bluuebunny/crossref_metadata_2025 huggingface dataset:
Dust continuum, CO, and  [C i] 1 − 0 lines: self-consistent H2 mass estimates and the possibility of globally CO-‘dark’ galaxies at z = 0.35
Authors: Dunne L , Maddox S J , Vlahakis C , Gomez H L
Published: November 2020

We present Atacama Large Millimetre Array observations of a small but statistically complete sample of 12 250-μm-selected galaxies at z = 0.35 designed to measure their dust submillimeter continuum emission as well as their  $\rm {^{12}CO(1-0)}$ and atomic carbon  [C i](3P1−3P0) spectral lines. This is the first sample of galaxies with global measures of all three H2-mass tracers and that shows star formation rates (4–26 $\rm M_{\odot}$ yr−1) and infrared luminosities ($1\!-\!6\times 10^{11}\,\rm L_{\odot}$) typical of star-forming galaxies in their era. We find a surprising diversity of morphology and kinematic structure; one third of the sample have evidence for interaction with nearby smaller galaxies, several sources have disjoint dust and gas morphology. Moreover, two galaxies have very high  $L^{\prime }_{\rm C\,{\small I}}$ / $L^{\prime }_{\rm {CO}}$ ratios for their global molecular gas reservoirs; if confirmed, such extreme intensity ratios in a sample of dust-selected, massive star-forming galaxies present a challenge to our understanding of interstellar medium. Finally, we use the emission of the three molecular gas tracers, to determine the carbon abundance,  $\rm {X_{C\,{\small I}}}$ , and CO–$\rm {H_2}$ conversion  αCO in our sample, using a weak prior that the gas-to-dust ratio is similar to that of the Milky Way for these massive and metal-rich galaxies. Using a likelihood method that simultaneously uses all three gas tracer measurements, we find mean values and errors on the mean of $\langle\alpha _{\rm {CO}}\rangle = 3.0\pm 0.5\, \rm {M}_{\odot }\, (\rm{K}\, \rm{kms}^{-1}\, \rm{pc}^2)^{-1}$ and $\langle \rm{X}_{\rm{CI}} \rangle =1.6\pm 0.1\times 10^{-5}$ (or $\alpha _{\rm{CI}} = 18.8\,\rm {M}_{\odot }\, (\rm{K}\, \rm{kms}^{-1}\, \rm{pc}^2)^{-1}$) and $\delta _{\rm {GDR}} = 128\pm 16$ (or $\alpha _{850} = 5.9\times 10^{12}\, \rm {W}\, \rm{Hz}^{-1}\,\rm {M}_{\odot }\,^{-1}$), where our starting assumption is that these metal-rich galaxies have an average gas-to-dust ratio similar to that of the Milky Way centred on $\rm{\delta} _{\rm {GDR}} =135$.
The weak imprint of environment on the stellar populations of galaxies
Authors: Trussler James , Maiolino Roberto , Maraston Claudia , Peng Yingjie , Thomas Daniel , Goddard Daniel , Lian Jianhui
Published: November 2020

We investigate the environmental dependence of the stellar populations of galaxies in Sloan Digital Sky Survey Data Release 7 (SDSS DR7). Echoing earlier works, we find that satellites are both more metal-rich (<0.1 dex) and older (<2 Gyr) than centrals of the same stellar mass. However, after separating star-forming, green valley, and passive galaxies, we find that the true environmental dependence of both stellar metallicity (<0.03 dex) and age (<0.5 Gyr) is in fact much weaker. We show that the strong environmental effects found when galaxies are not differentiated result from a combination of selection effects brought about by the environmental dependence of the quenched fraction of galaxies, and thus we strongly advocate for the separation of star-forming, green valley, and passive galaxies when the environmental dependence of galaxy properties are investigated. We also study further environmental trends separately for both central and satellite galaxies. We find that star-forming galaxies show no environmental effects, neither for centrals nor for satellites. In contrast, the stellar metallicities of passive and green valley satellites increase weakly (<0.05 and <0.08 dex, respectively) with increasing halo mass, increasing local overdensity and decreasing projected distance from their central; this effect is interpreted in terms of moderate environmental starvation (‘strangulation’) contributing to the quenching of satellite galaxies. Finally, we find a unique feature in the stellar mass–stellar metallicity relation for passive centrals, where galaxies in more massive haloes have larger stellar mass (∼0.1 dex) at constant stellar metallicity; this effect is interpreted in terms of dry merging of passive central galaxies and/or progenitor bias.
In Vivo Microbial Coevolution Favors Host Protection and Plastic Downregulation of Immunity
Authors: Ford Suzanne A , King Kayla C
Published: November 2020

Microbiota can protect their hosts from infection. The short timescales in which microbes can evolve presents the possibility that “protective microbes” can take-over from the immune system of longer-lived hosts in the coevolutionary race against pathogens. Here, we found that coevolution between a protective bacterium (Enterococcus faecalis) and a virulent pathogen (Staphylococcus aureus) within an animal population (Caenorhabditis elegans) resulted in more disease suppression than when the protective bacterium adapted to uninfected hosts. At the same time, more protective E. faecalis populations became costlier to harbor and altered the expression of 134 host genes. Many of these genes appear to be related to the mechanism of protection, reactive oxygen species production. Crucially, more protective E. faecalis populations downregulated a key immune gene, , known to be effective against S. aureus infection. These results suggest that a microbial line of defense is favored by microbial coevolution and may cause hosts to plastically divest of their own immunity.
Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA
Authors:   ERA-EDTA Council, Ortiz Alberto , Cozzolino Mario , Fliser Danilo , Fouque Denis , Goumenos Dimitrios , Massy Ziad A , Rosenkranz Alexander R , Rychlık Ivan , Soler Maria Jose , Stevens Kate , Torra Roser , Tuglular Serhan , Wanner Christoph , Gansevoort Ron T ,   ERACODA Working Group, Duivenvoorden Raphaël , Franssen Casper F M , Hemmelder Marc H , Hilbrands Luuk B , Jager Kitty J , Noordzij Marlies , Vart Priya , Gansevoort Ron T
Published: November 2020

Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.
Pharmacology The Science of Drugs
Authors: Winter Jerrold
Published: November 2020

Aldous Huxley once said that man was a pharmacologist before he was a farmer. Although written records rarely go back more than 5,000 or 6,000 years, there is reason to believe that humans did indeed experience the effects of a variety of drugs much earlier, perhaps even before the rise of agriculture some 12,000 years ago in the Nile Valley. Likely drugs available to the ancients include opiates, cocaine, tetrahydrocannabinol, cathinone, and numerous hallucinogens. But these were drugs in their crude natural forms: the opium poppy, coca leaves, hemp, khat, and a variety of other plant sources. Identification of pure chemicals and a science of drugs was much slower in coming. Pharmacology had to wait for the rise early in the 19th century of organic chemistry, largely in Germany, and physiology, chiefly in France and England. Pharmacology was born of the marriage of these two disciplines. Signifying its maturation in this country, the first department of pharmacology was established at Johns Hopkins University School of Medicine in 1893. Today, pharmacology is taught as a basic medical science, along with anatomy, pathology, physiology, biochemistry, and microbiology, to every medical student. Each of the drugs I mentioned earlier will be discussed in detail in the chapters that follow, but before we do this we need a basic pharmacological vocabulary and a little knowledge of how drugs act. Pharmacology deals with the interaction of chemicals with a living system: the human body. Although drugs act on every element of the body, we will be most interested in that most complex of organs, the brain. We are aware that a drug has acted upon our brains by the effects that it produces. These effects may be as direct and unequivocal as vomiting after apomorphine or convulsing after strychnine. These effects may be of such subtlety as to inspire poetry or to stimulate thoughts of God. Diffuse, relaxed pleasure or orgasmic high; tranquility or terror: Drugs can produce any of these reactions and more. Some drugs may even inspire us to love our fellow man.
Pharmacological Puritanism and the War on Drugs: All the King’s Horses and All the King’s Men . . .
Authors: Winter Jerrold
Published: November 2020

H. L. Mencken, arguably the leading satirist of the 20th century, said that American puritanism is characterized by the haunting fear that someone, somewhere, may be happy. If the source of that happiness is a drug, we might call it pharmacological puritanism. Followers of that faith abound, but I will mention just few. “There’s no such thing as recreational drug use” were the words of William Weld, head of the criminal division of the Attorney General’s office in 1988. A year later, in the midst of a cocaine epidemic, William Bennett, the first director of the Office of National Drug Control Policy (ONDCP) under President George H. W. Bush, expressed dual goals. The first was to construct 95,000 more federal prison cells for drug abusers and the second to make Washington, D.C., a drug-free city. He believed that calls for legalization of any psychoactive drug to be “morally scandalous.” John Walters, director of the ONDCP during George W. Bush’s tenure as president, believed that religion is the answer to drug abuse. Lest we think that pharmacological puritanism is a dying faith, we need only recall Attorney General Jeff Sessions’ comment in 2016 that “Good people don’t smoke marijuana.” It does make me wonder where, on the good–bad spectrum, lie the tens of millions of Americans who live in states and in the District of Columbia where marijuana is legal for recreational use. Among the general population, pharmacological puritanism appears to be uncommon. A survey of American college students found that the prime motives for drug use were to help with concentration, to increase alertness, and to get high. From the United Kingdom, David Nutt, chairman of the Department of Neuropsychopharmacology at Imperial College London, put it this way: “Drugs are taken for pleasure.” Whatever their numbers today or in the past, it is believers in pharmacological puritanism, with the absolutism which accompanies that faith, who are major contributors to the failure of our most recent war on drugs, now nearly a half-century old.
British Reception of Periodicity
Authors: Woods Gordon
Published: November 2020

The discovery of periodicity in the properties of the elements and its connection to their atomic weights is one of the most important advances in nineteenth-century chemistry. This chapter will consider the tables of John Newlands (1837–1898) and William Odling (1829–1921), which preceded that of Dmitrii Ivanovich Mendeleev (1834–1907). Mendeleev’s table was published in 1869, prior to his being aware of the UK precedents of his tabulation. The major portion of this chapter will extend the ideas advanced by Stephen Brush in The Reception of Mendeleev’s Periodic Law in America and Britain but will restrict itself to the dissemination of the periodicity concept within the United Kingdom. This will be monitored by recording its appearances in textbooks and examination papers, and in a wider context, by extracting data from Google Books. The periodic table has a rich history since its inception. It has evolved into many shapes, and indeed dimensions, yet retaining its essential periodic underpinning. In the United Kingdom it is seen as a “table,” whereas the French prefer “classification” and the Germans and Russians “system.” Mendeleev himself referred to his periodic law in his Faraday Lecture and never used the term “table,” thus it is ironic that his fame is linked to words that he appears never to have uttered. The arrangement of the elements in rows and columns is seen as a table, but why label it periodic? A related, more familiar word to non-chemists is periodical, normally referring to a magazine that appears at regular time intervals. Google Books is a powerful modern tool for investigating the usage of selected words or phrases over selected time intervals. The writer chose to use its advanced search for books in the English language. This meant that sources other than British, notably North American, are also included but the observed patterns are probably true for British books. The data compare the number of times the terms periodic table, periodic law, periodic classification, and periodic acid occurred in five-year intervals between 1870 and 1919.
C–H Functionalization
Authors: Taber Douglass F.
Published: November 2020

Masayuki Inoue of the University of Tokyo oxidized (Tetrahedron Lett. 2011, 52, 4654) the alkyl benzene 1 to the nitrate 2, which could be carried on to the amide 5, the nitrile 6, the alcohol 7, or the azide 8. X. Peter Zhang of the University of South Florida developed (Chem. Sci. 2012, 2, 2361) a Co catalyst for the cyclization of 7 to 8. Justin Du Bois of Stanford University reported (J. Am. Chem. Soc. 2011, 133, 17207) the oxidative cyclization of the sulfamate corresponding to 7 using a Ru catalyst. Seongmin Lee of the University of Texas showed (Org. Lett. 2011, 13, 4766) that the oxidative cyclization of 9 gave the amine 10 with high diastereoselectivity. Fabrizio Fabris of the Università di Venezia used (Tetrahedron Lett. 2011, 52, 4478) a Ru catalyst to oxidize 11 to the ketone 12. Ying-Yeung Yeung of the National University of Singapore found (Org. Lett. 2011, 13, 4308) that hypervalent iodine was sufficient to oxidize 13 to the ketone 14. Huanfeng Jiang of the South China University of Technology methoxycarbonylated (Chem. Commun. 2011, 47, 12224) 15 under Pd catalysis to give 16. Professor Inoue found (Org. Lett. 2011, 13, 5928) that the oxidative cyanation of 17 proceeded with high diastereoselectivity to give 18. Mamoru Tobisu and Naoto Chatani of Osaka University activated (J. Am. Chem. Soc. 2011, 133, 12984) 19 with a Pd catalyst to enable coupling with 20 to give 21. Rh-mediated intramolecular insertion is well known to proceed efficiently into secondary and tertiary C–H bonds. A. Srikrishna of the Indian Institute of Science, Bangalore found (Synlett 2011, 2343) that insertion into the methyl C–H of 22 also worked smoothly to deliver 23. The macrocyclic oligopeptide valinomycin 24 has nine isopropyl groups. It is remarkable, as observed (Org. Lett. 2011, 13, 5096) by Cosimo Annese of the Università di Bari and Paul G. Williard of Brown University, that direct oxidation of 24 with methyl(trifluoromethyl) dioxirane in acetone specifically hydroxylated at 8 (45.5%, our numbering), 7 (28.5%), and 6 (26%).
Carbon–Carbon Bond Formation: The Petrov Synthesis of Combretastatin A-4
Authors: Taber Douglass F.
Published: November 2020

Janine Cossy of ESPCI Paris (Org. Lett. 2011, 13, 4084) and Yasushi Obora of Kansai University (Chem. Lett. 2011, 40, 1055) independently developed conditions for the “borrowed hydrogen” condensation of acetonitrile with an alcohol 1 to give the nitrile 2. Akio Baba of Osaka University showed (Angew. Chem. Int. Ed. 2011, 50, 8623) that a ketene silyl acetal 4 could be condensed with a carboxylic acid 3 to give the β-keto ester 5. Timothy W. Funk of Gettysburg College found (Tetrahedron Lett. 2010, 51, 6726) that the cyclopropanol 6, readily prepared by Kulinkovich condensation of an alkene with an ester, opened with high regioselectivity to give the branched ketone 7. In an elegant application of C–H functionalization, Yong Hae Kim of KAIST and Kieseung Lee of Woosuk University added (Tetrahedron Lett. 2011, 52, 4662) the acetal 9 in a conjugate sense to 8 to give 10. Hitoshi Kuniyasu and Nobuaki Kambe of Osaka University devised (Tetrahedron Lett. 2010, 51, 6818) conditions for the Pd-catalyzed carbonylation of a silyl alkyne 11 to the ester 12 with high geometric control. Dennis G. Hall of the University of Alberta also observed (Chem. Sci. 2011, 2, 1305) good geometric control in the rearrangement of the vinyl carbinol 13 to the alcohol 14. Takashi Tomioka of the University of Mississippi condensed (J. Org. Chem. 2011, 76, 8053) the anion 16, prepared in situ from lithio acetonitrile and 1-iodobutane, with the aldehyde 15 to give a nitrile, which was carried onto the aldehyde 17, again with good control of geometry. Bruce H. Lipshutz of the University of California, Santa Barbara established (Org. Lett. 2011, 13, 3818) conditions for the Negishi coupling of an alkenyl halide 18 to give 20 with retention of alkene geometry. Daesung Lee of the University of Illinois, Chicago found (J. Am. Chem. Soc. 2011, 133, 12964) that a Pt catalyst rearranged a silyl cyclopropene 21 to the allene 22. Jan Deska of the Universität zu Köln prepared (Angew. Chem. Int. Ed. 2011, 50, 9731) the enantiomerically enriched allene 25 by lipase-mediated esterification of the prochiral 23.
Carbon–Carbon Bond Construction: The Baran Synthesis of (+)-Chromazonarol
Authors: Taber Douglass F.
Published: November 2020

Daniel J. Weix of the University of Rochester effected (Org. Lett. 2012, 14, 1476) the in situ reductive coupling of an alkyl halide 2 with an acid chloride 1 to deliver the ketone 3. André B. Charette of the Université de Montréal (not illustrated) developed (Nature Chem. 2012, 4, 228) an alternative route to ketones by the coupling of an organometallic with an in situ-activated secondary amide. Mahbub Alam and Christopher Wise of the Merck, Sharpe and Dohme UK chemical process group optimized (Org. Process Res. Dev. 2012, 16, 453) the opening of an epoxide 4 with a Grignard reagent 5. Ling Song of the Fujian Institute of Research on the Structure of Matter optimized (J. Org. Chem. 2012, 77, 4645) conditions for the 1,2-addition of a Grignard reagent (not illustrated) to a readily enolizable ketone. Wei-Wei Liao of Jilin University conceived (Org. Lett. 2012, 14, 2354) of an elegant assembly of highly functionalized quaternary centers, as illustrated by the conversion of 7 to 8. Antonio Rosales of the University of Granada and Ignacio Rodríguez-García of the University of Almería prepared (J. Org. Chem. 2012, 77, 4171) free radicals by reduction of an ozonide 9 in the presence of catalytic titanocene dichloride. In the absence of the acceptor 10, the dimer of the radical was obtained, presenting a simple alternative to the classic Kolbe coupling. Marc L. Snapper of Boston College found (Eur. J. Org. Chem. 2012, 2308) that the difficult ketone 12 could be methylenated following a modified Peterson protocol. Yoshito Kishi of Harvard University optimized (Org. Lett. 2012, 14, 86) the coupling of 15 with 16 to give 17. Masaharu Nakamura of Kyoto University devised (J. Org. Chem. 2012, 77, 1168) an iron catalyst for the coupling of 18 with 19. The specific preparation of trisubsituted alkenes is an ongoing challenge. Quanri Wang of Fudan University and Andreas Goeke of Givaudan Shanghai fragmented (Angew. Chem. Int. Ed. 2012, 51, 5647) the ketone 21 by exposure to 22 to give the macrolide 23 with high stereocontrol.
Reactions Involving Carbon–Carbon Bond Cleavage
Authors: Lambert Tristan H.
Published: November 2020

Although they have historically played a relatively lesser role in organic synthesis, the appearance of a number of interesting methods that utilize C–C bond cleavage has prompted coverage in this chapter. Christopher W. Bielawski at the University of Texas at Austin found (Chem. Sci. 2012, 3, 2986) that the diamidocarbene 1 inserted into the C(O)–C(O) bond of dione 2 to produce 3 at room temperature. The use of oxalate monoester 5 for the decarboxylative cross-coupling with pyridine 4 to produce 6 was reported (Tetrahedron Lett. 2012, 53, 5796) by Yi-Si Feng at Hefei University of Technology. The team of Junichiro Yamaguchi and Kenichiro Itami at Nagoya University developed (J. Am. Chem. Soc. 2012, 134, 13573) a decarbonylative C–H coupling method that allowed for the merger of oxazoles 7 and 8 to form 9, an intermediate on the way to muscoride A. The decarboxylative alkenylation of alcohols, such as in the conversion of 10 and n-propanol to alcohol 11, was reported (Chem. Sci. 2012, 3, 2853) by Zhong-Quan Liu at Lanzhou University. Guangbin Dong at the University of Texas at Austin reported (J. Am. Chem. Soc. 2013, 134, 20005) a rhodium-catalyzed C–C bond activation strategy for the enantioselective conversion of benzocyclobutenone 12 to tricycle 13. Rhodium catalysis was also employed (J. Am. Chem. Soc. 2012, 134, 17502) by Masahiro Murakami at Kyoto University in the ring expansion of benzocyclobutenol 14 to form 15, the regioselectivity of which is opposite to that of the thermal reaction. The tandem semipinacol-type migration/aldol reaction of cyclohexenone 16 to produce 17 was developed (Org. Lett. 2012, 14, 5114) by Yong-Qiang Tu and Fu-Min Zhang at Lanzhou University. A procedure for the synthesis of complex cyclopentenone 19 by the addition of vinyl Grignard to cyclobutanedione 18 was reported (J. Org. Chem. 2012, 77, 6327) by Teresa Varea at the University of Valencia in Spain. Michael A. Kerr at the University of Western Ontario found (J. Org. Chem. 2012, 77, 6634) that treatment of cyclopropane hemimalonate 20 with azide led to the formation of 21, which can be readily reduced to the corresponding γ-aminobutyric ester.
Synthesis and Reactions of Alkenes
Authors: Lambert Tristan H.
Published: November 2020

Christine L. Willis and Varinder K. Aggarwal at the University of Bristol have developed (Angew. Chem. Int. Ed. 2012, 51, 12444) a procedure for the diastereodivergent synthesis of trisubstituted alkenes via the protodeboronation of allylic boronates, such as in the conversion of 1 to either 2 or 3. An alternative approach to the stereoselective synthesis of trisubstituted alkenes involving the reduction of the allylic C–O bond of cyclic allylic ethers (e.g., 4 to 5) was reported (Chem. Commun. 2012, 48, 7844) by Jon T. Njardarson at the University of Arizona. A novel synthesis of allylamines was developed (J. Am. Chem. Soc. 2012, 134, 20613) by Hanmin Huang at the Chinese Academy of Sciences with the Pd(II)-catalyzed vinylation of styrenes with aminals (e.g. 6 + 7 to 8). Eun Jin Cho at Hanyang University showed (J. Org. Chem. 2012, 77, 11383) that alkenes such as 9 could be trifluoromethylated with iodotrifluoromethane under visible light photoredox catalysis. David A. Nicewicz at the University of North Carolina at Chapel Hill developed (J. Am. Chem. Soc. 2012, 134, 18577) a photoredox procedure for the anti-Markovnikov hydroetherification of alkenols such as 11, using the acridinium salt 12 in the presence of phenylmalononitrile (13). A unique example of “catalysis through temporary intramolecularity” was reported (J. Am. Chem. Soc. 2012, 134, 16571) by André M. Beauchemin at the University of Ottawa with the formaldehyde-catalyzed Cope-type hydroamination of allyl amine 15 to produce the diamine 16. A free radical hydrofluorination of unactivated alkenes, including those bearing complex functionality such as 17, was developed (J. Am. Chem. Soc. 2012, 134, 13588) by Dale L. Boger at Scripps, La Jolla. Jennifer M. Schomaker at the University of Wisconsin at Madison reported (J. Am. Chem. Soc. 2012, 134, 16131) the copper-catalyzed conversion of bromostyrene 19 to 20 in what was termed an activating group recycling strategy. A rhodium complex 23 that incorporates a new chiral cyclopentadienyl ligand was developed (Science 2012, 338, 504) by Nicolai Cramer at the Swiss Federal Institute of Technology in Lausanne and was shown to promote the enantioselective merger of hydroxamic acid derivative 21 and styrene 22 to produce 24.
Construction of Single Stereocenters
Authors: Lambert Tristan H.
Published: November 2020

James L. Leighton at Columbia University reported (Nature 2012, 487, 86) that the commercially available allylsilane 2 allylated acetoacetone (1) to furnish the enantioenriched tertiary carbinol 3. Alexander T. Radosevich demonstrated (Angew. Chem. Int. Ed. 2012, 51, 10605) that diazaphospholidine 5 induced the formal reductive insertion of 3,5-dinitrobenzoic acid to α-ketoester 4 to generate adduct 6 enantioselectively. Tehshik P. Yoon at the University of Wisconsin at Madison found (J. Am Chem. Soc. 2012, 134, 12370) that aminoalcohol derivative 9 could be prepared via an asymmetric iron-catalyzed oxyamination of diene 7 using oxaziridine 8. A procedure for the desymmetrization of 1,3-difluoropropanol 10 by nucleophilic displacement of an unactivated aliphatic fluoride to generate 11 was reported (Angew. Chem. Int. Ed. 2012, 51, 12275) by Günter Haufe at the University of Münster and Norio Shibata at the Nagoya Institute of Technology. An innovative procedure for the amination of unactivated olefins involving an ene reaction/[ 2,3]-rearrangement sequence (e.g., 12 to 13) was developed (J. Am. Chem. Soc. 2012, 134, 18495) by Uttam K. Tambar at the University of Texas Southwestern Medical Center. James P. Morken at Boston College demonstrated the stereospecific amination of borane 14 with methoxylamine to produce 15. The conversion of β-ketoester 16 to 18 by amination with 17 under oxidative conditions was reported (J. Am. Chem. Soc. 2012, 134, 18948) by Javier Read de Alaniz at the University of California at Santa Barbara. The electrophilic amination of silyl ketene acetal 19 with a functionalized hydroxylamine reagent to produce 20 was disclosed (Angew. Chem. Int. Ed. 2012, 51, 11827) by Koji Hirano and Masahiro Miura at Osaka University. Erick M. Carreira at ETH Zürich developed (Angew. Chem. Int. Ed. 2012, 51, 8652) the enantioconvergent thioetherification of alcohol 21 to produce 23 with high branched to linear selectivity and ee. The asymmetric conjugate addition of 2-aminothiophenol 25 to 24 catalyzed by mesitylcopper in the presence of ligand 26 was developed (Angew. Chem. Int. Ed. 2012, 51, 8551) by Naoya Kumagai and Masakatsu Shibasaki at the Institute of Microbial Chemistry in Tokyo. The enantioselective conversion of aldehyde 28 to α-fluoride 30 under catalysis by NHC 29 was developed (Angew. Chem. Int. Ed. 2012, 51, 10359) by Zhenyang Lin and Jianwei Sun at the Hong Kong University of Science and Technology.
Stereoselective C–O Ring Construction: The Keck Synthesis of Bryostatin I
Authors: Taber Douglass F.
Published: November 2020

Vladimir Gevorgyan of the University of Illinois, Chicago homologated (Angew. Chem. Int. Ed. 2011, 50, 2808) the ketone 1 to the epoxide 2 using cyanogen bromide. Manabu Abe of Hiroshima University optimized (J. Am. Chem. Soc. 2011, 133, 2592) the diastereoselectivity of the Paternò-Büchi addition of benzophenone 4 to the secondary allylic alcohol 3 to give 5. Debaraj Mukherjee of the Indian Institute of Integrative Medicine constructed (Org. Lett. 2011, 13, 576) the lactone 7 by adding acetate to 6, with remarkable regioselectivity and diastereoselectivity. Tristan H. Lambert of Columbia University employed (Org. Lett. 2011, 13, 740) cyclopropenium activation to cyclize the diol 8 to 9. Brian L. Pagenkopf of the University of Western Ontario designed (Org. Lett. 2011, 13, 572) a Co catalyst for the diastereoselective oxidative cyclization of 11 to 12. Goverdhan Mehta of the Indian Institute of Science, Bangalore, found (Tetrahedron Lett. 2011, 52, 1749) that the Z-diene 13 cyclized efficiently to give the cyclic ether 14. Fabien Gagosz of the Ecole Polytechnique found (J. Am. Chem. Soc. 2011, 133, 7696) that the protonated complex derived from the allene 15 abstracted a hydride from the distal benzyl group, leading to cyclization to 16. Haruhiko Fuwa of Tohoku University found (Org. Lett. 2011, 13, 1820) that the unsaturated thioester 17 cyclized under gentle acid catalysis. Unsaturated esters (not illustrated) can be cyclized under alkaline conditions (Tetrahedron Lett. 2011, 52, 1372). Malcolm D. McLeod of the Australian National University established (J. Org. Chem. 2011, 76, 1992) a combination of Escherichia coli-derived enzyme and an α-d-glucuronyl fluoride donor for converting an alcohol 19 to the corresponding glucuronide metabolite 20. En route to an improved synthesis of the schweinfurthins, potent antineoplastic agents, David F. Wiemer of the University of Iowa devised (J. Org. Chem. 2011, 76, 909) the cyclization/ benzyloxymethyl transfer cascade that transformed 21 into 22. The synthesis and biological activity of the bryostatins is developing into one of the great success stories of natural products chemistry. A key step in the total synthesis of bryostatin 1 25 designed (J. Am. Chem. Soc. 2011, 133, 744) by Gary E. Keck of the University of Utah was the Rainier cyclization of 23 to 24.
C–O Ring Formation
Authors: Lambert Tristan H.
Published: November 2020

A reductive radical cyclization of tetrahydropyran 1 to form bicycle 2 using iron(II) chloride in the presence of NaBH4 was reported (Angew. Chem. Int. Ed. 2012, 51, 6942) by Louis Fensterbank and Cyril Ollivier at the University of Paris and Anny Jutand at the Ecole Normale Supérieure. The enantioselective conversion of tetrahydrofuran 3 to spirocycle 5 via iminium ion-catalyzed hydride transfer/cyclization was developed (Angew. Chem. Int. Ed. 2012, 51, 8811) by Yong-Qiang Tu at Lanzhou University. Daniel Romo at Texas A&M University showed (J. Am. Chem. Soc. 2012, 134, 13348) that enantioenriched tricyclic β-lactone 8 could be readily prepared via dyotropic rearrangement of the diketoacid 6 under catalysis by chiral Lewis base 7. A dyotropic rearrangement was also utilized (Angew. Chem. Int. Ed. 2012, 51, 6984) by Zhen Yang at Peking University, Tuoping Luo at H3 Biomedicine in Cambridge, MA, and Yefeng Tang at Tsinghua University for the conversion of 9 to the bicyclic lactone 10. In terms of the enantioselective synthesis of β-lactones, Karl Scheidt at Northwestern University found that NHC catalyst 12 effects (Angew. Chem. Int. Ed. 2012, 51, 7309) the dynamic kinetic resolution of aldehyde 11 to furnish the lactone 13 with very high ee. Meanwhile, Xiaomeng Feng at Sichuan University has developed (J. Am Chem. Soc. 2012, 134, 17023) a rare example of an enantioselective Baeyer-Villiger oxidation of 4-alkyl cyclohexanones such as 14. The diastereoselective preparation of tetrahydropyran 18 by Lewis acid-promoted cyclization of cyclopropane 17 was accomplished (Org. Lett. 2012, 14, 6258) by Jin Kun Cha at Wayne State University. Stephen J. Connon at the University of Dublin reported (Chem. Commun. 2012, 48, 6502) the formal cycloaddition of aryl succinic anhydrides such as 18 with aldehydes to produce γ-butyrolactones, including 20, in high ee. The stereodivergent cyclization of 21 via desilylation-induced heteroconjugate addition to produce the complex tetrahydropyran 22 was discovered (Org. Lett. 2012, 14, 5550) by Paul A. Clarke at the University of York. Remarkably, while TFA produced a 13:1 diastereomeric ratio in favor of the cis diastereomer 22, the use of TBAF resulted in complete reversal of diastereoselectivity.
C–O Containing Natural Products
Authors: Lambert Tristan H.
Published: November 2020

It is thought that the pseudopterane class of diterpenoid natural products, of which 11-gorgiacerol is a member, arises biosynthetically by a photo-ring contraction of the related furanocembranes. Johann Mulzer at the University of Vienna has applied (Org. Lett. 2012, 14, 2834) this logic to realize the total synthesis of 11-gorgiacerol. Ringclosing metathesis of the butenolide 1 using the Grubbs second generation catalyst produced the tricycle 2. When irradiated, 2 undergoes a 1,3-rearrangement to furnish the natural product in good yield. Whether this rearrangement is concerted, or occurs stepwise via a diradical intermediate, is not known. Although ring-closing metathesis has become a reliable method for macrocycle construction, its use here to set what then becomes an extracyclic olefin is notable. Berkelic acid is produced by an extremophile bacterium penicillium species that lives in the toxic waters of an abandoned copper mine, and this natural product has been found to possess some very intriguing biological activities. Not surprisingly, berkelic acid has attracted significant attention from synthetic chemists, including Francisco J. Fañanás of Universidad de Oviedo in Spain, who has developed (Angew. Chem. Int. Ed. 2012, 51, 4930) a scalable, protecting-group free total synthesis. The key step in this route is the remarkable silver(I)-catalyzed coupling of alkyne 3 and aldehyde 4 to produce, after hydrogenation, the structural core 5 of (–)-berkelic acid on a gram scale. Some tools from the field of organocatalysis have been brought to bear (Angew. Chem. Int. Ed. 2012, 51, 5735) on a new total synthesis of the macrolide (+)-dactylolide by Hyoungsu Kim of Ajou University in Korea and Jiyong Hong of Duke University. The bridging tetrahydropyranyl ring is fashioned by way of an intramolecular 1,6-oxa conjugate addition of dienal 6 to produce 8 under catalysis by the secondary amine 7. Following some synthetic manipulations, the macrocyclic ring 12 is subsequently forged by an NHC-catalyzed oxidative macrolactonization using the carbene catalyst 10 and diphenoquinone 11 as the oxidant. A new approach to the nanomolar antimitotic agent spirastrellolide F methyl ester has been reported (Angew. Chem. Int. Ed. 2012, 51, 8739) by Alois Fürstner of the Max-Planck-Institut, Mülheim. Two elegant metal-catalyzed processes form the key basis of this strategy.
New Methods for C–N Ring Construction
Authors: Lambert Tristan H.
Published: November 2020

The reduction of pyridines offers an attractive approach to piperidine synthesis, and now Toshimichi Ohmura and Michinori Suginome of Kyoto University have developed (J. Am. Chem. Soc. 2012, 134, 3699) a rhodium-catalyzed hydroboration of pyridines, including the reaction of 1 to produce 3. Timothy J. Donohoe at the University of Oxford has found (Org. Lett. 2011, 13, 2074) that pyridinium silanes 4 undergo intramolecular hydride transfer by treatment with TBAF to produce dihydropyridones (e.g., 5) with good diastereoselectivity. Enantioselective amination of allylic alcohols has proven challenging, but Ross A. Widenhoefer at Duke University has reported (Angew. Chem. Int. Ed. 2012, 51, 1405) that a chiral gold catalyst can effect such intramolecular cyclizations with good enantioselectivity, as in the synthesis of 7 from 6. Alternatively, Masato Kitamura at Nagoya University has developed (Org. Lett. 2012, 14, 608) a ruthenium catalyst that operates at as low as 0.05 mol% loading for the conversion of substrates such as 8 to 9. Efforts to replace transition metal catalysts with alkaline earth metal-based alternatives have been gaining increasing attention, and Kai C. Hultzsch at Rutgers University has found (Angew. Chem. Int. Ed. 2012, 51, 394) that the magnesium complex 12 is capable of catalyzing intramolecular hydroamination (e.g., 10 to 11) with high enantioselectivity. Meanwhile, a stereoselective Wacker-type oxidation of tert-butanesulfinamides such as 13 to produce pyrrolidine derivatives 14 has been disclosed (Org. Lett. 2012, 14, 1242) by Shannon S. Stahl at the University of Wisconsin at Madison. Though highly desirable, Heck reactions have rarely proven feasible with alkyl halides due to competitive β-hydride elimination of the alkyl palladium intermediates. Sherry R. Chemler at the State University of New York at Buffalo has demonstrated (J. Am. Chem. Soc. 2012, 134, 2020) a copper-catalyzed enantioselective amination Heck-type cascade (e.g., 15 and 16 to 17) that is thought to proceed via radical intermediates. David L. Van Vranken at the University of California at Irvine has reported (Org. Lett. 2012, 14, 3233) the carbenylative amination of N-tosylhydrazones, which proceeds through η3-allyl Pd intermediates constructed via carbene insertion. This chemistry was applied to the two-step synthesis of caulophyllumine B from vinyl iodide 18 and N-tosylhydrazone 19.
Alkaloid Synthesis: Lycoposerramine Z (Bonjoch), Esermethole (Shishido), Goniomitine (Zhu), Grandisine (Taylor), Reserpine (Jacobsen)
Authors: Taber Douglass F.
Published: November 2020

Josep Bonjoch of the Universitat de Barcelona extended (Org. Lett. 2013, 15, 326) the Jørgensen variation of the Robinson annulation to the amine-substituted β-keto ester 1. The product cis-fused sulfonamide 3, readily brought to high ee by recrystallization, was carried onto (+)-lycoposerramine Z 4. Intramolecular ketene 2+2 cycloaddition is underdeveloped as a synthetic method. Kozo Shishido of the University of Tokushima observed (Org. Lett. 2013, 15, 200) high diastereoselectivity in the cyclization of 5 to 6. This set the stage for the synthesis of (-)-esermethole 7. Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne prepared (Angew. Chem. Int. Ed. 2013, 52, 3272) the cyclopentene 8 by coupling the alkenyl triflate with the salt of an α-alkyl arylacetic acid. Ozonolysis followed by reductive work-up led to a diamino keto aldehyde that cyclized to 9. Benzyl ether cleavage delivered (±)-goniomitine 10. Richard J.K. Taylor of the University of York developed (Angew. Chem. Int. Ed. 2013, 52, 1490) a powerful tandem conjugate addition-imination-methanolysis protocol. He had already prepared (+)-grandisine 11 from N-Boc prolinol. Amination-imination converted 11 to (+)-grandisine 12. This was opened by methanolysis to (+)-grandisine G 13. Four diastereomers are possible from the condensation of 14 and 15. Eric N. Jacobsen of Harvard University developed (Org. Lett. 2013, 15, 706) an organocatalyst that delivered 16 as the dominant diastereomer. This was readily converted to (+)-reserpine, the enantiomer of the natural product.
Heteroaromatic Construction: The Sato Synthesis of (–)-Herbindole
Authors: Taber Douglass F.
Published: November 2020

Troels Skrydstrup of Aarhus University devised (Angew. Chem. Int. Ed. 2012, 51, 4681) a gold-catalyzed protocol for the condensation of 1 with 2 to deliver the furan 3. Thomas A. Moss of AstraZeneca Mereside found (Tetrahedron Lett. 2012, 53, 3056) that readily-available α-chloroaldehydes such as 4 could be combined with 5 to make the furan 6. This same approach can be used to assemble pyrroles. Yong-Qiang Tu and Shao-Hua Wang of Lanzhou University developed (J. Org. Chem. 2012, 77, 4167) a Pd-cascade cyclization that transformed the ester 7 into the pyrrole 8. Cheol-Min Park of the Nanyang Technological University rearranged (Chem. Commun. 2012, 48, 3996; J. Am. Chem. Soc. 2012, 134, 4104) the oxime ether 10 to the pyrrole 11. Glenn C. Micalizio of Scripps/Florida established (J. Am. Chem. Soc. 2012, 134, 1352) a Ti-mediated coupling of 12 with an aromatic aldehyde to deliver the pyridine 13. Yoichiro Kuninobu, now at the University of Tokyo, and Kazuhiko Takai of Okayama University observed (Org. Lett. 2012, 14, 3182) high regioselectivity in the Re-mediated condensation of 14 with 15 to give the pyridine 16. Douglas M. Mans of GlaxoSmithKline, King of Prussia, cyclized (Org. Lett. 2012, 14, 1604) the amide 17 to the oxazole (not illustrated), leading, after intramolecular 4+2 cycloaddition, to the pyridine 18. Karl Hemming of the University of Huddersfield combined (Org. Lett. 2012, 14, 126) the cyclopropenone 20 with the imine 19 to construct the pyridine 21. Shu-Jiang Tu of Xuzhou University and Guigen Li of Texas Tech University condensed (Org. Lett. 2012, 14, 700) enamine 22 with the aldehyde hydrate 23 to give the pyrrole 24, which should be readily aromatized to the corresponding indole. Biaolin Yin of the South China University of Technology cyclized (Org. Lett. 2012, 14, 1098) the furan 25 to the indole 26. Richmond Sarpong of the University of California, Berkeley rearranged (J. Am. Chem. Soc. 2012, 134, 9946) the alkynyl cyclopropane 27 to an intermediate that was aromatized to the indole 28. Stefan France of Georgia Tech uncovered (Angew. Chem. Int. Ed. 2012, 51, 3198) an In catalyst that rearranged the cyclopropene 29 to the indole 30.
Organocatalytic Carbocyclic Construction: The You Synthesis of (–)-Mesembrine
Authors: Taber Douglass F.
Published: November 2020

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.
Diels-Alder Cycloaddition: Defucogilvocarcin V (Bodwell), (+)-Carrisone (Danishefsky), (+)-Fusarisetin A (Theodorakis), 9β-Presilphiperfolan-1α-ol (Stoltz), 7-Isocyano-11(20),14-epiamphilectadiene (Shenvi)
Authors: Taber Douglass F.
Published: November 2020

Graham J. Bodwell of Memorial University constructed (J. Org. Chem. 2012, 77, 8028) the third aromatic ring of defucogilvocarcin V 4 by the inverse electron demand addition of 1 to 2. The methyl ester 3 provided a useful departure point for the preparation of analogues of 4. Samuel J. Danishefsky of Columbia University and Sloan-Kettering found (Chem. Sci. 2012, 3, 3076) that the kinetic product from the addition of 5 to 6 could be equilibrated with a trace of acid to the more stable regioisomer 7. Oxidation to the enone followed by deoxygenation led to (+)-carissone 8. Michael E. Jung of UCLA developed (Org. Lett. 2012, 14, 5169) Me3Al-triflimide catalysts (not illustrated) for promoting difficult additions such as 5 to 6. Professor Danishefsky had demonstrated the efficacy of cyclobutenones as Diels-Alder dienophiles. More recently, he showed (J. Am. Chem. Soc. 2012, 134, 16080) that intramolecular cyclization of the cyclobutenone 9 led to the transfused, angularly substituted product 11. To prepare (+)-fusarisetin A 14, Emmanuel A. Theodorakis of the University of California San Diego needed (Chem. Sci. 2012, 3, 3378) the all-E geometric isomer of 12. He showed that equilibration of a 3:2 mixture with I2 led to a single dominant isomer that could be taken directly into the cycloaddition. Brian M. Stoltz of CalTech prepared (Angew. Chem. Int. Ed. 2012, 51, 9674) the triene 15 in enantiomerically enriched form by enantioselective allylation of a cycloheptenone derivative. Intramolecular cycloaddition of 15 established the tricyclic skeleton of 9β-presilphiperfolan-1α-ol 17. Ryan A. Shenvi of Scripps/La Jolla devised (J. Am. Chem. Soc. 2012, 134, 19604) the triene 19. Addition of 18 to 19 gave an intermediate that was unraveled with catalytic Yb(OTf)3 to give a trienone, which on heating engaged with the distal alkene to cyclize to 20. This set the stage for diastereoselective conjugate addition leading to 7-isocyano-11(20 ),14-epiamphilectadiene 21.
The Theodorakis Synthesis of (–)-Jiadifenolide
Authors: Taber Douglass F.
Published: November 2020

There has recently been a great deal of interest in the synthesis of natural products that promote neurite outgrowth. Emmanuel A. Theodorakis of the University of California, San Diego described (Angew. Chem. Int. Ed. 2011, 50, 3672) the preparation of one of the most potent (10 nM) of these, (–)-jiadifenolide 3. Fittingly, a key transformation en route to this highly oxygenated seco-prezizaane was the oxidative rearrangement of 1 to 2. The starting point for the synthesis was the commercially available diketone 4. Allylation followed by addition to 5 gave the prochiral triketone 6. Enantioselective aldol condensation following the Tu/Zhang protocol then delivered the bicyclic enone 7. Alkylation to give 8 proceeded with high diastereoselectivity, perhaps controlled by the steric bulk of the silyloxy group. Exposure of the protected ketone to the McMurry reagent PhNTf2 gave the enol triflate 9, which smoothly carbonylated to the lactone 10. Epoxidation with alkaline hydrogen peroxide followed by oxidation gave the carboxylic acid, which spontaneously opened the epoxide, leading to the bis lactone 1. With 1 in hand, the stage was set for the key oxidative rearrangement to 2. It was envisioned that epoxidation would generate the cis-fused 11, which on oxidation would undergo acid-catalyzed elimination to give 12. The newly freed OH would then be in position to engage the lactone carbonyl, leading to 2. In the event, oxidation of the epoxide with the Dess-Martin reagent required sonication for 2 h. The rearranged lactone, even though it was susceptible to further oxidation, was secured in 38% overall yield from 1. After hydrogenation and protection, preparation of the enol triflate 13 from the congested cyclopentanone necessitated the use of the more reactive Comins reagent. Hydrogenation of the trisubstituted alkene from coupling with Me3Al then required 90 atmospheres of H2 overpressure. Hydroxylation of the lactone 14 with the Davis oxaziridine followed by further oxidation to the ketone with the Jones reagent and deprotection then completed the synthesis of (–)-jiadifenolide 3.