Synthesis of guaiane sesquiterpenoids by a ring-closing metathesis annulation sequence

A new route for the synthesis of guaiane and nor-guaiane sesquiterpenoids is described, using a ring-closing metathesis annulation reaction sequence on a chiral enantiopure cycloheptenone derived from (R)-(−)-carvone.     

Directed ring-closing metathesis of trienes by silyl substitution

A synthetic strategy for ‘disarming’ a terminal alkene by substitution with a bulky silyl blocking group has been developed. In a series of model studies, sequential selective ring-closing metathesis of trienes followed by selective mono-hydrogenation of the resulting diene is described. The bulky silylated alkene is activated for a subsequent cross-metathesis reaction with a range of diverse alkenes by protodesilylation.     

Synthesis of psudoheliotridane via formal [3+2] annulation and ring-closing metathesis

Base-induced coupling/cyclization stepwise [3+2] annulation of α-sulfonylacetamide with (Z)-2-bromoacrylates yielded polysubstituted pyroglutamates with three contiguous chiral centers with trans-trans orientation in a one-pot synthesis. The pyrrolizidine skeleton was obtained via the ring-closing metathesis (RCM) method. This facile strategy was used to synthesize psudoheliotridane.     

Synthesis of the floresolide B hydroquinone lactone core using ring-closing metathesis

The hydroquinone lactone core of the floresolides was synthesized through a ring-closing metathesis (RCM) approach. Optimal RCM efficiency was obtained at higher reaction concentration. An unexpected Lewis acid-promoted rearrangement of the hydroquinone and other observations relevant to on-going total synthesis efforts are discussed.     

Synthesis of dinucleotides with 2′-C to phosphate connections by ring-closing metathesis

Four different nucleosides with olefinic 2′-modifications were prepared; 2′-C-methylene, 2′-C-(propen-1-yl), 2′-C-allyl and 2′-O-allyl uridines, respectively. These were incorporated into dinucleotides with allyl phosphate or vinyl phosphonate linkages. Hence, six different dinucleotides were studied as substrates for RCM reactions, and from four of these, cyclic dinucleotides with connections between 2′-C and phosphorus of 3-6 atoms were obtained.     

Synthesis of gem-difluoromethylenated massoialactone by ring-closing metathesis

4,4-Difluoromassoialactone has been synthesized for the first time via a very short sequence, where the ring-closing metathesis (RCM) was employed as a key step. The efficient procedure can easily be extended to the synthesis of other gem-difluoromethylenated α,β-unsaturated-δ-lactone moiety. In addition, the viability of RCM of high electron-deficient olefins has been demonstrated.     

On the mechanism of a double ring-closing metathesis reaction

A detailed study of the steps involved in the double ring-closing metathesis reaction of 2 to 3 has been carried out. Both the selectivity and mechanism were affected by choice of catalyst.     

Synthesis of sulfur-substituted quinolizidines and pyrido[1,2-a]azepines by ring-closing metathesis

Sulfur-substituted quinolizidines and pyrido[1,2-a]azepines (7) can be prepared by ring-closing metathesis (RCM) of 4-(phenylthio)-1,2,5,6-tetrahydropyridin-2-ones (6) bearing terminal alkenyl groups at both N-1 and C-6 positions, which are obtained from 3-(phenylthio)-3-sulfolene (1) in four steps. Some synthetic transformations of 2-(phenylthio)-1,6,9,9a-tetrahydroquinolizin-4-one (7a) and 2-(phenylthio)-1,6,9,10,10a-pentahydropyrido[1,2-a]azepin-4-one (7d) are also reported.     

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.     

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.     

A hexafluorobenzene promoted ring-closing metathesis to form tetrasubstituted olefins

Highly efficient formation of tetrasubstituted olefins is described by ring-closing metathesis (RCM) using catalyst 2 in presence of hexafluorobenzene. This combination with hexafluorobenzene shows an unexpected promoting effect, which requires low catalysts loadings and allows the conversion of deficient olefins in high yields and very short reaction times.     

Formal synthesis of valienamine using ring-closing metathesis

(1R,2S,3S,4R)-2,3,4-Tri-O-benzyl-5-(benzyloxymethyl)-cyclohex-5-ene-1,2,3,4-tetrol, a precursor of the α-glucosidase inhibitor, valienamine, was synthesised in eight steps from tetrabenzyl glucose. The key steps were the selective protection of an open-chain diol, and the formation of the cyclohexene ring by ring-closing metathesis with the trisubstituted olefin of valienamine correctly in place.     

A synthetic entry to 2,3-fused ring indole derivatives by ring-closing metathesis reactions

Six to eight-membered carbocycles and eight-membered azacycles fused to the 2,3-position of the indole ring, representing tricyclic substructures of several indole alkaloids, can be synthesized by RCM reactions from easily accessible dienic precursors.     

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.     

Synthesis of new boron analogues of cyclic carboxylic α-amino acids using ring-closing metathesis reactions

Ruthenium catalyzed ring-closing metathesis has been used as a key step for the synthesis of cyclic α-aminoboronic esters as, for example, boron-containing mimics of pipecolic, 2-azepanecarboxylic acid or baikiain.     

Total synthesis of 8-oxypseudopalmatine and 8-oxypseudoberberine via ring-closing metathesis

Concise synthesis of 8-oxypseudopalmatine and 8-oxypseudoberberine has been achieved using ruthenium-catalyzed ring-closing metathesis (RCM) as the key step, in which the RCM substrates, 3-arylisoquinolinones, were prepared by lithiated cycloaddition reaction with o-toluamides and benzonitriles.     

Diversity-oriented approach to spirocycles via ring-closing metathesis

We have demonstrated a simple and an efficient method for the synthesis of spirocycles starting with inexpensive and commercially available carbonyl compounds. Various spirocycles involving spiropropellane derivative have been assembled via ring-closing metathesis with the aid of Grubbs’ first generation catalyst.     

Facile synthesis of azocino[4,3-b]indoles by ring-closing metathesis

The azocino[4,3-b]indole system, tricyclic substructure of the indole alkaloids apparicine and ervaticine, is efficiently assembled by ring-closing metathesis of 2-allyl-3-(allylaminomethyl)indoles. The metathesis sites are introduced into the indole nucleus by reductive amination of a 3-formyl derivative with allylamine, followed by α-lithiation with subsequent electrophilic trapping with acrolein.     

Pd-catalyzed arylation/ring-closing metathesis approach to azabicycles

Palladium-catalyzed arylation followed by Grignard addition to imines and ring-closing metathesis, using Grubbs’ catalysts, provides a route to six-, seven-, and eight-membered azabicycles.     

A ring-closing metathesis approach to secosteroidal macrocycles

An efficient synthesis of secosteroidal macrocycles has been achieved via an oxidative ring-expansion/ring-opening sequence and a ring-closing metathesis reaction as the key steps.