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.

Substituted Benzenes: The Subba Reddy Synthesis of 7-Desmethoxyfusarentin

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Ethyl Cyanoacetate ◽  
Strong Acid ◽  
State University ◽  
Max Planck ◽  
University Of Texas ◽  
Ru Catalyst ◽  
Aryl Ketones ◽  
Peking University ◽  
University Of Bristol ◽  
The University

Andrey P. A ntonchick of the Max-Planck-Institut Dortmund devised (Org. Lett. 2012, 14, 5518) a protocol for the direct amination of an arene 1 to give the amide 3. Douglass A. Klumpp of Northern University showed (Tetrahedron Lett. 2012, 53, 4779) that under strong acid conditions, an arene 4 could be carboxylated to give the amide 6. Eiji Tayama of Niigata University coupled (Tetrahedron Lett. 2012, 53, 5159) an arene 7 with the α-diazo ester 8 to give 9. Guy C. Lloyd-Jones and Christopher A. Russell of the University of Bristol activated (Science 2012, 337, 1644) the aryl silane 11 to give an intermediate that coupled with the arene 10 to give 12. Ram A. Vishwakarma and Sandip P. Bharate of the Indian Institute of Integrative Medicine effected (Tetrahedron Lett. 2012, 53, 5958) ipso nitration of an areneboronic acid 13 to give 14. Stephen L. Buchwald of MIT coupled (J. Am. Chem. Soc. 2012, 134, 11132) sodium isocyanate with the aryl chloride 15 (aryl triflates also worked well) to give the isocyanate 16, which could be coupled with phenol to give the carbamate or carried onto the unsymmetrical urea. Zhengwu Shen of the Shanghai University of Traditional Chinese Medicine used (Org. Lett. 2012, 14, 3644) ethyl cyanoacetate 18 as the donor for the conversion of the aryl bromide 17 to the nitrile 19. Kuo Chu Hwang of the National Tsig Hua University showed (Adv. Synth. Catal. 2012, 354, 3421) that under the stimulation of blue LED light the Castro-Stephens coupling of 20 with 21 proceeded efficiently at room temperature. Lutz Ackermann of the Georg-August-Universität Göttingen employed (Org. Lett. 2012, 14, 4210) a Ru catalyst to oxidize the amide 23 to the phenol 24. Both Professor Ackermann (Org. Lett. 2012, 14, 6206) and Guangbin Dong of the University of Texas (Angew. Chem. Int. Ed. 2012, 51, 13075) described related work on the ortho hydroxylation of aryl ketones. George A. Kraus of Iowa State University rearranged (Tetrahedron Lett. 2012, 53, 7072) the aryl benzyl ether 25 to the phenol 26. The synthetic utility of the triazene 27 was demonstrated (Angew. Chem. Int. Ed. 2012, 51, 7242) by Yong Huang of the Shenzen Graduate School of Peking University.

C–H Functionalization

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Oxidative Cyclization ◽  
South Florida ◽  
Hypervalent Iodine ◽  
Direct Oxidation ◽  
University Of Texas ◽  
Ru Catalyst ◽  
University Of Technology ◽  
National University ◽  
Indian Institute Of Science ◽  
The University

Masayuki Inoue of the University of Tokyo oxidized (Tetrahedron Lett. 2011, 52, 4654) the alkyl benzene 1 to the nitrate 2, which could be carried on to the amide 5, the nitrile 6, the alcohol 7, or the azide 8. X. Peter Zhang of the University of South Florida developed (Chem. Sci. 2012, 2, 2361) a Co catalyst for the cyclization of 7 to 8. Justin Du Bois of Stanford University reported (J. Am. Chem. Soc. 2011, 133, 17207) the oxidative cyclization of the sulfamate corresponding to 7 using a Ru catalyst. Seongmin Lee of the University of Texas showed (Org. Lett. 2011, 13, 4766) that the oxidative cyclization of 9 gave the amine 10 with high diastereoselectivity. Fabrizio Fabris of the Università di Venezia used (Tetrahedron Lett. 2011, 52, 4478) a Ru catalyst to oxidize 11 to the ketone 12. Ying-Yeung Yeung of the National University of Singapore found (Org. Lett. 2011, 13, 4308) that hypervalent iodine was sufficient to oxidize 13 to the ketone 14. Huanfeng Jiang of the South China University of Technology methoxycarbonylated (Chem. Commun. 2011, 47, 12224) 15 under Pd catalysis to give 16. Professor Inoue found (Org. Lett. 2011, 13, 5928) that the oxidative cyanation of 17 proceeded with high diastereoselectivity to give 18. Mamoru Tobisu and Naoto Chatani of Osaka University activated (J. Am. Chem. Soc. 2011, 133, 12984) 19 with a Pd catalyst to enable coupling with 20 to give 21. Rh-mediated intramolecular insertion is well known to proceed efficiently into secondary and tertiary C–H bonds. A. Srikrishna of the Indian Institute of Science, Bangalore found (Synlett 2011, 2343) that insertion into the methyl C–H of 22 also worked smoothly to deliver 23. The macrocyclic oligopeptide valinomycin 24 has nine isopropyl groups. It is remarkable, as observed (Org. Lett. 2011, 13, 5096) by Cosimo Annese of the Università di Bari and Paul G. Williard of Brown University, that direct oxidation of 24 with methyl(trifluoromethyl) dioxirane in acetone specifically hydroxylated at 8 (45.5%, our numbering), 7 (28.5%), and 6 (26%).

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.

Arrays of Stereogenic Centers: The Barker Synthesis of (+)-Galbelgin

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Organic Chemistry ◽  
Indian Institute ◽  
Silver Catalyst ◽  
University Of Texas ◽  
Secondary Center ◽  
Stereogenic Centers ◽  
Enantioselective Epoxidation ◽  
Indian Institute Of Science ◽  
The University ◽  
Stereogenic Center

Gang Zhao of the Shanghai Institute of Organic Chemistry and Gang Zou of the East China University of Science and Technology devised (Adv. Synth. Catal. 2011, 353, 3129) an elegant catalyst for the direct enantioselective epoxidation of a simple acyclic enone 1. Ismail Ibrahem and Armando Córdova of Mid Sweden University and Stockholm University prepared (Adv. Synth. Catal. 2011, 353, 3114) 6 by combining three catalysts to effect the enantioselective addition of 5 to 4. Giovanni Casiraghi and Franca Zanardi of the Università degli Studi di Parma used (J. Org. Chem. 2011, 76, 10291) a silver catalyst to mediate the addition of 8 to 7 to give 9. Keiji Maruoka of Kyoto University condensed (Nature Chem. 2011, 3, 642) the diazo ester 10 with an aldehyde 4, leading, after reduction of the initial adduct and protection, to the diamine 11. Christoph Schneider of the Universität Leipzig effected (Synthesis 2011, 4050) the vinylogous addition of 13 to an imine 12, setting both stereogenic centers of 14. In the course of the coupling of 16 with the diol 15, Michael J. Krische of the University of Texas established (J. Am. Chem. Soc. 2011, 133, 12795) four new stereogenic centers. By adding (Chem. Commun. 2011, 47, 10557) an α-nitro ester 18 to the maleimide 19, Professor Maruoka established both the alkylated secondary center and the N-substituted quaternary center of 20. Srinivas Hotha of the Indian Institute of Science Education & Research and Torsten Linker of the University of Potsdam showed (Chem. Commun. 2011, 47, 10434) that the readily prepared lactone 21 could be opened to 23 without disturbing the stereogenic center adjacent to the carbonyls. Allan D. Headley and Bukuo Ni of Texas A&M University-Commerce devised (Synthesis 2011, 1993) a recyclable catalyst for the addition of an aldehyde 7 to a nitroalkene 24 in water to give 25. Alexandre Alexakis of the University of Geneva effected (Chem. Commun. 2011, 47, 7212) the triply convergent coupling of 26, 27, and 28 to give 29 as a single dominant diastereomer.

Progress in Alkene and Alkyne Metathesis: (+)-5- epi -Citreoviral(Funk) and ( ± )-Poitediol (Vanderwal)

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Active Form ◽  
Catalytic Amount ◽  
Max Planck ◽  
Fischer Carbene ◽  
Cross Metathesis ◽  
Mo Catalyst ◽  
Peking University ◽  
Ru Complexes ◽  
University Of Zurich ◽  
The University

The Fischer carbene 2 at 0.5 mol % gives only 12% conversion of 1 to 4 after 18 hours. Debra J. Wallace of Merck Process showed (Adv. Synth. Cat. 2009, 351, 2277) that addition of a catalytic amount of the inexpensive 3 activated 2 , leading to 95% conversion of 1 to 4 after 18 hours. Shazia Zaman of the University of Canterbury and Andrew D. Abell of the University of Adelaide found (Tetrahedron Lett. 2009, 50, 5340) that the catalyst 5, incorporating a polyethylene glycol (PEG) chain, was readily recovered in active form by precipitation and could be reused at least fi ve times. Zhu Yinghuai of the Institute of Chemical and Engineering Sciences, Singapore (Adv. Synth. Cat. 2009, 351, 2650), and Chao Che, Zhen Yang, and Biwang Jiang of Peking University (Chem. Commun. 2009, 5990) independently described the preparation of Ru complexes such as 5 bound to magnetic nanoparticles. The catalysts were easily recycled and reused, leaving < 4 ppm Ru in the product. Reto Dorta of the University of Zurich reported (J. Am. Chem. Soc. 2009, 131, 9498) that the complex 6 (Ar = 2,7-diisopropylnaphthyl) was a separable mixture of syn- and anti-isomers. The very reactive anti-isomer at 50 ppm converted neat 1 into 2 in 2 hours at room temperature. Richard R. Schrock of MIT devised (J. Am. Chem. Soc. 2009, 131, 10840) an efficient Mo catalyst for a long-sought transformation—the ethenolysis of long-chain alkenes such as 7. Robert A. Stockman of the University of Nottingham developed (Chem. Commun. 2009, 4399) a related Ru-catalyzed procedure: cross-metathesis ring opening with methyl acrylate 11. Amir A. Hoveyda of Boston College, a coauthor on the Schrock paper, used (J. Am. Chem. Soc. 2009, 131, 10652) a very similar Mo catalyst for the rapid cross-metathesis of an alkyne with ethene, leading after subsequent ring-closing metathesis to products such as 14. Alois Fürstner of the Max-Planck-Institut, Mülheim, described (J. Am. Chem. Soc. 2009, 131, 9468) a well-characterized Mo nitride complex that efficiently catalyzed the conversion of 15 into 16. Samir Bouzbouz of the Université de Rouen and Janine Cossy of ESPCI ParisTech established (Organic Lett. 2009, 11, 5446) conditions for the metathesis of alkenes with the linchpin 18.

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.

Transition Metal-Mediated Construction of Carbocycles: Dimethyl Gloiosiphone A (Takahashi), Pasteurestin A (Mulzer), and Pentalenene (Fox)

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Transition Metal ◽  
South Florida ◽  
Health Science ◽  
Pt Catalyst ◽  
Max Planck ◽  
Au Catalyst ◽  
Ru Catalyst ◽  
National University ◽  
Rh Catalyst ◽  
The University

There continue to be new developments in transition metal- and lanthanide-mediated construction of carbocycles. Although a great deal has been published on the asymmetric cyclopropanation of styrene, relatively little had been reported for other classes of alkenes. Tae-Jeong Kim of Kyungpook National University has devised (Tetrahedron Lett. 2007, 48, 8014) a Ru catalyst for the cyclopropanation of simple α-olefins such as 1. X. Peter Zhang of the University of South Florida has developed (J. Am.Chem. Soc. 2007, 129, 12074) a Co catalyst for the cyclopropanation of alkenes such as 5 having electron-withdrawing groups. Alexandre Alexakis of the Université de Genève has reported(Angew. Chem. Int. Ed. 2007, 46, 7462) simple monophosphine ligands that enabled enantioselective conjugate addition to prochiral enones, even difficult substrates such as 8. Seunghoon Shin of Hanyang University has found (Organic Lett. 2007, 9, 3539) an Au catalyst that effected the diastereoselective cyclization of 10 to the cyclohexene 11, and Radomir N. Saicic of the University of Belgrade has carried out (Organic Lett. 2007, 9, 5063), via transient enamine formation, the diastereoselective cyclization of 12 to the cyclohexane 13. Alois Fürstner of the Max-Planck- Institut, Mülheim has devised (J. Am. Chem. Soc. 2007, 129, 14836) a Rh catalyst that cyclized the aldehyde 14 to the cycloheptenone 15. Some of the most exciting investigations reported in recent months have been directed toward the direct diastereo- and enantioselective preparation of polycarbocyclic products. Rai-Shung Liu of National Tsing-Hua University has extended (J. Org. Chem. 2007, 72, 567) the intramolecular Pauson-Khand cyclization to the epoxy enyne 16, leading to the 5-5 product 17. Michel R. Gagné of the University of North Carolina has devised (J. Am. Chem. Soc. 2007, 129, 11880) a Pt catalyst that smoothly cyclized the polyene 18 to the 6-6 product 19. Yoshihiro Sato of Hokkaido University and Miwako Mori of the Health Science University of Hokkaido have described (J. Am. Chem. Soc. 2007, 129, 7730) a Ru catalyst for the cyclization of 20 to the 5-6-5 product 21. Each of these processes proceeded with high diastereocontrol.

Alkene and Alkyne Metathesis: Phaseolinic Acid (Selvakumar), Methyl 7-Dihydro-trioxacarcinoside B (Koert), Arglabin (Reiser) and Amphidinolide V (Fürstner)

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Organic Synthesis ◽  
Second Generation ◽  
Secondary Alcohol ◽  
Allylic Alcohol ◽  
Alkyne Metathesis ◽  
Max Planck ◽  
Ring Closing Metathesis ◽  
Relative Configuration ◽  
Stereogenic Centers ◽  
Ru Complexes

As N. Selvakumar of Dr. Reddy’s Laboratories, Ltd., Hyderabad approached (Tetrahedron Lett. 2007, 48, 2021) the synthesis of phaseolinic acid 6, there was some concern about the projected cyclization of 2 to 3, as this would involve the coupling of two electron-deficient alkenes. In fact, the Ru-mediated ring-closing metathesis proceeded efficiently. The product unsaturated lactone 3 could be reduced selectively to either the trans product 4 or the cis product 5. There has been relatively little work on the synthesis of the higher branched sugars, such as the octalose 13, a component of several natural products. The synthesis of 13 (Organic Lett. 2007, 9, 4777) by Ulrich Koert of the Philipps-University Marburg also began with a Baylis-Hillman product, the easily-resolved secondary alcohol 8. As had been observed in other contexts, cyclization of the protected allylic alcohol 9a failed, but cyclization of the free alcohol 9b proceeded smoothly. V-directed epoxidation then set the relative configuration of the stereogenic centers on the ring. Ring-closing metathesis to construct tetrasubstituted alkenes has been a challenge, and specially-designed Ru complexes have been put forward specifically for this transformation. Oliver Reiser of the Universität Regensburg was pleased to observe (Angew. Chem. Int. Ed. 2007, 46, 6361) that the second-generation Grubbs catalyst itself worked well for the cyclization of 17 to 18. Again in this synthesis, catalytic V was used to direct the relative configuration of the epoxide. Intramolecular alkyne metathesis is now well-established as a robust and useful method for organic synthesis. It was also known that Ru-mediated metathesis of an alkyne with ethylene could lead to the diene. The question facing (Angew. Chem. Int. Ed . 2007, 46, 5545) Alois Fürstner of the Max-Planck-Institut, Mülheim was whether these transformations could be carried out on the very delicate epoxy alkene 21. In fact, the transformations of 21 to 22 and of 22 to 23 proceeded well, setting the stage for the total synthesis of Amphidinolide V 25.

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.

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