- Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: Applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A
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The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol % of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73 % Z) epilachnene (15-membered ring: 91 % Z), ambrettolide (17-membered ring: 91 % Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97 % Z), and nakadomarin A (15-membered ring: up to 97 % Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule.
- Wang, Chenbo,Yu, Miao,Kyle, Andrew F.,Jakubec, Pavol,Dixon, Darren J.,Schrock, Richard R.,Hoveyda, Amir H.
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- Chemoenzymatic preparation of musky macrolactones
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Abstract A chemoenzymatic approach to some musk macrolactones has been explored by the optimization of macrolactonization catalyzed by Candida antarctica lipase B (Novozym 435). This fast and high yield optimized methodology represents a large improvement to previously reported results. The methodology was applied to the preparation of 16-hexadecanolide, exaltolide, ambrettolide and (15R)-15-hexadecanolide.
- Fortunati, Tancredi,D'Acunto, Mariantonietta,Caruso, Tonino,Spinella, Aldo
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p. 2357 - 2362
(2015/03/30)
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- Z-SELECTIVE METATHESIS CATALYSTS
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A novel chelated ruthenium-based metathesis catalyst bearing an N-2,6- diisopropylphenyl group is reported and displays near-perfect selectivity for the Z-olefin (>95%), as well as unparalleled TONs of up to 7,400, in a variety of homodimerization and industrially relevant metathesis reactions. This derivative and other new catalytically-active species were synthesized using an improved method employing sodium carboxylates to induce the salt metathesis and C-H activation of these chelated complexes. All of these new ruthenium-based catalysts are highly Z-selective in the homodimerization of terminal olefins.
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Paragraph 00076; 00078
(2014/07/07)
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- Stereoselective access to Z and e macrocycles by ruthenium-catalyzed Z-selective ring-closing metathesis and ethenolysis
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The first report of Z-selective macrocyclizations using a ruthenium-based metathesis catalyst is described. The selectivity for Z macrocycles is consistently high for a diverse set of substrates with a variety of functional groups and ring sizes. The same catalyst was also employed for the Z-selective ethenolysis of a mixture of E and Z macrocycles, providing the pure E isomer. Notably, an ethylene pressure of only 1 atm was required. These methodologies were successfully applied to the construction of several olfactory macrocycles as well as the formal total synthesis of the cytotoxic alkaloid motuporamine C.
- Marx, Vanessa M.,Herbert, Myles B.,Keitz, Benjamin K.,Grubbs, Robert H.
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supporting information
p. 94 - 97
(2013/04/10)
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- Highly active ruthenium metathesis catalysts exhibiting unprecedented activity and Z-selectivity
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A novel chelated ruthenium-based metathesis catalyst bearing an N-2,6-diisopropylphenyl group is reported and displays near-perfect selectivity for the Z-olefin (>95%), as well as unparalleled TONs of up to 7400, in a variety of homodimerization and industrially relevant metathesis reactions. This derivative and other new catalytically active species were synthesized using an improved method employing sodium carboxylates to induce the salt metathesis and C-H activation of these chelated complexes. All of these new ruthenium-based catalysts are highly Z-selective in the homodimerization of terminal olefins.
- Rosebrugh, Lauren E.,Herbert, Myles B.,Marx, Vanessa M.,Keitz, Benjamin K.,Grubbs, Robert H.
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supporting information
p. 1276 - 1279
(2013/03/14)
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- Z-SELECTIVE RING-CLOSING METATHESIS REACTIONS
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The present invention relates generally to olefin metathesis. In some embodiments, the present invention provides methods for Z-selective ring-closing metathesis.
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Page/Page column 161-163; 170-171; 175
(2013/02/28)
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- Odorant compositions containing macrocycles and processes for manufacturing the same
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The invention is concerned with odorant compositions which contain macrocycles, namely 15- to 17-membered compounds of the formula: wherein the dotted line signifies an optional additional bond, X and Y stand for methylene or C2-12-polymethylene, optionally substituted with an additional methyl group, and A signifies hydrogen or methyl in the case of the unsaturated compounds and methyl in the case of the saturated compounds, with the proviso that the unsaturated compounds are present to more than 80% in the cis form when A signifies hydrogen and are present to more than 50% in the cis form when A signifies methyl, with the exception of Z-oxacyclopentadec-6-en-2-one (15-membered ring), Z-oxacycloheptadec-8-en-2-one (17-membered ring), and Z-oxacycloheptadec-11-en-2-one (17-membered ring), a process for the manufacture of the compounds of formula I and the use of the compounds of formula I as odorants.
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- Ring closing alkyne metathesis. Comparative investigation of two different catalyst systems and application to the stereoselective synthesis of olfactory lactones, azamacrolides, and the macrocyclic perimeter of the marine alkaloid nakadomarin A
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Previously unknown ring closing metathesis reactions of diynes are described which open an efficient and stereoselective entry into macrocyclic (Z)-alkenes if the resulting cycloalkyne products are subjected to Lindlar reduction. This new two-step strategy offers significant advantages in stereochemical terms over conventional RCM of dienes which usually leads to (E,Z)-mixtures when applied to the formation of large rings. The tungsten alkylidyne complex (tBuO)3W≡CCMe3 (1a) and analogues thereof as well as a structurally unknown species formed in situ from Mo(CO)6 and p-chlorophenol effect the crucial alkyne metathesis reactions in a highly efficient manner, with the former catalyst being more tolerant toward structural variations of the substrates and polar functional groups. Applications to the stereoselective synthesis of the olfactory compounds ambrettolide 23 and yuzu lactone 24, the insect repellent azamacrolides epilachnene 31 and homoepilachnene 33, as well as to the fully functional building block 64 required for a total synthesis of the cytotoxic alkaloid nakadomarin A 51 highlight the relevance of this new concept for natural product chemistry. In the latter case, the diyne substrate 62 necessary for ring closing alkyne metathesis was obtained via a novel furan synthesis relying on a palladium-catalyzed opening of a vinyl epoxide followed by an oxidative cyclization of the heterocyclic ring.
- Fürstner, Alois,Guth, Oliver,Rumbo, Antonio,Seidel, Günter
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p. 11108 - 11113
(2007/10/03)
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- Preapration of 7,8,16-trihydroxy-hexadecanoic acid from aleuritic acid and a synthesis of E/Z-7-hexadecen-1,16-olides and hexalure
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Both threo/erythro 7,8,16-trihydroxy-hexadecanoic acids have been preapred from threo/erythro 9,10,16-trihydroxy-hexadecanoic acids (aleuritic acid), by interchanging the positions of the terminal carboxyl and hydroxyl groups through steps of appropriate oxidation-reduction on the dithianes obtained from the 16-oxo-9,10-dihydroxy-hexadecanoic acids.Cyclization of the corresponding 9,10-olefin with dibutyl tin oxide furnish E/Z-7-hexadecen-1,16-olides.Preparation of the insect pheromone hexalure is also reported.
- Tewari, Neera,Rohatgi, Amit,Bhushan, Kumar Hari,Subramanian, G. B. V.
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p. 851 - 855
(2007/10/03)
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- Cumulated Ylides XX. Syntheses of (E)-α,β-Unsaturated Macrocyclic Lactones by Intramolecular Wittig-Olefination via Triphenylphosphoranylideneketene
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Two methods for closure of macrocyclic lactone rings by intramolecular Wittig reaction of (ω-oxoalkoxy)carbonylmethylenetriphenylphosphoranes are described.The latter are easily accessible by addition of the appropriate (free or protected) ω-hydroxyalkanals to the cumulated ylide triphenylphosphoranylideneketene.Examples are then given for the use of these methods in natural product synthesis.
- Bestmann, Hans Juergen,Schobert, Rainer
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p. 419 - 423
(2007/10/02)
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- Synthesis of Ambrettolide from Phloionolic Acid
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The synthesis of ambrettolide (cis-hexadec-7-enolide) and its trans-stereoisomer is accomplished from threo-9,10,18-trihydroxyoctadecanoic acid (phloionolic acid derived from cork) via a high-yielding seven-stage synthesis.Since phloionolic acid has recently been obtained from cork in reasonable yield, the latter may be a commercial starting material for the preparation of ambrettolide.
- Sanz, Vicente,Seoane, Eliseo
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p. 1837 - 1840
(2007/10/02)
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