Ring-closing Olefin Metathesis Research Articles

ChemInform Abstract: The Application of Catalytic Ring-Closing Olefin Metathesis to the Synthesis of Unsaturated Oxygen Heterocycles.

ChemInform Abstract: The Application of Catalytic Ring-Closing Olefin Metathesis to the Synthesis of Unsaturated Oxygen Heterocycles.

Protecting-Group-Free and Catalysis-Based Total Synthesis of the Ecklonialactones

A concise and protecting-group-free total synthesis of optically pure ecklonialactones A (1) and B (2) is described. The successful route to these oxylipins isolated from various brown algae involves five transition-metal-catalyzed transformations in the longest linear sequence of 13 steps. The first chiral center was set by a rhodium-catalyzed 1,4-addition of an alkenyl boronate to the commercial butenolide 11, which was controlled by Carreira's carvone-derived diene ligand 21. Other key steps involve a ring-closing olefin metathesis effected by the ruthenium indenylidene complex 22 for the formation of the five-membered carbocycle, a vanadium-catalyzed, hydroxy-directed epoxidation, and a ring-closing alkyne metathesis (RCAM) to forge the macrocyclic ring. Because of the unusually high propensity of the oxirane of the ecklonialactones for ring-opening, this transformation was best achieved with [(Ph(3)SiO)(3)Mo[triple bond]CPh].OEt(2) (34) as the catalyst, which is a representative of a new generation of highly tolerant yet remarkably efficient molybdenum alkylidyne complexes. The ancillary triphenylsilanolate ligands in 34 temper the Lewis acidity of the molybdenum center and are not able to nucleophilically open the fragile epoxide ring. The final reduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene was accomplished either by Lindlar reduction or with the aid of nickel boride.

Model studies for the stereoselective construction of the BC-ring of armatol F based on Ireland-Claisen rearrangement and relay ring-closing olefin metathesis

Armatol F, isolated from the red alga Chondria armata as a polyether triterpene, has a fused tricyclic ether moiety (BCD-ring) with an unusual cis ring junction at C18–C19 between the C- and D-rings. En route to the total synthesis of armatol F, the stereoselective construction of the C18 and C19 stereocenters by Ireland-Claisen rearrangement and the formation of the C-ring by relay ring-closing olefin metathesis were established through the synthesis of monocyclic (C-ring) and bicyclic (BC-ring) model compounds.

A catenated anion receptor based on indolocarbazole

A catenated anion receptor has been prepared which consists of two interlocked indolocarbazole units and binds anions in the cage-like cavity by four hydrogen bonds. A catenated anion receptor 7 comprising two indolocarbazole units was prepared by olefin ring-closing metathesis using Grubbs’ catalyst. Receptor 7 possesses a cage-like cavity where anions are encapsulated by forming four hydrogen bonds in the order of Cl − > AcO − > N 3 - > H 2 PO 4 - > Br − > HSO 4 - > I − ≈ NO 3 - in 1% H 2 O/acetone.

Studies toward the total synthesis of armatol F: stereoselective construction of the C6 and C7 stereocenters and formation of the A-ring skeleton

Armatol F, isolated from the red alga Chondria armata as a polyether triterpene, has a solitary oxepane (A-ring) and a fused tricyclic ether moiety (BCD-ring). The A-ring features a rare cis-relationship between the hydroxy group at the quaternary carbon C6 and the carbon chain at C7. As part of our program toward the total synthesis of armatol F, a new stereoselective method for the construction of the C6 and C7 stereocenters has been developed based on chirality-transferring Ireland-Claisen rearrangement. The A-ring skeleton has also been synthesized from the rearrangement product by a process including ring-closing olefin metathesis.

ChemInform Abstract: A Straightforward Synthesis of Perbenzylated Conduritols from Alditols by Ring Closing Olefin Metathesis.

The synthesis of perbenzylated conduritols A, E and F has been achieved in six steps by formal conversion of galactitol, D-mannitol and D-glucitol into the respective terminal dienes, followed by ring closing olefin metathesis.

ChemInform Abstract: A Stereoselective Synthesis of (+)-Boronolide.

A stereoselective synthesis of (+)-boronolide is described. The key steps involve a stereoselective reduction of an α-hydroxy ketone, allylation of an α-hydroxy aldehyde and a ring-closing olefin metathesis of a homoallylic alcohol derived acrylate ester utilizing Grubbs' catalyst.

Introduction of All-Hydrocarbon i,i+3 Staples into α-Helices via Ring-Closing Olefin Metathesis

The introduction of all-hydrocarbon i,i+3 staples into alpha-helical peptide scaffolds via ring-closing olefin metathesis (RCM) between two alpha-methyl,alpha-pentenylglycine residues incorporated at i and i+3 positions, which lie on the same face of the helix, has been investigated. The reactions were found to be highly dependent upon the side-chain stereochemistry of the amino acids undergoing RCM. The i,i+3 stapling system established here provides a potentially useful alternative to the well-established i,i+4 stapling system now in widespread use.

ChemInform Abstract: Synthesis of Bicyclic Lactams via Ring Closing Olefin Metathesis and Intramolecular Heck Reaction.

The application of the ring closing olefin metathesis and the intramolecular Heck reaction as key steps in the synthesis of 6,5- and 7,5-fused enantiomerically pure bicyclic lactams starting from a chiral pyrrolidone is shown. The diolefinic cyclization precursors can be obtained by a combined electrochemical oxidation- N- acyliminium coupling reaction and a subsequent N-alkylation using an unsaturated alkyl bromide.

ChemInform Abstract: Synthetic Studies of Ingenol: Synthesis of in,out-Tricyclo[7.4.1.01,5]tetradecan-14-one.

Abstract in,out-Tricyclo[7.4.1.01,5]tetradecan-14-one was synthesized from γ-butyrolactone in 12 steps using ring-closing olefin metathesis as the key step.

ChemInform Abstract: Synthetic Studies of Antitumor Macrolide Laulimalide: A Stereoselective Synthesis of the C17-C28 Segment.

A stereoselective synthesis of the C17–C28 segment of the potent antitumor macrolide, laulimalide has been accomplished. The key steps are a ring-closing olefin metathesis to construct the dihydropyran unit, nucleophilic addition of an alkynyl anion to the Weinreb amide, stereoselective reduction of the resulting ketone to set the C20-hydroxyl stereochemistry, and elaboration of the C21–C22 trans-olefin geometry.

A Stereoselective Aldol Approach for the Total Synthesis of Herbarumin I and Stagonolide A

A stereoselective total synthesis of phytotoxic compounds herbarumin I and stagonolide A has been achieved utilizing Crimmin's protocol for non-Evans anti-aldol approach and a ring-closing olefin metathesis reaction as the key steps.

A general enantioselective route to the chamigrene natural product family

Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.

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.

Sequence Isomerism in [3]Rotaxanes

We describe a strategy for assembling different macrocycles onto a nonsymmetrical rotaxane thread in a precise sequence. If the macrocycles are small and rigid enough so that they cannot pass each other then the sequence is maintained mechanically, affording stereoisomerism in a manner reminiscent of atropisomerism. The method is exemplified through the synthesis of a pair of [3]rotaxane diastereomers that are constitutionally identical other than for the sequence of the different macrocycles on the thread. The synthesis features the iterative binding of different palladium(II) pyridine-2,6-dicarboxamide complexes to a pyridine ligand on the thread followed by their macrocyclization by ring-closing olefin metathesis. Removal of the palladium(II) from the first rotaxane formed frees the pyridine site to coordinate to a second, different, palladium(II) pyridine-2,6-dicarboxamide unit which, following macrocyclization, provides a multiring rotaxane of predetermined macrocycle sequence.

Cross-metathesis–based approaches to heteroaromatics: Combining catalysts for furan formation

Ring-closing olefin metathesis (RCM) is an effective method for the formation of cyclic alkenes (1). Recently, the aromatization of RCM products has emerged as a topic of intensive investigation (2). In this context, a variety of regiocontrolled protocols have been developed for the synthesis of diverse heteroaromatic compounds, such as pyridines, pyridazines, pyrroles, quinolines, and furans (2). In all reported approaches, a key strategic consideration relates to the requirement of intermolecular fragment union in advance of the key RCM event. Strategies based on the use of intermolecular alkene metathesis, termed cross-metathesis, would potentially streamline access to aromatic structures by uniting the key steps of fragment coupling and alkene formation. However, the use of cross-metathesis in the synthesis of aromatic heterocycles is prohibited by the fact that trans-alkene products predominate (3, 4), which are unsuitable for cycloaromatization. A report by Donohoe and Bower (3) in this issue of …

Synthesis of a Molecular Charm Bracelet via Click Cyclization and Olefin Metathesis Clipping

We describe the synthesis of a polycatenated cyclic polymer, a structure that resembles a molecular charm bracelet. Ruthenium-catalyzed ring-opening metathesis polymerization of an amino-containing cyclic olefin monomer in the presence of a chain transfer agent generated an alpha,omega-diazide functionalized polyamine. Cyclization of the resulting linear polyamine using pseudo-high-dilution copper-catalyzed click cyclization produced a cyclic polymer in 19% yield. The click reaction was then further employed to remove linear contaminants from the cyclic polymer using azide- and alkyne-functionalized scavenging resins, and the purified cyclic polymer product was characterized by gel permeation chromatography, (1)H NMR spectroscopy, and IR spectroscopy. Polymer hydrogenation and conversion to the corresponding polyammonium species enabled coordination and interlocking of diolefin polyether fragments around the cyclic polymer backbone using ruthenium-catalyzed ring-closing olefin metathesis to afford a molecular charm bracelet structure. This charm bracelet complex was characterized by (1)H NMR spectroscopy, and the catenated nature of the small rings was confirmed using two-dimensional diffusion-ordered NMR spectroscopy.

On the relationship between structure and reaction rate in olefin ring-closing metathesis

In the RCM reactions of a series of simple α,ω-dienes, the relative order of reactivity has been unambiguously determined showing that cyclohexene forms faster than cyclopentene or cycloheptene. 1,5-Hexadiene inhibits the RCM of 1,7-octadiene; 1,5-hexadiene cannot progress to the RCM product (cyclobutene) but forms an unexpectedly stable cyclic η(2)-complex.

Building a bridge between peptide chemistry and organic chemistry: Intramolecular macrocyclization reactions and supramolecular chemistry with helical peptide substrates

In our ongoing efforts to build a bridge between peptide chemistry and organic chemistry, we are currently investigating: (1) two types of intramolecular macrocyclization reactions in 3(10)-helical peptides, and (2) a peptido[2]rotaxane molecular machine as a supramolecular tool using a 3(10)-helical peptide as the axle. More specifically, we studied the following two reactions: (a) the intramolecular ring-closing olefin metathesis between two amino acid residues with side chains bearing an allyl group, and (b) the intramolecular Paternò-Yang photoreaction, using a benzophenone-based amino acid as a photoaffinity reagent for a Met residue. Both reactions involve formation of a new C--C bond. As for the supramolecular system examined, we were able to identify the two stations of a new peptido[2]rotaxane characterized by an -(Aib)(6)- axle and to reversibly switch the aromatic tetramide macrocyclic wheel from one station to the next. This article summarizes the information available in the literature from other groups and the published/unpublished data originated from our laboratory on these research areas.

Structure elucidation of hypocreolide A by enantioselective total synthesis

The nonenolide hypocreolide A was isolated from culture filtrates of the ascomycete Hypocrea lactea. It exhibits moderate antimicrobial activity against various tested fungi and bacteria. Since neither the relative nor the absolute stereochemistry of the compound could be initially assigned, a stereochemically flexible total synthesis was developed. The two stereogenic centers were formed in high enantioselectivity and yield using transition metal catalyzed asymmetric reactions. While attempts to construct the ten-membered lactone in a ring-closing olefin metathesis gave disappointing results, a combination of cross metathesis and macrolactonization provided the title compound in nine steps and 12% overall yield.