Enantioselective Construction of Alkylated Stereogenic Centers

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Phase Transfer ◽  
Enantioselective Hydrogenation ◽  
Gel Chromatography ◽  
Quaternary Centers ◽  
University Of Oxford ◽  
University Of Edinburgh ◽  
Enantioselective Alkylation ◽  
Silica Gel Chromatography ◽  
University Of Bristol ◽  
The University

Xiang-Ping Hu and Zhuo Zheng of the Dalian Institute of Chemical Physics developed (Organic Lett. 2009, 11, 3226; J. Org. Chem. 2009, 74, 9191) a family of Rh catalysts for the enantioselective hydrogenation of allylic phosphonates such as 1. Hon Wai Lam of the University of Edinburgh established (J. Am. Chem. Soc. 2009, 131, 10386) that an alkenyl heterocycle 3 could be reduced with high ee. The product 4 could be hydrolyzed to the carboxylic acid. Ken Tanaka of the Tokyo University of Agriculture and Technology showed (J. Am. Chem. Soc. 2009, 131, 12552) that an isopropenyl amide 6 could be hydroacylated with high ee. Gregory C. Fu of MIT observed (J. Am. Chem. Soc. 2009, 131, 14231) that nitromethane 9 could be added to the allenyl amide 8 to give 10, the product of γ-bond formation. Robert K. Boeckman Jr. of the University of Rochester devised (Organic Lett. 2009, 11, 4544) what appears to be a general protocol for the construction of alkylated ternary and quaternary centers: enantioselective hydroxymethylation of an aldehyde 11. In another approach to the construction of alkylated quaternary centers, Varinder K. Aggarwal of the University of Bristol demonstrated (Angew. Chem. Int. Ed. 2009, 48, 6289) that an enantiomerically enriched trifluoroborate salt 14 could be added to an aromatic aldehyde 15 with retention of absolute configuration. The salt 14 was prepared from the corresponding high ee secondary benzyl alcohol. Weinreb amides are versatile precursors to a variety of functional groups. Stephen G. Davies of the University of Oxford devised (Organic Lett. 2009, 11, 3254) a chiral Weinreb amide equivalent 17 that could be alkylated with high de. The minor diastereomer from the alkylation was readily separable by silica gel chromatography. Keiji Maruoka of Kyoto University established (Angew. Chem. Int. Ed. 2009, 48, 5014) that a chiral phase transfer catalyst was effective for the enantioselective alkylation of the alkynyl ester 19. Emmanuel Riguet of the Université de Reims Champagne-Ardenne developed (Tetrahedron Lett. 2009, 50, 4283) an improved catalyst for the enantioselective addition of malonate 22 to cyclohexenone 21.

Stereocontrolled C-N Ring Construction: The Pyne Synthesis of Hyacinthacine B 3

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Organic Chemistry ◽  
Conjugate Addition ◽  
Enantioselective Hydrogenation ◽  
Pd Catalyst ◽  
University Of Michigan ◽  
Palo Alto ◽  
University Of Toronto ◽  
University Of Oxford ◽  
University Of Bristol ◽  
The University

Keiji Maruoka of Kyoto University found (Organic Lett. 2010, 12, 1668) that the diazo amide 1 derived from the Oppolzer sultam condensed with the imine 2 to give the aziridine 3 with high stereocontrol. Andrei K. Yudin of the University of Toronto observed (Angew. Chem. Int. Ed. 2010, 49, 1607) that the unprotected aziridine aldehyde 4, which exists as a mixture of dimers, condensed smoothly with the Ohira reagent 5 to give the alkynyl aziridine 6. David M. Hodgson of the University of Oxford successfully (Angew. Chem. Int. Ed. 2010, 49, 2900) deprotonated the azetidine thioamide 7 to give, after allylation, the azetidine 8. Varinder K. Aggarwal of the University of Bristol devised (Chem. Commun. 2010, 267) a Pd catalyst for the cyclocarbonylation of an alkenyl aziridine 9 to give the β-lactam 10. Iain Coldham of the University of Sheffield used (J. Org. Chem. 2010, 75, 4069) the ligand they had developed to effect enantioselective allylation of the pyrrolidine derivative 11. The corrresponding piperidine worked as well. John P. Wolfe of the University of Michigan established (Organic Lett. 2010, 12, 2322) that the Pd-mediated cyclization of 13 to 15 could be effected with high diastereocontrol. Christopher G. Frost of the University of Bath optimized (Angew. Chem. Int. Ed. 2010, 49, 1825) the tandem Ru-mediated conjugate addition/cyclization of 16 to give 18 in high ee. Barry M. Trost of Stanford University extended (J. Am. Chem. Soc. 2010, 132, 8238) their studies of trimethylenemethane cycloaddition to the ketimine 19, leading to the substituted pyrrolidine 21 in high ee. Pher G. Andersson of Uppsala University optimized (J. Am. Chem. Soc. 2010, 132, 8880) an Ir catalyst for the enantioselective hydrogenation of readily prepared tetrahydropyridines such as 22. Min Shi of the Shanghai Institute of Organic Chemistry devised (J. Org. Chem. 2010, 75, 3935) a Pd catalyst for enantioselective conjugate addition to the prochiral pyridone 24. Xiaojun Huang of Roche Palo Alto prepared (Tetrahedron Lett. 2010, 51, 1554) the monoacid 26 by enantioselective methanolysis of the anhydride. Selective formylation of the ester led to the pyridone 27.

Construction of Alkylated Stereogenic Centers

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Phase Transfer ◽  
Conjugate Addition ◽  
Enantioselective Hydrogenation ◽  
Boronic Acids ◽  
National University ◽  
Cu Catalyst ◽  
Institute Of Technology ◽  
Enantioselective Alkylation ◽  
Seoul National University ◽  
The University

Andreas Pfaltz of the University of Basel and Keisuke Suzuki of the Tokyo Institute of Technology showed (Angew. Chem. Int. Ed. 2010, 49, 881) that the iodohydrin of 1 did not interfere with the enantioselective hydrogenation. J. R. Falck of UT Southwestern developed (J. Am. Chem. Soc. 2010, 132, 2424) a procedure for coupling arene boronic acids with a cyano triflate 3, readily available in high ee from the corresponding aldehyde. Anita R. Maguire of University College Cork devised (J. Am. Chem. Soc. 2010, 132, 1184) a Cu catalyst for the enantioselective C-H insertion cyclization of 5 to 6. Jin-Quan Yu of Scripps/La Jolla established (J. Am. Chem. Soc. 2010, 132, 460) a complementary enantioselective C-H functionalization protocol, converting the prochiral 7 into 8 in high ee. Xumu Zhang of Rutgers University effected (Angew. Chem. Int. Ed. 2010, 49, 4047) enantioselective branching hydroformylation of 9 to give 10. T. V. RajanBabu of Ohio State University established (J. Am. Chem. Soc. 2010, 132, 3295) the enantioselective hydrovinylation of a diene 11 to the diene 12. Gregory C. Fu extended (J. Am. Chem. Soc. 2010, 132, 1264, 5010) Ni-mediated cross-coupling, both with alkenyl and aryl nucleophiles, to the racemic bromoketone 13. Hyeung-geun Park and Sang-sup Jew of Seoul National University used (Organic Lett. 2010, 12 , 2826) their asymmetric phase transfer protocol to effect the enantioselective alkylation of the amide 15. Kyung Woon Jung of the University of Southern California showed (J. Org. Chem. 2010, 75, 95) that the oxidative Pd-mediated Heck coupling of arene boronic acids to 17 could be effected in high ee. Nicolai Cramer of ETH Zurich observed (J. Am. Chem. Soc. 2010, 132, 5340) high enantioinduction in the cleavage of the prochiral cyclobutanol 19. Alexandre Alexakis of the University of Geneva achieved (Organic Lett. 2010, 12, 1988) the long-sought goal of efficient enantioselective conjugate addition of a Grignard reagent to an unsaturated aldehyde 21. Professor Alexakis also established (Organic Lett. 2010, 12, 2770) conditions for enantioselective conjugate addition to a nitrodiene 23. This procedure worked equally well for β-alkynyl nitroalkenes.

Practical Enantioselective Construction of Arrays of Stereogenic Centers: The Jørgensen Synthesis of the Autoregulator IM-2

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
University Of Pennsylvania ◽  
Gel Chromatography ◽  
Max Planck ◽  
West Virginia University ◽  
Clemson University ◽  
Stereogenic Centers ◽  
Cu Catalyst ◽  
Enantioselective Epoxidation ◽  
Silica Gel Chromatography ◽  
The University

Armando Córdova of Stockholm University found (Angew. Chem. Int. Ed. 2008, 47, 8468) that the enantiomerically-enriched diastereomers from aminosulfenylation of 1 were readily separable by silica gel chromatography. Benjamin List of the Max-Planck-Institut, Mülheim developed (Angew. Chem. Int. Ed. 2008, 47, 8112) what appears to be a general protocol for the enantioselective epoxidation of enones such as 4. Paolo Melchiorre of the Università di Bologna devised (Angew. Chem. Int. Ed. 2008, 47 , 8703) a related protocol for the enantioselective aziridination of enones. Xue-Long Hue of the Shanghai Institute of Organic Chemistry and Yun-Dong Wu of the Hong Kong University of Science and Technology optimized (J. Am. Chem. Soc. 2008, 130 , 14362) a Cu catalyst for enantioselective Mannich homologation of imines such as 6. Guofu Zhong of Nanyang Technological University, Singapore established (Angew. Chem. Int. Ed. 2008, 47, 10187; Organic Lett. 2008 , 10 , 4585) that enantioselective α-aminoxylation of an ω-alkenyl aldehyde such as 9 could lead to defined arrays of stereogenic centers. George A. O’Doherty of West Virginia University devised (Organic Lett. 2008, 10, 3149) a protocol for the enantioselective hydration of 12 to 13 . René Peters, now at the University of Stuttgart, designed (Angew. Chem. Int. Ed. 2008, 47, 5461) an Al catalyst for the enantioselective combination of an acyl bromide 15 with an aldehyde 14 to deliver the β–lactone 16. Hajime Ito and Masaya Sawamura of Hokkaido University established (J. Am. Chem. Soc. 2008, 130, 15774) that the allenyl borane from 17 added to aldehydes such as 18 with high ee. Keiji Maruoka of Kyoto University developed (Tetrahedron Lett. 2008, 49, 5369) an organocatalyst for the Mannich homologation of an aldehyde such as 20 to 21. R. Karl Dieter of Clemson University showed (Organic Lett. 2008, 10, 2087) that 23, readily prepared in high ee, could be displaced sequentially with two different Grignard reagents, to give 24. Jeffrey W. Bode, now at the University of Pennsylvania, found (Organic Lett. 2008, 10, 3817) that bisulfite adducts such as 25 served well for the addition of unstable chloroaldehydes to 26 to give 27.

Transition Metal-Mediated Ring Construction: The Yu Synthesis of 1-Desoxyhypnophilin

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Transition Metal ◽  
Quinone Methide ◽  
Michigan State University ◽  
State University ◽  
Enantiomerically Pure ◽  
Quaternary Centers ◽  
University Of Oxford ◽  
National University ◽  
Cu Catalyst ◽  
The University

Both 1 and 3 are inexpensive prochiral starting materials. Tae-Jong Kim of Kyungpook National University devised (Organomet. 2008, 27, 1026) a chiral Cu catalyst that efficiently converted 1 (other ring sizes worked as well) to the enantiomerically pure ester 2. Alexandre Alexakis of the University of Geneva found (Adv. Synth. Cat. 2008, 350, 1090) a chiral Cu catalyst that mediated the enantioselective coupling of 3 with Grignard reagents such as 4 . The π-allyl Pd complex derived from 6 is also prochiral. Barry M. Trost of Stanford University showed (Angew. Chem. Int. Ed. 2008, 47, 3759) that with appropriate ligand substitution, coupling with the phthalimide 7 proceeded to give 8, readily convertible to (-)-oseltamivir (Tamiflu) 9, in high ee. Jonathan W. Burton of the University of Oxford found (Chem Commun. 2008, 2559) that Mn(OAc)3 -mediated cyclization of 10 delivered the lactone 12 with high diastereocontrol. John Montgomery of the University of Michigan observed (Organic Lett. 2008, 10, 811) that the Ni-catalyzed cyclization of 12 also proceeded with high diastereocontrol. Ken Tanaka of the Tokyo University of Agriculture and Technology combined (Angew. Chem. Int. Ed. 2008, 47, 1312) Rh-catalyzed ene-yne cyclization of 14 with catalytic ortho C-H functionalization, leading to 16 in high ee. Eric N. Jacobsen of Harvard University designed (Angew. Chem. Int. Ed. 2008, 47, 1469) a chiral Cr catalyst for the intramolecular carbonyl ene reaction, that converted 17 to 18 in high ee. Using a stoichiometric prochiral Cr carbene complex 20 and the enantiomerically-pure secondary propargylic ether 19, Willam D. Wulff of Michigan State University prepared (J. Am. Chem. Soc. 2008, 130, 2898) a facially-selective Cr-complexed o -quinone methide intermediate, that cyclized to 21 with high ee. A variety of methods have been put forward for the transition metal-mediated construction of polycarbocyclic systems. One of the more powerful is the enantioselective Rh-catalyzed stitching of the simple substrate 22 into the tricycle 23 devised (J. Am. Chem. Soc. 2008, 130, 3451) by Takanori Shibata of Waseda University. Inter alia, ozonolysis of 23 delivered the cyclopentane 24 containing two all-carbon quaternary centers.

The Rawal Synthesis of N-Methylwelwitindolinone D Isonitrile

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Biological Activity ◽  
Multidrug Resistance ◽  
Carcinoma Cells ◽  
Gel Chromatography ◽  
Unsaturated Ketone ◽  
Human Carcinoma ◽  
Synthetic Strategy ◽  
Single Diastereomer ◽  
Silica Gel Chromatography ◽  
The University

The complex polycyclic structure of N-methylwelwitindolinone D isonitrile 3 was assigned in 1999. The welwitinines show an intriguing range of biological activity, including reversal of P-glycoprotein-mediated multidrug resistance in human carcinoma cells. Viresh H. Rawal of the University of Chicago described (J. Am. Chem. Soc. 2011, 133, 5798) the first synthesis of 3, using as a key step the Pd-catalyzed cyclization of 1 to 2. The ketone 1 was assembled by the convergent coupling of 7 with 11. The indole 7 was readily available by Batcho-Leimgruber cyclization of commercial 4 to 5. The expected 3-acylation followed by N -methylation delivered the stable ketone 6. The unstable 7 was prepared as needed. The anisole 8 was the starting material for the preparation of the alicyclic diene 11. Although this synthesis was carried out in the racemic series, enantiomerically enriched 9 could be prepared by Shi epoxidation of the β,γ-unsaturated ketone from Birch reduction The alcohol 7 was not stable to silica gel chromatography. The mixture of 11 with the crude alcohol 7 was therefore activated by the addition of TMSOTf, then added via cannula to aqueous HClO4 in THF to deliver the coupled product 1 as a single diastereomer. The remarkable cyclization of 1 to 2 required extensive screening. Eventually it was found that a combination of ( t -Bu)3 P with Pd(OAc)2 as the Pd source worked well. This concise convergent synthetic strategy makes the welwitinine core 2 available in gram quantities. There were two problems to be solved in the conversion of 2 to 3. The first was the installation of the oxy bridge. Indoles are notoriously sensitive to overoxidation. Nevertheless, addition of an acetone solution of dimethyl dioxirane to the bromo ketone 12 over 24 hours gave clean conversion to 13. The remaining challenge was the conversion of the aldehyde of 13 to the isonitrile. Kim had described the inversion of an oxime to the isothiocyanate. Optimization of this protocol led to the thiourea 14 as the best for this transformation. Mild desulfurization then delivered N -methylwelwitindolinone D isonitrile 3.

Enantioselective Construction of Arrays of Stereogenic Centers: The Breit Synthesis of (+)-Bourgeanic Acid

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Enantioselective Hydrogenation ◽  
Pt Catalyst ◽  
Dipolar Cycloaddition ◽  
Unsaturated Ester ◽  
Asymmetric Allylation ◽  
One Pot ◽  
University Of Texas ◽  
La Jolla ◽  
University Of Bristol ◽  
The University

Kyungsoo Oh of Indiana University Purdue University Indianapolis devised (Organic Lett. 2009, 11, 5682) a new ligand that with Cu delivered predominantly one diastereomer of the Henry adduct 3, and with Zn delivered the other. Liu-Zhu Gong of the University of Science and Technology of China reported (Angew. Chem. Int. Ed. 2009, 48, 6503) the Darzens condensation of the diazoacetamide 5 with a variety of aldehydes to give the corresponding epoxy amides with high diastereo- and enantiocontrol. Michael J. Krische of the University of Texas, Austin, applied (Organic Lett. 2009, 11, 3108, 3112) his asymmetric allylation to a variety of primary diols including 7, leading to the homologated product 9. M. Christina White of the University of Illinois showed (J. Am. Chem Soc. 2009, 131, 11707) that Pd-mediated oxidative amination of carbamate 10 delivered the protected 1,3-amino alcohol 11 with high diastereocontrol. James P. Morken of Boston College devised (J. Am. Chem Soc. 2009, 131, 9134) a Pt catalyst for the asymmetric bis-boration of dienes. The allyl borane prepared from 12 added with high stereocontrol to benzaldehyde, to give, after oxidation, the diol 13. Carlos F. Barba III of Scripps/La Jolla optimized (Angew. Chem. Int. Ed. 2009, 48, 9848) an organocatalyst for the enantioselective conjugate addition of an alkoxy aldehyde 15 to a nitroalkene. Do Hyun Ryu of Sungkyunkwan University found (Chem. Commun. 2009, 5460) that an organocatalyst could also mediate the dipolar cycloaddition of a diazo ester 18 to an unsaturated aldehyde, giving 19 with high diastereo- and enantiocontrol. Francesco Fini and Luca Bernardi of the University of Bologna developed (J. Am. Chem Soc. 2009, 131, 9614) an organocatalyst that effected enantioselective dipolar cycloaddition of the nitrone derived from 20 to the unsaturated ester 21. Kevin Burgess of Texas A&M optimized (J. Am. Chem Soc. 2009, 131, 13236) an Ir catalyst for the enantioselective hydrogenation of trisubstituted alkenes such as 23. In the course of a synthesis of (+)-faranal, Varinder K. Aggarwal of the University of Bristol described (Angew. Chem. Int. Ed. 2009, 48, 6317) a one-pot procedure for the conversion of the allyl borane 25 into 27.

scholarly journals Sir David Cecil Smith. 21 May 1930—29 June 2018

2019 ◽  
Vol 67 ◽  
pp. 401-419
Author(s):  
Angela E. Douglas
Keyword(s):  
Agricultural Science ◽  
Leadership Roles ◽  
Experimental Science ◽  
Ecological Processes ◽  
University Of Oxford ◽  
International Authority ◽  
Invertebrate Animals ◽  
University Of Edinburgh ◽  
University Of Bristol

David Smith was an international authority in the biological discipline of symbiosis and an influential leader in academic life. Through his work on photosynthetic symbioses in lichens and invertebrate animals, David transformed the field of symbiosis from a study of taxonomy and morphology into an experimental science. In particular, he applied novel radiotracer techniques to demonstrate that lichens are metabolically dynamic, with photosynthetically-fixed carbon transferred from symbionts to lichen host at high rates. His subsequent study of diverse symbioses led him to develop common principles underlying symbioses, including the regulated transfer of metabolites between partners and the role of ecological processes of colonization and community assembly in the establishment of symbioses. In his academic service, David had multiple leadership roles, including head of the Department of Botany at University of Bristol (1974–1980), head of the Department of Agricultural Science at University of Oxford (1980–1987), principal of University of Edinburgh (1987–1994) and president of Wolfson College, University of Oxford (1994–2000). David was biological secretary of the Royal Society (1983–1987) and he was knighted in 1986.

Sign in / Sign up

Export Citation Format

Share Document