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A concise, unified and stereoselective total synthesis of (+)-gabosine C and (+)-4- epi -gabosine J from a common polyhydroxylated cyclohexenol intermediate which was synthesized from readily available D-ribose has been described. The synthetic avenue includes stereoselective Grignard reaction, silyl ether deprotection followed by acetate migration, RCM reaction, oxidative diol cleavage, hydroxymethylation and oxidative rearrangement as key steps. Image 1 • Asymmetric total synthesis of (+)-Gabosine C and (+)-4- epi -Gabosine J from a common intermediate. • Deprotection followed by acetate group migration, RCM reaction and oxidative rearrangement reaction as key steps. • Functionalisation of common intermediate to carbasugars. [ABSTRACT FROM AUTHOR]

The synthesis of the benz[ a ]anthracene skeleton of the angucyclines is described. Key steps involve the Suzuki-Miyaura reaction, isomerization of an aromatic allyl substituent to the corresponding styrene, and the use of the ring closing metathesis reaction to construct a benzene ring. For example, exposure of 3-allyl-2-bromo-1,4,5-trimethoxynaphthalene to (2-formyl-4-methoxyphenyl)boronic acid under palladium catalysis conditions resulted in the formation of 2-(3-allyl-1,4,5-trimethoxynaphthalen-2-yl)-5-methoxybenzaldehyde. This 2-naphthyl benzaldehyde then underwent a Wittig reaction to furnish 3-allyl-1,4,5-trimethoxy-2-(4-methoxy-2-vinylphenyl)naphthalene. Isomerization of the allyl group of this compound afforded the diene, ( E )-1,4,5-trimethoxy-2-(4-methoxy-2-vinylphenyl)-3-(prop-1-en-1yl)naphthalene. Exposure of the formed diene to the Grubbs II catalyst resulted in the formation of the benzanthracene, 3,7,8,12-tetramethoxytetraphene, which was easily oxidized to the corresponding quinone. [ABSTRACT FROM AUTHOR]

The first synthesis of (7 S ,9 R )-decarestrictine H and (7 R ,9 R )-decarestrictine H as well as the improved synthesis of decarestrictine J were achieved. The overall yields of (7 S ,9 R )-decarestrictines H and J were 20.9% each in nine to ten steps from ( R )-Roche ester using a unified synthetic route via esterification with 3,3-ethylenedioxyhex-5-enoic acid and ring-closing metathesis, which were the key steps. The relative stereochemistry of decarestrictine H was determined to be 7,9- syn by comparing the spectral data of the natural product and synthetic epimers of decarestrictines H. [ABSTRACT FROM AUTHOR]

The use of asymmetric phthalocyanines (Pcs) as platforms for the preparation of several asymmetric hexatriazolyl-monohydroxyphthalocyanines via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was investigated. Asymmetric Pcs 5a and 5b were prepared through statistical macrocyclization of phthalonitriles (Pns) 1a and 2 to give PMB-protected 4a and 4b , which afforded asymmetric Pcs 5a and 5b after acidic cleavage. The ‘ROMP-Capture-Release’ method as a synthetic approach to prepare asymmetric Pc 5b was also evaluated. TIPS-protection of the terminal alkynes was necessary to prevent cross-coupling during the ring-opening metathesis polymerization (ROMP) step. Zinc Pc 5b was successfully used as a scaffold for functional modification under CuAAC conditions using several azides bearing hydrophobic, photo-crosslinkable, or electroactive moieties. Monitoring the CuAAC reaction by both UV/Vis and FTIR spectroscopies provided insight into the role of azide equivalent, reaction time, and catalyst on reaction progress. [ABSTRACT FROM AUTHOR]

Herein, we describe our progress toward the total synthesis of dodecahedrane, a complex and highly symmetrical hydrocarbon that bears twelve fused rings arranged in a cage-like architecture. Central to our approach is a late-stage [2+2+2+2+2] polyene cyclization cascade, which is expected to construct five new bonds and ten new rings in a single transformation. Toward this end, we describe efforts to synthesize key monomeric fragments, along with successful dimerization studies using a pinacol coupling approach. Subsequent studies include an attempted olefin metathesis rearrangement cascade in addition to a successful intramolecular photochemical [2+2] reaction. Although attempts to elaborate the photocycloaddition product were unsuccessful, our studies provide access to complex dimeric scaffolds and are expected to help guide our future total synthesis studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Asymmetric total synthesis of (+)-neplanocin A was concisely achieved from readily available d -galactose via the regioselective and diastereoselective amination of carbocyclic polybenzyl ether using chlorosulfonyl isocyanate and intramolecular olefin metathesis using second-generation Grubbs catalyst. [ABSTRACT FROM AUTHOR]

The syntheses of four macrocyclic molecular rotors are described. The starting oxosteroids, 5β-androsterone, and 23-oxosarsasapogenin, were subjected to Grignard ethynylation followed by Sonogashira coupling with 1,4-diiodobenzene. The obtained acyclic dimers were further transformed into the corresponding 3-esters with terminal double bonds. These compounds were converted into the final products via an RCM protocol. [ABSTRACT FROM AUTHOR]

The scope and limitations of the simple synthesis of functionalized quinolizidin-4-ones by chemoselective N-alkenylation of N H pyridin-2(1 H )-ones (2-pyridones), regioselective addition of lithium allyl(di- n -butyl)magnesates(1-) to N -alkenylpyridin-2(1 H )-ones, followed by ring closing metathesis (RCM) is described. A number of functionalizations introduced into quinolizidin-4-one rings demonstrated the high prospect of the strategy proposed in scaffold synthesis. Their extension to the syntheses of pyrido[1,2- a ]azepin-4-one and pyrido[1,2- a ]azocin-4-one derivatives as well as to spiro-fused compounds is also presented. [ABSTRACT FROM AUTHOR]

Abstract: A highly selective and atom efficient ‘trifluoroacetic ester/ketone metathesis’ has been sincerely witnessed. Enolizable alkyl (at least two non-hydrogen atoms) aryl ketones were found to react readily with ethyl trifluoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones (TFMKs), and aromatic acid esters, which were quite different from the general Claisen condensation products, 1,3-diketones. The outcome of the reaction between ketone and ethyl trifluoroacetate is strongly related to the structures of substrates, the steric congestion caused by alkyl group is in favor of the C–C bond cleavage. DFT investigation further disclosed that the metathesis reaction was a kinetically favored pathway. Using only a slight excess of cheap trifluoromethylation reagent, simple operation and mild conditions make it a practical method for preparation of TFMKs on large scale, as well as a new choice of converting aryl alkyl ketones to aromatic acid esters. [Copyright &y& Elsevier]

Abstract: Using epoxy chiral building blocks readily derived from d-gluconolactone as the source of the stereogenic centers, both (6R,8R)- and (6R,8S)-isomers of (E)-1-chlorotridec-1-ene-6,8-diol were synthesized. The vinylchloro unit was installed onto the substrate carbon chain in an approximately 9:1 (E)/(Z) ratio via a condensation of CrCl2/CHCl3 with a terminal aldehyde. A tosylation protocol featuring addition of H2O was also developed for a highly polar tetraol. The synthetic products allowed for re-acquisition of the NMR spectra of better quality and revealed some delicate yet unignorable discrepancies in the 13C NMR for the natural isomer obtained by synthesis and that isolated some 30 years ago from the marine cyanophyte. The puzzling discrepancies were eventually shown to be caused by deuteration of the hydroxyl groups. [Copyright &y& Elsevier]

Abstract: Ring-closing metathesis (RCM) and sequential Yb(OTf)3 promoted Diels–Alder reactions of sulfamide-linked enynes proceeded selectively in one-pot to afford a series of bicyclic and tricyclic sulfamides. Excellent levels of diastereoselectivity are observed for the cycloaddition step, with only the endo-adducts being isolated. The protocol was further extended to incorporate a one-pot RCM–cross metathesis (CM)–Diels–Alder sequence, permitting rapid access to high levels of molecular complexity from simple and easily accessible precursors. [Copyright &y& Elsevier]

Abstract: Prior studies have shown an effective way to produce diverse ligand sets for catalyst discovery is by using mixtures of monodentate forms to generate catalysts in situ. Research described here was performed to illustrate that alkene-functionalized monodentate ligands could be used in this way and in another that increases the diversity of the ligand library in an interesting way. Specifically, we hypothesized that as well as being used as monomers, these alkenes could be cross metathesized in situ immediately before the catalysis step. This combination of metathesis to form ligands in situ, then catalysis is referred to here as metacatalysis. In the event, a library of quinidine and quinine alkaloid-derived phosphites were tested as mixtures of monomers and dimers formed via metathesis in situ. The data obtained illustrated that metacatalysis can be used to identify ligands that positively and negatively modulate enantioselectivities in iridium-mediated hydrogenations of α,β-unsaturated carboxylic acid derivatives, relative to the mixtures of the monomeric forms used. [Copyright &y& Elsevier]

Abstract: The naturally occurring nucleoside sinefungin has found considerable use in biological investigations. More extensive sinefungin studies have been limited because few analogues have been reported due to the synthetic challenges associated with such studies. Reported herein are preparative ways to two carbocyclic sinefungin analogues: 6′-deaminocarbocyclic sinefungin and (S)-6′-hydroxy-6′-deaminocarbocyclic sinefungin. The synthetic routes were made efficient and practical by the application of two metathesis reactions employing second generation Grubbs catalyst. [Copyright &y& Elsevier]

The cascade reaction of thiopyrano[4,3- b ]indole-3(5 H)-thiones and dimethyl acetylenedicarboxylate (DMAD) was found. The mechanism has been investigated in detail by DFT PCM/B3LYP/6–311++G(d,p) quantum chemical calculations. Initially, the reaction occurs via an alkyne–thiocarbonyl metathesis mechanism. At the next stages, unprecedented rearrangement takes place: thiopyrane ring opening and thiophene ring closure proceed. Cycloaddition of intermediate thioketone and a second equivalent of DMAD leads to the resulting thiopyrano[4,3- b ]indole derivative bearing thienyl substituent. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Intramolecular Diels–Alder reaction of trienones embedded in a sugar derivative with or without Me substituents on the diene part has been investigated for synthesis of hydrindanes with angular oxygen functionality. One of these adducts has been transformed to a functionalized bicyclic skeleton present in galiellalactone. [Copyright &y& Elsevier]

Abstract: Muscenone® is a valuable perfume ingredient consisting of a mixture of the E- and Z-isomers of 1 in racemic form as the major constituents. Among them, it is the (R,Z)-isomer, which exhibits the most favorable musk character and by far the lowest threshold; for these superior olfactory properties, pure (R,Z)-1 has recently been commercialized too. We present an efficient route to this precious compound based on an iron-catalyzed cross coupling reaction, a molybdenum-catalyzed alkyne metathesis for the formation of the macrocyclic ring, and a nickel-catalyzed semi-hydrogenation. [Copyright &y& Elsevier]

Abstract: Model cross and ring-closing metathesis strategies toward the C1–C8-linear carbon skeleton are presented. The introduction of a four-atom tether enables the formation of 12-membered rings in good-to-excellent yields and stereoselectivity. Furthermore, the study revealed that the cross-metathesis approach and the formation of medium ring sizes via ring-closing metathesis are much less favorable. [Copyright &y& Elsevier]

Abstract: A sequence of ring-closing metathesis and palladium-catalyzed formate reduction was developed for preparing O-heterocycles with an exocyclic olefin and applied to the asymmetric synthesis of zoapatanol. The key vicinal stereocenters in zoapatanol were constructed from the l-malic acid-derived lactone by successive chelation-controlled addition of alkyl groups. The O-allylations to prepare the dienes for RCM were achieved with the tertiary alcohols bearing internal olefins. The ring opening of oxepane, a new reaction pathway for the Pd-formate reduction, is also reported. [Copyright &y& Elsevier]

Abstract: A simplified analogue of the C1–C11 fragment of peloruside A has been synthesised starting from a monoprotected 2,2-dimethylpropane-1,3-diol. Oxidation, asymmetric allylation and acryloylation provided a substrate for ring-closing metathesis to a δ-lactone. Reduction, acylation and homologation with trimethyl(vinyloxy)silane provided a protected C3–C11 analogue in a stereoisomer manner. Introduction of the C1–C2 fragment and incorporation of the 2,3-syn stereochemistry was achieved by a boron-mediated Evans aldol reaction. [Copyright &y& Elsevier]

Abstract: The structures proposed for natural butanolides piliferolides A and C have been synthesized. The allylic and lactone stereogenic centers in the target structures were derived from d-mannitol, while that near the side-chain terminal was taken from (R)-propylene oxide. The synthetic samples helped to reveal that a signal at around δ 2.0ppm was missing in the 1H NMR data listing for the structures proposed for natural piliferolides, whereas the δ 29.7ppm signal in the 13C NMR reported for the structure proposed for natural piliferolide C most likely stemmed from the impurities in the chromatography solvent. [ABSTRACT FROM AUTHOR]

Abstract: The rearrangement of dihydropyrans and dihydrofurans featuring appending olefins has been studied. The rearranged products bear resemblance with polyunsaturated di- and trisaccharides. Examples of functionalization prior to, or following, rearrangement are provided suggesting that the method should be useful for the synthesis of nonclassical saccharides. This work also illustrates the power of cascade methatetic processes for increasing molecular complexity starting from relatively simple heterocycles. [Copyright &y& Elsevier]

Abstract: Formation of a nine-membered cyclic ether with E-configurated double bond was observed during construction of 5-9-5 tricycles through RCM of dienes. Ring fusion stereochemistry in the products oxonenes was found to have profound influence on the olefin geometry. cis-anti-cis 5-9-5 tricycle was obtained with Z-configurated olefin while cis-syn-cis 5-9-5 system was obtained with E- as well as Z-configurated double bond with the former predominating. [ABSTRACT FROM AUTHOR]

Abstract: The attempted first stereoselective synthesis of 2,2′-biindoline using a metathesis-Sharpless asymmetric dihydroxylation strategy results in the synthesis of the heterocycle in poor to modest stereoselectivity. Attempts to improve the ee by varying the heteroatom protecting groups in key intermediates did not enhance the outcome of the Sharpless AD reaction. Therefore a limitation of this AD reaction is the use of 1,4-substituted but-2-enes where these substituents are ortho-substituted aromatics. [ABSTRACT FROM AUTHOR]

Abstract: Even though the macrolides of the iejimalide family are of marine origin, whereas those of the archazolid series derive from terrestrial myxobacteria, a comparison of their constitution, stereochemistry, and biological activity suggests that these natural products are close structural and functional relatives. Guided by this perception, compound 5 was prepared, which hybridizes the macrolactone core of iejimalide B (2) with the tail of archazolid A (3). The cytotoxicity profile of this chimera, as determined with a panel of 12 human cancer cell lines, corresponds to that of the parent compound 2, although its potency is lower. This outcome may be interpreted on the basis of molecular dynamics calculations, which suggest that the low energy conformations of 2 and 5 are similar but the energetic barriers between the relevant conformers are distinctly higher for the hybrid structure. The synthesis of 5 hinged on a regioselective functionalization of 2,4-dibromothiazole 6, a highly selective CBS-reduction of ketone 8, a Suzuki cross coupling of vinyl boronate 17 with the elaborate alkenyl iodide 16, and a productive closure of the macrocycle by RCM, which requires the selective activation of two out of eight double bonds present in the cyclization precursor 20 by the second-generation Grubbs catalyst 21. [ABSTRACT FROM AUTHOR]

Abstract: A tandem dienyne metathesis based strategy has been developed for construction of the core tricyclic framework found in the lepadiformine and cylindricine alkaloids. 2-Pentenyl-2-ethynylpyrollidine acrylamide that serves as the starting material for the key ruthenium carbene catalyzed metathesis process is prepared by using a concise route starting with l-proline. [Copyright &y& Elsevier]

Abstract: An unprecedented chiral spiropiperidine oxindole system was synthesized starting from enantiopure quaternary 3-aminooxindole and relying on a ring closing metathesis as the key step. This compound acts as an highly constrained Freidinger γ-lactam, adopting a type II β-turn conformation in solution, as assessed by modelling and spectroscopical studies. [Copyright &y& Elsevier]

Abstract: A direct route for the synthesis of highly functionalized angularly substituted hydrindanes has been developed. The key step involves RO–RCM of an appropriately functionalized norbornene derivative. The hydrindane derivative obtained in this way has been used to accomplish a formal synthesis of bakkenolide-A. This protocol has also been extended for the synthesis of an advanced intermediate to the synthesis of the diterpene umbellactal. [Copyright &y& Elsevier]

Abstract: Herein, we describe the first glycoconjugate macrocyclic thiolcarbonate namely (Z)-10(S)-[3′-O-acetyl-1′,2′-O-isopropylidene-4′-deoxy-d-erythrofuranose]-4,7,9-trihydro-10H-8-thia-1,3-oxathiecin-2-one (17a) using a strategy based on two key steps synthesis: (i) a haloalkylation of vic-diol via their cyclic thionocarbonate derivatives; (ii) a macrocyclisation using ring closing metathesis reaction. Detailed here is a newly developed extension of vic-diol halogenation via the cyclic thionocarbonate function but using a range of alkyl halides other than the customarily used MeI. For example, with 1,2-O-isopropylidene-5,6-O-thionocarbonate-d-glucose (1) and allyl bromide, the 5-allylthiolcarbonate-6-bromo-6-deoxy-d-glucose derivative 6 was obtained in good yield. The later submitted to 6-allythioetherification and ring closing metathesis (RCM) with Grubbs second generation gave stereoselectively the target oxathiecinone 17a in 75% yield for the RCM step. [Copyright &y& Elsevier]

Abstract: Five new C–C bonded steroidal homodimers derived from deoxycholic acid, pregnenolone, and progesterone were synthesized by an olefin metathesis reaction assisted by microwave heating. Microwave improved the yield and accelerated the reaction allowing the use of less catalyst with good results (2.5mol%). Due to the bulky nature of the steroidal skeleton the more favorable E-dimers were formed as the sole or major products depending on the linker length. [Copyright &y& Elsevier]

Abstract: Functionalization of β-carbolines is a challenge as numerous natural alkaloids with different biological activities present this heterocycle. The RCM is used herein with allyl-, vinyl-, ethynyl-, and propargyl-β-carbolines to generate additionally fused hetero- and carbocycles, and it is combined with other cyclization processes to achieve great molecular complexity in one synthetic step. Thus, an RCM–Diels–Alder sequence gives pentacyclic compounds related with certain alkaloids. On the other hand, vinylpyrrolo[2,1-a]-β-carbolines and vinyl-β-carbolines give different products upon reaction with activated dienophiles. Thus, a novel domino processes affords complex polycycles like 35–38. Other alkynes like 3-butyn-2-one give a Stevens rearrangement. [Copyright &y& Elsevier]

Abstract: A range of amides fitted with (E) or (Z) disubstituted alkene groups were prepared and evaluated in intramolecular Kulinkovich–de Meijere reactions. The corresponding aminocyclopropanes were obtained with high diastereoselectivity. Good yields could be achieved with substrates bearing suitable substitutions at the olefin moieties. [Copyright &y& Elsevier]

Abstract: The preparation of several organic–inorganic hybrid materials by sol–gel process derived from Hoveyda-type monomers is described. One of them presents a nitro group at the para position with respect to the alkoxy moiety. These materials were treated with Grubbs catalysts to generate the corresponding Hoveyda–Grubbs carbene ruthenium complexes covalently bonded to the silica matrix, which were tested as recyclable catalysts for diene and enyne RCM. Electronic effects of the nitro group resulted in enhanced activity of the catalyst. Whereas the recyclability decreased in RCM of dienes, the presence of this electron-withdrawing group was highly advantageous for the RCM of enynes, the reusability being greatly improved. [Copyright &y& Elsevier]