Heteroaromatic Construction: The Sperry Synthesis of (+)-Terreusinone

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Pt Catalyst ◽  
State University ◽  
Keto Ester ◽  
North Carolina State University ◽  
Colorado State University ◽  
Rh Catalyst ◽  
La Jolla ◽  
The University ◽  
Technological University ◽  
Convergent Assembly

Akio Saito and Yuji Hanzawa of Showa Pharmaceutical University found (Tetrahedron Lett. 2011, 52, 4658) that an alkynyl keto ester 1 could be oxidatively cyclized to the furan 2. Eric M. Ferreira of Colorado State University showed (Org. Lett. 2011, 13, 5924) that depending on the conditions, a Pt catalyst could cyclize 3 to either 4 or 5. Shunsuke Chiba of Nanyang Technological University used (J. Am. Chem. Soc. 2011, 133, 13942) Cu catalysis for the oxidation of 6 to the pyrrole 7. Vladimir Gevorgyan of the University of Illinois at Chicago devised (Org. Lett. 2011, 13, 3746) a convergent assembly of the pyrrole 10 from the alkyne 8 and the alkyne 9. Dale L. Boger of Scripps La Jolla extended (J. Am. Chem. Soc. 2011, 133, 12285) the scope of the Diels-Alder addition of the triazine 11 to an alkyne 12 to give the pyridine 13. Tomislav Rovis, also of Colorado State University, used (Chem. Commun. 2011, 47, 11846) a Rh catalyst to add an alkyne 15 to the oxime 14 to give the pyridine 16. Sensuke Ogoshi of Osaka University, under Ni catalysis, added (J. Am. Chem. Soc. 2011, 133, 18018) a nitrile 18 to the diene 17 to give the pyridine 19. Alexander Deiters of North Carolina State University showed (Org. Lett. 2011, 13, 4352) that the complex tethered diyne 20 combined with 21 with high regiocontrol to give 22. Yong-Min Liang of Lanzhou University prepared (J. Org. Chem. 2011, 76, 8329) the indole 24 by cyclizing the alkyne 23. Xiuxiang Qi and Kang Zhao of Tianjin University found (J. Org. Chem. 2011, 76, 8690) that the enamine 25 could be oxidatively cyclized to the indole 26. Kazuhiro Yoshida and Akira Yanagisawa of Chiba University established (Org. Lett. 2011, 13, 4762) that ring-closing metathesis converted the keto ester 27 to the indole 28. Alessandro Palmieri and Roberto Ballini of the Università di Camerino observed (Adv. Synth. Catal. 2011, 353, 1425) that the pyrrole 30 spontaneously added to the nitro acrylate 29 to give an adduct that cyclized to 31 on exposure to acid.

Metal-Mediated Ring Construction: The Hoveyda Synthesis of (–)-Nakadomarin A

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Preliminary Investigation ◽  
State University ◽  
Colorado State University ◽  
Nakadomarin A ◽  
Sterically Demanding ◽  
National University ◽  
Rh Catalyst ◽  
Seoul National University ◽  
The University ◽  
Technological University

John F. Hartwig of the University of California, Berkeley effected (J. Am. Chem. Soc. 2013, 135, 3375) selective borylation of the cyclopropane 1 to give 2. It would be particularly useful if this borylation could be made enantioselective. Eric M. Ferreira of Colorado State University showed (Org. Lett. 2013, 15, 1772) that the enantomeric excess of 3 was transferred to the highly substituted cyclopropane 4. Antonio M. Echavarren of ICIQ Tarragona demonstrated (Org. Lett. 2013, 15, 1576) that Au-mediated cyclobutene construction could be used to form the medium ring of 6. Joseph M. Fox of the University of Delaware developed (J. Am. Chem. Soc. 2013, 135, 9283) what promises to be a general enantioselective route to cyclobutanes such as 8 by way of the intermediate bicyclobutane (not illustrated). Huw M.L. Davies of Emory University reported (Org. Lett. 2013, 15, 310) a preliminary investigation in this same direction. Masahisa Nakada of Waseda University prepared (Org. Lett. 2013, 15, 1004) the cyclopentane 10 by enantioselective cyclization of 9 followed by reductive opening. Young-Ger Suh of Seoul National University cyclized (Org. Lett. 2013, 15, 531) the lactone 11 to the cyclopentane 12. Xavier Ariza and Jaume Farràs of the Universitat de Barcelona optimized (J. Org. Chem. 2013, 78, 5482) the Ti-mediated reductive cyclization of 13 to 14. The hydrogenation catalyst reduced the intermediate Ti–C bond without affecting the alkene. Erick M. Carreira of ETH Zürich observed (Angew. Chem. Int. Ed. 2013, 52, 5382) that a sterically demanding Rh catalyst mediated the highly diastereoselective cyclization of 15 to 16. The ketone 16 was the key intermediate in a synthesis of the epoxyisoprostanes. Jianrong (Steve) Zhou of Nanyang Technological University used (Angew. Chem. Int. Ed. 2013, 52, 4906) a Pd catalyst to effect the coupling of 17 with the prochiral 18. Geum-Sook Hwang and Do Hyun Ryu of Sungkyunkwan University devised (J. Am. Chem. Soc. 2013, 135, 7126) a boron catalyst to effect the addition of the diazo ester 21 to 20. They showed that the sidechain stereocenter was effective in directing the subsequent hydrogenation of 22.

Organocatalytic Ring Construction: The Corey Synthesis of Coraxeniolide A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Michael Addition ◽  
State University ◽  
Henry Reaction ◽  
Max Planck ◽  
Keto Ester ◽  
Colorado State University ◽  
University Of Cambridge ◽  
Diastereomeric Mixture ◽  
The University ◽  
Technological University

Armando Córdova of Stockholm University has found (Tetrahedron Lett. 2008, 49, 4209) that the organocatalyst 3a effected enantioselective conjugate addition of bromonitromethane 2 to the α,β-unsaturated aldehyde 1, to give the cyclopropane 4 as a ~ 1:1 diastereomeric mixture, both in high ee. Tomislav Rovis of Colorado State University has published (J. Org. Chem. 2008, 73, 2033) a detailed account of his development of catalysts such as 6, that effected enantioselective cyclization of 5 to 7 with excellent ee. Karl Anker Jørgensen of Aarhus University has employed (J. Am. Chem. Soc. 2008, 130, 4897) chiral quaternary salts derived from quinine that mediated the enantioselective addition of prochiral rings such as 8 to the allenoate ester 9 to give 10 with high ee. Organocatalysts have also been used to prepare more highly substituted cyclohexane derivatives. Guofu Zhong of Nanyang Technological University used (Organic Lett. 2008, 10, 2437) a quinine-derived secondary amine to catalyze the Michael addition of 12 to 11 followed by intramolecular aldol (Henry) reaction, to give 13. When Professor Jørgensen attempted (Angew. Chem. Int. Ed. 2008, 47, 121) the related addition of 14 and 15 using catalyst 3a, he did not observe the expected Michael-Michael sequence. Rather, the initial Michael addition was followed by a Morita-Baylis-Hillman condensation, to give 16. The β-keto ester 16 existed primarily in its enol form. Organocatalysts can also be used to prepare polycyclic systems. Professor Jørgensen has found (Chem. Commun. 2008, 3016) that condensation of 14 with acetone dicarboxylate 17, again using catalyst 3a, gave the bicyclic β-keto ester 18. Matthew J. Gaunt of the University of Cambridge observed (J. Am. Chem. Soc. 2008, 130, 404) that for the cyclization of 19, catalyst 3b was superior to catalyst 3a. The power of desymmetrization of prochiral intermediates was illustrated by the report (J. Am. Chem. Soc. 2008, 130, 6737) from Benjamin List of the Max-Planck-Institute, Mülheim of the cyclization of 21 to 23. Organocatalysts can also be used to prepare larger rings.

Functionalization and Homologation of C-H Bonds

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Crop Protection ◽  
Oxidative Cyclization ◽  
South Florida ◽  
State University ◽  
Ru Catalyst ◽  
University Of Oklahoma ◽  
Princeton University ◽  
La Jolla ◽  
The University ◽  
Technological University

Justin Du Bois of Stanford University developed (J. Am. Chem. Soc. 2010, 132, 10202) a Ru catalyst for the stereoretentive hydroxylation of 1 to 2. John T. Groves of Princeton University effected (J. Am. Chem. Soc. 2010, 132, 12847) equatorial chlorination of the test substrate 3. Kenneth M. Nicholas of the University of Oklahoma found (J. Org. Chem. 2010, 75, 7644) that I2 catalyzed the amination of 5. Thorsten Bach of the Technische Universität München established (Org. Lett. 2010, 12, 3690) that the amination of 7 proceeded with significant diastereoselectivity. Phil S. Baran of Scripps/La Jolla compiled (Synlett 2010, 1733) an overview of the development of C-H oxidation. Tethering can improve the selectivity of C-H functionalization. X. Peter Zhang of the University of South Florida devised (Angew. Chem. Int. Ed. 2010, 49, 10192) a Co catalyst for the cyclization of 9 to 10. Teck-Peng Loh of Nanyang Technological University established (Angew. Chem. Int. Ed. 2010, 49, 8417) conditions for the oxidation of 11 to 12. Jin-Quan Yu, also of Scripps/La Jolla, effected (J. Am. Chem. Soc. 2010, 132, 17378) carbonylation of methyl C-H of 13 to give 14. Sunggak Kim, now also at Nanyang Technological University, established (Synlett 2010, 1647) conditions for the free-radical homologation of 15 to 17. Gong Chen of Pennsylvania State University extended (Org. Lett. 2010, 12, 3414) his work on remote Pd-mediated activation by cyclizing 18 to 19. Many schemes have been developed in recent years for the oxidation of substrates to reactive electrophiles. Gonghua Song of the East China University of Science and Technology and Chao-Jun Li of McGill University reported (Synlett 2010, 2002) Fe nanoparticles for the oxidative coupling of 20 with 21. Zhi-Zhen Huang of Nanjing University found (Org. Lett. 2010, 12, 5214) that protonated pyrrolidine 25 was important for mediating the site-selective coupling of 24 with 23. Y. Venkateswarlu of the Indian Institute of Chemical Technology, Hyderabad, was even able (Tetrahedron Lett. 2010, 51, 4898) to effect coupling with a cyclic alkene 28. AB3217-A 32, isolated in 1992, was shown to have marked activity against two spotted spider mites. Christopher R. A. Godfrey of Syngenta Crop Protection, Münchwilen, prepared (Synlett 2010, 2721) 32 from commercial anisomycin 30a. The key step in the synthesis was the oxidative cyclization of 30b to 31.

Enantioselective Synthesis of Alcohols and Amines: The Fujii/Ohno Synthesis of (+)-Lysergic Acid

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Kinetic Resolution ◽  
Lysergic Acid ◽  
Enantioselective Synthesis ◽  
Amino Acid Derivative ◽  
State University ◽  
University Of Arkansas ◽  
Keto Ester ◽  
Colorado State University ◽  
Quaternary Center ◽  
The University

Ramón Gómez Arrayás and Juan C. Carretero of the Universidad Autónoma de Madrid effected (Chem. Commun. 2011, 47, 6701) enantioselective conjugate borylation of an unsaturated sulfone 1, leading to the alcohol 2. Robert E. Gawley of the University of Arkansas found (J. Am. Chem. Soc. 2011, 133, 19680) conditions for enantioselective ketone reduction that were selective enough to distinguish between the ethyl and propyl groups of 3 to give 4. Vicente Gotor of the Universidad de Oviedo used (Angew. Chem. Int. Ed. 2011, 50, 8387) an overexpressed Baeyer-Villiger monoxygenase to prepare 6 by dynamic kinetic resolution of 5. Li Deng of Brandeis University prepared (J. Am. Chem. Soc. 2011, 133, 12458) 8 in high ee by kinetic enantioselective migration of the alkene of racemic 7. Bernhard Breit of the Freiburg Institute for Advanced Studies established (J. Am. Chem. Soc. 2011, 133, 20746) the oxygenated quaternary center of 10 by the addition of benzoic acid to the allene 9. Keith R. Fandrick of Boehringer Ingelheim constructed (J. Am. Chem. Soc. 2011, 133, 10332) the oxygenated quaternary center of 13 by enantioselective addition of the propargylic nucleophile 12 to 11. Yian Shi of Colorado State University devised (J. Am. Chem. Soc. 2011, 133, 12914) conditions for the enantioselective transamination of the α-keto ester 14 to the amine 15. Professor Deng added (Adv. Synth. Catal. 2011, 353, 3123) 18 to an enone 17 to give the protected amine 19. Song Ye of the Institute of Chemistry, Beijing effected (J. Am. Chem. Soc. 2011, 133, 15894) elimination/addition of an unsaturated acid chloride 20 to give the γ-amino acid derivative 22. Frank Glorius of the Universität Münster added (Angew. Chem. Int. Ed. 2011, 50, 1410) an aldehyde 23 to 24 to give the amide 25. Sentaro Okamoto of Kanagawa University designed (J. Org. Chem. 2011, 76, 6678) an organocatalyst for the enantioselective Steglich rearrangement of 26, creating the aminated quaternary center of 27. Most impressive of all was the report (Org. Lett. 2011, 13, 5460) by Hélène Lebel of the Université de Montréal of the direct enantioselective C–H amination of 28 to give 29.

Heteroaromatic Synthesis: The Tokuyama Synthesis of (−)-Rhazinilam

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Ni Catalyst ◽  
State University ◽  
Colorado State University ◽  
Ru Catalyst ◽  
Opioid Ligands ◽  
University Of Wisconsin ◽  
Rh Catalyst ◽  
Indian Institute Of Science ◽  
The University ◽  
École Polytechnique

Mei-Huey Lin of the National Changhua University of Education rearranged (J. Org. Chem. 2014, 79, 2751) the initial allene derived from 1 to the γ-chloroenone. Displacement with acetate followed by hydrolysis led to the furan 2. A. Stephen K. Hashmi of Ruprecht-Karls-Universität Heidelberg showed (Angew. Chem. Int. Ed. 2014, 53, 3715) that the Au-catalyzed conversion of the bis alkyne 3, mediated by 4, proceeded selectively to give 5. Tehshik P. Yoon of the University of Wisconsin used (Angew. Chem. Int. Ed. 2014, 53, 793) visible light with a Ru catalyst to rearrange the azide 6 to the pyrrole 7. Cheol-Min Park, now at UNIST, found (Chem. Sci. 2014, 5, 2347) that a Ni catalyst reorganized the methoxime 8 to the pyrrole 9. A Rh catalyst converted 8 to the corresponding pyridine (not illustrated). In the course of a synthesis of opioid ligands, Kenner C. Rice of the National Institute on Drug Abuse optimized (J. Org. Chem. 2014, 79, 5007) the preparation of the pyridine 11 from the alcohol 10. Vincent Tognetti and Cyrille Sabot of the University of Rouen heated (J. Org. Chem. 2014, 79, 1303) 12 and 13 under micro­wave irradiation to give the 3-hydroxy pyridine 14. Tomislav Rovis of Colorado State University prepared (J. Am. Chem. Soc. 2014, 136, 2735) the pyridine 17 by the Rh-catalyzed combination of 15 with 16. Fabien Gagosz of the Ecole Polytechnique rearranged (Angew. Chem. Int. Ed. 2014, 53, 4959) the azirine 18, readily available from the oxime of the β-keto ester, to the pyridine 19. Matthias Beller of the Universität Rostock used (Chem. Eur. J. 2014, 20, 1818) a Zn catalyst to mediate the opening of the epoxide 21 with the aniline 20. A Rh cata­lyst effected the oxidation and cyclization of the product amino alcohol to the indole 22. Sreenivas Katukojvala of the Indian Institute of Science Education & Research showed (Angew. Chem. Int. Ed. 2014, 53, 4076) that the diazo ketone 23 could be used to anneal a benzene ring onto the pyrrole 24, leading to the 2,7-disubstituted indole 25.

Diels-Alder Cycloaddition: Fawcettimine (Williams), Apiosporic Acid (Helmchen), Marginatone (Abad- Somovilla), Okilactomycin (Hoye), Vinigrol (Barriault), Plakotenin (Bihlmeier/Klopper)

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Natural Product ◽  
Diels Alder ◽  
State University ◽  
University Of Minnesota ◽  
Enantiomerically Pure ◽  
Colorado State University ◽  
Institute Of Technology ◽  
La Jolla ◽  
The University ◽  
Stereogenic Center

Highly substituted dienes and dienophiles are often reluctant participants in intermolecular Diels-Alder cycloaddition. Nevertheless, Robert M. Williams of Colorado State University, in the course of a synthesis of fawcettimine 4, was able (J. Org. Chem. 2012, 77, 4801) to prepare 3 by combining the enone 1 with the diene 2. Günter Helmchen of the Universität Heidelberg set (J. Org. Chem. 2012, 77, 4491) the single stereogenic center of 5 by Ir-catalyzed allylic alkylation. The Lewis acid that promoted the cycloaddition also conveniently removed the trityl protecting group, leading to 6, that was saponified to apiosporic acid 7. Antonio Abad-Somovilla of the Universidad de Valencia prepared (J. Org. Chem. 2012, 77, 5664) the triene 8 in enantiomerically pure form from carvone. Despite the additional substitution on the diene, cycloaddition proceeded smoothly to give 9, which was carried on to marginatone 10. One could envision that okilactomycin 13 could be formed by an intramolecular Diels-Alder cycloaddition. Thomas R. Hoye of the University of Minnesota observed (Org. Lett. 2012, 14, 828) that the tetraene tetronic acid corresponding to 11 was inert, but that the methyl ether 11 cyclized smoothly to 12. Demethylation then gave the natural product The complex polycyclic structure of vinigrol 16 challenged organic synthesis chemists for many years, until a route was established by Phil Baran of Scripps/La Jolla (Highlights September 6, 2010). Louis Barriault cyclized (Angew. Chem. Int. Ed. 2012, 51, 2111) 14 to 15 en route to a late intermediate in the Baran synthesis It had been hypothesized that the natural product plakotenin 19 was formed naturally from a tetraene corresponding to 17. The tetraene 17 was prepared and the cyclization was successful, “confirming” both the structure of the natural product and the biosynthetic hypothesis. Angela Bihlmeier and Wim Klopper of the Karlsruhe Institute of Technology calculated (J. Am. Chem. Soc. 2012, 134, 2154) the relative energies of the four competing transition states for the cyclization, leading to a correction of the structure of 18, and so of the natural product 19.

Enantioselective Construction of Arrays of Stereogenic Centers

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Claisen Rearrangement ◽  
Cinchona Alkaloid ◽  
State University ◽  
Henry Reaction ◽  
University Of Pittsburgh ◽  
Colorado State University ◽  
Boston University ◽  
Complementary Approach ◽  
La Jolla ◽  
The University

An impressive array of new catalysts for enantioselective homologation have been reported. Carlos F. Barbas III of Scripps/La Jolla has found (Angew. Chem. Int. Ed. 2007, 46, 5572 ) that the commercial amino acid 3 mediated the addition of dihydroxyacetone 2 to an aldehyde such as 1 to give the triol 4 with high enantio- and diastereocontrol. Takashi Ooi of Nagoya University has devised (J. Am. Chem. Soc. 2007, 129, 12392) the catalyst 6 for the anti addition (Henry reaction) of nitro alkanes such as 5 to aldehydes. Takayoshi Arai of Chiba University has developed (Organic Lett. 2007, 9, 3595) a complementary catalyst (not shown) that mediated syn addition. Jonathan A. Ellman of the University of California, Berkeley has uncovered (J. Am. Chem. Soc. 2007, 129, 15110) the catalyst 10 for the aza-Henry reaction. Yian Shi of Colorado State University has found (J. Am. Chem. Soc. 2007, 129, 11688) ligands for Pd that direct the absolute sense of the addition of 13 to dienes such as 12. Bernhard Breit of Albert-Ludwigs-Universität, Freiburg has devised conditions (Adv. Synth. Cat. 2007, 349, 1891) for the Rh-catalyzed hydroformylation of α-olefins such as 15, and same-pot proline-catalyzed condensation of the linear aldehyde so produced with a branched aldehyde such as 17 to give, after reductive workup, the branched diol 18. Scott G. Nelson of the University of Pittsburgh has established (J. Am. Chem. Soc. 2007, 129, 11690) conditions, using Cinchona alkaloid derived catalysts, for the condensation of the imine surrogate 19 with the ketene precursor 20, to give the Mannich product 21. Scott E. Schaus of Boston University has developed (J. Am. Chem. Soc. 2007, 129, 15398) a complementary approach, based on catalyzed addition of isolated allyl borinates such as 23 to the activated imine 22. Kálmán J. Szabó of Stockholm University has found (J. Am. Chem. Soc. 2007, 129, 13723) that substituted allyl borinates can be prepared and reacted in situ. Martin Hiersemann of the Universität Dortmund has reported (Organic Lett. 2007, 9, 4979) the remarkable Cu*-catalyzed Claisen rearrangement of the prochiral 24, leading to 25 and thus to the versatile intermediate 27.

Construction of Stereochemical Arrays

2015 ◽  
Author(s):  
Tristan H. Lambert
Keyword(s):  
Kinetic Resolution ◽  
Alder Reaction ◽  
State University ◽  
Rhodium Catalysis ◽  
Colorado State University ◽  
Allyl Sulfide ◽  
Institute Of Technology ◽  
Quaternary Stereocenters ◽  
The University ◽  
Technological University

The unprecedented enantioselective 1,8-addition of azlactone 1 to acylpyrrole 2 catalyzed by triaminophosphorane 3 was reported (J. Am. Chem. Soc. 2012, 134, 19370) by Takashi Ooi at Nagoya University. Tomislav Rovis at Colorado State University developed (Angew. Chem. Int. Ed. 2012, 51, 12330) the asymmetric oxidative hetero-Diels-Alder reaction of propionaldehyde (5) and ketone 6 to produce lactone 8, catalyzed by NHC catalyst 7 in the presence of phenazine. A related NHC catalyst 11 was utilized (Angew. Chem. Int. Ed. 2012, 51, 8276) by Xue-Wei Liu at Nanyang Technological University for the homoenolate addition of enal 9 to nitrodiene 10 to furnish 12 with high ee. The vinylogous conjugate addition of butenolide 13 to 15 to produce 16 with exquisite stereoselectivity was accomplished (Angew. Chem. Int. Ed. 2012, 51, 10069) by Kuo-Wei Huang at KAUST, Choon-Hong Tan at Henan University and Nanyang Technological University, and Zhiyong Jiang at Henan University. The enantioselective production of lactone 18 was achieved (J. Am. Chem. Soc. 2012, 134, 20197) by Jeffrey S. Johnson at the University of North Carolina at Chapel Hill by dynamic kinetic resolution (DKR) of α-keto ester 17. A related DKR strategy was employed (Org. Lett. 2012, 14, 6334) by Brinton Seashore-Ludlow at the KTH Royal Institute of Technology and Peter Somfai at Lund University in Sweden and the University of Tartu in Estonia for hydrogenation of α-amino-β-ketoester 19 to furnish aminoalcohol 21 with high Shigeki Matsunaga and Motomu Kanai at the University of Tokyo developed (Angew. Chem. Int. Ed. 2012, 51, 10275) a unique strategy for the selective production of the cross-aldol adduct 24 by in situ generation of an aldehyde enolate from allyloxyborane 23 under rhodium catalysis. The highly diastereoselective construction of adduct 26 bearing two adjacent quaternary stereocenters by ketone allylation with allyl sulfide 25 was reported (Angew. Chem. Int. Ed. 2012, 51, 7263) by Takeshi Takeda at the Tokyo University of Agriculture and Technology. Wen-Hao Hu at East China Normal University reported (Nature Chem. 2012, 4, 733) the enantioselective three-component coupling of diazoester 27, N-benzylindole (28), and imine 29 to furnish 31 under the action of Rh2(OAc)4 and phosphoric acid 30.

C–H Functionalization: The Ono/Kato/Dairi Synthesis of Fusiocca-1,10(14)-diene-3,8β,16-triol

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Cytochrome P450 ◽  
Iron Catalyst ◽  
State University ◽  
Colorado State University ◽  
Carbon Carbon Bond ◽  
National University ◽  
Rh Catalyst ◽  
Hydride Abstraction ◽  
Osaka Prefecture ◽  
The University

Theodore A. Betley of Harvard University devised (J. Am. Chem. Soc. 2011, 133, 4917) an iron catalyst for inserting the nitrene from 2 into the C–H of 1 to give 3. Bernhard Breit of the Freiburg Institute for Advanced Studies uncovered (J. Am. Chem. Soc. 2011, 133, 2386) a Rh catalyst that effected the intriguing hydration of a terminal alkyne 4 to the allylic ester 5. Yian Shi of Colorado State University specifically oxidized (Org. Lett. 2011, 13, 1548) one of the two allylic sites of 6 to give 7. Kálmán J. Szabó of Stockholm University optimized (J. Org. Chem. 2011, 76, 1503) the allylic oxidation of 9 to 10, using the inexpensive sodium perborate. Masayuki Inoue of the University of Tokyo specifically carbamoylated (Tetrahedron Lett. 2011, 52, 2885) the acetonide 12 to give 14. Stephen Caddick of University College London added (Tetrahedron Lett. 2011, 52, 1067) the formyl radical from 15 to 16 to give 17. Ilhyong Ryu of Osaka Prefecture University and Maurizio Fagnoni of the University of Pavia employed (Angew. Chem. Int. Ed. 2011, 50, 1869) a related strategy to effect the net transformation of 18 to 20. There are many examples of the oxidation of ethers and amines to reactive intermediates that can go on to carbon–carbon bond formation. Ram A. Vishwakarma of the Indian Institute of Integrative Medicine observed (Chem. Commun. 2011, 47, 5852) that with an iron catalyst, the aryl Grignard 22 smoothly coupled with THF 21 to give 23. Gong Chen of Pennsylvania State University effected (Angew. Chem. Int. Ed. 2011, 50, 5192) specific remote C–H arylation of 24, leading to 26. Takahiko Akiyama of Gakushuin University established (J. Am. Chem. Soc. 2011, 133, 2424) conditions for intramolecular hydride abstraction, effecting the conversion of 27 to 28. C–H functionalization in nature is often mediated by cytochrome P450 oxidation. Zhi Li of the National University of Singapore showed (Chem. Commun. 2011, 47, 3284) that a particular cytochrome P450 selectively oxidized 29 to the alcohol 30, leaving the chemically more reactive benzylic position intact.

scholarly journals Preface: Modern Heterocycle Synthesis and Functionalization

Synlett ◽  
2021 ◽  
Vol 32 (02) ◽  
pp. 140-141
Author(s):  
Louis-Charles Campeau ◽  
Tomislav Rovis
Keyword(s):  
Active Pharmaceutical Ingredient ◽  
Associate Professor ◽  
Columbia University ◽  
State University ◽  
Heterocycle Synthesis ◽  
Colorado State University ◽  
University Of Toronto ◽  
Process Chemistry ◽  
The University ◽  
Small Molecule Therapeutics

obtained his PhD degree in 2008 with the late Professor Keith Fagnou at the University of Ottawa in Canada as an NSERC Doctoral Fellow. He then joined Merck Research Laboratories at Merck-Frosst in Montreal in 2007, making key contributions to the discovery of Doravirine (MK-1439) for which he received a Merck Special Achievement Award. In 2010, he moved from Quebec to New Jersey, where he has served in roles of increasing responsibility with Merck ever since. L.-C. is currently Executive Director and the Head of Process Chemistry and Discovery Process Chemistry organizations, leading a team of smart creative scientists developing innovative chemistry solutions in support of all discovery, pre-clinical and clinical active pharmaceutical ingredient deliveries for the entire Merck portfolio for small-molecule therapeutics. Over his tenure at Merck, L.-C. and his team have made important contributions to >40 clinical candidates and 4 commercial products to date. Tom Rovis was born in Zagreb in former Yugoslavia but was largely raised in southern Ontario, Canada. He earned his PhD degree at the University of Toronto (Canada) in 1998 under the direction of Professor Mark Lautens. From 1998–2000, he was an NSERC Postdoctoral Fellow at Harvard University (USA) with Professor David A. Evans. In 2000, he began his independent career at Colorado State University and was promoted in 2005 to Associate Professor and in 2008 to Professor. His group’s accomplishments have been recognized by a number of awards including an Arthur C. Cope Scholar, an NSF CAREER Award, a Fellow of the American Association for the Advancement of Science and a ­Katritzky Young Investigator in Heterocyclic Chemistry. In 2016, he moved to Columbia University where he is currently the Samuel Latham Mitchill Professor of Chemistry.

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