The Magnus Synthesis of ( ± )-Codeine

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Michael Addition ◽  
Allylic Alcohol ◽  
Fluoride Ion ◽  
Relative Configuration ◽  
University Of Texas ◽  
Conjugate Reduction ◽  
Starting Point ◽  
Aqueous Conditions ◽  
Synthetic Approaches ◽  
The University

Although there have been many synthetic approaches to morphine and its methyl ether codeine 3, the pentacyclic structure of these Papaver alkaloids continues to intrigue organic chemists. Philip Magnus of the University of Texas devised (J. Am. Chem. Soc . 2009, 131, 16045) an elegant route to 3 based on the conversion of 1 to 2 by way of an intramolecular Michael addition. The starting point for the synthesis was the commercial bromoaldehyde 4. Coupling with 5 delivered the substituted biphenyl 6, which was carried on to the mixed bromo acetal 8. On exposure to fluoride ion, 8 was desilylated, and the intermediate phenoxide cyclized with impressive facility to give 1. Exposure of 1 to nitromethane delivered the tetracyclic 2. This reaction apparently was initiated by Henry addition of the nitromethane to the aldehyde. The intramolecular Michael addition of the intermediate Henry adduct then proceeded to give the desired cis diastereomer of the newly formed ring. Finally, loss of water gave 2. Conjugate reduction of the nitroalkene 2 led to 9 with remarkable diastereocontrol. Exposure of 9 to LiAlH4 converted the nitro group to the amine and the enone to the allylic alcohol. On exposure to acid, the hemiacetal was hydrolyzed. The liberated aldehyde underwent reductive amination with the free amine, while at the same time ionic cyclization closed the ether ring. N-acylation completed the conversion to 10. The ether 10 had previously been converted to codeine and then, in a single demethylation step, to morphine. In that synthesis, the alkene of 10 was directly epoxidized. The resulting “up” epoxide reacted only sluggishly with phenylselenide anion, and the relative configuration of the resulting allylic alcohol had to be inverted by oxidation followed by reduction. In the current synthesis, exposure of the alkene 10 to dibromohydantoin under aqueous conditions to form the bromohydrin effected concomitant arene bromination, to give, after base treatment, the “down” epoxide 12. Phenylselenide opening of the epoxide was then facile, and the product allylic alcohol had the correct relative configuration for codeine and morphine. The extra Br was of no consequence, as it was removed by the final LiAlH4 reduction.

The Keck Synthesis of Epothilone B

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Total Synthesis ◽  
Secondary Alcohol ◽  
Allylic Alcohol ◽  
Ring Closing Metathesis ◽  
Relative Configuration ◽  
University Of Utah ◽  
Epothilone B ◽  
Hydride Reduction ◽  
Epothilone A ◽  
The University

The total synthesis of Epothilone B 4, the first natural product (with Epothilone A) to show the same microtubule-stabilizing activity as paclitaxel (Taxol®), has attracted a great deal of attention since that activity was first reported in 1995. The total synthesis of 4 devised (J. Org. Chem. 2008, 73, 9675) by Gary E. Keck of the University of Utah was based in large part on the stereoselective allyl stannane additions (e.g. 1 + 2 → 3 ) that his group originated. The allyl stannane 2 was prepared from the acid chloride 5. Exposure of 5 to Et3N generated the ketene, that was homologated with the phosphorane 6 to give the allene ester 7. Cu-mediated conjugate addition of the stannylmethyl anion 8 then delivered 2. The silyloxy aldehyde 1 was prepared from the ester 9 by reduction with Dibal. Felkincontrolled 1,2-addition of the allyl stannane 2 established the relative configuration of the secondary alcohol of 3, that was then used to control the relative configuration of the new alcohol in 10. Addition of the crotyl borane 12 to the derived aldehyde 11 also proceeded with high diastereocontrol. The other component of 4 was prepared from the aldehyde 14. Enantioselective allylation, by the method the authors developed, delivered the alcohol 16. The Z trisubstituted alkene was then assembled by condensing the aldehyde 17 with the phosphorane 18. Dibal reduction of the product lactone 19 gave a diol, the allylic alcohol of which was selectively converted to the chloride with the Corey-Kim reagent. Hydride reduction then delivered the desired homoallylic alcohol, that was converted to the phosphonium salt 21. Condensation of 21 with 13 gave the diene, that was carried on to Epothilone B 4. The synthesis of Epothilone B 4 as originally conceived by the authors depended on ring-closing metathesis of the triene 22. They prepared 22, but on exposure to the second-generation Grubbs catalyst it was converted only to 23. The authors concluded that the trans acetonide kept 22 in a conformation that did not allow the desired macrocyclization.

Best Synthetic Methods: C-C Bond Construction

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Allylic Alcohol ◽  
Synthetic Methods ◽  
Grignard Reagents ◽  
Ni Catalyst ◽  
University Of Texas ◽  
University Of British Columbia ◽  
Terminal Alkene ◽  
Major Producer ◽  
The University ◽  
Linear Product

Nobuaki Kambe of Osaka University found (Tetrahedron Lett. 2009, 50, 5644) that with a Ni catalyst, Grignard reagents coupled preferentially with primary alkyl iodides, even in the presence of the usually reactive ketone. Maurice Santelli of the Université d’Aix-Marseille devised (Tetrahedron Lett. 2009, 50, 5238) a protocol for the conversion of a ketal 4 to the doubly homologated product 6. Brian T. Gregg of AMRI established (Tetrahedron Lett. 2009, 50, 3978; Tetrahedron Lett. 2009, 50, 7070) a procedure for the homologation of a nitrile 7 to the amine 9. Replacement of the NaBH4 with a second Grignard reagent led to the α-quaternary amine (not shown). Toshiaki Murai of Gifu University independently developed (J. Org. Chem. 2009, 74, 5703) a protocol for coupling two Grignard reagents with the linchpin reagent 11 to give the amine 12. Laurel L. Schafer of the University of British Columbia demonstrated (Angew. Chem. Int. Ed. 2009, 48, 8361) Ta-catalyzed intramolecular addition of a methyl amine 14 to the terminal alkene 13 to give 15. Jason S. Kingsbury of Boston College extended (Organic Lett. 2009, 11, 3202) the Roskamp protocol to unstable diazo alkanes such as 17, to give 18. Katsukiyo Miura of Saitama University found (Organic Lett. 2009, 11, 5066) that Pt catalyzed the branched addition of a terminal alkenyl silane 19 to an aldehyde 16 to give the branched adduct 20. Silanes such as 19 are readily prepared directly from the corresponding terminal alkene. Kálmán J. Szabó of Stockholm University observed (J. Org. Chem. 2009, 74, 5695) that the allyl boronate derived from the allylic alcohol 21 could add to the aldehyde 23 to give, depending on the solvent, either the branched product 24 or the linear product 25. The Wittig reaction is a major producer of by-product waste in chemical synthesis. Yong Tang of the Shanghai Institute of Organic Chemistry found (J. Org. Chem. 2007, 72, 6628) that Ph3As could serve catalytically in the condensation of 26 with an aldehyde. Christopher J. O’Brien of the University of Texas at Arlington and Gregory A. Chass of the University of Wales described (Angew. Chem. Int. Ed. 2009, 48, 6836) a related procedure using a cyclic phosphine.

Organic Functional Group Conversion

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Hong Kong ◽  
Allylic Alcohol ◽  
Primary Alcohols ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
University Of Texas ◽  
University Of Wisconsin ◽  
Pan American ◽  
Acetate Formation ◽  
The University

Pradeep Kumar of the National Chemical Laboratory, Pune, developed (Tetrahedron Lett. 2010, 51, 744) a new procedure for the conversion of an alcohol 1 to the inverted chloride 3. Michel Couturier of OmegaChem devised (J. Org. Chem. 2010, 75, 3401) a new reagent for the conversion of an alcohol 4 to the inverted fluoride 6. For both reagents, primary alcohols worked as well. Patrick H. Toy of the University of Hong Kong showed (Synlett 2010, 1115) that diethyl-lazodicarboxylate (DEAD) could be used catalytically in the Mitsunobu coupling of 7. Employment of 8 minimized competing acetate formation. In another application of hyper-valent iodine chemistry, Jaume Vilarrasa of the Universitat de Barcelona observed (Tetrahedron Lett. 2010, 51, 1863) that the Dess-Martin reagent effected the smooth elimination of a pyridyl selenide 10. Ken-ichi Fujita and Ryohei Yamaguchi of Kyoto University extended (Org. Lett. 2010, 12, 1336) the “borrowed hydrogen” approach to effect conversion of an alcohol 12 to the sulfonamide 13. Dan Yang, also of the University of Hong Kong, developed (Org. Lett. 2010, 12, 1068, not illustrated) a protocol for the conversion of an allylic alcohol to the allylically rearranged sulfonamide. Shu-Li You of the Shanghai Institute of Organic Chemistry used (Org. Lett. 2010, 12, 800) an Ir catalyst to effect rearrangement of an allylic sulfinate 14 to the sulfone. Base-mediated conjugation then delivered 15. K. Rama Rao of the Indian Institute of Chemical Technology, Hyderabad, devised (Tetrahedron Lett. 2010, 51, 293) a La catalyst for the conversion of an iodoalkene 16 to the alkenyl sulfide 17. Alkenyl selenides could also be prepared. James M. Cook of the University of Wisconsin, Milwaukee, described (Org. Lett. 2010, 12, 464, not illustrated) a procedure for coupling alkenyl iodides and bromides with N-H heterocycles and phenols. Hansjörg Streicher of the University of Sussex showed (Tetrahedron Lett. 2010, 51, 2717) that under free radical conditions, the carboxylic acid derivative 18 could be decarboxylated to the alkenyl iodide 19. Bimal K. Banik of the University of Texas–Pan American found (Synth. Commun. 2010, 40, 1730) that water was an effective solvent for the microwave-mediated addition of a secondary amine 21 to a Michael acceptor 20.

Functional Group Transformations

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Gold Catalyst ◽  
Sulfonyl Chloride ◽  
Allylic Alcohol ◽  
West Virginia University ◽  
Israel Institute ◽  
University Of Texas ◽  
Amino Amide ◽  
Cu Catalyst ◽  
Institute Of Technology ◽  
The University

Mark Gandelman of the Technion–Israel Institute of Technology devised (Adv. Synth. Catal. 2011, 353, 1438) a protocol for the decarboxylative conversion of an acid 1 to the iodide 3. Doug E. Frantz of the University of Texas, San Antonio effected (Angew. Chem. Int. Ed. 2011, 50, 6128) conversion of a β-keto ester 4 to the diene 5 by way of the vinyl triflate. Pei Nian Liu of the East China University of Science and Technology and Chak Po Lau of the Hong Kong Polytechnic University (Adv. Synth. Catal. 2011, 353, 275) and Robert G. Bergman and Kenneth N. Raymond of the University of California, Berkeley (J. Am. Chem. Soc. 2011, 133, 11964) described new Ru catalysts for the isomerization of an allylic alcohol 6 to the ketone 7. Xiaodong Shi of West Virginia University optimized (Adv. Synth. Catal. 2011, 353, 2584) a gold catalyst for the rearrangement of a propargylic ester 8 to the enone 9. Xue-Yuan Liu of Lanzhou University used (Adv. Synth. Catal. 2011, 353, 3157) a Cu catalyst to add the chloramine 11 to the alkyne 10 to give 12. Kasi Pitchumani of Madurai Kamaraj University converted (Org. Lett. 2011, 13, 5728) the alkyne 13 into the α-amino amide 15 by reaction with the nitrone 14. Katsuhiko Tomooka of Kyushu University effected (J. Am. Chem. Soc. 2011, 133, 20712) hydrosilylation of the propargylic ether 16 to the alcohol 17. Matthew J. Cook of Queen’s University Belfast (Chem. Commun. 2011, 47, 11104) and Anna M. Costa and Jaume Vilarrasa of the Universitat de Barcelona (Org. Lett. 2011, 13, 4934) improved the conversion of an alkenyl silane 18 to the iodide 19. Vinay Girijavallabhan of Merck/Kenilworth developed (J. Org. Chem. 2011, 76, 6442) a Co catalyst for the Markovnikov addition of sulfide to an alkene 20. Hojat Veisi of Payame Noor University oxidized (Synlett 2011, 2315) the thiol 22 directly to the sulfonyl chloride 23. Nicholas M. Leonard of Abbott Laboratories prepared (J. Org. Chem. 2011, 76, 9169) the chromatography-stable O-Su ester 25 from the corresponding acid 24.

Does Web-Scale Discovery Make a Difference?

2012 ◽  
pp. 456-468 ◽  
Author(s):  
Jan Kemp
Keyword(s):  
Undergraduate Students ◽  
San Antonio ◽  
First Year ◽  
Full Text Article ◽  
University Of Texas ◽  
Library Research ◽  
Discovery Service ◽  
Starting Point ◽  
Online Catalog ◽  
The University

The University of Texas at San Antonio Libraries implemented the Summon1™ Discovery Service in January 2010 to provide a convenient starting point for library research, particularly for undergraduate students who are less experienced in library research. Librarians thought Summon™ would help users find and use materials more effectively; therefore, implementation of the discovery tool was expected to positively influence collections use. At the end of the first year following Summon™ implementation, statistics on the use of collections showed significant increases in the use of electronic resources: link resolver use increased 84%, and full-text article downloads increased 23%. During the same period, use of the online catalog decreased 13.7%, and use of traditional indexing and abstracting database searches decreased by 5%. The author concludes that the increases in collections use are related to adoption of a Web-scale discovery service.

Metal-Mediated C–C Ring Construction: The Ding Synthesis of (−)-Indoxamycin B

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Claisen Rearrangement ◽  
Iron Catalyst ◽  
Gold Catalyst ◽  
State University ◽  
Relative Configuration ◽  
University Of Texas ◽  
Diethyl Zinc ◽  
Single Diastereomer ◽  
The University ◽  
Oregon State University

Shou-Fei Zhu of Nankai University developed (Angew. Chem. Int. Ed. 2014, 53, 13188) an iron catalyst that effected the enantioselective cyclization of 1 to 2. Bypassing diazo precursors, Junliang Zhang of East China Normal University used (Angew. Chem. Int. Ed. 2014, 53, 13751) a gold catalyst to cyclize 3 to 4. Taking advantage of energy transfer from a catalytic Ir complex, Chuo Chen of University of Texas Southwestern carried out (Science 2014, 346, 219) intramolec­ular 2+2 cycloaddition of 5, leading, after dithiane formation, to the cyclobutane 6. Intramolecular ketene cycloaddition has been limited in scope. Liming Zhang of the University of California Santa Barbara found (Angew. Chem. Int. Ed. 2014, 53, 9572) that intramolecular oxidation of an intermediate Ru vinylidene led to a species that cyclized to the cyclobutanone 8. James D. White of Oregon State University devised (J. Am. Chem. Soc. 2014, 136, 13578) an iron catalyst that mediated the enantioselective Conia-ene cyclization of 9 to 10. Xiaoming Feng of Sichuan University observed (Angew. Chem. Int. Ed. 2014, 53, 11579) that the Ni-catalyzed Claisen rearrangement of 11 proceeded with high diastereo- and enantiocontrol. The relative configuration of the product 12 was not reported. Robert H. Grubbs of Caltech showed (J. Am. Chem. Soc. 2014, 136, 13029) that ring opening cross metathesis of 13 with 14 delivered the Z product 15. Mn(III) cyclization has in the past required a stoichiometric amount of inorganic oxidant. Sangho Koo of Myong Ji University found (Adv. Synth. Catal. 2014, 356, 3059) that by adding a Co co- catalyst, air could serve as the stoichiometric oxidant. Indeed, 16 could be cyclized to 17 using inexpensive Mn(II). Matthias Beller of the Leibniz-Institüt für Katalyse prepared (Angew. Chem. Int. Ed. 2014, 53, 13049) the cyclohexene 20 by coupling the racemic alcohol 18 with the amine 19. Paultheo von Zezschwitz of Philipps-Universität Marburg added (Chem. Commun. 2014, 50, 15897) diethyl zinc in a conjugate sense to 21, then reduced the product to give 22. Depending on the reduction method, either diastereomer of the product could be made dominant. Nuno Maulide of the University of Vienna dis­placed (Angew. Chem. Int. Ed. 2014, 53, 7068) the racemic chloride 23 with diethyl zinc to give 24 as a single diastereomer.

C–C Bond Construction: The Hou Synthesis of (−)-Brevipolide H

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Conjugate Addition ◽  
University Of Illinois ◽  
University Of Texas ◽  
Heck Cyclization ◽  
University Of Technology ◽  
Propargylic Alcohol ◽  
Irkutsk Institute ◽  
Aqueous Conditions ◽  
The University

Yao Fu and Lei Liu of the University of Science and Technology of China devised (Chem. Eur. J. 2014, 20, 15334) conditions for the coupling of a halide 2 with a tosyl­ate 1 with inversion of absolute configuration, leading to 3. Hegui Gong of Shanghai University coupled (J. Am. Chem. Soc. 2014, 136, 17645) the glucosyl bromide 4 with an anhydride 5 to give the ketone 6. Luigi Vaccaro of the Università di Perugia showed (Org. Lett. 2014, 16, 5721) that TBAF promoted the opening of the epoxide 7 with the ketene silyl acetal 8, leading to the lactone 9. Valérie Desvergnes and Yannick Landais of the University of Bordeaux assembled (Chem. Eur. J. 2014, 20, 9336) the diketone 12 by using a Stetter catalyst to promote the conjugate addition of the acyl silane 11 to the enone 10. Thomas Werner of the Leibniz-Institute for Catalysis reported (Eur. J. Org. Chem. 2014, 6873) the enantioselective conversion of the prochiral triketone 13 to the bicyclic enone 15 by an intramolecular Wittig reaction, mediated by 14. Elizabeth H. Krenske of the University of Queensland and Christopher J. O’Brien also reported (Angew. Chem. Int. Ed. 2014, 53, 12907) progress (not illustrated) on catalytic Wittig reactions. Michael J. Krische of the University of Texas showed (J. Am. Chem. Soc. 2014, 136, 11902) that Ru-mediated addition of 17 to the aldehyde derived in situ from 16 gave 18 with high Z-selectivity. Vladimir Gevorgyan of the University of Illinois at Chicago constructed (J. Am. Chem. Soc. 2014, 136, 17926) the trisubstituted alkene 20 by the intramolecular Heck cyclization of 19. Kálmán J. Szabó of Stockholm University opti­mized (Chem. Commun. 2014, 50, 9207) the Pd-catalyzed borylation of the alkene 21 followed by in situ addition to the aldehyde 22 to give 23. Boris A. Trofimov of the Irkutsk Institute of Chemistry Siberian Branch devel­oped (Eur. J. Org. Chem. 2014, 4663) aqueous conditions for the preparation of a propargylic alcohol 26 by the addition of an alkyne 25 to the ketone 24. Huanfeng Jiang of the South China University of Technology prepared (Angew. Chem. Int. Ed. 2014, 53, 14485) the alkyne 28 by the oxidative elimination of the tosylhydrazone 27.

Arrays of Stereogenic Centers: The Davies Synthesis of Acosamine

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Conjugate Addition ◽  
Michigan State University ◽  
State University ◽  
One Pot ◽  
Relative Configuration ◽  
University Of Texas ◽  
Stereogenic Centers ◽  
National University ◽  
The University ◽  
Mediated Oxidation

Babak Borhan of Michigan State University found (Angew. Chem. Int. Ed. 2011, 50, 2593) that the ligand developed for asymmetric osmylation worked well for the enantioselective cyclization of 1 to 2. Kyungsoo Oh of IUPUI devised (Org. Lett. 2011, 13, 1306) a Co catalyst for the stereocontrolled addition of 4 to 3 to give 5. Michael J. Krische of the University of Texas Austin prepared (Angew. Chem. Int. Ed. 2011, 50, 3493) 8 by Ir*-mediated oxidation/addition of 7 to 6. Yixin Lu of the National University of Singapore employed (Angew. Chem. Int. Ed. 2011, 50, 1861) an organocatalyst to effect the stereocontrolled addition of 10 to 9. Naoya Kumagai and Masakatsu Shibasaki of the Institute of Microbial Chemistry, Tokyo took advantage (J. Am. Chem. Soc. 2011, 133, 5554) of the soft Lewis basicity of 13 to effect stereocontrolled condensation with 12. Yujiro Hayashi of the Tokyo University of Science found (Angew. Chem. Int. Ed. 2011, 50, 2804, not illustrated) that aqueous chloroacetaldehyde participated well in crossed aldol condensations. Andrew V. Malkov, now at Loughborough University, and Pavel Kocovsky of the University of Glasgow showed (J. Org. Chem. 2011, 76, 4800) that the inexpensive mixed crotyl silane 16 could be added to 15 with high stereocontrol. Shigeki Matsunaga of the University of Tokyo and Professor Shibasaki opened (J. Am. Chem. Soc. 2011, 133, 5791) the meso aziridine 18 with malonate 19 to give 20. Masahiro Terada of Tohoku University effected (Org. Lett. 2011, 13, 2026) the conjugate addition of 22 to 21 with high stereocontrol. Jinxing Ye of the East China University of Science and Technology reported (Angew. Chem. Int. Ed. 2011, 50, 3232, not illustrated) a related conjugate addition. Kian L. Tian of Boston College observed (Org. Lett. 2011, 13, 2686) that the kinetic hydroformylation of 24 set the relative configuration of two stereogenic centers. Alexandre Alexakis and Clément Mazet of the Université de Genève established (Angew. Chem. Int. Ed. 2011, 50, 2354) a tandem one-pot procedure for the addition of 26 to 27 to give 28.

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