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.     

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.     

Cross-metathesis and ring-closing metathesis reactions of amino acid-based substrates

Olefin tethers of variable length, introduced into a natural amino acid (side-chain of Ser, Cys; N-terminus of Arg; C-terminus of Phe and Tic; and in both the side-chain and either the N- or C-terminus of Ser, Cys and Tyr), undergo metathesis on treatment with Grubbs' second generation catalyst. Side-chain linked dimers of Ser, Cys and Tyr were obtained by cross-metathesis, while olefin installation at the N- and C-terminus led to dimers of Arg and Phe (or Tic), respectively. Ring-closing metathesis of the doubly alkenylated derivatives of Ser, Cys and Tyr gave 12-, 20- and 24-membered macrocycles.     

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.     

A novel synthesis of substituted quinolines using ring-closing metathesis (RCM): its application to the synthesis of key intermediates for anti-malarial agents

A method for synthesizing substituted quinolines using ruthenium-catalyzed ring-closing metathesis as a key step has been developed. Substituted 1,2-dihydroquinolines, 4-silyloxy-1,2-dihydroquinoline and 4-methoxy-1,2-dihydroquinoline, were successfully synthesized in excellent yields via ene-ene metathesis and silyl or alkyl enol ether-ene metathesis, respectively. The synthetic intermediates of the antimalarial agents quinine, chloroquine, and PPMP-quinine hybrid were efficiently synthesized by this methodology.     

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.     

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.     

Expeditious synthesis of helianane and C-10 halogenated heliananes employing ring-closing metathesis

An expeditious synthesis of the marine sesquiterpene helianane enclosing an unusual benzoxocane ring system is described employing ring-closing metathesis as the key step. Helianane has been further converted to the naturally occurring C-10 bromo and chloro derivatives.     

Parallel synthesis of individual shikimic acid-like molecules using a mixture-operation strategy and ring-closing enyne metathesis

Three new diastereomeric shikimic acid analogues (4-amino-3,5-dihydroxyl-cyclohex-1-en-carboxylic acids, 16) bearing a C-4 amino group were synthesized in parallel by a mixture-operation protocol. Ring-closing enyne metathesis (RCEYM) under ethylene atmosphere was successfully employed to construct the desired carbocycles in high efficiency. The absolute configurations of each final product were confirmed by the 1D and 2D NMR techniques.     

A systematic strategy for preparation of uncommon sugars through enzymatic resolution and ring-closing metathesis

A systematic synthetic strategy has been developed for producing uncommon sugars. This method involved kinetic resolution allylic alcohol followed by ring-closing-metathesis (RCM) to generate optical pure lactones as the common precursors. After further derivatization, four representative uncommon sugar units were successfully synthesized.     

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.     

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.     

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.     

An isomerization-ring-closing metathesis strategy for the synthesis of substituted benzofurans

Twelve substituted benzofurans were synthesized from their corresponding substituted 1-allyl-2-allyloxybenzenes using ruthenium-mediated C- and O-allyl isomerization followed by ring-closing metathesis.     

Conversion of chiral unsaturated cyanohydrins into chiral carba- and heterocycles via ring-closing metathesis

Aliphatic unsaturated cyanohydrins 1-3 served as starting materials in the synthesis of a set of new chiral unsaturated cyclic 1,2-ethanolamines. Combining a Grignard addition-NaBH₄ reduction sequence with a ring-closing metathesis afforded unsaturated cyclic 1,2-ethanolamines 7-11 and 22-25 in good yields and high ee (96-99%). The conversion of cyanohydrins 1-3 via a DIBAL reduction-transimination-NaBH₄ reduction sequence, using allylamine, followed by ring-closing metathesis yielded tetrahydropyridines 28, tetrahydroazepinols 33 and tetrahydroazocinols 34 in high yields and excellent ee (97-99%).     

Microwave-assisted ring-closing metathesis of diallylamines: a rapid synthesis of pyrrole and pyrroline derivatives

The ring-closing metathesis (RCM) reactions of diallylamines occurred under controlled microwave irradiation. In addition to the high reaction rate, the key features of the reaction are that it can be carried out without deactivation of the substrates and without the use of Lewis acids.     

Ring-closing metathesis for the synthesis of heteroaromatics: evaluating routes to pyridines and pyridazines

Ring-closing olefin metathesis (RCM) has been applied to the efficient synthesis of densely and diversely substituted pyridine and pyridazine frameworks. Routes to suitable metathesis precursors have been investigated and the scope of the metathesis step has been probed. The metathesis products function as precursors to the target heteroaromatic structures via elimination of a suitable leaving group, which also facilitates earlier steps by serving as a protecting group at nitrogen. Further functionalisation of the metathesis products is possible both prior to and after aromatisation. The net result is a powerful strategy for the de novo synthesis of highly substituted heteroaromatic scaffolds.     

Design of new synthetic strategies to cyclophanes via ring-closing metathesis

A simple synthetic methodology to cyclophanes containing hydroxyl groups has been reported. The key steps involved here are: Grignard reaction, double Claisen rearrangement, and ring-closing metathesis. The strategy reported here is protecting group-free synthesis.     

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.