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.

Establishing Arrays of Stereogenic Centers: The Sato/Chida Synthesis of (-)-Kainic Acid

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Catalyst System ◽  
Allylic Alcohol ◽  
University Of Pennsylvania ◽  
Ni Catalyst ◽  
Max Planck ◽  
Stereogenic Centers ◽  
University College London ◽  
Enantioselective Addition ◽  
La Jolla ◽  
The University

Benjamin List of the Max-Planck-Institut, Mülheim, devised (J. Am. Chem. Soc. 2010, 132, 10227) a catalyst system for the stereocontrolled epoxidation of a trisubstituted alkenyl aldehyde 1. Takashi Ooi of Nagoya University effected (Angew. Chem. Int. Ed. 2010, 49, 7562; see also Org. Lett. 2010, 12, 4070) enantioselective Henry addition to an alkynyl aldehyde 3. Madeleine M. Joullié of the University of Pennsylvania showed (Org. Lett. 2010, 12, 4244) that an amine 7 added selectively to an alkynyl aziridine 6. Yutaka Ukaji and Katsuhiko Inomata of Kanazawa University developed (Chem. Lett. 2010, 39, 1036) the enantioselective dipolar cycloaddition of 9 with 10. K. C. Nicolaou of Scripps/La Jolla observed (Angew. Chem. Int. Ed. 2010, 49, 5875; see also J. Org. Chem. 2010, 75, 8658) that the allylic alcohol from enantioselective reduction of 12 could be hydrogenated with high diastereocontrol. Masamichi Ogasawara and Tamotsu Takahashi of Hokkaido University added (Org. Lett. 2010, 12, 5736) the allene 14 to the acetal 15 with substantial stereocontrol. Helen C. Hailes of University College London investigated (Chem. Comm. 2010, 46, 7608) the enzyme-mediated addition of 18 to racemic 17. Dawei Ma of the Shanghai Institute of Organic Chemistry, in the course of a synthesis of oseltamivir (Tamiflu), accomplished (Angew. Chem. Int. Ed. 2010, 49, 4656) the enantioselective addition of 21 to 20. Shigeki Matsunaga of the University of Tokyo and Masakatsu Shibasaki of the Institute of Microbial Chemistry developed (Org. Lett. 2010, 12, 3246) a Ni catalyst for the enantioselective addition of 23 to 24. Juthanat Kaeobamrung and Jeffrey W. Bode of ETH-Zurich and Marisa C. Kozlowski of the University of Pennsylvania devised (Proc. Natl. Acad. Sci. 2010, 107, 20661) an organocatalyst for the enantioselective addition of 27 to 26. Yihua Zhang of China Pharmaceutical University and Professor Ma effected (Tetrahedron Lett. 2010, 51, 3827) the related addition of 27 to 29. There have been scattered reports on the stereochemical course of the coupling of cyclic secondary organometallics. In a detailed study, Paul Knochel of Ludwig-Maximilians- Universität München showed (Nat. Chem. 2020, 2, 125) that equatorial bond formation dominated, exemplified by the conversion of 31 to 33.

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.

Best Synthetic Methods: Functional Group Transformations

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Gold Catalyst ◽  
Allylic Alcohol ◽  
Synthetic Methods ◽  
Columbia University ◽  
Ru Catalyst ◽  
University Of Georgia ◽  
Alkyl Groups ◽  
Saturated Aldehyde ◽  
Borrowing Hydrogen ◽  
The University

Vinyl glycine 2 is a useful precursor to a variety of amino acids. Timothy E. Long of the University of Georgia found (Tetrahedron Lett. 2009, 50, 5067) that the o-nitrophenyl sulfoxide 1 eliminated smoothly in refluxing toluene. Alicia Boto and Rosendo Hernández of IPNA La Laguna observed (Tetrahedron Lett. 2009, 50, 3974) that a related selenoxide elimination proceeded to give the single regioisomer 4. Avelino Corma of the Universidad Politécnica de Valencia developed ( Chemical Commun. 2009, 4947) a gold catalyst for the selective hydroboration of alkynes over alkenes. Eiji Shirakawa and Tamio Hayashi of Kyoto University devised (Chemical Commun. 2009, 5088) a Ru catalyst for the conversion of an alkenyl triflate such as 8 to the corresponding bromide. Tristan H. Lambert of Columbia University found (J. Am. Chem. Soc. 2009, 131, 13930) that the dichloride 11 smoothly converted a variety of alcohols into the corresponding chlorides. Crown ethers have been used to promote SN2 reactivity by solubilizing the metal cation. Sungyul Lee of Kyunghee University, Dae Yoon Chi of Sogang University, and Choong Eui Song of Sungkyunkwan University demonstrated (Angew. Chem. Int. Ed. 2009, 48, 7683) that the inexpensive polyethylene glycols were also effective. Mugio Nishizawa of Tokushima Bunri University devised (Synlett 2009, 1175) conditions for the rapid regioselective hydration of hydroxy alkynes such as 15. Jaume Vilarrasa of the Universitat de Barcelona developed (Organic Lett. 2009, 11, 4414) a mild alternative protocol for the Nef reaction, converting a nitroalkane such as 17 into the corresponding ketone under neutral conditions. Clément Mazet of the University of Geneva optimized (Tetrahedron Lett. 2009, 50, 4141) the Ir-catalyzed conversion of an allylic alcohol 19 into the saturated aldehyde. Jonathan M. J. Williams of the University of Bath established (Angew. Chem. Int. Ed. 2009, 48, 7375) that under Ir-catalyzed “borrowing hydrogen” conditions, alkyl amines could donate alkyl groups to anilines such as 21. Danfeng Huang and Yulai Hu of Northwest Normal University devised (Organic Lett. 2009, 11, 4474) a simple protocol for conversion of an acid 23 to the Weinreb amide 24. of the Universitat

New Methods for Carbon-Carbon Bond Construction

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Allylic Alcohol ◽  
Ni Catalyst ◽  
University Of Michigan ◽  
Carbon Carbon Bond ◽  
University Of Technology ◽  
Duke University ◽  
Michael Acceptors ◽  
Leaving Groups ◽  
The University

Mohammad Navid Soltani Rad of Shiraz University of Technology has shown (Tetrahedron Lett. 2007, 48, 6779) that with tosylimidazole (TsIm) activation in the presence of NaCN, primary, secondary and tertiary alcohols are converted into the corresponding nitriles. Gregory C. Fu of MIT has devised (J. Am. Chem. Soc. 2007, 129, 9602) a Ni catalyst that mediated the coupling of sp3-hybridized halides such as 3 with sp3-hybridized organoboranes such as 4, to give 5. Usually, carbanions with good leaving groups in the beta position do not couple efficiently, but just eliminate. Scott D. Rychnovsky of the University of California, Irvine has found (Organic Lett . 2007, 9, 4757) that initial protection of 6 as the alkoxide allowed smooth reduction of the sulfide and addition of the derived alkyl lithium to the amide 7 to give 8. Doubly-activated Michael acceptors such as 11 are often too unstable to isolate. J. S. Yadav of the Indian Institute of Chemical Technology, Hyderabad has shown (Tetrahedron Lett. 2007, 48, 7546) that Baylis-Hillman adducts such as 9 can be oxidized in situ, with concomitant Sakurai addition to give 12. Rather than use the usual Li or Na or K enolate, Don M. Coltart of Duke University has found (Organic Lett. 2007, 9, 4139) that ketones such as 13 will condense with amides such as 14 to give the diketone 15 on exposure to MgBr2. OEt2 and i -Pr2 NEt. Simultaneously, Gérard Cahiez of the Université de Cergy (Organic Lett. 2007, 9, 3253) and Janine Cossy of ESPCI Paris (Angew. Chem. Int. Ed. 2007, 46, 6521) reported that Fe salts will catalyze the coupling of sp2 -hybridized Grignard reagents such as 17 with alkyl halides. John Montgomery of the University of Michigan has described (J. Am. Chem. Soc. 2007, 129, 9568) the Ni-mediated regio- and enantioselective addition of an alkynes 20 to an aldehyde 19 to give the allylic alcohol 21. In a third example of sp2 - sp3 coupling, Troels Skrydstrup of the University of Aarhus has established (J. Org. Chem. 2007, 72, 6464) that Negishi coupling with alkenyl phosponates such as 23 proceeded efficiently.

Best Synthetic Methods: Reduction

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Direct Reduction ◽  
Synthetic Methods ◽  
Cancer Center ◽  
Michigan State University ◽  
State University ◽  
University Of Texas ◽  
Ru Catalyst ◽  
Reaction Matrix ◽  
National University ◽  
The University

Jaiwook Park of Pohang University of Science and Technology has developed (Org. Lett. 2007, 9, 3417) a procedure for the preparation of Pd-impregnated magnetic Fe nanoparticles. This effective hydrogenation catalyst was attracted to an external magnet and so was easily separated from the reaction matrix. Duk Keun An of Kangwon National University has found (Chem. Lett. 2007, 36, 886) that by including NaOtBu, Dibal reduction of an ester such as 3 can be made to reliably stop at the aldehyde 4. By using the easily-prepared pentaflurophenyl ester 5, Panagiota Moutevelis-Minakakis of the University of Athens was able to reduce an acid to the alcohol 6. Lionel A. Saudan of Firmenich SA, Geneva has devised (Angew. Chem. Int. Ed. 2007, 46, 7473) a Ru catalyst that will hydrogenate an ester such as 7 to the alcohol 8 without reducing an internal alkene. Norio Sakai of the Tokyo University of Science has established (J. Org. Chem. 2007, 72, 5920) what promises to be a general route to ethers 10, by direct reduction of the corresponding ester 9. Hideo Nagashima of Kyushu University has developed ( Chem. Commun. 2007, 4916) a Ru catalyst that effected selective hydrogenation of an amide 11 to the amine 12 without reducing ketones or esters. Alternatively, Jason S. Tedrow of Amgen Inc., Thousand Oaks, CA has found (J. Org. Chem. 2007, 72, 8870) that a protocol developed by Robert E. Maleczka, Jr. of Michigan State University was effective for reducing an aryl ketone 13 to the corresponding hydrocarbon 14 without reducing the amide. The stereocontrolled reductive amination of cyclic ketones such as 15 has been a continuing challenge. Shawn Cabral of Pfizer, Inc. in Groton, CT has reported (Tetrahedron Lett. 2007, 48, 7134) complementary reagent combinations, leading selectively to either 16 or 17. To control catalytic hydrogenation, it is often desirable to control the H2 supply. John S. McMurray of the University of Texas M. D. Anderson Cancer Center in Houston has shown (J. Org. Chem. 2007, 72, 6599) that Et3SiH is a convenient H2 source. Nitro alkanes add to aldehydes to give nitro alkenes such as 20.

Enantioselective Synthesis of Alcohols and Amines: The Zhu Synthesis of (+)-Trigonoliimine A

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Secondary Alcohol ◽  
Allylic Alcohol ◽  
Princeton University ◽  
Terminal Alkene ◽  
National University ◽  
Amino Amide ◽  
Enantioselective Epoxidation ◽  
Enantioselective Addition ◽  
Institute Of Technology ◽  
The University

The enantioselective epoxidation of a terminal alkene 1 has been a long-sought goal of organic synthesis. Albrecht Berkessel of the University of Cologne devised (Angew. Chem. Int. Ed. 2013, 52, 8467) a Ti catalyst that mediated the conversion of 1 to 2. Zhi Li of the National University of Singapore described (Chem. Commun. 2013, 49, 11572) a cell-based system that effected the enantioselective epoxidation of 3 to 4. Antonio Mezzetti of ETH Zürich and Francesco Santoro of Firmenich SA car­ried out (Angew. Chem. Int. Ed. 2013, 52, 10352) the enantioselective hydrogena­tion of 5 to the allylic alcohol 6. Elena Fernández of the Universitat Rovira i Virgilli and Andrew Whiting of Durham University devised (Org. Lett. 2013, 15, 4810) a protocol for the enantioselective conjugate borylation of the imine derived from 7, leading to the secondary alcohol 8. Benjamin List of the Max-Planck-Institute für Kohlenforschung, Mülheim and Choong Eui Song of Sungkyunkwan University con­densed (Angew. Chem. Int. Ed. 2013, 52, 12143) the thioester 10 with the aldehyde 9 to give the alcohol 11. Toshiro Harada of the Kyoto Institute of Technology developed (Org. Lett. 2013, 15, 4198) a general procedure for the enantioselective addition of a terminal alkene 12 to an aldehyde 9. As illustrated by the preparation of 13, this appears to be tolerant of a variety of organic functional groups. Professor Harada also established (Chem. Eur. J. 2013, 19, 17707) a protocol for the enantioselective addition of an alkyne 14 to an aldehyde to give the branched product 15. Chun-Jiang Wang and Xumu Zhang of Wuhan University hydrogenated (Angew. Chem. Int. Ed. 2013, 52, 8416) the alkyne 16 to the protected allylic amine 17. Keiji Maruoka of Kyoto University effected (J. Am. Chem. Soc. 2013, 135, 18036) the enantioselective α-amination of an aldehyde 18, to give 19. David W. C. MacMillan of Princeton University described (J. Am. Chem. Soc. 2013, 135, 11521) a comple­mentary approach, not illustrated. David J. Fox of the University of Warwick reduced (Chem. Commun. 2013, 49, 10022) the ketone 20, then rearranged the resulting sec­ondary alcohol to the α-amino amide 21.

Alkene Reactions: The Xu/Loh Synthesis of Vitamin A1

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Phase Transfer ◽  
University Of Delaware ◽  
One Pot ◽  
Wacker Oxidation ◽  
Terminal Alkene ◽  
Peking University ◽  
Markovnikov Addition ◽  
The University ◽  
Convenient Preparation ◽  
Linear Product

Abdolreza Rezaeifard and Maasoumeh Jafarpour of the University of Birjand devised (J. Am. Chem. Soc. 2013, 135, 10036) an easily-scaled protocol for the Mo-catalyzed “on water” epoxidation of an alkene 1 to 2, using molecular O₂. Needing to epoxidize the sensitive alkene 3 to 5, Douglass F. Taber of the University of Delaware developed (Org. Synth. 2013, 90, 350) a convenient preparation of mmol quantities of the versa­tile oxidant dimethyldioxirane 4. Robert H. Grubbs of Caltech showed (Angew. Chem. Int. Ed. 2013, 52, 9751) that the Wacker oxidation of internal alkenes could proceed with high regioselectivity, as exemplified by the conversion of 6 to 7. David A. Nicewicz of the University of North Carolina demonstrated (J. Am. Chem. Soc. 2013, 135, 10334) the remarkable anti-Markovnikov addition of the acid 9 to the alkene 8, to give 10. Pieter C. A. Bruijnincx and Robertus J. M. Klein Gebbink of the University of Utrecht established (Chem. Eur. J. 2013, 19, 15012) a robust one-pot protocol for epoxidation, epoxide hydrolysis and periodate cleavage, for the net oxidative cleav­age of the alkene 11 to the aldehydes 12 and 13. Tomoki Ogoshi of Kanazawa University observed (Org. Lett. 2013, 15, 3742) that permanganate with a phase transfer catalyst could selectively oxidize the linear alkene 14 to 15 in the presence of branched alkenes. Davood Azarifar of Bu-Ali Sina University devised (Synlett 2013, 24, 1377) the reagent 17 as a useful alternative to ozone, as illustrated by the oxidation of 16 to 18. Ning Jiao of Peking University effected (J. Am. Chem. Soc. 2013, 135, 11692) the unsymmetrical cleavage of the alkene 19 to the nitrile aldehyde 20. Tiow-Gan Ong of the Academia Sinica added (Org. Lett. 2013, 15, 5358) 22 to the alkene 21 to give the linear product 23. This could be hydrolyzed to the acid, or reduced and hydrolyzed to the aldehyde. Joost N. H. Reek of the University of Amsterdam isomerized (ACS Catal. 2013, 3, 2939) the terminal alkene of 24 to the internal alkene, then hydroformylated that directly to give the α-methyl branched alde­hyde 25.

Stereocontrolled Construction of Arrays of Stereogenic Centers: The Mullins Synthesis of (-)-Lasiol

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Aldol Condensation ◽  
Catalyst System ◽  
Geometric Isomer ◽  
Ni Catalyst ◽  
University Of Texas ◽  
Enantioselective Epoxidation ◽  
Institute Of Technology ◽  
Tandem Cyclization ◽  
Catalyst Systems ◽  
The University

Hisashi Yamamoto of the University of Chicago devised (J. Am. Chem. Soc. 2010, 132, 7878) catalyst systems for the enantioselective epoxidation of a Z -homoallylic alcohol 1. Michael J. Krische of the University of Texas developed (J. Am. Chem. Soc. 2010, 132, 1760) a catalyst system for the highly stereoselective addition of the vinyl acetal 5 to an aldehyde 4. Joëlle Prunet of the University of Glasgow showed (Tetrahedron Lett. 2010, 51, 256) that the tandem cyclization/Julia olefination from 7 also proceeded with high stereocontrol. Professor Yamamoto established (J. Am. Chem. Soc. 2010, 132, 5354) that depending on conditions, the aldol condensation of 10 could be directed selectively toward either diastereomer of the product 12. James M. Takacs of the University of Nebraska effected (J. Am. Chem. Soc. 2010, 132, 1740) the enantioselective hydroboration of 10. The other geometric isomer of 10 gave the alternative diastereomer of 12, also with high ee. John Limanto and Shane W. Krska of Merck Process optimized (Organic Lett . 2010, 12, 512) the dynamic kinetic reduction of 13 , giving 14 with excellent diastereocontrol. Professor Krische extended (J. Am. Chem. Soc. 2010, 132, 4562) his reductive homologation to the (racemic) carbonate 15, delivering 16 with excellent dr and ee. Hirokazu Urabe of the Tokyo Institute of Technology showed (Organic Lett. 2010, 12, 1012) that a Grignard reagent under iron catalysis opened the epoxide 17, readily available by Jørgensen-Cordova epoxidation followed by homologation, with clean inversion and high regiocontrol. Fraser F. Fleming of Duquesne University developed (Organic Lett. 2010, 12, 3030) a general route to quaternary alkylated centers by alkylation of nitriles such as 19. Shigeki Matsunaga and Masakatsu Shibasaki of the University of Tokyo devised (J. Am. Chem. Soc. 2010, 132, 3666) a Ni catalyst for the stereoselective conjugate addition of the lactam 22 to a nitroalkene 21. Aldehydes can also be added to nitroalkenes with high dr and ee, as illustrated by the conversion of 24 to 26 reported (J. Am. Chem. Soc. 2010, 132, 50) by Bukuo Ni of Texas A&M University, Commerce.

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.

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