Diels-Alder Cycloaddition: (+)-Armillarivin (Banwell), Gelsemiol (Gademann), (+)-Frullanolide (Liao), Myceliothermophin A (Uchiro), Peribysin E (Reddy), Caribenol A (Li/Yang)

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Elevated Pressure ◽  
Diels Alder ◽  
Cope Rearrangement ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Enantiomerically Pure ◽  
Peking University ◽  
National University ◽  
Diastereoselective Addition ◽  
The University

Martin G. Banwell of the Australian National University prepared (Org. Lett. 2013, 15, 1934) the enantiomerically pure diol 1 by fermentation of the aromatic precursor. Diels-Alder addition of cyclopentenone 2 proceeded well at elevated pressure to give 3, the precursor to (+)-armillarivin 4. Karl Gademann of the University of Basel found (Chem. Eur. J. 2013, 19, 2589) that the Diels-Alder addition of 6 to 5 proceeded best without solvent and with Cu catalysis to give 7. Reduction under free radical conditions led to gelsemiol 8. Chun-Chen Liao of the National TsingHua University carried out (Org. Lett. 2013, 15, 1584) the diastereoselective addition of 10 to 9. A later oxy-Cope rearrangement established the octalin skeleton of (+)-frullanolide 12. D. Srinivasa Reddy of CSIR-National Chemical Laboratory devised (Org. Lett. 2013, 15, 1894) a strategy for the construction of the angularly substituted cis-fused aldehyde 15 based on Diels-Alder cycloaddition of 14 to the diene 13. Further transformation led to racemic peribysin-E 16. An effective enantioselective catalyst for dienophiles such as 14 has not yet been developed. Hiromi Uchiro of the Tokyo University of Science prepared (Tetrahedron Lett. 2012, 53, 5167) the bicyclic core of myceliothermophin A 19 by BF3•Et2O-promoted cyclization of the tetraene 17. The single ternary center of 17 mediated the formation of the three new stereogenic centers of 18, including the angular substitution. En route to caribenol A 22, Chuang-Chuang Li and Zhen Yang of the Peking University Shenzen Graduate School assembled (J. Org. Chem. 2013, 78, 5492) the triene 20 from two enantiomerically pure precursors. Inclusion of the radical inhibitor BHT sufficed to suppress competing polymerization, allowing clean cyclization to 21. Methylene blue has also been used (J. Am. Chem. Soc. 1980, 102, 5088) for this purpose.

Diels–Alder Cycloaddition: Pancratistatin (Cho), Nootkatone (Reddy), Platensimycin (Zhang/Lee), Scabronine G (Nakada), Isoglaziovianol (Trauner)

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Aldol Condensation ◽  
Diels Alder ◽  
Cancer Center ◽  
Columbia University ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Intramolecular Cycloaddition ◽  
Enantiomerically Pure ◽  
Peking University ◽  
The University

Samuel J. Danishefsky of Columbia University and the Memorial Sloan-Kettering Cancer Center made (Proc. Natl. Acad. Sci. 2013, 110, 10904) the unexpected obser­vation that methylation of the enolate derived from conjugate addition to the readily-prepared 1 followed by intramolecular alkene metathesis led to the trans fused ketone 2. This can be contrasted to the diastereo- and regioisomer 3, the product from Diels-Alder cycloaddition of 2-methylcyclohexenone to isoprene. The trans ring fusion of 2 is particularly significant because ozonolysis followed by aldol condensation would deliver the angularly-methylated trans-fused 6/5 C–D ring system of the steroids and related natural products. Cheon-Gyu Cho of Hanyang University added (Org. Lett. 2013, 15, 5806) the activated dienophile 4 to the dienyl lactone to give, after oxidation, the dibro­mide 5. Debromination followed by oxidation led to the antineoplastic lactam pancratistatin 6. D. Srinivasa Reddy of CSIR-National Chemical Laboratory Pune devised (J. Org. Chem. 2013, 78, 8149) a cascade protocol of Diels-Alder cycloaddition of 8 to the diene 7, followed by intramolecular aldol condensation, to give the enone 9. Oxidative manipulation followed by methylenation completed the synthesis of the commercially important grapefruit flavor nootkatone 10. Xinhao Zhang and Chi-Sing Lee of the Peking University Shenzen Graduate School uncovered (J. Org. Chem. 2013, 78, 7912) another cascade transformation, intermolecular addition of 11 to 12 followed by intramolecular Conia-ene cyclization, to give the tricyclic 13. Further manipulation led to an established intermediate for the total synthesis of platensimycin 14. Masahisa Nakada of Waseda University prepared (Angew. Chem. Int. Ed. 2013, 52, 7569) the enantiomerically-pure allene 15. Oxidation of the phenol to the monoketal of the cyclohexadienone set the stage for intramolecular cycloaddition to give 16. Oxidative cleavage followed by intramolecular alkene metathesis led to (+)-scabronine G 17. Dirk Trauner of the University of Munich assembled (Org. Lett. 2013, 15, 4324) the enantiomerically-pure alcohol 18. Oxidation gave the quinone, leading to intra­molecular Diels–Alder cycloaddition. The free alcohol then added to the exocyclic alkene of that product, to give, after further oxidation, the ether 19. Deprotection fol­lowed by reduction then completed the synthesis of (−)-isoglaziovianol 20.

Organocatalyzed C–C Ring Construction: The Bradshaw/Bonjoch Synthesis of (−)-Cermizine B

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
San Antonio ◽  
Bond Formation ◽  
Bryn Mawr ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Enantiomerically Pure ◽  
University Of Texas ◽  
National University ◽  
Institute Of Technology ◽  
The University

In a continuation of his studies (OHL20141229, OHL20140811) of organocatalyzed 2+2 photocycloaddition, Thorsten Bach of the Technische Universität München assembled (Angew. Chem. Int. Ed. 2014, 53, 7661) 3 by adding 2 to 1. Li-Xin Wang of the Chengdu Institute of Organic Chemistry also used (Org. Lett. 2014, 16, 6436) an organocatalyst to effect the addition of 5 to 4 to give 6. Shuichi Nakamura of the Nagoya Institute of Technology devised (Org. Lett. 2014, 16, 4452) an organocatalyst that mediated the enantioselective opening of the aziridine 7 to 8. Zhi Li of the National University of Singapore cloned (Chem. Commun. 2014, 50, 9729) an enzyme from Acinetobacter sp. RS1 that reduced 9 to 10. Gregory C. Fu of Caltech developed (Angew. Chem. Int. Ed. 2014, 53, 13183) a phosphine catalyst that directed the addition of 12 to 11 to give 13. Armido Studer of the Westfälische Wilhelms-Universität Münster showed (Angew. Chem. Int. Ed. 2014, 53, 9622) that 15 could be added to 14 to give 16 in high ee. Akkattu T. Biju of CSIR-National Chemical Laboratory described (Chem. Commun. 2014, 50, 14539) related results. The photostimulated enantioselective ketone alkylation developed (Chem. Sci. 2014, 5, 2438) by Paolo Melchiorre of ICIQ was powerful enough to enable the alkyl­ation of 17 with 18 to give 19, overcoming the stereoelectronic preference for axial bond formation. David W. Lupton of Monash University established (J. Am. Chem. Soc. 2014, 136, 14397) the organocatalyzed transformation of the dienyl ester 20 to 21. James McNulty of McMaster University added (Angew. Chem. Int. Ed. 2014, 53, 8450) azido acetone 23 to 22 to give 24 in high ee. There are sixteen enantiomerically-pure diastereomers of the product 27. John C.-G. Zhao of the University of Texas at San Antonio showed (Angew. Chem. Int. Ed. 2014, 53, 7619) that with the proper choice of organocatalyst, with or without subsequent epimerization, it was possible to selectively prepare any one of eight of those diastereomers by the addition of 26 to 25. William P. Malachowski of Bryn Mawr College showed (Tetrahedron Lett. 2014, 55, 4616) that 28, readily prepared by a Birch reduction protocol, was converted by heating followed by exposure to catalytic Me3P to the angularly-substituted octalone 29.

Stereocontrolled Construction of Arrays of Stereogenic Centers

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Aldol Condensation ◽  
Simple Procedure ◽  
Unsaturated Ester ◽  
Magnesium Bromide ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Enantiomerically Pure ◽  
Stereogenic Centers ◽  
Diastereoselective Addition ◽  
The University

Complex natural products and even some complex pharmaceuticals contain arrays of stereogenic centers. Sometimes, the desired array is readily available from a natural product, but usually, such arrays of multiple stereogenic centers must be assembled. Armando Córdova of Stockholm University has reported (Angew. Chem. Int. Ed. 2007, 46, 778) a simple procedure for the organocatalyst-mediated addition of the nitrene equivalent 2 to an α, β-unsaturated aldehyde to give the protected aziridine 4 in high ee. Organocatalysis was also used (Organic Lett. 2007, 9, 1001) by Arumugam Sudalai of the National Chemical Laboratory, Pune, to effect coupling of the aldehyde 5 with dibenzylazodicarboxylate 6 to give, following the List procedure, the intermediate aldehyde 7. Osmylation of the derived unsaturated ester 8 proceeded with high diastereocontrol, to give 9. Products 4 and 9 have adjacent stereogenic centers. Hisashi Yamamoto of the University of Chicago has introduced (J. Am. Chem. Soc. 2007, 129, 2762) the linchpin reagent acetaldehyde “super”silyl enol ether 11. Diastereoselective addition of 11 to the enantiomerically-pure aldehyde 10, with concomitant silyl transfer, followed by the addition of allyl magnesium bromide delivered the protected triol 12 in high de and ee. Arrays that combine alkylated and oxygenated or aminated centers are also important. Akio Kamimura of Yamaguchi University took (J. Org. Chem. 2007, 72, 3569) a Baylis- Hillman like approach, adding thiophenoxide to t -butyl acrylate in the presence of an enantiomerically-pure aldehyde N-sulfinimine such as 13 to give the adduct 14 with high diastereocontrol. Keiji Maruoka of Kyoto University has designed (Angew. Chem. Int. Ed. 2007, 46, 1738) the chiral amine 17, that catalyzed the condensation of an aldehyde with ethyl glyoxylate 16 with high enantiocontrol. In a very thoughtful approach, Liu-Zhu Gong of the University of Science and Technology of China in Hefei extended (Chem. Commun. 2007, 736) the now-classic aldol condensation of cyclohexanone to 4-substituted cyclohexanones such as 19. The product 21 could be carried in many directions, including to the Bayer-Villiger product 22. Arrays of alkylated and polyalkylated centers have been among the most challenging to prepare.

Organocatalyzed C–C Ring Construction: The Mihovilovic Synthesis of Piperenol B

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
State University ◽  
Air Oxidation ◽  
Microbial Oxidation ◽  
Max Planck ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Northwestern University ◽  
National University ◽  
The University ◽  
Oregon State University

M. Kevin Brown of Indiana University prepared (J. Am. Chem. Soc. 2015, 137, 3482) the cyclobutane 3 by the organocatalyzed addition of 2 to the alkene 1. Karl Anker Jørgensen of Aarhus University assembled (J. Am. Chem. Soc. 2015, 137, 1685) the complex cyclobutane 7 by the addition of 5 to the acceptor 4, followed by conden­sation with the phosphorane 6. Zhi Li of the National University of Singapore balanced (ACS Catal. 2015, 5, 51) three enzymes to effect enantioselective opening of the epoxide 8 followed by air oxidation to 9. Gang Zhao of the Shanghai Institute of Organic Chemistry and Zhong Li of the East China University of Science and Technology added (Org. Lett. 2015, 17, 688) 10 to 11 to give 12 in high ee. Akkattu T. Biju of the National Chemical Laboratory combined (Chem. Commun. 2015, 51, 9559) 13 with 14 to give the β-lactone 15. Paul Ha-Yeon Cheong of Oregon State University and Karl A. Scheidt of Northwestern University reported (Chem. Commun. 2015, 51, 2690) related results. Dieter Enders of RWTH Aachen University constructed (Chem. Eur. J. 2015, 21, 1004) the complex cyclopentane 20 by the controlled com­bination of 16, 17, and 18, followed by addition of the phosphorane 19. Derek R. Boyd and Paul J. Stevenson of Queen’s University Belfast showed (J. Org. Chem. 2015, 80, 3429) that the product from the microbial oxidation of 21 could be protected as the acetonide 22. Ignacio Carrera of the Universidad de la República described (Org. Lett. 2015, 17, 684) the related oxidation of benzyl azide (not illustrated). Manfred T. Reetz of the Max-Planck-Institut für Kohlenforschung and the Philipps-Universität Marburg found (Angew. Chem. Int. Ed. 2014, 53, 8659) that cytochrome P450 could oxidize the cyclohexane 23 to the cyclohexanol 24. F. Dean Toste of the University of California, Berkeley aminated (J. Am. Chem. Soc. 2015, 137, 3205) the ketone 25 with 26 to give 27. Benjamin List, also of the Max-Planck-Institut für Kohlenforschung, reported (Synlett 2015, 26, 1413) a parallel investigation. Philip Kraft of Givaudan Schweiz AG and Professor List added (Angew. Chem. Int. Ed. 2015, 54, 1960) 28 to 29 to give 30 in high ee.

Diels–Alder Cycloaddition: Sarcandralactone A (Snyder), Pseudopterosin (−)-G-J Aglycone (Paddon-Row/Sherburn), IBIR-22 (Westwood), Muironolide A (Zakarian), Platencin (Banwell), Chatancin (Maimone)

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Absolute Configuration ◽  
Alder Reaction ◽  
Diels Alder ◽  
University Of California ◽  
Enantiomerically Pure ◽  
Protein Protein Interaction ◽  
South Wales ◽  
National University ◽  
The Absolute ◽  
The University

En route to sarcandralactone A 3, Scott A. Snyder of Scripps Florida effected (Angew. Chem. Int. Ed. 2015, 54, 7842) Diels–Alder cycloaddition of the activated enone 1 to the Danishefsky diene. On exposure to trifluoroacetic acid, the adduct was unraveled to the ene dione 2. Michael N. Paddon-Row of the University of New South Wales and Michael S. Sherburn of the Australian National University prepared (Nature Chem. 2015, 7, 82) the allene 4 in enantiomerically-pure form. Sequential cycloaddition with 5 followed by 6 gave an adduct that was decarbonylated to 7. Further cycloaddition with nitro­ethylene 8 led to the pseudopterosin (−)-G-J aglycone 9. The protein–protein interaction inhibitor JBIR-22 12 contains a quaternary α-amino acid pendant to a bicyclic core. Nicholas J. Westwood of the University of St. Andrews set (Angew. Chem. Int. Ed. 2015, 54, 4046) the absolute configuration of the core 11 by using an organocatalyst to activate the cyclization of 10. Metal catalysts can also be used to set the absolute configuration of a Diels–Alder cycloaddition. In the course of establishing the structure of the marine natural prod­uct muironolide A 15, Armen Zakarian of the University of California, Santa Barbara cyclized (J. Am. Chem. Soc. 2015, 137, 5907) the enol form of 13 preferentially to the diastereomer 14. Unactivated intramolecular Diels–Alder cycloadditions have been carried out with more and more challenging substrates. A key step in the synthesis (Chem. Asian. J. 2015, 10, 427) of (−)-platencin 18 by Martin G. Banwell, also of the Australian National University, was the cyclization of 16 to 17. In another illustration of the power of the unactivated intramolecular Diels–Alder reaction, Thomas J. Maimone of the University of California, Berkeley cyclized (Angew. Chem. Int. Ed. 2015, 54, 1223) the tetraene 19 to the tricycle 20. Allylic chlo­rination followed by reductive cyclization converted 20 to chatancin 21.

Stereoselective C-N Ring Construction

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Organic Chemistry ◽  
Diels Alder ◽  
Wolff Rearrangement ◽  
Enantiomerically Pure ◽  
Amino Esters ◽  
Shanghai Institute ◽  
Single Diastereomer ◽  
Peking University ◽  
Convenient Route ◽  
The University

Ryoichi Kuwano of Kyushu University showed (J. Am. Chem. Soc. 2008, 130, 808) that diastereomerically and enantiomerically pure pyrollidines such as 2 could be prepared by hydrogenation of the corresponding pyrrole. Victor S. Martín of Universidad de la Laguna found (Organic Lett. 2008, 10, 2349) that the stereochemical outcome of the pyrrolidine-forming Nicholas cyclization could be directed by the protecting group on the N. Jianbo Wang of Peking University established (J. Org. Chem. 2008, 73, 1971) a convenient route to diazo esters such as 6. N-H insertion led to the pyrrolidine, which Zhen-Jiang Xu of the Shanghai Institute of Organic Chemistry and Chi-Ming Che of the University of Hong Kong showed (Organic Lett. 2008, 10, 1529) could be reduced with high diastereoselectivity to the hydroxy ester 7. Alternatively, Professor Wang found that photochemical Wolff rearrangement of 6 delivered the pyrrolidone 8 . Martin J. Slater and Shiping Xie of GlaxoSmithKline optimized (J. Org. Chem. 2008, 73, 3094) the hydroquinine catalyzed enantioselective 3+2 cycloaddition of 9 and 10, leading to the pyrrolidine 11 with high diastereocontrol. Shu Kobayashi of the University of Tokyo developed (Adv. Synth. Cat. 2008, 350, 647) a practical protocol for the aza Diels-Alder construction of enantiomerically-pure piperidines such as 14 . Biao Yu of the Shanghai Institute of Organic Chemistry cyclized (Tetrahedron Lett. 2008, 49, 672) the product from the proline-catalyzed enantioselective aldol of 15 and 16, leading to the substituted piperidine 17 . Michael Shipman of the University of Warwick described (Tetrahedron Lett. 2008, 49, 250) the cyclization of the aziridine derived from 18, that proceeded to give 19 as a single diastereomer, apparently via kinetic side-chain protonation. Takeo Kawabata of Kyoto University found (J. Am. Chem. Soc. 2008, 130, 4153) that intramolecular alkylation to form four, five and six-membered rings from amino esters such as 21 proceeded with remarkable enantioretention. Géraldine Masson and Jieping Zhu of CNRS, Gif-sur-Yvette, condensed (Organic Lett. 2008, 10, 1509) cinnamaldehyde 23 with cyanide and an ω-alkenyl amine to give the intramolecular aza-Diels-Alder substrate 24. Hongbin Zhai of the Shanghai Institute of Organic Chemistry acylated (J. Org. Chem. 2008, 73, 3589) 26 with 27, leading to the ring-closing metathesis precursor 28.

Organocatalytic Carbocyclic Construction: The You Synthesis of (–)-Mesembrine

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Elevated Pressure ◽  
University Of California ◽  
Cope Rearrangement ◽  
Unsaturated Aldehyde ◽  
State University ◽  
Colorado State University ◽  
13C Isotope ◽  
National University ◽  
Enantioselective Acylation ◽  
The University

Frank Glorius of the Universität Münster devised (Angew. Chem. Int. Ed. 2011, 50, 12626) a catalyst for the enantioselective acylation of a cyclopropene 1 to the ketone 3. Geum-Sook Hwang of Chungnam National University and Do Hyun Ryu of Sungkyunkwan University effected (J. Am. Chem. Soc. 2011, 133, 20708) the enantioselective addition of the diazo ester 5 to an α,β-unsaturated aldehyde 4 to give the cyclopropane 6. We showed (J. Org. Chem. 2011, 76, 7614) that face-selective allylation of an α-iodo enone 7 followed by Suzuki coupling and oxy-Cope rearrangement delivered the cyclopentanone 9. Karl Anker Jørgensen of Aarhus University combined (Org. Lett. 2011, 13, 4790) two organocatalysts to effect the addition of 11 to an α,β-unsaturated aldehyde 10, leading to the cyclopentenone 12. Tomislav Rovis of Colorado State University also used (Chem. Sci. 2011, 2, 1835) two organocatalysts to condense 13 with 14 to give the cyclopentanone 15. Gregory C. Fu, now at CalTech, found (J. Am. Chem. Soc. 2011, 133, 12293) that both enantiomers of the racemic allene 16 combined with 17 to give the cyclopentene 18 in high ee. Piotr Kwiatkowski of the University of Warsaw found (Org. Lett. 2011, 13, 3624) that under elevated pressure (8–10 kbar), enantioselective conjugate addition of nitromethane proceeded well even with a β-substituted cyclohexenone 19. Marco Bella of the Università di Roma observed (Adv. Synth. Catal. 2011, 353, 2648) remarkable diastereoselectivity in the addition of the aldehyde 22 to an activated acceptor 21. Following the procedure of List, Jiong Yang of Texas A&M University cyclized (Org. Lett. 2011, 13, 5696) 24 to 25 in high ee. Bor-Cherng Hong of the National Chung Cheng University described (Synthesis 2011, 1887) the double Michael combination of 26 with 27 to give 28 in high ee. Observing a secondary 13C isotope effect only at the β-carbon of 30, Li Deng of Brandeis University concluded (Chem. Sci. 2011, 2, 1940) that the addition to 29 was stepwise, not concerted. In contrast, the cyclization of 32 to 33 reported (Org. Lett. 2011, 13, 3932) by Tadeusz F. Molinski of the University of California San Diego likely was concerted.

Substituted Benzenes: The Reddy Synthesis of Isofregenedadiol

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Rhode Island ◽  
Benzene Derivative ◽  
Allyl Ester ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
University Of Technology ◽  
Simple Protocol ◽  
Peking University ◽  
The University ◽  
Technological University

Jianbo Wang of Peking University (Org. Lett. 2011, 13, 4988) and Patrick Y. Toullec and Véronique Michelet of Chimie ParisTech (Org. Lett. 2011, 13, 6086) developed conditions for the electrophilic acetoxylation of a benzene derivative 1. Seung Hwan Cho and Sukbok Chang of KAIST (J. Am. Chem. Soc. 2011, 133, 16382) and Brenton DeBoef of the University of Rhode Island (J. Am. Chem. Soc. 2011, 133, 19960) devised protocols for the electrophilic imidation of a benzene derivative 3. Vladimir V. Grushin of ICIQ Tarragona devised (J. Am. Chem. Soc. 2011, 133, 10999) a simple protocol for the cyanation of a bromobenzene 6 to the nitrile 7. Hua-Jian Xu of the Hefei University of Technology (J. Org. Chem. 2011, 76, 8036) and Myung-Jong Jin of Inha University (Org. Lett. 2011, 13, 5540) established conditions for the efficient Heck coupling of a chlorobenzene 8. Jacqueline E. Milne of Amgen/Thousand Oaks reduced (J. Org. Chem. 2011, 76, 9519) the adduct from the addition of 11 to 12 to deliver the phenylacetic acid 13. Jeffrey W. Bode of ETH Zurich effected (Angew. Chem. Int. Ed. 2011, 50, 10913) Friedel-Crafts alkylation of 14 with the hydroxamate 15 to give the meta product 16. B.V. Subba Reddy of the Indian Institute of Chemical Technology, Hyderabad took advantage (Tetrahedron Lett. 2011, 52, 5926) of the directing ability of the amide to effect selective ortho acetoxylation of 17. Similarly, Frederic Fabis of the Université de Caen Basse-Normandie used (J. Org. Chem. 2011, 76, 6414) the methoxime of 19 to direct ortho bromination, leading to 20. Teck-Peng Loh of Nanyang Technological University showed (Chem. Commun. 2011, 47, 10458) that the carbamate of 21 directed ortho C–H functionalization to give the ester 23. Yoichiro Kuninobu and Kazuhiko Takai of Okayama University rearranged (Chem. Commun. 2011, 47, 10791) the allyl ester 24 directly to the ortho-allylated acid 25. Youhong Hu of the Shanghai Institute of Materia Medica (J. Org. Chem. 2011, 76, 8495) and Graham J. Bodwell of Memorial University (J. Org. Chem. 2011, 76, 9015) condensed a chromene 26 with a nucleophile 27 to give the arene 28. C.V. Ramana of the National Chemical Laboratory prepared (Tetrahedron Lett. 2011, 52, 4627) the arene 31 by condensing 29 with 30 with high regioselectivity.

Functionalization of C-H Bonds: The Baran Synthesis of Dihydroxyeudesmane

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Columbia University ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Du Bois ◽  
Rh Catalyst ◽  
Hydride Abstraction ◽  
Mcgill University ◽  
Radical Removal ◽  
The University ◽  
Useful Yield

Arumugam Sudalai of the National Chemical Laboratory, Pune reported (Tetrahedron Lett. 2008, 49, 6401) a procedure for hydrocarbon iodination. With straight chain hydrocarbons, only secondary iodination was observed. Chao-Jun Li of McGill University uncovered (Adv. Synth. Cat. 2009, 351, 353) a procedure for direct hydrocarbon amination, converting cyclohexane 1 into the amine 3. Justin Du Bois of Stanford University established (Angew. Chem. Int. Ed. 2009, 48, 4513) a procedure for alkane hydroxylation, converting 4 selectively into the alcohol 6. The oxirane 8 usually also preferentially ozidizes methines, hydroxylating steroids at the C-14 position. Ruggero Curci of the University of Bari found (Tetrahedron Lett. 2008, 49, 5614) that the substrate 7 showed some C-14 hydroxylation, but also a useful yield of the ketone 9. The authors suggested that the C-7 acetoxy group may be deactivating the C-14 C-H. C-H bonds can also be converted directly to carbon-carbon bonds. Mark E. Wood of the University of Exeter found (Tetrahedron Lett. 2009, 50, 3400) that free-radical removal of iodine from 10 followed by intramolecular H-atom abstraction in the presence of the trapping agent 11 delivered 12 with good diastereo control. Professor Li observed (Angew. Chem. Int. Ed. 2008, 47, 6278) that under Ru catalysis, hydrocarbons such as 13 could be directly arylated. He also established (Tetrahedron Lett. 2008, 49, 5601) conditions for the direct aminoalkylation of hydrocarbons such as 13, to give 17. Huw M. L. Davies of Emory University converted (Synlett 2009, 151) the ester 4 to the homologated diester 19 in preparatively useful yield using the diazo ester 18, the precursor to a selective, push-pull stabilized carbene. Intramolecular bond formation to an unactivated C-H can be even more selective. Guoshen Liu of the Shanghai Institute of Organic Chemistry developed (Organic Lett. 2009, 11, 2707) an oxidative Pd system that cyclized 20 to the seven-membered ring lactam 21 . Professor Du Bois devised (J. Am. Chem. Soc. 2008 , 130, 9220) a Rh catalyst that effected allylic amination of 22, to give 23 with substantial enantiocontrol. Dalibor Sames of Columbia University designed (J. Am. Chem. Soc. 2009, 131, 402) a remarkable cascade approach to C-H functionalization. Exposure of 24 to Lewis acid led to intramolecular hydride abstraction. Cyclization of the resulting stabilized carbocation delivered the tetrahydropyan 25 with remarkable diastereocontrol.

Synthesis of Naturally Occurring Cyclic Ethers: Boivivianin B (Murakami), SC- Δ 13 -9-IsoF (Taber), Brevisamide (Panek, Lindsley,Ghosh), Gambierol (Mori)

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Absolute Configuration ◽  
Cyclic Ether ◽  
Diels Alder ◽  
Synthetic Methods ◽  
Hydroxy Ketone ◽  
Total Syntheses ◽  
Enantiomerically Pure ◽  
Boston University ◽  
Gambierdiscus Toxicus ◽  
The University

The challenge of controlling the relative and absolute configuration of highly substituted cyclic ether-containing natural products continues to stimulate the development of new synthetic methods. Masahiro Murakami of Kyoto University showed (J. Org. Chem. 2009, 74, 6050) that Rh-mediated addition of an aryl boronic acid to 1 proceeded with high syn diastereocontrol, giving 3. This set the stage for Au-mediated rearrangement, leading to 4. We found (J. Org. Chem. 2009, 74, 5516) that asymmetric epoxidation of 5 followed by exposure to AD-mix could be used to prepare each of the four diastereomers of 6. We carried 6 on the isofuran 7, using a stereodivergent strategy that allowed the preparation of each of the 32 enantiomerically pure diastereomers of the natural product. Following up on the synthesis of brevisamide 16 described (Organic Highlights, November 16, 2009) by Kazuo Tachibana of the University of Tokyo, three groups reported alternative total syntheses. James S. Panek of Boston University prepared (Organic Lett. 2009, 11, 4390) the cyclic ether of 16 by addition of the enantiomerically pure silane 9 to 8. Craig W. Lindsley of Vanderbilt University used (Organic Lett. 2009, 11, 3950) SmI2 to effect the cyclization of 11 to 12. Arun K. Ghosh of Purdue University employed (Organic Lett. 2009, 11, 4164) an enantiomerically pure Cr catalyst to direct the absolute configuration in the hetero Diels-Alder addition of 14 to 13. Rubottom oxidation of the enol ether so formed led to the α-hydroxy ketone 15. Yuji Mori of Meijo University described (Organic Lett. 2009, 11, 4382) the total synthesis of the Gambierdiscus toxicus ladder ether gambierol 19. A key strategy, used repeatedly through the sequence, was the exo cyclization of an epoxy sulfone, illustrated by the conversion of 17 to 18. The epoxy sulfones were prepared by alkylating the anions derived from preformed epoxy sulfones such as 20.

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