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 huperzine B through ring closing metathesis

Huperzine B and its analogues were obtained through ring closing metathesis of N-alkenyl amine to the corresponding tricyclic compounds.     

Synthesis of [6-6-6] ABE tricyclic ring analogues of methyllycaconitine

A new synthesis of the bridged [6-6-6] ABE tricyclic ring analogues of methyllycaconitine with the C-1 oxygenated substituents has been developed using an efficient aza-annulation of β-enamino ketone followed by a facile decarboxylation to form BE rings. Subsequent elaboration to form the A ring was achieved by a transannular acyl radical cyclization with concomitant equipment of the key C-1 oxygen functionality.     

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 spirocyclic butenolides by ring closing metathesis

Spirocyclic butenolides were efficiently prepared by a ring closing metathesis strategy.     

Synthesis of bruguierol A employing ring closing metathesis

An expedient synthesis of bruguierol A encompassing a novel 2,3-benzo-8-oxabicyclo[3.2.1]octane ring system is described employing ring closing metathesis to generate the oxa-bridged tricyclic core.     

Examination of the olefin-olefin ring closing metathesis to prepare Latrunculin B

Three subunits of the potent actin polymerization inhibitor Latrunculin B were synthesized and assembled using olefin-olefin ring closing metathesis chemistry to close the 14-membered macrocycle. Metathesis reactions of substrates with various remote protecting group patterns were examined and gave 6,7-E-lactones as the preferred products.     

Synthesis of cycloalkenyl geminal bisphosphonates by ring closing metathesis

Five‐ and six‐membered cycloalkenyl bisphosphonates were obtained by ring closing metathesis (RCM) reactions of diethyl bis(alkenyl)methylene bisphosphonates using ruthenium alkylidene catalysts. The substitution pattern on the double bonds involved in the reaction greatly influences the reaction rate. The synthesis of the starting materials was carried out by dialkylation of tetraethyl methylene bisphosphonate or through a Michael addition of Grignard reagents to tetraethyl vinylidene bisphosphonate followed by alkylation, depending on the structure of the required substrate. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:332–338, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20622     

Synthesis of sulphur-containing heterocycles by ring closing diene metathesis

We have shown that, surprisingly, the Schrock molybdenum alkylidene catalyst 1 can perform ring closing metathesis reactions on substrates containing a sulphide group, converting diallyl sulphide 5 to 2,5-dihydrothiophene 6 with >99 % conversion. By contrast, the ruthenium alkylidene catalyst 2, which is generally more tolerant of functional groups in the substrate, is unreactive towards diallylsulphide. However even the molybdenum catalyst 1 proved unable to catalyse ring closure of tetrathiafulvalene derivative 7.     

Synthesis of a para-quinone macrolactam related to geldanamycin by ring closing metathesis

Model studies conducted with the α,β,γ,δ-unsaturated 3-alkenyl-2,4,5-trimethoxyanilides 11 revealed that a ring closing metathesis (RCM) of these compounds is possible if the ansa chain contains more than 14 atoms. The (Z)-configurated products 12c-e were obtained in good yields (77-87%) and with perfect simple diastereoselectivity. Since the oxidation of the 2,4,5-trimethoxyanilides led predominantly to undesired ortho-quinones such as 15 or to para-azaquinones such as 16 the macrocyclic 2,5-di-iso-propoxy-4-methoxyanilide 22 was prepared. The iso-propyl protecting groups could be selectively cleaved and the intermediate para-hydroquinone oxidized on air to the desired para-quinone 2 (86% yield). The compound shows some key features (macrolactam ring with the same ring size, α,β,γ,δ-unsaturated anilide, para-quinone) of geldanamycin.     

Asymmetric synthesis of unusual fused tricyclic beta-lactam structures via aza-cycloadditions/ring closing metathesis

Conveniently substituted bis-beta-lactams, pyrrolidinyl-beta-lactams, and piperidinyl-beta-lactams undergo ring-closing methatesis using Grubbs' carbene, Cl(2)(Cy(3)P)(2)Ru=CHPh, to give medium-sized rings fused to bis-2-azetidinone, pyrrolidinyl-2-azetidinone, or piperidinyl-2-azetidinone systems. The diolefinic cyclization precursors can be obtained from optically pure 4-oxoazetidine-2-carbaldehydes bearing an extra alkene tether at position 1 or 3 of the beta-lactam ring via [2 + 2] cycloaddition of imino 2-azetidinones, N-metalated azometine ylide [3 + 2] cycloaddition, and subsequent N-acylation of the pyrrolidinyl nitrogen atom, or through aza-Diels-Alder cycloaddition of 2-azetidinone-tethered imines. Under standard reaction conditions, the combination of cycloaddition reactions of 2-azetidinone-tethered imines with ring-closing methatesis offers an asymmetric entry to a variety of unusual fused tricyclic 2-azetidinones bearing two bridgehead nitrogen atoms.     

First synthesis of a branched beta-C-tetrasaccharide using a triple ring closing metathesis cyclization

The first synthesis of a branched beta-C-tetrasaccharide has been carried out through the use of an esterification-ring closing metathesis (RCM) strategy. The precursor triacid 2a was readily prepared via standard chemical methods from a known starting material, and dehydrative coupling with an excess of olefin alcohol 1a gave triester 3a in excellent yield. Methylenation of the triester 3a and subsequent triple RCM reaction was followed by an in situ hydroboration-oxidation to furnish the branched beta-C-tetrasaccharide 6a in good overall yield.     

Synthesis of pyranonaphthoquinone antibiotics involving the ring closing metathesis of a vinyl ether

The synthesis of two antibiotic pyranonaphthoquinones was performed by a straightforward synthetic route utilizing ring closing metathesis. Vinylation of 3-(1-propenyl)-2-hydroxymethyl-1,4-dimethoxynaphthalene under iridium catalysis and subsequent ring closing metathesis of 3-(1-propenyl)-2-vinyloxymethyl-1,4-dimethoxynaphthalene with Grubbs' catalyst paved the way to the natural antibiotics pentalongin and psychorubrin.     

Synthesis of chiral macrocyclic sugar-peptide hybrids by ring closing metathesis approach

Furanoside and peptide appended bis-olefins afforded monomeric 12- to 18-membered cyclic olefins fused to furanoside rings via RCM approach using Grubbs’ Catalyst.     

Synthesis of 2′-O,3′-O bicyclic adenosine analogues using ring closing metathesis

The synthesis of 2′-O,3′-O bicyclic adenosine derivatives is presented as the first examples of a new family of 13-membered ring bicyclic nucleoside analogues. Cyclisation was achieved through ring closing metathesis (RCM) on a diene intermediate using Grubbs’ catalyst. The Z and E isomers were purified and characterised.     

Stereoselective synthesis of (+)-pericosine B and (+)-pericosine C using ring closing metathesis approach

Stereoselective synthesis of (+)-pericosine B and (+)-pericosine C were achieved from d-ribose using RCM and RCEYM as key steps.     

Four-component Pd-catalysed cascade/ring closing metathesis. Synthesis of heterocyclic enones

A palladium-catalysed four-component process is described involving carbon monoxide, allene and aryl/heteroaryl iodides generating (π-allyl) palladium species, which are intercepted by alkene tethered nitrogen nucleophiles to afford 1,6- and 1,7-dienones. Subsequent ring closing metathesis affords five- and six-membered N-heterocyclic enones. The N-heterocyclic enones are active dipolarophiles in 1,3-dipolar cycloaddition reactions as exemplified by azomethine ylide and nitrone cycloadditions.     

Total Synthesis of ent-lepadin F and G by a tandem ene-yne-ene ring closing metathesis

The first total synthesis of the decahydroquinoline-alkaloids lepadin F and G is described. As key steps, the decahydroquinoline skeleton has been synthesized by utilizing a tandem ene-yne-ene ring closing metathesis of an acyclic precursor followed by a stereoselective hydrogenation of the resulting diene moiety. The selectivity of these two steps was achieved by a well-directed hydroxyl protection strategy. The synthesized compounds were found to be enantiomers of natural lepadin F and G, consequently the absolute configuration of the natural compounds could be assigned.     

Synthesis of phosphorus containing medium ring heterocycles by sequential Claisen rearrangement and ring closing metathesis

An efficient method for the synthesis of novel medium ring phosphorus containing heterocycles starting from phenol derivatives by ruthenium catalyzed ring closing metathesis is described. This work deals with a sequential aromatic Claisen-rearrangement, coupling of an allyl/vinyl phosphonate, and ring closing metathesis reaction. All of these reactions were carried out at ambient temperature to afford the medium-sized phosphorus heterocycles in excellent yields.     

Synthesis of pentahydroxy indolizidine alkaloids using ring closing metathesis: attempts to find the correct structure of uniflorine A

Ring closing metathesis of d-glucose derived diene-substrate containing nitrogen functionality followed by asymmetric dihydroxylation afforded sugar substituted dihydroxylated pyrrolidines 8a-c which on 1,2-acetonide deprotection and reductive amination afforded putative uniflorine A 2a and its analogues 2b-c, respectively.