Studies directed toward the synthesis of the scabrosins: validation of a tandem enyne metathesis approach

A synthetic approach to the scabrosin family of antibiotics using a ruthenium carbene-catalyzed tandem metathesis and a Pd(II)-catalyzed cyclization is described. The chiral propargyl amino acid is furnished through enantioselective phase-transfer propargylation. The synthesis of the cyclohexadiene ring system is achieved through ring synthesis using tandem enyne metathesis, previously developed in our lab. The complementary methods of methylene-free and 1,5-hexadiene-alkyne metatheses are compared. The indoline heterocycles are formed using a two-step chloroacetoxylation (Bäckvall reaction) with subsequent nucleophilic attack by an amide nucleophile. The indoline subunits were joined and cyclized to furnish the core diketopiperazine ring. The stereochemical assignment of intermediates is also discussed.     

Selective tandem enyne metathesis for the synthesis of functionalized cycloheptadienes

The regio- and site-selective ring expansion of dienes and the regioselective ring expansion of substituted cyclopentenes provide 1,3-cycloheptadienes by enyne metathesis under methylene-free conditions. Site-selectivity results from differential ring strain among two different cycloalkenes in diene reactants. The high regioselectivity found in the ring expansion of tetrahydroindene (THI) is explained on the basis of a selective ring opening by the second generation Grubbs' ruthenium carbene complex. The ring opening of substituted cyclopentenes and cyclopentene contained in a bicyclic ring system was also achieved. The ring expansion of bicyclic dienes provided seven-membered dienes contained in the bicyclo[5.2.0]nonane ring system. Details of the structural analysis are also discussed. A mechanistic analysis is provided to account for the data presented herein.     

Stereoconvergent Synthesis of Z-1,3-Disubstituted-1,3-Dienes by Uphill Photocatalysis

A variety of 1-aryl-1,3-dienes were isomerized from E to Z isomers by photocatalysis using Ru(bpy)₃[PF₆]₂ and blue LED light. Enrichment of the Z-isomer is thought to occur by selective triplet energy transfer from the photocatalyst to the stereoisomeric mixture. The 1,3-diene starting materials are easily made by catalytic ene-yne metathesis (EYM). To access 1,3-diene Z-stereoisomers directly, a one pot procedure was developed. Additional 1,3-dienes were investigated for both isomerization and Z-enrichment. The combination of cross EYM with photocatalysis allows for the stereoconvergent synthesis of Z-1,3-dienes.     

An alternative stereoselective synthesis of greensporone C

Greensporone C, a new 14-membered resorcylic acid lactone, has been synthesized from inexpensive and commercially available starting materials. This convergent synthesis utilizes Cross metathesis using the Grubbs Hoveyda catalyst, alkylation of 1,3-dithiane and Yamaguchi macrolactonization as key steps.     

Synthesis of fused imidazo azepine derivatives by sequential van Leusen/enyne metathesis reactions

A facile synthesis of fused imidazo azepine derivatives by a van Leusen/intramolecular enyne metathesis synthetic sequence is reported. The two-step reaction sequence generates compounds of significant molecular complexity from simple starting materials in an expedient fashion with good overall yields.     

Synthesis of six-membered cyclic siloxanes via enyne metathesis with a ruthenium catalyst generated in situ

The catalytic system in situ generated by combination of [RuCl₂(p-cymene)]₂ as a ruthenium source, 1,3-bis(mesityl)imidazolinium chloride (MesH₂ImCl) as a bulky electron-releasing carbene precursor and cesium carbonate as a base, is shown to be an efficient catalyst for the metathesis reaction of propargylic allylsilyl ethers R¹---CCCR₂---O---SiMe₂---CH₂CH=CH₂. The metathesis products, the cyclic siloxanes, were obtained after complete conversion of the enynes in 67–87% isolated yields. These six-membered ring compounds contain the 1,3-diene unit that is used in Diels–Alder reaction and give access to heterobicyclic derivatives. The resulting cyclic siloxanes are selectively opened under oxidative conditions with H₂O₂ to afford allylic diols, with fluoride to form conjugated triene and under hydrogenation conditions with Pd/C catalyst to give a tetrasubstituted alkene.     

Toward the synthesis of amphidinolide P: optimization of a model ene–yne metathesis fragment coupling

Ene–yne cross metathesis was assessed for use as a key fragment coupling in a planned total synthesis of amphidinolide P. A terminal alkyne containing a β,γ-epoxide was synthesized and employed as the alkyne partner in an intermolecular ene–yne metathesis. In the alkene substrate, optimal functionality and reaction conditions were determined. An unprotected allyl alcohol was found to be critical for both high yield and high E-selectivity. Fewer equivalents of the alkene resulted in incomplete reaction and side reactions consumed the terminal alkyne. The best ruthenium carbene precatalysts were found to be the Hoveyda–Grubbs carbene complexes.     

A phase‐separable second‐generation hoveyda‐grubbs catalyst for ring‐opening metathesis polymerization

Polyisobutylene‐supported second‐generation Hoveyda‐Grubbs catalyst is shown to be an effective nonpolar phase tag for ring‐opening metathesis polymerization (ROMP). The catalytic activities of the supported Ru–carbene complex in ROMP are comparable to those of their homogeneous counterparts. The separability of these catalysts leads to lower Ru contamination (0.5 ppm levels) in the polymer products in comparison to the nonsupported Hoveyda‐Grubbs catalyst (10 PPM). © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of oxepine-, oxocine- and azepine-annulated carbazole derivatives by combined Claisen rearrangement and diene/enyne metathesis

A new route to various medium ring heterocycle-annulated tetra-, penta- and hexacyclic carbazole derivatives has been developed using successive applications of three atom economic processes, viz. Claisen rearrangement, olefin metathesis and Diels-Alder reactions.     

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.     

Grubbs催化剂合成研究进展

烯烃复分解反应通过催化使两个烯烃碳碳双键断裂,再重新组合形成新的碳碳双键,是以烯烃作为底物构建碳碳双键的重要方法.从反应类型来分,烯烃复分解反应主要有：关环复分解反应（RCM）,开环复分解聚合反应（ROMP）,交叉复分解反应（CM）及非环二烯复分解反应（ADMET）.在天然产物的全合成,药物化学和材料科学中均有广     

Enolesters as chain end-functionalizing agents for the living ring opening metathesis polymerization

Functional enolethers have previously been used to introduce functional end groups at the chain end of ruthenium carbene complex initiated living ring opening metathesis polymers. Here, we investigated whether the weaker π-donating enolesters could equally be used in regio selective reactions with ruthenium carbene complexes and thus as polymer end-functionalization reagents. Enolesters such as vinyl acetate, butenyl acetate, 3-(4-(tert-butoxy)phenyl)propenyl acetate and 6-(((benzyloxy)carbonyl)amino)hex-1-en-1-yl acetate were used as living ROMP terminating agents. All gave the expected end groups proving that enolesters are synthetically easily accessible targets for living ROMP end-functionalization. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2983–2990     

Efficient synthesis of 19-31 membered macrocyclic tetralactones via ring closing metathesis in ionic liquids

The ring closing metathesis reaction in the presence of Grubbs catalyst was demonstrated using several ionic liquids to synthesize a range of macrocyclic tetralactones having ring size of 19 to 31 membered with different spacers. The ionic liquid [mmim][PF₆] was found to be an excellent solvent and the recovery of the catalyst was demonstrated. X-ray analysis of a representative macrocyclic tetralactone was also reported.     

A Molecular modeling study of the changes of some steric properties of the precatalysts during the olefin metathesis reaction

The productive self‐metathesis of 1‐octene with a series of new phosphine ligated Grubbs‐type precatalysts was studied. The resulting structures were used to compare some steric properties of the new precatalysts with those of well‐known precatalysts. The possibility of α‐CC agnostic stabilization as well as the ability of the ligands to shield the metal was studied. A comparison of the obtained data, pointed to the unlikelihood that α‐CC agostic stabilization is a major contribution to the stabilization of the various metallacyclobutane rings. The similarity in the ability of the ligands to shield the metal also raised questions about the comparison of experimentally observed trends with those obtained theoretically. © 2014 Wiley Periodicals, Inc.     

Characterization of the micellar ring opening metathesis polymerization in water of a norbornene derivative initiated by Hoveyda‐Grubbs' catalyst

Solubilization of the hydrophobic Hoveyda‐Grubbs' catalyst in micellar aqueous phase has been achieved using dodecyl and cetyl ammonium chloride as surfactants. The domain of solubilization has been estimated before carrying out ring‐opening metathesis polymerization in these micellar solutions with a hydrophilic monomer. Kinetics orders have been determined relative to monomer, initiator, and surfactant. A good control of the molecular weight has been obtained for ratios [micelles]/[initiator] over 1. The better control of the polymerization obtained in micellar solution has been explained by a difference of reactivity leading to a more efficient initiation step in the presence of the micelles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2833–2844, 2008     

Synthesis of (+)-7a-epi-7-deoxycasuarine via cross metathesis

Olefin cross metathesis of vinyl pyrrolidine derivatives has been explored, culminating in a concise synthesis of (+)-7a-epi-7-deoxycasuarine in nine steps, from commercially available starting materials.     

Synthesis of 2,6-dioxabicyclo[3.3.0]octenes by tandem ring-rearrangement/cross metathesis

A facile synthesis of stereodefined 2,6-dioxabicyclo[3.3.0]octene derivatives from the vinyl ether of endo-7-oxanorbornen-2-ol via tandem ring-opening/ring-closing(ring-rearrangement)/cross metathesis is reported.     

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.     

A cross metathesis strategy for the synthesis of highly functionalized conjugated cyanodienes: synthesis of the C3-C17 framework of (−)-borrelidin

A cross metathesis strategy for the synthesis of highly functionalized conjugated cyanodienes was developed and was successfully applied in the synthesis of the C3-C17 framework of (−)-borrelidin.     

Cross-metathesis of 1,3-dienes with electron-deficient olefins

Cross-metathesis reactions between 1,3-dienes and electron-deficient olefins have been investigated. Terminal monosubstituted 1,3-dienes afforded low yields of the desired CM products due to competing cleavage of the internal double bond. This undesired cleavage is successfully suppressed in the case of 1,3-dienes containing a sterically more congested internal double bond. Methyl vinyl ketone as the coupling partner was shown to provide the best yields.