The Kozmin Synthesis of Spirofungin A

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0089 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Absolute Configuration ◽

Journal Article ◽

Ring System ◽

Spatial Proximity ◽

Silyl Ether ◽

Secondary Alcohols ◽

Ring Closing Metathesis ◽

Cross Metathesis ◽

The University ◽

Flexible Ring

Often, 6,6-spiroketals such as Spirofungin A 3 have a strong anomeric bias. Spirofungin A does not, as the epimer favored by double anomeric stabilization suffers from destabilizing steric interactions. In his synthesis of 3, Sergey A. Kozmin of the University of Chicago took advantage (Angew. Chem. Int. Ed. 2007, 46, 8854) of the normally-destablizing spatial proximity of the two alkyl branches of 3, joining them with a siloxy linker to assure the anomeric preference of the spiroketal. The assembly of 1 showcased the power of asymmetric crotylation, and of Professor Kozmin’s linchpin cyclopropenone ketal cross metathesis. To achieve the syn relative (and absolute) configuration of 6, commercial cis-2-butene was metalated, then condensed with the Brown (+)-MeOB(Ipc)2 auxiliary. The accompanying Supporting Information, accessible via the online HTML version of the journal article, includes a succinct but detailed procedure for carrying out this homologation. For the anti relative (and absolute) configuration of 9, it is more convenient to use the tartrate 8 introduced by Roush. Driven by the release of the ring strain inherent in 10, ring opening cross metathesis with 6 proceeded to give the 1:1 adduct 11 in near quantitative yield. The derived cross-linked silyl ether 12 underwent smooth ring-closing metathesis to the dienone 1. On hydogenation, the now-flexible ring system could fold into the spiro ketal. With the primary and secondary alcohols bridged by the linking silyl ether, only one anomeric form, 2, of the spiro ketal was energetically accessible. A remaining challenge was the stereocontrolled construction of the trisubstituted alkene. To this end, the aldehyde 13 was homologated to the dibromide 14. Pd-mediated coupling of the alkenyl stannane 15 with 14 was selective for the E bromide. The residual Z bromide was then coupled with Zn(CH3)2 to give 16. These steps, and the final steps to complete the construction of spirofungin A 3 , could be carried out without exposure to equilibrating acid, so the carefully established spiro ketal confi guration was maintained.

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Advances in Alkene and Alkyne Metathesis

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0026 ◽

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.

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C–O Ring Construction: Sauropus Hexoside (Xie/Wu), (+)-Ipomeamarone (Usuki), Decytospolide A (Fujioka), Cytospolide P (Goswami), (+)-Didemniserinolipid B (Tong), Gymnothelignan N (She)

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0051 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Biological Activity ◽

Hong Kong ◽

Absolute Configuration ◽

Second Generation ◽

Science And Technology ◽

Conjugate Addition ◽

The Other ◽

Reductive Cyclization ◽

Silyl Ether ◽

Ring Closing Metathesis

A range of biological activity was observed for the group of 3,6-anhydro-2-deoxy hexosides, of which 3 is representative, isolated from Sauropus rostratus. Wei-Jia Xie and Xiao-Ming Wu of China Pharmaceutical University prepared (Org. Lett. 2014, 16, 5004) 3 by the dealkylative cyclization of 1 to 2. (+)-Ipomeamarone 6 is a phytoalexin isolated from mold-damaged sweet potatoes. Yoshinosuke Usuki of Osaka City University assembled (Chem. Lett. 2014, 43, 1882) 6 by the diastereoselective cyclization of 4 to 5. Hiromichi Fujioka of Osaka University protected (Org. Lett. 2014, 16, 3680) the enone of 7 by the conjugate addition of triphenylphosphine. Diastereoselective reduction of the other ketone followed by deprotection of the enone and cyclization led to 8, that was hydrogenated to decytospolide A 9. En route to cytospolide P 12, Rajib Kumar Goswami of the Indian Association for the Cultivation of Science had planned (J. Org. Chem. 2014, 79, 7689) the ring-closing metathesis of 10. This failed, but cyclization of the corresponding silyl ether to 11 was successful with the second-generation Hoveyda catalyst. Rongbiao Tong of the Hong Kong University of Science and Technology set (J. Org. Chem. 2014, 79, 6987) the absolute configuration of (+)-didemniserinolipid B 15 by Sharpless asymmetric osmylation of the alkene 13. Oxidative Achmatowicz rearrangement/bicycloketalization then delivered 14. Xuegong She of Lanzhou University observed (Org. Lett. 2014, 16, 4440) remarkable diastereoselectivity in the reductive cyclization of 16 to 17. Oxidation of 17 led to regioselective cyclization to gymnothelignan N 18.

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

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0030 ◽

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.

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

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0031 ◽

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.

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

Organic Synthesis ◽

10.1093/oso/9780199965724.003.0034 ◽

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.

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

Organic Synthesis ◽

10.1093/oso/9780190200794.003.0033 ◽

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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Concise Total Synthesis of Curvulone B

Synlett ◽

10.1055/a-1297-6838 ◽

2020 ◽

Author(s):

Debendra K. Mohapatra ◽

Shivalal Banoth ◽

Utkal Mani Choudhury ◽

Kanakaraju Marumudi ◽

Ajit C. Kunwar

Keyword(s):

Total Synthesis ◽

Stereoselective Synthesis ◽

Ring System ◽

Bond Forming ◽

Cross Metathesis ◽

Bond Forming Reactions ◽

Key Steps

AbstractA concise and convergent stereoselective synthesis of curvulone B is described. The synthesis utilized a tandem isomerization followed by C–O and C–C bond-forming reactions following Mukaiyama-type aldol conditions for the construction of the trans-2,6-disubstituted dihydropyran ring system as the key steps. Other important features of this synthesis are a cross-metathesis, epimerization, and Friedel–Crafts acylation.

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