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.     

Total synthesis of (-)-callipeltoside A

A total synthesis of (-)-callipeltoside A (1) has been achieved. The core macrocycle was made via a dual macrolactonization/pyran hemiketal formation reaction, developed to circumvent issues related to the reversible nature of acylketene formation from β-keto lactone substrates. Initial approaches to the core of the natural product that revolved around ring-closing metathesis (RCM) and relay ring-closing metathesis (RRCM) reactions are also described.     

An Evans-Tishchenko-ring-closing metathesis approach to medium-ring lactones

A new approach to the synthesis of medium-ring lactones is reported based on sequential Evans-Tishchenko and ring-closing metathesis (RCM) reactions. High diastereoselectivity (>95:5) is demonstrated in the Evans-Tishchenko reaction of unsaturated aldehydes with unsaturated beta-hydroxy ketones, and conditions for the RCM cyclization of the resultant dienes have been optimized to give high yields of medium ring lactones. The synthetic utility of this sequence is demonstrated through generation of the fully functionalized core of octalactin A. [reaction: see text].     

Application of RCM reaction in the construction of ABC ring of micrandilactone A

[reaction: see text] The functionalized ABC ring system of micrandilactone A was successfully constructed in 14 steps. The key reactions in this synthesis are the intermolecular Diels-Alder reaction (IMDA) and the eneyne ring-closing metathesis (RCM) reaction.     

Synthesis of (+)-didemniserinolipid B via ketalization/ring-closing metathesis

A modular synthesis of didemniserinolipid B is reported. Central to this synthesis was the use of a ketalization/ring-closing metathesis (K/RCM) strategy to establish the 6,8-dioxabicyclo[3.2.1]octane core. The C10 axial alcohol was established via a selective epoxidation, followed by reductive trans-diaxial epoxide opening. The serinol and unsaturated ester side chains were introduced by a Williamson etherification and cross metathesis, respectively.     

Diversity-oriented synthesis of bicyclic ring systems via a conjugate addition/aldol/RCM process

Diversity-oriented synthesis(DOS) has been widely applied in the generation of a large collection of highly functionalized molecules with diverse chemical skeletons.Herein,we report the diversity-oriented synthesis of a series of structurally diverse bicyclic substrates via an efficient tandem conjugate addition/aldol process followed by ring-closing metathesis(RCM).This approach allows us to efficiently prepare a number of structurally complex molecules for the further chemical biology studies.     

Synthesis of the fused polyether core of hemibrevetoxin B by two-directional ring-closing metathesis

The tetracyclic fused polyether core of the marine natural product hemibrevetoxin B has been prepared in an efficient manner by using a strategy in which ring-closing metathesis (RCM) reactions were employed for ring synthesis. Simultaneous construction of the A and D rings was accomplished by double two-directional RCM of a tetraene. [reaction: see text]     

Facile synthesis of versatile functionalized amino caprolactams using RCM reactions of α-amino acrylamide

We report an efficient synthetic methodology allowing access to functionalized α-amino caprolactams using ring-closing metathesis (RCM). A very high tolerance of α-amino acrylamide RCM precursors toward functional groups is demonstrated. The synthetic pathway is facile, and can be extended to prepare a variety of substituted amino caprolactams in good to excellent yields. These compounds serve as versatile building blocks for the synthesis of some important natural products and their analogues.     

New strategy for the construction of a monotetrahydrofuran ring in Annonaceous acetogenin based on a ruthenium ring-closing metathesis: application to the synthesis of Solamin

An original convergent total synthesis of Solamin (type A annonaceous acetogenin) was achieved. The central THF core was obtained by means of a ring-closing metathesis (RCM) reaction using a ruthenium imidazolylidene complex. The RCM substrate was prepared from a vinyl-substituted epoxide by reaction with an allyl alcohol, both synthesized from propargylic alcohol. The flexibility of the strategy should be useful in preparing various natural and unnatural annonaceous acetogenins.     

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 2-phosphonopyrroles via a one-pot RCM/oxidation sequence

A four-step synthesis of 2-phosphonopyrroles is presented starting from suitable aldehydes. The key step in the synthesis involves a one-pot ring-closing metathesis/oxidation sequence of a functionalized alpha-aminoalkenyl phosphonate. Notwithstanding the presence of a nucleophilic nitrogen atom and high substitution patterns in the substrate, the results of the RCM reaction are excellent using mild reaction conditions. Furthermore, a synergism is observed between the RCM catalyst and the oxidizing agent, causing higher oxidation rates and allowing reaction for substrates that normally fail to ring close under standard RCM conditions.     

Enantioselective synthesis of [1,2]-oxazinone scaffolds and [1,2]-oxazine core structures of FR900482

Several chiral unsaturated [1,2]-oxazinone heterocycles have been synthesized by iridium-catalyzed allylic substitution and ring-closing metathesis (RCM) reaction in high yields with excellent enantiomeric excesses. In addition, the synthesis of [1,2]-oxazine core structures of FR900482 was achieved via iridium-catalyzed allylic substitution, followed by RCM and Heck reactions, respectively.     

Metathesis studies to cyclic enol phosphonamidates

The development of cyclic, six membered enol phosphonamidates utilizing the ring-closing metathesis (RCM) reaction is discussed. Phosphonamidic monochloridates are generated and further functionalized to an array of acyclic, enol phosphonamidates. Subsequent metathesis affords both desired RCM product and corresponding cross metathesis (CM) dimer. Efforts to optimize formation of desired RCM product, while minimizing CM products are discussed, with interesting steric and electronic factors governing reactivity patterns. This strategy allows for generation of cyclic enol phosphonamidates, with ultimate application to C(6)-substituted analogs of the anti-cancer agent, cyclophosphamide.     

An efficient synthesis of oseltamivir phosphate (Tamiflu) via a metal-mediated domino reaction and ring-closing metathesis

An efficient synthesis of the influenza neuraminidase inhibitor prodrug oseltamivir phosphate (Tamiflu) from cheap, commercially available d-ribose is described. The main features of this approach comprise a metal (Zn, In)-mediated domino reaction and ring-closing olefin metathesis (RCM) of the resultant functionalized dienes to produce the Tamiflu skeleton. The synthesis described in this Letter represents a new and efficient transformation of a shikimic acid derivative into a 1,2-diamino compound which involved oxidation of an alcohol followed by reductive amination, regioselective ring opening of an amino pentylidene ketal and stereospecific nucleophilic replacement of a triflate with an azide.     

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.     

Ring-closing metathesis (RCM) based synthesis of the macrolactone core of amphidinolactone A

A convergent synthesis of the macrolactone core of amphidinolactone A has been achieved, in a 10 step linear sequence with 32% overall yield, through a ring-closing metathesis reaction as the macrolactonization step. The RCM precursor was obtained by the union of acid and alcohol fragments derived from (R)-epichlorohydrin and (R)-2,3-O-isopropylidene glyceraldehyde, respectively.     

RCM-mediated stereoselective synthesis of three novel tetrahydroisoquinoline tetracyclic core frameworks

Three novel tetrahydroisoquinoline tetracyclic core frameworks were stereoselectively synthesized. The key steps included a ring-closing metathesis (RCM)-mediated cyclization and a subsequent intramolecular S_N2 N(O)-substituted reaction. This simple method for tetracyclic core synthesis facilitates the further exploration of the chemical space of tetrahydroisoquinoline alkaloids.     

Total synthesis of natural (−)- and unnatural (+)-Melearoride A

This communication details the first total synthesis of the 13-membered macrolide, (?)-Melearoride A, as well as unnatural (+)-Melearoride A. The synthesis features a concise 13 step synthesis (11 steps longest linear sequence) that offers flexible stereo-control and multiple opportunities for unnatural analog synthesis to delve into antifungal SAR. The route features a cuprate addition, an Evans asymmetric alkylation, and a ring-closing metathesis (RCM) to close the 13-membered macrocyclic core.     

Application of tandem Ugi reaction/ring-closing metathesis in multicomponent synthesis of unsaturated nine-membered lactams

A new straightforward entry into unsaturated nine-membered lactams of potential use as external reverse turn inducers was developed. It is based on an Ugi multicomponent reaction using two unsaturated substrates, followed by highly stereoselective ring-closing metathesis (RCM). The synthesis of a nine-membered secondary lactam by RCM is reported for the first time.     

Total synthesis and determination of relative and absolute configuration of multiplolide A

A flexible approach for total syntheses of possible multiplolide A diastereomers establishing the relative and absolute configuration is documented. The adopted strategy features ring-closing metathesis (RCM) as the key reaction and screening of a set of substrates for the feasibility of RCM in general and for the requisite E-configuration of ring olefin in particular. Selective protecting groups manipulation prior to the assembly of the central macrocyclic core was instrumental in installing the epoxide functionality on a fully deprotected nonenolide at the end of the synthesis.