Alkene and Alkyne Metathesis: Grandisol (Goess), 8-Epihalosilane (Kouklovsky/Vincent), (+)-Chinensiolide B (Hall)

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Boll Weevil ◽  
Alkyne Metathesis ◽  
Ring Closing Metathesis ◽  
Enantiomerically Pure ◽  
Ru Catalyst ◽  
Complementary Approach ◽  
Terminal Substituent ◽  
Furman University ◽  
The Cost ◽  
The University

The cost of using Grubbs-type catalysts could be reduced dramatically if the turnover could be improved. Richard L. Pederson of Materia found (Organic Lett. 2010, 12, 984) that in MTBE at 50°C, the ring-closing metathesis of 1 proceeded to completion in 8 hours with just 500 ppm of H2 catalyst 2. Jianhui Wang of Tianjin University constructed (Angew. Chem. Int. Ed. 2010, 49, 4425) a modified H2 catalyst 5 tethered to a nitrobenzospiropyran. After the cyclization of 4 to 6 was run in CH2Cl2, the mixture was irradiated with visible light, converting 5 into its ionic form, which could be extracted with glycol/methanol, leaving little Ru residue in the cyclized product. In the dark, the catalyst reverted and could be extracted back into CH2Cl2 and reused. In a complementary approach, David W. Knight of Cardiff University found (Tetrahedron Lett. 2010, 51, 638) that the residual Ru after metathesis could be reduced to < 2 ppm simply by stirring the product with H2O2. Cyclopropenes such as 6 are readily available in enantiomerically pure form by the addition of diazoacetates to alkynes. Christophe Meyer and Janine Cossy of ESPCI ParisTech showed (Organic Lett. 2010, 12, 248) that with a Ti additive, G2 cyclized 7 to 8. Siegfried Blechert of the Technische Universität Berlin devised (Angew. Chem. Int. Ed. 2010, 49, 3972) the chiral Ru catalyst 11, which converted the prochiral 9 to 12 in high ee. Daesung Lee of the University of Illinois, Chicago, explored (J. Am. Chem. Soc. 2010, 132, 8840) the cyclization of the diyne 13 with 14 under G2 catalysis. Depending on the terminal substituent, the cyclization could be directed selectively to 15 or 16. Bran C. Goess of Furman University took advantage (J. Org. Chem. 2010, 75, 226) of alkyne ring-closing metathesis for the conversion of 17 to 18. Selective hydrogenation then delivered the boll weevil pheromone grandisol 19. Cyrille Kouklovsky and Guillaume Vincent of the Université de Paris Sud extended (J. Org. Chem. 2010, 75, 4333) ring-opening/ring-closing metathesis to the nitroso Diels-Alder adduct 20. Reduction led to 8-epihalosilane 22.

Total Synthesis by Alkene Metathesis: Amphidinolide X (Urpí/Vilarrasa), Dactylolide (Jennings), Cytotrienin A (Hayashi), Lepadin B (Charette), Blumiolide C (Altmann)

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
First Generation ◽  
Allylic Alcohols ◽  
Silyl Ether ◽  
Ring Closing Metathesis ◽  
Enantiomerically Pure ◽  
Ru Catalyst ◽  
Mo Catalyst ◽  
Metathesis Catalysts ◽  
The University ◽  
Medium Rings

To assemble the framework of the cytotoxic macrolide Amphidinolide X 3, Fèlix Urpí and Jaume Vilarrasa of the Universitat de Barcelona devised (Organic Lett. 2008, 10, 5191) the ring-closing metathesis of the alkenyl silane 1. No Ru catalyst was effective, but the Schrock Mo catalyst worked well. In the course of a synthesis of (-)-Dactylolide 6, Michael P. Jennings of the University of Alabama offered (J. Org. Chem. 2008, 73, 5965) a timely reminder of the particular reactivity of allylic alcohols in ring-closing metathesis. The cyclization of 4 to 5 proceeded smoothly, but attempted ring closing of the corresponding bis silyl ether failed. Polyenes such as ( + )-Cytotrienin A 8 are notoriously unstable. It is remarkable that Yujiro Hayashi of the Tokyo University of Science could (Angew. Chem. Int. Ed. 2008, 47, 6657) assemble the triene of 8 by the ring-closing metathesis of the highly functionalized precursor 7. Bicyclo [2.2.2] structures such as 9 are readily available by the addition of, in this case, methyl acrylate to an enantiomerically-pure 2-methylated dihydropyridine. André B. Charette of the Université de Montréal found (J. Am. Chem. Soc. 2008, 130, 13873) that 9 responded well to ring-opening/ring-closing metathesis, to give the octahydroquinoline 10. Functional group manipulation converted 10 into the Clavelina alkaloid ( + )-Lepadin B 11. The construction of trisubstituted alkenes by ring-closing metathesis can be difficult, and medium rings with their transannular strain are notoriously challenging to form. Nevertheless, Karl-Heinz Altmann of the ETH Zürich was able (Angew. Chem. Int. Ed. 2008, 47, 10081), using the H2 catalyst, to cyclize 12 to cyclononene 13, the precursor to the Xenia lactone ( + )-Blumiolide C 14. It is noteworthy that these fi ve syntheses used four different metathesis catalysts in the key alkene forming step. For the cyclization of 7, the use of the Grubbs first generation catalyst G1, that couples terminal alkenes but tends not to interact with internal alkenes, was probably critical to success.

Alkene and Alkyne Metathesis: (+)-Anamarine (Sabitha), ( ± )-Pseudotabersonine (Martin), Lactimidomycin (Fürstner)

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Indian Institute ◽  
Alkyne Metathesis ◽  
Max Planck ◽  
Ring Closing Metathesis ◽  
University Of Texas ◽  
Ru Catalyst ◽  
Cross Metathesis ◽  
University Of Zurich ◽  
Indian Institute Of Science ◽  
The University

Masato Matsugi of Meijo University showed (J. Org. Chem. 2010, 75, 7905) that over five iterations, the fluorous-tagged Ru catalyst 1b was readily recovered and reused for the cyclization of 2 to 3. Hengquan Yang of Shanxi University reported (Chem. Commun. 2010, 46, 8659) that the Hoveyda catalyst 1a encapsulated in mesoporous SBA-1 could also be reused several times. Jean-Marie Basset of KAUST Catalysis Center, Régis M. Gauvin of Université Lille, and Mostafa Taoufik of Université Lyon 1 described (Chem. Commun. 2010, 46, 8944) a W catalyst on silica that was also active for alkene metathesis. Reto Dorta of the University of Zurich, exploring several alternatives, found (J. Am. Chem. Soc. 2010, 132, 15179) that only 4c cyclized cleanly to 5. Karol Grela of the Polish Academy of Sciences showed (Synlett 2010, 2931) that 3-nitropropene (not illustrated) participated in cross-metathesis when catalyst 1c was used. Shawn K. Collins of the Université de Montré al complexed (J. Am. Chem. Soc. 2010, 132, 12790) 6 with a quinolinium salt to direct paracyclophane formation. Min Shi of the Shanghai Institute of Organic Chemistry incorporated (Org. Lett. 2010, 12, 4462) the cyclopropene 8 in cross-metathesis, to give 10. A. Srikrishna of the Indian Institute of Science (Bangalore) constructed (Synlett 2010, 3015) the cyclooctenone 12 by ring-closing metathesis. LuAnne McNulty of Butler University established (J. Org. Chem. 2010, 75, 6001) that a cyclic boronic half acid 15, prepared by ring-closing metathesis, coupled with an iodoalkene 16 to deliver the diene 17 with high geometric control. Gowravaram Sabitha of the Indian Institute of Chemical Technology, Hyderabad, en route to (+)-anamarine 21, observed (Tetrahedron Lett. 2010, 51, 5736) that the tetraacetate 18b would not participate in cross-metathesis. Fortunately, 18a , an earlier intermediate in the synthesis, worked well. Stephen F. Martin of the University of Texas prepared (Org. Lett. 2010, 12, 3622) (±)-pseudotabersonine 24 by way of a spectacular metathesis that converted 22 to 23. Ring-closing alkyne metathesis was a key step in the total synthesis of lactimidomycin 27 reported (J. Am. Chem. Soc. 2010, 132, 14064) by Alois Fürstner of the Max-Planck- Institut Mülheim.

Advances in Alkene and Alkyne Metathesis

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Acetic Acid ◽  
Diels Alder ◽  
Alkyne Metathesis ◽  
Santa Barbara ◽  
Ring Closing Metathesis ◽  
Enol Ethers ◽  
Cross Metathesis ◽  
Simple Filtration ◽  
The University ◽  
Academy Of Sciences

As alkene metathesis is extended to more and more challenging substrates, improved catalysts and solvents are required. Robert H. Grubbs of Caltech developed (Organic Lett. 2008, 10, 441) the diisopropyl complex 1, that efficiently formed the trisubstituted alkene 6 by cross metathesis of 4 with 5. Hervé Clavier and Stephen P. Nolan of ICIQ, Tarragona, and Marc Mauduit of ENSC Rennes found (J. Org. Chem. 2008, 73, 4225) that after cyclization of 7 with the complex 2b, simple filtration of the reaction mixture through silica gel delivered the product 8 containing only 5.5 ppm Ru. The merit of CH2Cl2 as a solvent for alkene metathesis is that the catalysts (e.g. 1 - 3) are very stable. Claire S. Adjiman of Imperial College and Paul C. Taylor of the University of Warwick established (Chem. Commun. 2008, 2806) that although the second generation Grubbs catalyst 3 is not as stable in acetic acid, for the cyclization of 9 to 10 it is a much more active catalyst in acetic acid than in CH2Cl2 . Bruce H. Lipshutz of the University of California, Santa Barbara observed (Adv. Synth. Cat . 2008, 350, 953) that even water could serve as the reaction solvent for the challenging cyclization of 11 to 12, so long as the solubility- enhancing amphiphile PTS was included. Ernesto G. Mata of the Universidad Nacional de Rosario explored (J. Org. Chem. 2008, 73, 2024) resin isolation to optimize cross-metathesis, finding that the acrylate 13 worked particularly well. Karol Grela of the Polish Academy of Sciences, Warsaw optimized (Chem. Commun. 2008, 2468) cross-metathesis with a halogenated alkene 16. Jean-Marc Campagne of ENSC Montpellier extended (J. Am. Chem. Soc. 2008, 130, 1562) ring-closing metathesis to enynes such as 19. The product diene 20 was a reactive Diels-Alder dienophile. István E. Markó of the Université Catholique de Louvain applied (Tetrahedron Lett. 2008, 49, 1523) the known (OHL 20070122) ring-closing metathesis of enol ethers to the cyclization of the Tebbe product from 23. The ether 24 was oxidized directly to the lactone 25.

The Evans Synthesis of (–)-Nakadomarin A

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Organic Synthesis ◽  
Allyl Alcohol ◽  
First Generation ◽  
Direct Conversion ◽  
Heck Coupling ◽  
Ring Closing Metathesis ◽  
Selective Activation ◽  
Enantiomerically Pure ◽  
Ru Catalyst ◽  
Nakadomarin A

(–)-Nakadomarin A (4), isolated from the marine sponge Amphimedon sp. off the coast of Okinawa, shows interesting cytotoxic and antibacterial activity. David A. Evans of Harvard University prepared (J. Am. Chem. Soc. 2013, 135, 9338) 4 by coupling the enantiomerically pure lactam 2 with the prochiral lactam 1. The preparation of 1 began with the aldehyde 5. Following the Comins protocol, addition of lithio morpholine to the carbonyl gave an intermediate that could be metalated and iodinated. Protection of the aldehyde followed by Heck coupling with allyl alcohol gave the aldehyde 7. Addition of the phosphorane derived from 8 followed by deprotection gave 9 with the expected Z selectivity. Addition of the phosphonate 10 was also Z selective, leading to the lactam 1. The preparation of 2 began with the enantiomerically pure imine 12. The addition of 13 was highly diastereoselective, setting the absolute configuration of 15. Alkylation with the iodide 16 delivered 17, which was closed to 2 under conditions of kinetic ring-closing metathesis, using the Grubbs first generation Ru catalyst. The condensation of 1 with 2 gave both of the diastereomeric products, with a 9:1 preference for the desired 3. Experimentally, acid catalysis alone did not effect cyclization, suggesting that the cyclization is proceeding via silylated intermediates. The diastereoselectivity can be rationalized by a preferred extended transition state for the intramolecular Michael addition. Selective activation of 3 followed by reduction gave 18, which underwent Bischler-Napieralski cyclization to give an intermediate that could be reduced to (–)-nakadomarin A (4). It was later found that exposure of 3 to Tf2O and 19 followed by the addition of Redal gave direct conversion to 4. It is instructive to compare this work to the two previous syntheses of 4 that we have highlighted, by Dixon (OHL May 3, 2010) and by Funk (OHL July 4, 2011). Together, these three independent approaches to 4 showcase the variety and dexterity of current organic synthesis.

The Fürstner Synthesis of Amphidinolide F

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Amino Alcohol ◽  
Aldol Condensation ◽  
Free Acid ◽  
The Other ◽  
Unsaturated Ester ◽  
Alkyne Metathesis ◽  
Max Planck ◽  
Ring Closing Metathesis ◽  
Enantiomerically Pure ◽  
Metathesis Catalyst

The amphidinolides, having zero, one, or (as exemplified by amphidinolide F 3) two tetrahydrofuran rings, have shown interesting antineoplastic activity. It is a tribute to his development of robust Mo catalysts for alkyne metathesis that Alois Fürstner of the Max-Planck-Institut für Kohlenforschung Mülheim could with confidence design (Angew. Chem. Int. Ed. 2013, 52, 9534) a route to 3 that relied on the ring-closing metathesis of 1 to 2 very late in the synthesis. Three components were prepared for the assembly of 1. Julia had already reported (J. Organomet. Chem. 1989, 379, 201) the preparation of the E bromodiene 5 from the sulfone 4. The alcohol 7 was available by the opening of the enantiomerically-pure epoxide 6 with propynyl lithium, followed by oxidation following the Pagenkopf pro­tocol. Amino alcohol-directed addition of the organozinc derived from 5 to the alde­hyde from oxidation of 7 completed the assembly of 8. Addition of the enantiomer 10 of the Marshall butynyl reagent to 9 followed by protection, oxidation to 11, and addition of, conveniently, the other Marshall enan­tiomer 12 led to the protected diol 13. Silylcupration–methylation of the free alkyne set the stage for selective desilylation and methylation of the other alkyne. Iodination then completed the trisubstituted alkene of 14. Methylation of the crystalline lactone 15, readily prepared from D-glutamic acid, led to a mixture of diastereomers. Deprotonation of that product followed by an aque­ous quench delivered 16. Reduction followed by reaction with the phosphorane 17 gave the unsaturated ester, that cyclized with TBAF to the crystalline 18. The last ste­reogenic center of 22 was established by proline-mediated aldol condensation of the aldehyde 19 with the ketone 20. To assemble the three fragments, the ketone of 21 was converted to the enol triflate and thence to the alkenyl stannane. Saponification gave the free acid 22, that was acti­vated, then esterified with the alcohol 18. Coupling of the stannane with the iodide 14 followed by removal of the TES group led to the desired diyne 1. It is noteworthy that the Mo metathesis catalyst is stable enough to tolerate the free alcohol of 1 in the cyclization to 2.

Alkene Metathesis: Synthesis of Panaxytriol (Lee), Isofagomine (Imahori and Takahata), Elatol (Stoltz), 5-F2t -Isoprostane (Snapper), and Ottelione B (Clive)

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Grignard Reagent ◽  
Conjugate Addition ◽  
Ring Closing Metathesis ◽  
University Of Illinois ◽  
Enantiomerically Pure ◽  
University Of Alberta ◽  
Cross Metathesis ◽  
Grubbs Catalysts ◽  
The University ◽  
First And Second Generation

Alkene metathesis has been used to prepare more and more challenging natural products. The first and second generation Grubbs catalysts 1 and 2 and the Hoveyda catalyst 3 are the most widely used. Daesung Lee of the University of Illinois at Chicago designed (Organic Lett. 2008, 10, 257) a clever chain-walking cross metathesis, combining 4 and 5 to make 6. The diyne 3 was carried on (3R, 9R, 10R )-Panaxytriol 7. Tatsushi Imahori and Hiroki Takahata of Tohoku Pharmaceutical University found (Tetrahedron Lett. 2008, 49, 265) that of the several derivatives investigated, the unprotected alcohol 8 cyclized most efficiently. Selective cleavage of the monosubstituted alkene followed by hydroboration delivered the alkaloid Isofagomine 10. Brian M. Stoltz of Caltech established (J. Am. Chem. Soc. 2008 , 130 , 810) the absolute configuration of the halogenated chamigrene Elatol 14 using the enantioselective enolate allylation that he had previously devised. A key feature of this synthesis was the stereocontrolled preparation of the cis bromohydrin. Marc L. Snapper of Boston College opened (J. Org. Chem. 2008, 73, 3754) the strained cyclobutene 15 with ethylene to give the diene 16. Remarkably, cross metathesis with 17 delivered 18 with high regioselectivity, setting the stage for the preparation of the 5-F2t - Isoprostane 19. Derrick L. J. Clive of the University of Alberta assembled (J. Org. Chem. 2008, 73, 3078) Ottelione B 26 from the enantiomerically-pure aldehyde 20. Conjugate addition of the Grignard reagent 21 derived from chloroprene gave the kinetic product 22, that was equilibrated to the more stable 23. Addition of vinyl Grignard followed by selective ring-closing metathesis then led to 26.

The Smith Synthesis of (−)-Nodulisporic Acid D

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Functional Group ◽  
University Of Pennsylvania ◽  
Magnesium Bromide ◽  
Ring Closing Metathesis ◽  
Enantiomerically Pure ◽  
Model Study ◽  
Silyl Enol Ether ◽  
Robinson Annulation ◽  
The University ◽  
Stereogenic Center

The nodulisporic acids, isolated from the endophytic fungus Nodulisporium sp., show promising insecticidal activity. Amos B. Smith III of the University of Pennsylvania envisioned (J. Am. Chem. Soc. 2015, 137, 7095) the construction of the central indole of nodulisporic acid D 4 by the convergent coupling of the chloroaniline 1 with the enol triflate 2. The preparation of 2 began (Org. Process Res. Dev. 2007, 11, 19) with the mono­ketal 5 of the Wieland–Miescher ketone, available in enantiomerically-pure form by organocatalyzed Robinson annulation. Condensation with thiophenol and formal­dehyde gave 6, which, under dissolving metal conditions, was reduced to an enolate that was trapped as the silyl enol ether 7. Condensation again with formaldehyde gave 8, that was converted by reduction and protecting group exchange to the ketone 9. Pd-catalyzed formylation of the derived enol triflate led to 10. The Cu-meditated conjugate addition of vinyl magnesium bromide to the unsatu­rated aldehyde 10 was carefully optimized to maximize equatorial addition, away from the angular methyl group. Subsequent C-methylation of the aldehyde was achieved by generating the Li enolate and carrying out the alkylation in diglyme. With 11 in hand, the third carbocyclic ring was assembled by 1,2-addition of vinylmagnesium bromide to the aldehyde followed by ring-closing metathesis and oxidation to give 12. Hydrogenation followed by functional group interconversion then completed the assembly of the enol triflate 2. The stereogenic center of 1 was established by Enders alkylation of 13 with the iodide 14. The ketone 15 was best liberated by ozonolysis under non-epimerizing conditions. The critical Barluenga indole construction that formed 3 also required careful optimization in a model study, the key observation being the value of the Buchwald ligand RuPhos. The conditions developed were found, remarkably, to be compatible with the aldehyde functional group, so subsequent Horner–Wadsworth–Emmons condensation with 16 could be carried out directly, to complete the synthe­sis of (−)-nodulisporic acid D 4.

C–O Ring Construction: The Tong Synthesis of (−)-Aculeatin A

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
University Of Pittsburgh ◽  
Enantiomerically Pure ◽  
Complementary Approach ◽  
Single Diastereomer ◽  
Pure Alcohol ◽  
Peking University ◽  
Duke University ◽  
Purdue University ◽  
Leaving Groups ◽  
The University

Oxetanes are both interesting structural elements and activated leaving groups. James A. Bull of Imperial College London cyclized (Chem. Commun. 2014, 50, 5203) the tosylate 1 to the oxetane with LiHMDS, then alkylated the product using the same base to give 2. J. S. Yadav of CSIR-Indian Institute of Chemical Technology estab­lished (Org. Lett. 2014, 16, 836) conditions for the cyclization of 3 to 4. Hiroaki Sasai of Osaka University used (Chem. Commun. 2013, 49, 11224) a Pd(II)–Pd(IV) cycle to convert 5 to 6. Lauri Vares of the University of Tartu dem­onstrated (Tetrahedron Lett. 2014, 55, 3569) that the racemic epoxide 7, a mixture of diastereomers, could be cyclized to 8 as a single diastereomer in high ee. Alistair Boyer of the University of Glasgow converted (Org. Lett. 2014, 16, 1660) the tria­zole 9, prepared from the corresponding alkyne, to the intermediate 10, that could be hydrolyzed to the ketone or reduced to the amine. Subhas Chandra Roy of the Indian Association for the Cultivation of Science devised (Eur. J. Org. Chem. 2014, 2980) a Ti(III)- mediated cascade conjugate addition–cyclization for the assembly of 12 from 11. Paul E. Floreancig of the University of Pittsburgh reported (Angew. Chem. Int. Ed. 2014, 53, 4926) the highly diastereoselective reductive cyclization of 13 to 14. Arun K. Ghosh of Purdue University prepared (J. Org. Chem. 2014, 79, 5697) the ketone 16 from the enantiomerically-pure alcohol 15. Professor Ghosh also described (Org. Lett. 2014, 16, 3154) a complementary approach to tetrahydropyrans based on the hetero Diels–Alder addition of the alkynyl aldehyde 18 to the diene 17 to give 19. Xin-Shan Ye of Peking University found (J. Org. Chem. 2014, 79, 4676) that the alcohol 20 could be cyclized to 21 with NBS, and to the diastereomer with PhSeCl. Jiyong Hong of Duke University showed (Org. Lett. 2014, 16, 2406) that an organo­catalyst could be used to mediate the cyclization of 22 to the oxepane 23. Mingji Dai, also of Purdue University, reported (Angew. Chem. Int. Ed. 2014, 53, 6519) the car­bonylative macrocyclization of the diol 24 to the lactone 25.

Advances in Alkene Metathesis: The Hoveyda Synthesis of (+)-Quebrachamine

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
University Of Iowa ◽  
Enantiomerically Pure ◽  
Ru Catalyst ◽  
Cross Metathesis ◽  
Mo Catalyst ◽  
Conformational Effects ◽  
Ru Complexes ◽  
Metathesis Catalysts ◽  
La Rioja ◽  
The University

There are two major impediments to scaling up alkene metathesis: reducing the amount of the expensive Ru catalyst required, and minimizing residual Ru in the product. Robert H. Grubbs of Caltech developed (Organic Lett. 2009, 11, 1261) a family of silica-supported Ru complexes, exemplified by 1. At 0.75 mol % of 1, the rate of cyclization of 2 to 3 was maintained over eight cycles. The solution of product 3 showed < 5 ppb Ru. Hassan S. Bazzi and David E. Bergbreiter of the Texas A&M campuses in Qatar and College Station also reported (Organic Lett. 2009, 11, 665) a durable polymer-bound Ru metathesis catalyst that maintained its activity over many cycles. Most metathesis catalysts are strongly E selective. Amir H. Hoveyda of Boston College designed (J. Am. Chem. Soc. 2009, 131, 3844) a chiral Mo catalyst that was both highly enantioselective and strongly Z selective, converting the prochiral 4 into the alkene 6. Professor Hoveyda also took advantage (J. Am. Chem. Soc. 2009, 131, 8378) of the known propensity of Ru metathesis catalysts for H bonding, showing that metathesis of the prochiral cyclopropene 7 proceeded with remarkable diastereocontrol. This appears to be a generally useful protocol for assembling enantiomerically pure alkylated quaternary stereogenic centers. It is also possible to encapsulate the Ru catalyst. Ned B. Bowden of the University of Iowa pioneered the use of PDMS thimbles for this purpose. He has now shown (Organic Lett. 2009, 11, 33) that by subsequently adding AD-mix, cross-metathesis can be followed directly by enantioselective dihydroxylation. Ring-opening cross-metathesis of an unsymmetrical alkene such as 13 could give two different products. Alberto Avenoza and Jesús H. Busto of the Universidad de La Rioja established (J. Org. Chem. 2009, 74, 1736) that by tuning the electronic nature of the participating alkene, either product can be obtained with high selectivity. Metathesis can be used to close larger rings. Conformational effects are important. Motoo Tori of Tokushima Bunri University observed (Tetrahedron Lett. 2009, 50, 2225) that although 18 cyclized efficiently, the other three precursors that were diastereomeric on the cyclopentane ring did not undergo ring-closing metathesis.

Advances in Alkene Metathesis: The Kobayashi Synthesis of (+)-TMC-151C

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Ethyl Acrylate ◽  
Cascade Process ◽  
Aqueous Mixtures ◽  
University Of Minnesota ◽  
Ring Closing Metathesis ◽  
Ru Catalyst ◽  
Cross Metathesis ◽  
Mo Catalyst ◽  
Institute Of Technology ◽  
The University

Shazia Zaman of the University of Canterbury and Andrew D. Abell of the University of Adelaide devised (Tetrahedron Lett. 2011, 52, 878) a polyethylene glycol-tagged Ru catalyst that is effective for alkene metathesis in aqueous mixtures, cyclizing 1 to 2. Bruce H. Lipshutz of the University of California, Santa Barbara developed (J. Org. Chem. 2011, 76, 4697, 5061) an alternative approach for aqueous methathesis, and also showed that CuI is an effective cocatalyst, converting 3 to 5. Christian Slugovc of the Graz University of Technology showed (Tetrahedron Lett. 2011, 52, 2560) that cross metathesis of the diene 6 with ethyl acrylate 7 could be carried out with very low catalyst loadings. Robert H. Grubbs of the California Institute of Technology designed (J. Am. Chem. Soc. 2011, 133, 7490) a Ru catalyst for the ethylenolysis of 9 to 10 and 11. Thomas R. Hoye of the University of Minnesota showed (Angew. Chem. Int. Ed. 2011, 50, 2141) that the allyl malonate linker of 12 was particularly effective in promoting relay ring-closing metathesis to 13. Amir H. Hoveyda of Boston College designed (Nature 2011, 471, 461) a Mo catalyst that mediated the cross metathesis of 14 with 15 to give 16 with high Z selectivity. Professor Grubbs designed (J. Am. Chem. Soc. 2011, 133, 8525) a Z selective Ru catalyst. Damian W. Young of the Broad Institute demonstrated (J. Am. Chem. Soc. 2011, 133, 9196) that ring closing metathesis of 17 followed by desilylation also led to the Z product, 18. Thomas E. Nielsen of the Technical University of Denmark devised (Angew. Chem. Int. Ed. 2011, 50, 5188) a Ru-mediated cascade process, effecting ring-closing metathesis of 19, followed by alkene migration to the enamide, and finally diastereoselective cyclization to 20. In the course of a total synthesis of (–)-goniomitine, Chisato Mukai of Kanazawa University showed (Org. Lett. 2011, 13, 1796) that even the very congested alkene of 22 smoothly participated in cross metathesis with 21 to give 23. En route to leustroducsin B, Jeffrey S. Johnson of the University of North Carolina protected (Org. Lett. 2011, 13, 3206) an otherwise incompatible terminal alkyne as its Co complex 24, allowing ring closing methathesis to 25.

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