Synthesis of cyclic dienamide using ruthenium-catalyzed ring-closing metathesis of ene-ynamide

Ring-closing metathesis of ene-ynamide, which has alkene and ynamide moieties in a molecule, using a second-generation ruthenium carbene complex produced nitrogen-containing heterocycles, which have a dienamide moiety, in high yields. Diels-Alder reaction of the cyclized product with dienophile proceeded smoothly to give an indole or quinoline derivative in high yield.     

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 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.     

Enantioselective ruthenium-catalyzed ring-closing metathesis

[reaction: see text] The first enantioselective ruthenium olefin metathesis catalysts have been prepared, and high enantiomeric excesses (up to 90%) are observed in the desymmetrization of achiral trienes. A model consistent with the stereochemical outcome of the reactions is described and suggests side-on olefin binding and reorganization of the halide ligands.     

Synthesis of cyclic peptides by ring-closing metathesis

The synthesis of a series of "amide to amide" cyclized peptides by ring-closing metathesis (RCM) as well as a convenient synthesis for the linear precursors is described. In addition, the influence of the length of the alkene substituents and the influence of the peptide sequence is investigated, leading to a set of general rules to obtain "amide to amide" cyclized peptides by RCM.     

Synthesis of cyclic sulfones by ring-closing metathesis

A general and highly efficient synthesis of cyclic sulfones based on ring-closing metathesis has been developed. The synthetic utility of the resulting cyclic sulfones was demonstrated by their participation in stereoselective Diels-Alder reactions and transformation to cyclic dienes by the Ramberg-B?cklund reaction.     

Synthesis of cyclic peptidosulfonamides by ring-closing metathesis

N-Protected beta-aminoethanesulfonyl chlorides (2a-e) were used in the preparation of sulfonamides 4, 8, 11a-c, and 15. Ring-closing metathesis of sulfonamides 4 and 8 did not lead to the expected nine-membered cyclic peptidosulfonamides. In contrast, the allylated peptidosulfonamides 11a-c and 15 turned out to be suitable precursor systems for ring-closing metathesis using second-generation Grubbs catalyst and nine-membered cyclic peptidosulfonamides were obtained in 47-60% yields. The possibility for incorporation of these cyclic peptidosulfonamides into a peptide sequence was illustrated by the incorporation of an amino acid on the "S"- or "N"-terminus leading to 16 and 18-20, respectively. A model of cyclic peptidosulfonamide 16 hints at an extended-like structure.     

Construction of carbocyclic ring of indoles using ruthenium-catalyzed ring-closing olefin metathesis

The selective synthesis of substituted indoles was achieved by the ring-closing olefin metathesis (RCM)/elimination sequence or the RCM/tautomerization sequence of functionalized pyrrole precursors. The RCM/elimination sequence was also applied to double ring closure to yield a substituted carbazole.     

Efficient microwave-assisted formation of functionalized 2,5-dihydropyrroles using ruthenium-catalyzed ring-closing metathesis

A rapid method for the formation of functionalized 2,5-dihydropyrroles using ruthenium-catalyzed ring-closing metathesis under microwave irradiation is presented. The diene substrates were efficiently prepared from aza-Baylis-Hillman adducts.     

Synthesis of cyclic proline-containing peptides via ring-closing metathesis

[reaction: see text] Several dienes embedded in di- and tripeptides which incorporate proline have been prepared and subjected to ring-closing metathesis. Bicyclic peptides of well-defined amide geometry and of varying ring sizes were prepared. Several limitations of the cyclization step were revealed.     

Synthesis of 4,4-difluoroglycosides using ring-closing metathesis

4-Deoxy-4,4-difluoro-glycosides have been synthesised for the first time via a direct sequence involving ring-closing metathesis and indium-mediated difluoroallylation with 1-bromo-1,1-difluoropropene in water. Two protecting group strategies were explored, one to allow protection of the primary C-6 hydroxyl group throughout the sequence, while the second was intended to allow deprotection after RCM and before dihydroxylation. The benzyl ether could be used in the first role, and pivaloyl is effective in the second. Dihydroxylations were highly stereoselective and controlled by the orientation of the glycosidic C-O bond.     

Synthesis of spirocyclic thiazolidinediones using ring-closing metathesis and one-pot sequential ring-closing/cross metathesis

A novel synthetic route to spirocyclic thiazolidinediones is reported by utilizing ring-closing metathesis (RCM). A selective cross metathesis (CM) of N-allyl azaspiro derivatives with different olefins has been demonstrated to prepare substituted azaspiro-[4.4]nonenediones. The X-ray crystal structure of a spirocyclic thiazolidinedione dimer is described, which has been prepared in two steps from thiazolidinedione using a one-pot sequential ring-closing and self metathesis. Cross metathesis proceeds smoothly with both electron rich and poor olefins. The symmetrical bis-thiazolidinedione spirocyclic system can be used as CM coupling partner with olefins. One-pot sequential RCM-CM has been developed for the synthesis of substituted spirocyclic compounds. The methodology allows a quick access to thia-azaspiro-[4.4]nonene and -[4.5]decene-dione ring systems from readily available starting materials which are not otherwise accessible.     

Synthesis of cyclic sulfamoyl carbamates and ureas via ring-closing metathesis

Synthetic routes to a diverse set of cyclic sulfamoyl carbamates and ureas are reported. These routes utilize 3-component coupling, Mitsunobu alkylation, and ring-closing metathesis using the second-generation Grubbs catalyst to achieve the synthesis of the target S-heterocyclic compounds. Cyclic S-heterocycles ranging from 9- to 11-membered rings have been obtained.     

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.     

The pivotal role of symmetry in the ruthenium-catalyzed ring-closing metathesis of olefins

The synthesis of Ru-based precatalysts with N-heterocyclic carbene (NHC) ligands bearing syn- and anti-methyl groups on the NHC backbone and aryl N-substituents with differing steric bulk was carried out. The catalytic behavior of the monophospine Ru precatalysts (7a, 7b, 8a, and 8b) was compared to the corresponding family of phosphine-free catalysts (9a, 9b, 10a and 10b) in the ring-closing metathesis (RCM) of olefins. These catalysts showed high efficiency in RCM reactions and the syn-isomers 7a and 9a, in particular, proved to be among the most active catalysts in the formation of tetrasubstituted olefins through RCM. DFT studies on the entire RCM catalytic cycle of hindered olefins were performed to rationalize the different behaviors of catalysts with syn- and anti-methyl groups on the NHC backbone. Theoretical results not only disclosed how NHC symmetry influences the overall activity of the catalyst, but also gave relevant and more general indications on the crucial steps of the RCM of olefins.     

Synthesis of cyclic phosphonate analogues of (lyso)phosphatidic acid using a ring-closing metathesis reaction

We describe a versatile and efficient method for the preparation of acyloxy-substituted six-membered cyclic phosphonates using the ring-closing metathesis. After closure, the key cyclic phosphonate intermediate was dihydroxylated and converted to a new class of conformationally constrained PA and LPA analogues. The oleoyloxy-substituted cyclic phosphonate 4 had unique receptor-selective properties as a ligand, showing partial activation of the LPA2 GPCR and weak antagonism of the LPA1 GPCR.     

Synthesis of cyclitols via ring-closing metathesis

A convenient synthesis of enantiomerically pure and differentially protected l-chiro- and myo-inositols as well as conduritols B and F from 2,3,4-tri-O-benzyl-d-xylopyranose via ring-closing metathesis is reported. The facile synthesis of conduritol B constitutes a short formal synthesis of (−)-cyclophellitol.     

Synthesis of coumarins by ring-closing metathesis using Grubbs’ catalyst

A novel generally applicable synthesis of coumarins from phenolic substrates utilizing ring-closing metathesis is described. This sequence involves O-allylation of phenols followed by ortho-Claisen rearrangement, subsequent based-induced isomerization affording 2-(1-propenyl)phenols, acylation with acryloyl chloride, and finally ring-closing metathesis (RCM) with Grubbs’ second generation catalyst.     

Formation of polycyclic lactones through a ruthenium-catalyzed ring-closing metathesis/hetero-Pauson-Khand reaction sequence

Processes that form multiple carbon-carbon bonds in one operation can generate molecular complexity quickly and therefore be used to shorten syntheses of desirable molecules. We selected the hetero-Pauson-Khand (HPK) cycloaddition and ring-closing metathesis (RCM) as two unique carbon-carbon bond-forming reactions that could be united in a tandem ruthenium-catalyzed process. In doing so, complex polycyclic products can be obtained in one reaction vessel from acyclic precursors using a single ruthenium additive that can catalyze sequentially two mechanistically distinct transformations.