Ring-closing Olefin Metathesis Research Articles

Access to Ring‐Fused Azepino[3,4‐b]indole‐1,5‐dione Derivatives by Ring‐Closing Olefin Metathesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ring‐Closing Olefin Metathesis of 2,2′‐Divinylbiphenyls: A Novel and General Approach to Phenanthrenes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A concise synthetic route to the conduritols from pentoses

A short synthetic strategy for preparation of the conduritols is described. The key step employs a zinc-mediated fragmentation of protected methyl 5-deoxy-5-iodo-d-pentofuranosides followed by an allylation of the intermediate aldehyde in the same pot. The allylation is performed with 3-bromopropenyl benzoate and occurs with good diastereoselectivity. An amino group can be introduced in the product by trapping the intermediate aldehyde as the imine prior to the allylation. The functionalised 1,7-octadienes, thus obtained, are converted into protected conduritols by ring-closing olefin metathesis.

Synthesis of 5/7-, 5/8- and 5/9-bicyclic lactam templates as constraints for external β-turns

The 5/7-, 5/8- and 5/9-bicyclic lactams 3, 17, 5 and 6 have been synthesised as single diastereoisomers by a route involving ring closing olefin metathesis. The X-ray crystal structure of the amino acid hydrochloride has been carried out and compared to that of the saturated external beta-turn constraint 18.

Total Synthesis of Ingenol

A total synthesis of the biologically important diterpene ingenol has been completed. Ring-closing olefin metathesis was used to construct the strained "inside-outside" tetracyclic skeleton, and a series of diastereoselective reactions were employed to complete the synthesis. Another naturally occurring ingenane, 20-deoxyingenol, has also been prepared.

γ-Lactone-Tethered Ring-Closing Metathesis. A Route to Enantiomerically Enriched γ-Lactones α,β-Fused to Medium-Sized Rings

[reaction: see text] The stereoselective alkylation of alpha-(phenylsulfonyl)-beta-[(methoxycarbonyl)methyl]-gamma-lactones obtained by the base-induced cyclization of enantiomerically enriched alpha-[(phenylthio)acyl]-alpha,beta-unsaturated esters and ring-closing olefin metathesis (RCM) are the basis of a new approach for gaining access to gamma-lactones that are alpha,beta-fused to medium-sized carbocycles and cyclic ethers.

Stereoselective Photochemical 1,3-Dioxolane Addition to 5-Alkoxymethyl-2(5H)-furanone: Synthesis of Bis-tetrahydrofuranyl Ligand for HIV Protease Inhibitor UIC-94017 (TMC-114)

A convenient synthesis of (3R,3aS,6aR)-3-hydroxyhexahydrofuro[2,3-b]furan, a high-affinity nonpeptidal ligand for HIV protease inhibitor UIC-94017, is described. This inhibitor is undergoing advanced clinical trials. The synthesis utilizes a novel stereoselective photochemical 1,3-dioxolane addition to 5(S)-benzyloxymethyl-2(5H)-furanone as the key step. The requisite furanone derivative was prepared in high enantiomeric excess by an immobilized lipase-catalyzed selective acylation of (+/-)-1-(benzyloxy)-3-buten-2-ol and a ring-closing olefin metathesis with Grubbs' catalyst. Optically active bis-THF was converted to protease inhibitor 2 (UIC-94017).

Total Synthesis of Brevetoxin-B

Brevetoxin-B (BTX-B), produced by the red tide organism, Gymnodium breve Davis, is the first member of marine polycyclic ethers to be structurally elucidated and one of the most potent neurotoxins. The structural feature is a trans-fused polycyclic ether ring system with 23 stereocenters. Its unique, complex structure and potent biological activity have attracted the attention of synthetic organic chemists. Total synthesis of BTX-B has been accomplished via the coupling of the ABCDEFG and IJK-ring segments, each ether ring of which was stereoselectively and efficiently constructed on the basis of SmI2-induced intramolecular cyclization, 6-endo-cyclization of hydroxy epoxide, ring-closing olefin metathesis, and SmI2-induced intramolecular Reformatsky-type reaction. Several kinds of double reactions at the left and right sides were efficiently used through the synthesis.

Formal Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis

The construction of strained carbon skeletons by ring-closing olefin metathesis (RCM) was investigated. With well-designed diene 4, RCM was found to be applicable to the formation of a highly strained inside-outside bicyclo[4.4.1]undecane skeleton of ingenol, a bioactive diterpenoid, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of the ketone with an allylic chloride unit, 26, and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 6, the key intermediate aldehyde 9 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol.

A Unified Approach to Quinolizinium Cations and Related Systems by Ring-Closing Metathesis

[reaction: see text] The first example of an olefin ring-closing metathesis reaction on cationic heteroaromatic systems is described. Dihydroquinolizinium cations and a variety of related cationic systems are synthesized in an efficient approach from N-alkenyl alpha-vinyl azinium salts using Grubbs' catalysts.

Synthesis of a cryptand with tetrahedral connectivity using multiple ring-closing olefin metathesis

By connecting six terminal olefins sequentially in one molecule under metathesis conditions, three macrocycles were formed efficiently in one pot yielding a novel cryptand with tetrahedral connectivity.

Ring-closing olefin metathesis of 2,2'-divinylbiphenyls: a novel and general approach to phenanthrenes.

[reaction: see text] The ring-closing olefin metathesis (RCM) of 2,2'-divinylbiphenyls, using a second-generation RCM ruthenium-based catalyst, leads to differently substituted phenanthrenes in quantitative yield under very mild reaction conditions, independent of both nature and position of the groups present on the biphenyl moiety.

Access to ring-fused azepino[3,4- b]indole-1,5-dione derivatives by ring-closing olefin metathesis

The new ring-fused azepino[5,6- b]indole derivatives 3 , 4 and 5 were prepared from diene precursors 8 , 9 , 13 and 15 in fair yields via a final ring-closing olefin metathesis.

A New Ruthenium-Based Olefin Metathesis Catalyst Coordinated with 1,3-Dimesityl-1,4,5,6-tetrahydropyrimidin-2-ylidene: Synthesis, X-ray Structure, and Reactivity

The new ruthenium olefin metathesis catalyst 4 bearing a 5,5‘-dimethyl-1,3-dimesityl-1,4,5,6-tetrahydropyrimidin-2-ylidene ligand was first synthesized from (PCy_3)_2(Cl)_2Ru ═ CHPh (1). The X-ray crystal structure of complex 4 has been determined and shows that the N-mesityl group of the six-membered carbene ligand and the benzylidene moiety are in close proximity (2.9 A). This catalyst demonstrates moderate reactivity for both ring-closing olefin metathesis and ring-opening metathesis polymerization.

Total Synthesis of (+)‐SCH 351448.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Versatile approach for the synthesis of novel seven-membered iminocyclitols via ring-closing metathesis dihydroxylation reaction

Seven-membered iminocyclitols with diverse diastereomers were prepared starting with d- and l-serines and employing ring-closing olefin metathesis and dihydroxylation reaction sequence. The iminocyclitols were assayed for glycosidase inhibition and compound 20 was found to be a competitive inhibitor for β-glucosidase with K i 26.3 μM.

Synthesis of phosphorus and sulfur heterocycles via ring-closing olefin metathesis.

Synthesis of phosphorus and sulfur heterocycles via ring-closing olefin metathesis.

Synthesis of Vinyl Fluorides by Ring‐Closing Metathesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Total synthesis of (+)-SCH 351448.

Total synthesis of SCH 351448 was accomplished employing the ring-closing olefin metathesis reaction for the preparation of the 28-membered macrodiolide.

The first example of ring-closing olefin metathesis of dehydroamino acids: an application to the synthesis of azabicyclo[X.Y.0]alkanes

The first example of ring-closing metathesis reaction of dehydroamino acids using ruthenium-based catalyst leading to the azabicyclo[X.Y.0]alkanes has been demonstrated. A preliminary investigation into the scope and limitations of the method will be presented.