using a 4-armed star polymer precursor, synthesized by means of the ATRP of methyl acrylate using a tetrafunctional initiator (Scheme 2). Since the ATRP has been recognized as a versatile means to give living star polymers upto hexafunctionalities by using multi-functional initiators, complex multicyclic polymers will be obtainable through the MPC process with end-functional star polymers.

A double ring-closing olefin metathesis approach to [3]catenanes

A [3]catenane with peripheral olefinic macrocycles was conveniently synthesized via a double ring-closing olefin metathesis. Highlights of this work include the synthesis of a 65-membered macrocycle featuring two phenanthroline ligands, a Cu(I)-templated synthesis of a [3]pseudorotaxane, and the key double ring-closing olefin metathesis to afford the desired [3]catenane in 71% yield.

Palladium-Catalyzed Double Annulations To Construct Multisubstituted Benzodifurans

Efficient synthetic routes to construct multisubstituted benzo[1,2-b:5,4-b']difurans and benzo[1,2-b:4,5-b']difurans from bis(allyloxy)bis(alkynyl)benzenes or bis(alkynyl)dihydroxybenzenes and allylic halides utilizing palladium-catalyzed double annulations is reported. By further applying a double ring-closing metathesis reaction, pentacyclic compounds were also prepared.

Synthesis of a Bis‐macrocycle Containing Two Back‐to‐Back Rigidly Connected 1,10‐Phenanthroline Units as a Central Core and its Incorporation in a Handcuff‐Like Catenane

A bis-macrocycle containing two back-to-back connected 1,10-phenanthroline chelates has been prepared. The synthetic strategy involves the preparation of a monocyclic precursor consisting of a 1,10-phenanthroline-5,6-dione fragment incorporated in a 30-membered ring. This important intermediate has been prepared via two distinct routes, both strategies relying on the use of a ketal as a 1,2-dione protective group. A four-component condensation reaction between two molecules of the macrocyclic dione and two equivalents of ammonia (used in large excess) in the presence of a reducing agent (Na(2)S(2)O(4)) leads to the desired bis-ring in good yield. The most direct synthetic route allows preparation of the bis-macrocycle in seven steps from 1,10-phenanthroline in an overall yield of 14 %. Using the now well-established "gathering and threading" effect of copper(I), a doubly threaded species could be obtained in quantitative yield, in which each ring of the bis-macrocycle is threaded by a "molecular string". These fragments bear terminal allylic groups, which are used to prepare the final catenane by performing a double ring-closing metathesis reaction. This final cyclisation reaction is high yielding and affords the desired catenane consisting of a bis-macrocycle of which the two cyclic units are threaded by a large ring. The compound has been fully characterised by classical techniques. Electronic spectroscopy and electrochemical measurements suggest that the two copper complex subunits do not interact electronically, in spite of the aromatic nature of the bridging ligand between the two metal centres.

Towards the synthesis of insulated oligoynes: A ring-closing-metathesis approach to molecular encapsulation

Masked hexayne 18 was prepared in 11 steps from commercially available reagents. The four butenyl substituents contained within the two arylsilane residues in 18 have been used in a double ring-closing-metathesis operation in an attempt to encapsulate the π-conjugated framework. When 18 was treated with Grubbs’ 1st generation metathesis catalyst however, double ring-closing metathesis provided macrocycle 19 as the major product in good yield. Reasons why the macrocycle in 19 crowns, rather than encapsulates, the π-conjugated framework are discussed.

Novel stereoselective synthesis of enantiopure (+)- N-Boc-norpandamarilactonine-A, the intermediate for pandamarilactonines

A novel synthesis of enantiopure N-Boc-norpandamarilactonine-A was established by employing a double ring-closing metathesis of a tetraene derivative, as a key step, where two five-membered rings were constructed in one step. N-Boc-Norpandamarilactonine-A was also converted to ent-norpandamarilactonine-A, and subsequently to pandamarilactonine-A and B.

Exploiting catalyst characteristics: A protocol for increasing diastereoselectivity in a double ring-closing metathesis reaction

A procedure for obtaining increased selectivity in a diastereoselective double ring-closing metathesis reaction is presented. The key to success was design of a substrate, which directed the reaction mechanism through a selective pathway and use of a suitable catalyst combination to achieve the desired balance between reactivity and selectivity.

A Practical Synthesis of (±)-α-Isosparteine from a Tetraoxobispidine Core

[reaction: see text] The title alkaloid was synthesized in racemic form from 3,7-diallyl-2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane (7) by a regioselective diallylation reaction followed by double ring-closing olefin metathesis and exhaustive reduction. Tetraoxobispidine 7 was itself prepared in three simple operations from dimethyl malonate. The entire sequence to alpha-isosparteine was conducted on a multigram scale and proceeded without recourse to chromatography.

Use of N?N Bond Stereodynamics in Ring-Closing Metathesis to Form Medium-Sized Rings and Macrocycles.

A unique strategy based on double ring-closing metathesis for the formation of a 14-membered macrocyclic enamide has been developed. This strategy hinges upon the well-known stereodynamic and conformational behavior of N-substituted diacylhydrazines, which promotes an effective ring-closing metathesis of hydrazine-derived dienes and enynes to form 8- to 14-membered rings.

Development of a Novel Chiral Spiro Ligand Bearing Oxazoline.

Abstract The synthesis of bis(oxazoline) ligand 1 bearing a spiro skeleton is achieved via double ring-closing metathesis (RCM) of tetraene 2 and subsequent oxazoline ring formation using N-bromosuccinimide (NBS). The Cu-spiro bis(oxazoline) complexes prepared from 1 and Cu(OTf)2 or Cu(OAc)2 act efficiently as chiral catalysts for promoting carbonyl-ene reactions or Henry reactions with good enantiocontrol.

Highly Selective Synthesis of Bicyclic Quinolizidine Alkaloids and Their Analogues via Double RCM Reaction of N‐Alkynyl‐N‐(1,ω)‐alkadienyl Acrylamides.

AbstractFor Abstract see ChemInform Abstract in Full Text.