Ring-closing Olefin Metathesis Research Articles

Total Synthesis of (±)-α-Isosparteine, (±)-β-Isosparteine, and (±)-Sparteine from a Common Tetraoxobispidine Intermediate

The three title alkaloids were separately prepared in stereocontrolled fashion from a common tetraoxobispidine precursor, 3,7-diallyl-2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane (16). Bisimide 16 was generated from malonate via acid promoted cyclization of the Knoevenagel condensation adduct 1,1,3,3-propanetetracarboxamide. (+/-)-alpha-Isosparteine (dl-2) was elaborated from 16 in 28% overall yield by a two-directional synthetic sequence composed of four reactions: double addition of allylmagnesium bromide, ring-closing olefin metathesis (RCM), hydrogenation, and borane mediated reduction. (+/-)-beta-Isosparteine (dl-3) was targeted along similar lines by a strategic reversal in allylation and reduction operations on the core synthon. Thus, 16 was advanced to dl-3 in five steps and 12% overall yield by a reaction sequence commencing with sodium borohydride mediated reduction and followed by double Sakurai-type allylation of the resulting bishemiaminal. The synthesis of dl-3 was concluded by RCM and then global reduction (H2, Pd/C; LiAlH4). The final target, (+/-)-sparteine (dl-1), was secured in six steps and 11% overall yield from 16 by monoreduction and Sakurai allylation, followed by allyl Grignard addition and then RCM and global reduction as before. Reasons for the inherent C2-type regioselectivity of net double nucleophilic additions to tetraoxobispidines are discussed and enantioselective oxazaborolidine mediated reduction of the N,N'-dibenzyl congener of 16 is reported.

Synthesis of Substituted Benzenes and Phenols by Ring‐Closing Olefin Metathesis

New synthetic approaches to substituted aromatic compounds are reported. Ring-closing olefin metathesis (RCM)/dehydration and RCM/tautomerization are the key processes in the synthesis of substituted benzenes 3 and phenols 6, respectively. Readily accessible 1,5,7-trien-4-ols 7, which are the precursors of benzenes, were prepared from beta-halo-alpha,beta-unsaturated aldehydes 11 or beta-halo-alpha,beta-unsaturated esters 19 by utilizing reliable transformations in which cross-coupling with vinylic metal reagents 12 and allylation with allylic metal reagents 13 were employed as carbon-carbon bond forming reactions. RCM of 7, followed by dehydration, afforded a wide variety of substituted benzenes 3. In addition, RCM of 1,5,7-trien-4-ones 9, which were prepared by oxidation of 7, furnished various substituted phenols 6 by automatic tautomerization.

New Efficient RCM-Mediated Synthesis of Pyrrolidine Derivatives

Fast and effective ring-closing olefin metathesis (RCM) of diallyamine derivatives of coumarin, quinolone, pyridine, and substituted benzene, using first-generation RCM ruthenium-based catalyst, leads to corresponding pyrrolidine derivatives in 70–95% yields under very mild conditions.

Ring-closing olefin metathesis in the aqueous phase of amphiphilic conetworks consisting of fluorophilic and hydrophilic compartments

A Grubbs–Hoveyda-Type metathesis catalyst bearing a tris(perfluoroalkyl)silyl tag was immobilized in the fluorophilic phase of amphiphilic conetworks (APCNs). This catalytic system was applied to ring-closing metathesis (RCM) reactions in aqueous media. Different substrates were evaluated and with 10 mol% of catalyst at 60 °C good conversions were observed. Reuse of the catalytic system was possible, but resulted generally in lower conversions.

Synthesis of macrocyclic trypanosomal cysteine protease inhibitors

The importance of cysteine proteases in parasites, compounded with the lack of redundancy compared to their mammalian hosts makes proteases attractive targets for the development of new therapeutic agents. The binding mode of K11002 to cruzain, the major cysteine protease of Trypanosoma cruzi was used in the design of conformationally constrained inhibitors. Vinyl sulfone-containing macrocycles were synthesized via olefin ring-closing metathesis and evaluated against cruzain and the closely related cysteine protease, rhodesain.

Asymmetric multicomponent reactions: convenient access to acyclic stereocenters and functionalized cyclopentenoids

Asymmetric multicomponent reactions of optically active phenyl dihydrofuran, keto ester or N-tosyl imino ester, and allylsilane provided functionalized phenyl tetrahydrofurans with multiple stereogenic centers diastereoselectively. Cleavage of the resulting substituted tetrahydrofurans readily provided acyclic derivatives with three contiguous asymmetric centers via an acyloxycarbenium ion intermediate. Ring closing olefin metathesis, using Grubbs catalyst, afforded functionalized cyclopentene derivatives in optically active form. A one-pot tandem tetrahydrofuran ring cleavage followed by ring closing olefin metathesis also provided functionalized cyclopentenes in good yield.

A double ring-closing olefin metathesis approach to [3]catenanes

A [3]catenane with peripheral olefinic macrocycles was conveniently synthesized via a double ring-closing olefin metathesis. Highlights of this work include the synthesis of a 65-membered macrocycle featuring two phenanthroline ligands, a Cu(I)-templated synthesis of a [3]pseudorotaxane, and the key double ring-closing olefin metathesis to afford the desired [3]catenane in 71% yield.

Total Synthesis of Hypermodified Epothilone Analogs with Potent in Vitro Antitumor Activity

The convergent total synthesis of hypermodified epothilone analogs 1 and 2 has been achieved with the stereoselective cyclopropanation of allylic alcohol 17 and ring-closing olefin metathesis with diene 22 as the key steps. In spite of significant structural differences between these analogs and the natural epothilone scaffold, 1 and 2 are potent inducers of tubulin polymerization and inhibit the growth of human cancer cells in vitro with sub-nM IC50 values.

Synthesis of Silole Skeletons via Metathesis Reactions

Silole skeletons are constructed by ring-closing olefin metathesis of silicon-tethered dienes and trienes. A silicon-tethered enyne is also converted to a 2-alkenyl-1-silaindene via ruthenium-catalyzed ring-closing enyne metathesis.

A Thermally Switchable Latent Ruthenium Olefin Metathesis Catalyst

The synthesis and characterization of a cis-dichloro sulfur chelated olefin metathesis catalyst is presented. The catalyst was extremely stable at room temperature in solution under ambient conditions and was shown to exhibit a thermo-switchable behavior for ring-closing olefin metathesis of diethyl diallylmalonate, being active at 80 °C and inactive at room temperature.

Synthesis and structure of a heterocyclic ansa pyrrole amino acid

We report a synthetic route to ansa pyrrole amino acids via olefin ring-closing metathesis of diene precursors in the presence of Grubbs I catalyst. The dienes were prepared by Grignard addition to pyrrole sulfinyl imines. The success of the macrocyclic ring closure depends on the dienes structure and only in the case of the 13-membered compound 28 sufficient material could be isolated by preparative HPLC separation to investigate its structure spectroscopically. As also rationalized by our computations at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level of theory, 28 is configurationally stable.

The Catalytic Asymmetric Total Synthesis of Elatol

Described in this report is the first total synthesis of elatol, a halogenated sesquiterpene in the chamigrene natural product family. The key disconnections in our synthetic approach include an enantioselective decarboxylative allylation to form the all-carbon quaternary stereocenter and a ring-closing olefin metathesis to concomitantly form the spirocyclic core as well as the fully substituted chlorinated olefin. This strategy represents a general platform for accessing the chamigrene natural product family, as demonstrated by the synthesis of (+)-laurencenone B as an intermediate in our route.

Concise stereoselective synthesis of cis-3-alkoxy-2-carbomethoxy medium-ring oxacycles from ( R)-3-(3-butenyl)-4-propynoyloxazolidin-2-one

A concise process for the stereoselective synthesis of chiral cis-3-alkoxy-2-carbomethoxy medium-ring oxacycles from ( R)-3-(3-butenyl)-4-propynoyloxazolidin-2-one ( 1) was developed. The process includes five major steps: (i) hetero-Michael reaction between an alcohol and 1, (ii) stereoselective reduction of the resulting ketone, featuring stereochemical assistance of the neighboring oxazolidin-2-one group, (iii) esterification with an alkoxy acetic acid, (iv) chirality-transferring Ireland–Claisen rearrangement of the resulting 3-alkoxyallyl glycolate ester to provide a syn-2,3-dialkoxy carboxylate ester, and (v) relay ring-closing olefin metathesis to form a medium-ring ether along with the simultaneous removal of the oxazolidin-2-one moiety.

Synthesis of the EF-Ring of Ciguatoxin 3C Based on the [2,3]-Wittig Rearrangement and Ring-Closing Olefin Metathesis

The EF-ring segment of ciguatoxin 3C, a causative toxin of ciguatera fish poisoning, was synthesized in three major steps: 1,4-addition for the C20O-C27 bond connection, chirality transferring anti selective [2,3]-Wittig rearrangement for the construction of the anti-2-hydroxyalkyl ether part, and ring-closing olefin metathesis for the F-ring formation.

Oligometallic Template Strategy for Ring-Closing Olefin Metathesis: Highly Cis- and Trans-Selective Synthesis of a 32-Membered Macrocyclic Tetraoxime

An oligometallic template effect was observed on the cis/trans selectivity of a 32-membered macrocyclic tetraoxime in ring-closing olefin metathesis of an acyclic diallyl derivative H4L; the metathesis of heterotrinuclear complex LZn2M (M=Ca2+, La3+) afforded the cis isomer, whereas uncomplexed H4L gave the trans isomer.

Synthesis of enantiomerically pure cycloalkenols via combination strategy of enzyme-catalyzed reaction and RCM reaction

The preparation of three types of cyclic alkenols, ( S)-2-cyclohexenol, ( R)-2,5-dihydrobenzo[ b]oxepin-5-ol, and ( R)-5,6-dihydro-2 H-benzo[ b]oxocin-6-ol, has been accomplished in enantiomerically pure forms as model compounds using a combination of a lipase-catalyzed reaction and a ring closing olefin metathesis (RCM) reaction.

Synthetic study on 13-oxyingenol: construction of the full carbon framework

13-Oxyingenol is a diterpenoid isolated from Euphorbia kansui, and its derivatives have strong anti-HIV activity. We achieved the construction of inside– outside framework of 13-oxyingenol by using ring-closing olefin metathesis.

Bifunctional [c2]Daisy-Chains and Their Incorporation into Mechanically Interlocked Polymers

A strategy for the formation of mechanically interlocked polymers is presented. Ring-closing olefin metathesis has been shown to provide a very high yielding route to [c2]daisy-chains suitably functionalized to allow their one-step conversion to bisolefins which can be used as monomers in ADMET polymerizations to afford mechanically interlocked polymers. Metathesis, in two different guises is making a hitherto unreachable goal in synthesis a reality.

An Efficient Route to Benzene and Phenol Derivatives via Ring-Closing Olefin Metathesis

Without the formation of inseparable regioisomers, -various substituted phenol derivatives 2 and benzene derivatives 4 were prepared through RCM-tautomerization and RCM-dehydration protocols. A new synthetic route to precursors 1 and 3 enabled efficient access to these aromatic compounds.

Synthesis of L‐ido‐Configured Six‐ and Seven‐Membered Carba‐Sugars.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.