Synthesis of an eight-membered cyclic pseudo-dipeptide using ring closing metathesis

Ring closing metathesis of diallylglycine 6 provided cyclic Z-olefin 7 in 80% yield. The reaction was promoted by substitution of the amide nitrogen with the 2,4-dimethoxybenzyl group allowing for the required cis diallylglycine amide rotamer. Removal of the protecting groups provided cyclic dipeptide 2, a constrained scaffold useful in peptidomimetic research.     

Synthesis of styrenes using ruthenium-catalyzed ring-closing enyne metathesis

The synthesis of substituted styrenes was achieved by ring-closing enyne metathesis (RCEM)/elimination of enyne substrates 12. The synthetic approach was also effective for a different type of enyne substrate 14, yielding corresponding styrene 15.     

Synthesis of oxacyclic dienes via ring-closing enyne metathesis: difference in construction of eight-membered rings

A series of oxacyclic diene compounds, especially eight-membered products bearing a single oxygen atom which have not been reported previously, were successfully synthesized via ring-closing enyne metathesis using the second-generation Grubbs catalyst. In contrast to the construction of the five-membered rings, completely opposite substrate selectivity that methyl substituted internal alkyne showed much higher reactivity than terminal alkyne was observed in building eight-membered ring derivatives.     

Synthesis of (+)-anatoxin-a using enyne metathesis

Synthesis of N-tosylanatoxin-a was achieved by metathesis of enyne in cis-substituents on a pyrrolidine derivative. Metathesis reactions of enyne having terminal alkyne using various ruthenium-carbene complexes did not give a good results. However, when the terminal alkyne was protected with a TMS group, the reaction proceeded smoothly using a second-generation ruthenium-carbene complex to give the desired cyclized compound in high yield. Oxymercuration followed by Dess-Martin oxidation afforded N-tosylanatoxin-a.     

Cycloheptadiene ring synthesis by tandem intermolecular enyne metathesis

[reaction: see text] The tandem intermolecular enyne metathesis between 1-alkynes and cyclopentene is reported, providing 2-substituted 1,3-cycloheptadienes. The success of the intermolecular reaction hinges on an appropriate balance between cycloalkene ring strain and reactivity of the alkyne.     

Cross enyne metathesis of para-substituted styrenes: a kinetic study of enyne metathesis

[Reaction: see text] The intermolecular enyne metathesis between alkynes and styrene derivatives was developed to study electronic effects in enyne metathesis. A Hammett plot for the overall reaction, catalyst initiation and vinyl carbene turnover was determined with the second generation Grubbs ruthenium carbene catalyst.     

Ethylene-promoted intermolecular enyne metathesis

[reaction: see text] Intermolecular enyne metathesis between functional group-rich alkynes and vinyl ethers was promoted by ethylene cometathesis. The concentration of ethylene was optimized to suppress the competing formation of butadiene through background ethylene metathesis. The role of ethylene appears to be both protective and rate enhancing.     

Group-selective ring-closing enyne metathesis

The ring-closing metathesis (RCM) of dienynes represents a powerful methodology for the construction of mono- and bicyclic systems containing 1,3-diene functionality. Despite its synthetic potential, the utility of dienyne RCM is significantly reduced due to poor group selectivity. To circumvent this shortcoming, several strategies utilizing steric hindrance, electronic variation, relay metathesis and ring-closure kinetics have been implemented to exert control over the reaction pathways. This article highlights a variety of methods to achieve group-selective enyne RCM of dienynes.     

A cascade enyne/ring closing metathesis approach to angularly fused dioxatriquinanes

An expedient and first tandem enyne/ring closing metathesis approach on a sugar furanose template leading to a novel angularly fused dioxa-triquinane is described here.     

A stereoselective enyne cross metathesis

[reaction: see text] Intermolecular enyne metathesis reaction of alkynes with olefins catalyzed by second-generation Grubbs catalyst (1) proceeded stereoselectively under ethylene atmosphere to produce 1,3-disubstituted butadienes with E stereochemistry.     

Ethylene-promoted versus ethylene-free enyne metathesis

The role of ethylene in promoting metathesis of acetylenic enynes is probed within the context of ring-closing enyne metathesis, using first- and second-generation Grubbs catalysts. Under inert atmosphere, rapid catalyst deactivation is observed by calibrated GC-FID analysis for substrates with minimal propargylic bulk. MALDI-TOF mass spectra reveal a Ru(enyne)(2) derivative that exhibits very low reactivity toward both enyne and ethylene. Under ethylene, formation of this species is suppressed. Enynes with bulky propargylic groups are not susceptible to this catalyst deactivation pathway, even under N(2) atmosphere.     

Synthesis of biaryl compounds using tandem ruthenium-catalyzed ring-closing metathesis

Tandem ring-closing enyne metathesis (RCEM)/ring-closing olefin metathesis (RCM) of tetraenynes with Grubbs second-generation catalyst, followed by elimination, was found to be a new and efficient synthetic approach to biaryl compounds. A preliminary asymmetric version of this approach, which used homochiral Ru-alkylidene catalysts, is also presented.     

Synthetic study of (+)-anthramycin using ring-closing enyne metathesis and cross-metathesis

Synthesis of (+)-anthramycin was examined. A pyrrolobenzodiazepine skeleton could be synthesized by reductive cyclization of pyrrolidine derivative, which was obtained by enyne metathesis. The conjugated enamide ester part of (+)-anthramycin derivative was constructed by cross-metathesis.     

Ruthenium-catalyzed ring-opening and ring-closing enyne metathesis

[reaction: see text]. When a CH2Cl2 solution of an enyne containing the cycloalkene moiety was stirred in the presence of ruthenium-carbene complex (10 mol %) at room temperature under ethylene gas (1 atm), ring-opening and ring-closing metathesis occurred to afford cyclized triene. The reaction was carried out under argon gas, and no cyclized product was obtained. Enynes with a terminal alkyne gave good results.     

Synthesis and ring-opening metathesis polymerization of eight-membered unsaturated lactams and related monomers

Novel eight-membered ring unsaturated lactams were synthesized and tested as monomers for the ruthenium-catalyzed ring-opening metathesis polymerization (ROMP). The reaction of a N-protected cyclic alkeneamine was also investigated. The Grubbs’ benzylidene complexes RuCl₂(=CHPh)(PCy₃)₂ or RuCl₂(=CHPh)(PCy₃)(IMesH₂) and selected ruthenium–arene species bearing either phosphine or stable Arduengo-type N-heterocyclic carbene ligands served as catalyst precursors. In most cases, isomerization of the starting materials took place and only 1-benzyl-1-aza-2-ketocyclooct-5-ene afforded a polymeric product. This polyamide was characterized by numerous analytical techniques.     

Synthesis and characterisation of four- and eight-membered ring auralactam complexes

The reactions of the cyclo-aurated gold(III) dihalide complex [{C₆H₃(CH₂NMe₂)-2-(OMe)-5}AuCl₂] with N-cyanoacetylurethane [NCCH₂C(O)NHCO₂Et], 2-benzoylacetanilide [PhC(O)CH₂C(O)NHPh] and acetoacetanilide [MeC(O)CH₂C(O)NHPh], and [{C₆H₄(CH₂NMe₂)-2}AuCl₂] with acetoacetanilide in dichloromethane with excess silver(I) oxide gives the first examples of auralactam complexes, containing (O)---CHR′ four-membered rings. A single-crystal X-ray diffraction study on the complex [{C₆H₄(CH₂NMe₂)-2}A H(COMe)}] reveals similar structural features to related metallalactam complexes of platinum(II) and palladium(II). When a CDCl₃ solution of the complex [{C₆H₃(CH₂NMe₂)-2-(OMe)-5}A HCN}] is allowed to stand for 18 h, a novel dimerisation reaction occurs, giving the insoluble product [{C₆H₃(CH₂NMe₂)-2-(OMe)-5}Au{N(CO₂Et)C(O)CHCN}]₂·2CDCl₃, characterised by an X-ray structure determination. The dimer contains an eight-membered A

Full-size image

ring.     

Synthesis of cholaphanes by ring closing metathesis

The synthesis of cholaphanes by ring closing metathesis (RCM) of 3α,7α,12α,24-tetraol allyl derivatives, obtained from cholic acid, was attempted. The reactions of tetraol 3,24-diallyl ether or 3,24-diacrylate were not satisfactory. However, diallyl derivatives of disteroidal 3,3′- or 24,24′-ortho-phthalates reacted smoothly affording cyclic dimers in good yields. In all the reactions studied, the E isomers of the macrocycles were obtained in excess.     

Synthesis of [6,n] cis-fused ring compounds via Cr-mediated dearomatisation-ring-closing metathesis

cis-Fused [6,8], [6,7], [6,6] and [6,5] ring systems containing a cyclohexadiene ring unit, a cycloenone ring and a quaternary carbon at the ring junction were obtained in only two steps from [Cr(CO)3(eta6-p-methoxyphenyl oxazoline)]. The sequence proceeds via diastereoselective addition of three C-substituents across an arene double bond, followed by allylation and ring closing metathesis (RCM). RAMP-hydrazone and (R)-isopropyloxazoline were used as chiral auxiliaries to provide, after removal of the auxiliaries, the enantiomerically highly enriched [6,7] cis-fused system.     

Synthesis of spiro-pyridopyridine analogues by Grubbs' catalyst mediated alkene and enyne metathesis reaction

A practical synthesis of spiro-naphthyridinone derivatives is described by the combination of the Claisen rearrangement and ring-closing metathesis/ring-closing enyne metathesis process. The RCM or RCEM proceeded smoothly in the presence of Grubbs' first generation catalyst at room temperature under a nitrogen atmosphere.     

Ruthenium dihydride complexes as enyne metathesis catalysts

Ruthenium–catalyzed enyne metathesis is a reliable and efficient method for the formation of 1,3-dienes, a common structural motif in synthetic organic chemistry. The development of new transition-metal complexes competent to catalyze enyne metathesis reactions remains an important research area. This report describes the use of ruthenium (IV) dihydride complexes with the general structure RuH₂Cl₂(PR₃)₂ as new catalysts for enyne metathesis. These ruthenium (IV) dihydrides have been largely unexplored as catalysts in metathesis-based transformations. The reactivity of these complexes with 1,6 and 1,7-enynes was investigated. The observed reaction products are consistent with the metathesis activity occurring through a ruthenium vinylidene intermediate.