Acceleration effect of an allylic hydroxy group on ring-closing enyne metathesis of terminal alkynes: scope, application, and mechanistic insights

An interesting acceleration effect of an allylic hydroxy group on ring-closing enyne metathesis has been found. Ring-closing enyne metathesis of terminal alkynes possessing an allylic hydroxy group proceeded smoothly without the ethylene atmosphere generally necessary to promote the reaction. The synthesis of (+)-isofagomine with the aid of this efficient reaction has been demonstrated. Mechanistic studies of the acceleration effect were also carried out. Results of NMR studies suggested that the reaction proceeded via an "ene-then-yne" pathway. Kinetic studies indicated switching of the rate-determining step as a consequence of the presence of an allylic hydroxy group. These results suggest acceleration of the reentry step of Ru-carbene species by the allylic hydroxy group.     

Tandem cyclopropanation/ring-closing metathesis of dienynes

Certain dienynes give cyclorearrangement by tandem cyclopropanation/ring-closing alkene metathesis, triggered by either a ruthenium carbene or noncarbene ruthenium(II) precatalyst. The process represents a variation of enyne metathesis where presumed cyclopropyl carbene intermediates undergo a consecutive ring-closing metathesis. A mechanistic proposal is offered, and sequential use of catalysts provided a tandem ring-closing enyne/alkene metathesis product.     

Allylic alkylation and ring-closing metathesis in sequence: a successful cohabitation of Pd and Ru

An allylic alkylation/ring-closing metathesis domino catalytic process, wherein a palladium and a ruthenium catalyst are concomitantly present in the reaction mixture from the outset of the reaction, is developed. Evidence for Grubbs' catalysts activity in allylic alkylation is also reported.     

A new entry to the phenanthridine ring system

A new synthesis of phenanthridine derivatives having three-point diversity has been developed based on the sequential application of three-atom economic processes viz. aza-Claisen rearrangement, ring-closing enyne metathesis and Diels–Alder reaction as key steps. An unexpected isomerisation was observed during aza-Claisen rearrangement of N-allylanilines which may open up new opportunities in heterocyclic synthesis.     

Preparation of alkenyl cyclopropanes through a ruthenium-catalyzed tandem enyne metathesis-cyclopropanation sequence

Acyclic enynes undergo a tandem enyne metathesis/cyclopropanation sequence in the presence of Grubbs' 1st generation metathesis catalyst and diazo compounds. In practice, the acyclic substrates in the presence of the ruthenium alkylidene first undergo a ring-closing enyne metathesis to generate cyclic 1,3-dienes; then upon addition of a diazo compound, these products are cyclopropanated selectively at the more accessible olefin. Overall, the reaction sequence converts acyclic enynes into vinyl cyclopropanes in single operation through two unique ruthenium-catalyzed transformations.     

Stereocontrolled synthesis of (-)-galanthamine

An enantioselective synthesis of (-)-galanthamine has been realized in 11 linear steps starting from isovanillin. A Mitsunobu aryl ether forming reaction was used to assemble the galanthamine backbone, which was stitched together using enyne ring-closing metathesis, Heck, and N-alkylation reactions affording the tetracyclic ring system. Control of relative and absolute stereochemistry was derived from an easily accessible enantiomerically enriched propargylic alcohol 13.     

Application of a domino intramolecular enyne metathesis/cross metathesis reaction to the total synthesis of (+)-8-epi-xanthatin

[reaction: see text] The first total synthesis of the novel sesquiterpene lactone (+)-8-epi-xanthatin (1) has been achieved starting from the commercially available ester 8. The synthesis features an asymmetric aldol reaction and palladium-catalyzed carbonylation/lactonization sequence leading to 4 and a domino ring-closing enyne metathesis/cross metathesis reaction to afford 1.     

Diversity-oriented approach to biologically relevant molecular frameworks starting with beta-naphthol and using the Claisen rearrangement and olefin metathesis as key steps

A diversity-oriented approach for the synthesis of various structurally different molecular frameworks from readily accessible and common precursors is described. A Claisen rearrangement followed by ring-closing metathesis or ethylene-promoted ring-closing enyne metathesis has been utilized as the key synthetic transformation to generate naphthoxepine derivatives. The ring-closing metathesis approach has also been used to generate spirocyclic compounds and the pleiadene framework.     

Construction of building-blocks for polyether synthesis using sequential catalytic ring-closing enyne and cross metathesis

Highly functionalised six- and seven-membered cyclic ethers bearing a variety of side chains have been synthesised using ring-closing enyne metathesis and subsequent cross metathesis of the intermediate diene; one-pot enyne and cross metathesis has also been accomplished, allowing ring construction and side chain introduction to be performed in a single operation.     

Studies directed toward the total synthesis of lancifodilactone G: an expeditious route to the ABC subunit

An efficient entry to the ABC network of lancifodilactone G is outlined. The C ring is constructed by way of enyne ring-closing metathesis. The AB component is established via a base-mediated biomimetic oxy-Michael addition--lactonization sequence.     

Efficient method for the synthesis of chiral pyrrolidine derivatives via ring-closing enyne metathesis reaction

[reaction: see text] A series of new pyrrolidine derivatives were prepared directly in very good yields, from the substrates containing a basic or nucleophilic N atom via ring-closing enyne metathesis reaction under mild reaction conditions. Moreover, the reaction occurs smoothly without the presence of ethylene gas.     

Synthesis of spiro-pyridopyridine analogues by Grubbs' catalyst mediated alkene and enyne metathesis reaction

A practical synthesis of spiro-naphthyridinone derivatives is described by the combination of the Claisen rearrangement and ring-closing metathesis/ring-closing enyne metathesis process. The RCM or RCEM proceeded smoothly in the presence of Grubbs' first generation catalyst at room temperature under a nitrogen atmosphere.     

Some allylic substituent effects in ring-closing metathesis reactions: allylic alcohol activation

[formula: see text] Dienes 2a-e were used to study allylic substituent effects in the ring-closing metathesis reaction (RCM). Both the steric and electronic character of the allylic substituents were found to influence alkene reactivities. Free allylic hydroxyl groups exert a large activating effect on the RCM reaction rates.     

Asymmetric synthesis of (-)-dihydroxanthatin by the stereoselective Oshima-Utimoto reaction

[reaction: see text]. The catalytic stereoselective Oshima-Utimoto reaction is useful for the construction of five-membered oxacycles from simple starting materials and was employed for the preparation of the lactone group in the asymmetric synthesis of (-)-11alpha,13-dihydroxanthatin. Completion of the synthesis is facilitated by ring-closing enyne metathesis and alkene cross metathesis reactions.     

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 allocolchicines using sequential ring-closing enyne metathesis-Diels-Alder reactions

New allocolchinoids having functionality in the C ring at position C10 or C11 have been synthesized using the enyne ring-closing metathesis (RCM) reaction for construction of the seven-membered ring and a Diels-Alder-aromatization sequence for the elaboration of the aromatic ring C. [reaction: see text].     

Efficient synthesis of 4-vinyl α,β-unsaturated γ-lactams by ring-closing enyne metathesis reactions

The ring-closing enyne metathesis reaction of alkyl 2-substituted-2-(N-alkynyl acrylamido)esters using the first-generation Grubbs’ catalyst afforded five-membered lactams bearing a 1,3-diene moiety in high isolated yields. In the reaction process, the presence of ethylene gas is essential.     

Stereoselective synthesis of fluoro-homoneplanocin A as a potential antiviral agent

Fluoro-homoneplanocin A (4) was synthesized from d-ribose, via the enyne ring-closing metathesis of 9, the stereoselective opening of epoxide 23a with fluoride, and a simultaneous oxidation-elimination reaction. The key intermediate 8 is expected to serve as a versatile intermediate for the synthesis of carbanucleosides.     

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.     

Metathesis and metallotropy: a versatile combination for the synthesis of oligoenynes

We have demonstrated that the combined use of enyne metathesis and metallotropic [1,3]-shift of the corresponding alkynyl ruthenium carbenes is a powerful synthetic tool to construct oligoenynes. In this reaction, alkynyl carbene intermediates formed from an initial ring-closing metathesis reaction (RCM) undergo repetitive [1,3]-shifts and RCMs to give the final products. Linear poly-1,3-diynes containing repeating functionality of the type -[XCH2CCCCCH2]n- generated long-chain conjugated oligoenynes up to n = 5.