bluuebunny/crossref_metadata_2025 huggingface dataset:
Earth Heat and Lunar Gravity Geothermal And Tidal Energy
Authors: McElroy Michael B.
Published: November 2020

To this point, we have discussed the current status and future prospects of energy from coal, oil, natural gas, nuclear, wind, solar, and hydro. With the exception of the contribution from nuclear, the ultimate origin of the energy for all of these sources is the sun— energy captured millions of years ago by photosynthesis in the case of the fossil fuels (coal, oil, and natural gas), energy harvested from contemporary inputs in the case of wind and solar. We turn now to a discussion of the potential for generation of electricity from geothermal sources and ocean tides. Decay of radioactive elements in the Earth’s interior provides the dominant source for the former; energy extracted from the gravitational interaction of the Earth and moon is the primary source for the latter. There are two main contributions to the energy reaching the surface from the Earth’s interior. The first involves convection and conduction of heat from the mantle and core. The second reflects the contribution from decay of radioactive elements in the crust, notably uranium, thorium, and potassium. The composite geothermal source, averaged over the Earth, amounts to about 8 × 10– 2 W m– 2, approximately 3,000 times less than the energy absorbed from the sun. As a consequence of the presence of the internal source, temperatures increase at an average rate of about 25°C per kilometer as a function of depth below the Earth’s surface. The rate of increase is greater in regions that are tectonically active, notably in the western United States and in the region surrounding the Pacific Ocean (the so- called Ring of Fire) — less in others. Of particular interest in terms of harvesting the internal energy source to produce electricity are hydrothermal reservoirs, subsurface environments characterized by the presence of significant quantities of high- temperature water formed by exposure to lava or through contact with unusually hot crustal material. The water contained in hydrothermal reservoirs is supplied for the most part by percolation from the surface through overlying porous rock. The conditions required for production of these hydrothermal systems are relatively specialized.
Sacred Bovines
Authors: Allchin Douglas
Published: November 2020

Some assumptions about biology are so deeply rooted in our thinking that they seem beyond question. These concepts - expressed in playful jargon - are our sacred bovines. With a light-hearted spirit, Douglas Allchin sets out to challenge many of these common beliefs about science and life. Allchin draws on fascinating insights from science to illustrate the ironies in many widespread beliefs. Be prepared to challenge the notion that male and female are fixed natural categories. Or that evolution implies cutthroat competition in human society. Or that we struggle against a fundamental immoral nature. Or that genes establish our identity. Or that science progresses through rare leaps of genius. Or that politics and emotions inevitably taint good science. Sacred Bovines revels in revelations about the nature of science. Reflecting on the many errors in commonly accepted, everyday ideas also fosters creative thinking. How do we challenge assumptions? How do we "think outside the box"? The many examples here provide inspiration and guidance, further elaborated in a retrospective epilogue. An additional "Afterword for Teachers" highlights how the essays can foster learning about the nature of science and describes some practical classroom strategies.
Ahead of the Curve
Authors: Allchin Douglas
Published: November 2020

Graphs function plainly to summarize data. They hardly seem momentous. They are not like a famous discovery, whose significance is often marked by an eponymous name: Mendel’s laws, the Watson and Crick model of DNA, Darwinian theory. Who would name a mere graph? They seem mundane fragments of science, hardly worth celebrating. A notable exception, however, is the Keeling Curve (Figure 2.1). This simple graph depicts the steady rise in the concentration of carbon dioxide (CO2) in the Earth’s atmosphere over the last half century. It helps document how humans have transformed the atmosphere and, with it, the Earth’s temperature. The Keeling Curve is a linchpin in the evidence that humans have changed the planet’s climate. The Keeling Curve starts in 1958 and continues uninterrupted for over five decades. The scale of the data is extraordinary, an ideal rarely achieved in science. The hard data from real-time measurements show the steady accumulation of CO2 from burning fossil fuels. The results, presented in a simple yet striking visual format, serve to warn an energy-hungry culture of its environmental hubris. Although just a graph, it is monumental in scope and significance. The Keeling Curve, viewed in retrospect, raises an interesting question about how science works. How do such important long-term data sets emerge? Often we assume that scientific investigations find just what they intend to find. That is an implicit lesson of the tidy scientific method, as widely presented (see essay 5). But should we trust this sacred bovine? Could anyone have predicted this curve or its importance in advance? How did these important data originate? What happened before the graph was fully created? What happened, literally, ahead of the Curve? The Keeling Curve is named after its creator, Charles David Keeling. In the 1950s, as a handsome young man frequently enjoying the great outdoors (Figure 2.2), he hardly fit the stereotypical image of a scientist clad in a white coat, isolated in a lab. Indeed, with a fresh degree in chemistry, he turned down many job opportunities because he wanted to be closer to nature on the West Coast.
Male, Female, and/ or — ?
Authors: Allchin Douglas
Published: November 2020

Intersex individuals are coming out of the closet. Witness, for example, the 2003 Pulitzer Prize in Fiction for Jeffrey Eugenides’s Middlesex. The story follows someone with 5-alpha-reductase deficiency, or late-onset virilization. Imagine yourself raised as a girl, discovering at puberty (through cryptic, piecemeal clues) that you are male instead. Or male also? Or male only now? Or “just” newly virile? The condition confounds the conventionally strict dichotomy between male and female, masculine and feminine. It teases a culture preoccupied with gender. What are male and female, biologically? How does nature define the sexes, and sex itself? The questions seem simple enough. Seeking answers, however, may yield unexpected lessons—about the role of biological definitions; about assumptions concerning universals, rarities, and “normality”; and about the power of mistaken conceptions of nature to shape culture. Conceptualizing sex as male and female seems straightforward. In the standard version (familiar even to those unschooled in biology), females have two X chromosomes, while males have an X and a Y. They have different gametes: one moves, one stays stationary. These differences seem foundational. They seem to explain why male and female organisms have contrasting gonads, contrasting hormone-mediated physiologies, and contrasting secondary sex characteristics. Once-homologous organs follow divergent developmental trajectories. Perhaps even contrasting behaviors express the purported evolutionary imperative of each gamete: the “promiscuous,” uncaring male of cheap sperm, and the cunning, protective female of big-investment eggs. The apparent alignment of the two sexes through all levels of biological organization seems to validate this categorization as scientifically sound. Good biologists know better. First, sex may be determined in many ways. Birds use a “reversed,” WZ system, where females have the distinctive chromosome. Many insects have a haplodiploid system, where sex is determined by having a single or double set of all the chromosomes. Crocodiles and turtles develop their sex in response to temperature cues, not genes alone. The spoonworm Bonellia responds instead to whether females are absent or already present in the area.
Respect for Life
Authors: Allchin Douglas
Published: November 2020

“Respect for life” is a rallying cry among many animal rights activists. They target the use of animals in research, the wearing of fur coats, the hunting of wolves and whales, and more. They deplore, too, dissection in biology classes (essay 26). Ironically, in many of these high-profile cases, “respect for life” seems to mean not a universal respect for all life, but rather a narrow “respect for life-like-us.” The values seem associated primarily with mammals. A little knowledge of biology might broaden the scope of such sentiments, with perhaps some stunning consequences. We observe life in many forms. From cuddly kittens to slithering snakes and spooky spiders. From huge, awesome blue whales to microscopic, one-celled organisms. From lilies to “sea lilies,” which are more closely related to starfish and sea urchins than to plants. And we are related to all of them. That is the startling lesson of evolution. We share ancestry with all these creatures. But how often is the grandeur in this view of life eclipsed by narrower feelings? For example, one hears much fuss over dissection in biology classes—of cats and frogs and fetal pigs. One hears very little objection to dissecting crickets, scallops, or worms. Why? While activists raid research laboratories where mammals are used, no wellspring of objection has emerged about a popular school lab exercise on the survival rates of sowbugs in different environmental conditions, although it assures wholesale death for some populations. Where is the hue and cry over bouquets of fresh-cut roses? Yet all are living. Animal rights advocates frequently express outrage at killing animals for fur. But rarely do we see outrage over leather jackets, which are basically just fur hides without the hair. Leather shoes, leather belts, leather hats, leather gloves, leather bags, leather wallets, leather briefcases, leather watch straps, leather key fobs, leather whatever: there are animal hides everywhere. Shouldn’t we be equally if not more outraged about the disparity of wealth between the persons who buy fur coats and the persons who, despite animal rights, want them but cannot afford them?
Reality Without Reification: Philosophy of Chemistry’s Contribution to Philosophy of Mind
Authors: Banchetti-Robino Marina Paola , Noël Llored Jean-Pierre
Published: November 2020

CHEMIST AND PHILOSOPHER of chemistry Joseph E. Earley has recently argued that, in order to resolve some of its most seemingly intractable problems, philosophy of mind should take into consideration the work currently being done in philosophy of chemistry. This is because there exist obvious parallels between questions that inform philosophy of chemistry and the so-called hard problem of consciousness in philosophy of mind. As David Chalmers describes it, the hard problem of consciousness is that of explaining the relationship between physical phenomena, such as brain states, and experience (i.e., phenomenal consciousness, mental states, or events with phenomenal qualities or “qualia”). The “hard problem” is related to the problem of the reduction of mental states to brain states and of the emergence of mental phenomena from physical phenomena. Similar issues are encountered in philosophy of chemistry, such as the reduction of higher-level chemical phenomena to lower-level physical states and the emergence of the higher-level phenomena from the lower-level states. An important and related concern that arises in both philosophical subfields, particularly when dealing with emergence, is the question of “downward causation,” that is, the question of whether the higher levels, such as chemical properties or mental states, exert downward causal influence over the lower levels, such as fundamental physical states or brain states. Given the parallels between these two fields, Earley argues that there are three different ways in which philosophy of chemistry can be of assistance to philosophy of mind. The first is by “developing an extended mereology applicable to chemical combinations.” The suggestion is that, if successful, such an extended mereology may also be applicable to the whole-parts relationships between complex systems such as the brain (and its associated mental phenomena) and individual brain states. A second way is by “testing whether ‘singularities’ prevent reduction of chemistry to microphysics.” If chemical “singularities” indeed prevent such reduction, one might extrapolate that mental “singularities” might also prevent the reduction of mental states to electrochemical interactions in the brain.
The Chemistry of Soils
Authors: Sposito Garrison
Published: November 2020

The second edition of The Chemistry of Soils, published in 2008, has been used as a main text in soil-science courses across the world, and the book is widely cited as a reference for researchers in geoscience, agriculture, and ecology. The book introduces soil into its context within geoscience and chemistry, addresses the effects of global climate change on soil, and provides insight into the chemical behavior of pollutants in soils. Since 2008, the field of soil science has developed in three key ways that Sposito addresses in this third edition. For one, research related to the Critical Zone (the material extending downward from vegetation canopy to groundwater) has undergone widespread reorganization as it becomes better understood as a key resource to human life. Secondly, scientists have greatly increased their understanding of how organic matter in soil functions in chemical reactions. Finally, the study of microorganisms as they relate to soil science has significantly expanded. The new edition is still be comprised of twelve chapters, introducing students to the principal components of soil, discussing a wide range of chemical reactions, and surveying important human applications. The chapters also contain completely revised annotated reading lists and problem sets.
Soil Colloids
Authors: Sposito Garrison
Published: November 2020

Soil colloidsare solid soil particles with diameters ranging from 0.01 to 10 μm, which means they range from clay to fine silt in size. The chemical composition of these particles may be that of a single mineral or humus, but usually they are heterogeneous mixtures of inorganic and organic materials. Regardless of their composition, the characteristic properties of soil colloids are that they are small in size and relatively insoluble in water. Soil colloids exhibit shapes and sizes that reflect both chemical composition and the effects of weathering processes. Kaolinite particles, for example, are roughly hexagonal plates comprising perhaps 50 unit layers, with each unit layer being a wafer having the thickness of about 0.7 nm, which are stacked irregularly and held together through hydrogen bonding. In soils, weathering produces rounding of the corners of the kaolinite hexagons and coats them with iron oxyhydroxide and humus polymers (Fig. 10.1). Fracturing of the plates also is apparent, along with a stair-step topography caused by the stacking of unit layers with different lateral dimensions. These heterogeneous features lead to soil kaolinite aggregates that are not well organized, with many stair-stepped clusters of stacked plates, interspersed with plates in edge-face contact, evidently because of differing surface charge on the edges and faces. Similar observations have been made for 2:1 clay minerals. Illite, for example, has platy particles comprising unit layers stacked irregularly, although the bonding mechanism for the stacking is cross-linking through an inner sphere surface complex of K+, not hydrogen bonding. These particles also exhibit a stair-step surface topography as well as frayed edges produced by weathering. Coatings of Al-hydroxy and humus polymers may be present. Additional complexity comes from nonuniform isomorphic substitutions, with regions of layer charge approaching 2.0 grading to regions with layer charge near 0.5. Smectite and vermiculite have lesser tendency to form colloids comprising extensive stacks because their layer charge is less than that of illite and, therefore, is less conducive to inner sphere surface complexation with K+.
Steven Weinberg: The Conjectural Sublime
Authors: Gross Alan G.
Published: November 2020

Steven Weinberg had been working for some time on the problem of the strong force that holds together the components of an atom’s nucleus. He was getting nowhere. “Suddenly,” while driving home in his red Camaro, insight arrived. He did not have the wrong answer to the problem of the strong force but the right answer to a different, equally interesting problem: …And I realized the massless particle in this theory that had given me so much trouble had nothing to do with the heavy particles that feel the strong interaction; it was the photon, the particle of which light was composed, that is responsible for electric and magnetic forces and that indeed has zero mass. I realized that what I had cooked up was an approach not just to understanding the weak interaction but to unifying the theories of the weak and electromagnetic forces into what has since come to be called the electroweak theory… “A Model of Leptons” is a paper of which he is justly proud. It has garnered 4,503 citations; a copy has been offered for sale at $950. This is the physicist at his mathematical best, a language he speaks as if it were his native tongue. Another incident confirms Weinberg’s extraordinary talent. Physicist Rich Muller has a bright idea. After several tries, however, the mathematics continues to defeat him. Despondent, he walks down the hall to an office where Steven Weinberg is chatting with Freeman Dyson. The two agree to help: …Weinberg went to the blackboard, wrote down the first equation. “And then he did some manipulations on it,” said Muller, “and stood back.” Dyson said, “I think if you make a substitution of variables now— .” Weinberg said, “Oh, yes, of course,” and wrote several more lines. “I was taking notes,” Muller said, “but I wasn’t sure what he was doing.” Weinberg paused in his writing, and Dyson said, “Now evaluate the delta function,” and Weinberg said, “Oh, okay.” Weinberg wrote down a few more lines, and Dyson said, “Good. You’ve proven it.”
Organic Functional Group Interconversion
Authors: Taber Douglass F.
Published: November 2020

Feng Li of the Nanjing University of Science and Technology devised (Chem. Commun. 2014, 50, 8303) a combination of reagents that directly converted the alcohol 1 to the protected amine 2. Yong-Sheng Bao and Bao Zhaorigetu of Inner Mongolia Normal University selectively (J. Org. Chem. 2014, 79, 6715) demethylated the tertiary amine 4, leading to the amide 5. Christopher W. Bielawski of the University of Texas devel­oped (Chem. Eur. J. 2014, 20, 13487) the reagent 7 for the conversion of an alcohol 6 to the bromide 8. The diiodo analogue of 7 also worked well. Ross Denton of the University of Nottingham showed (Chem. Commun. 2014, 50, 7340) that the reagent 10 efficiently mediated the Mitsunobu coupling of 9 with ben­zoic acid to give 11. The other product of the reaction, Ph₃ P=O, could be converted back to 10. Silas P. Cook of Indiana University established (J. Am. Chem. Soc. 2014, 136, 9521) conditions for the selective conversion of the bromide 12 to the boronate 13. Gwilherm Evano of the Université Libre de Bruxelles converted (Chem. Commun. 2014, 50, 11907) the alkenyl iodide 14 to the nitrile 15 using acetone cyanohydrin as the nitrile anion source. Seth B. Herzon of Yale University developed (Angew. Chem. Int. Ed. 2014, 53, 7892) an improved Ru catalyst for the hydration of a terminal alkyne 16 to the aldehyde 17. Clément Mazet of the University of Geneva used (Chem. Commun. 2014, 50, 10592) an Ir catalyst for the isomerization of a 2,2-disubstituted epoxide 18 to the aldehyde 19. Laurent El Kaïm of the Ecole Polytechnique, Laurence Grimaud of UMPC, and Roland Jacquot and Philippe Marion of Solvay showed (Synthesis 2014, 46, 1802) that in the presence of glutaronitrile 21, AlCl₃ was an effective catalyst for the conversion of an acid 20 to the nitrile 22. Yi-Si Feng and Hua-Jian Xu of the Hefei University of Technology found (Org. Lett. 2014, 16, 4586) that a carboxylic acid 23 could be coupled with diphenyl disul­fide under decarboxylating conditions, leading to the sulfide 24. Kenneth M. Doll of USDA Peoria observed (ACS Catal. 2014, 4, 3517) that decarboxylation of the unsat­urated carboxylic acid 25 with a Ru catalyst delivered the alkene 26 as a mixture of regioisomers.
Organic Functional Group Protection
Authors: Taber Douglass F.
Published: November 2020

Sentaro Okamoto of Kanagawa University developed (Tetrahedron Lett. 2014, 55, 7039) an organocatalyst that mediated the selective acylation of 1 to give the pri­mary acetate 2. Philip A. Albiniak of Ball State University devised (Tetrahedron Lett. 2014, 55, 7133) a reagent 4 for the simple preparation of a t-butyl ether 5 from an alcohol 3. Attempted deprotection of 6 tended to divert to the dioxolane. Toshio Nishikawa of Nagoya University developed (Synlett 2014, 25, 2498) an oxidative protocol that gave clean conversion to the desired 7. Alan S. Goodman of Rutgers University found (Angew. Chem. Int. Ed. 2014, 53, 10160) an Ir catalyst that generated the phenol 9 from the aryl alkyl ether 8. In the course of a synthesis of Sch 725674, Kavirayani R. Prasad of the Indian Institute of Science, Bangalore deprotected (Org. Lett. 2014, 16, 4001) the dithi­ane 10 to yield the sensitive aldol product 11. Karl Anker Jørgensen of Aarhus University observed (Chem. Commun. 2014, 50, 15689) that the nitro isoxazole 12, having served to activate sequential Michael addition, was readily cleaved to the acid 13. Jiang Cheng of Changzhou University used (Chem. Commun. 2014, 50, 8412) CuCN to convert 14 to 15. Pradeep Kumar of CSIR-National Chemistry Laboratory effected (Tetrahedron Lett. 2014, 55, 7172) oxidative deallylation of 16, leading to 17. Hiroyuki Morimoto and Takashi Ohshima of Kyushu University found (Chem. Commun. 2014, 50, 12623) that NH₄I promoted the hydrazinolysis of the amide 18, giving 19 without racemization. Franco Ghelfi of the Università degli Studi di Modena e Reggio Emilia prepared (Eur. J. Org. Chem. 2014, 6734) 21 by desulfonylating 20 to 21 with H₂SO₄ in acetic acid. Hans Adolfsson of Stockholm University reduced (Org. Lett. 2014, 16, 680) the amide 22 to the enamine 23. The N-vinyl amine could be hydrolyzed, but it is also a versatile intermediate for other transformations. Automated peptide synthesis can be hindered by difficult sequences. Judit Tulla-Puche and Fernando Albericio of IRB Barcelona showed (Chem. Eur. J. 2014, 20, 15031) that the substituted benzyl group of 24 facilitated such syntheses, and that it could be readily removed to give 25 by exposure to NH₄I and trifluoroacetic acid.
Alkene Reactions: The Xu/Loh Synthesis of Vitamin A1
Authors: Taber Douglass F.
Published: November 2020

Abdolreza Rezaeifard and Maasoumeh Jafarpour of the University of Birjand devised (J. Am. Chem. Soc. 2013, 135, 10036) an easily-scaled protocol for the Mo-catalyzed “on water” epoxidation of an alkene 1 to 2, using molecular O₂. Needing to epoxidize the sensitive alkene 3 to 5, Douglass F. Taber of the University of Delaware developed (Org. Synth. 2013, 90, 350) a convenient preparation of mmol quantities of the versa­tile oxidant dimethyldioxirane 4. Robert H. Grubbs of Caltech showed (Angew. Chem. Int. Ed. 2013, 52, 9751) that the Wacker oxidation of internal alkenes could proceed with high regioselectivity, as exemplified by the conversion of 6 to 7. David A. Nicewicz of the University of North Carolina demonstrated (J. Am. Chem. Soc. 2013, 135, 10334) the remarkable anti-Markovnikov addition of the acid 9 to the alkene 8, to give 10. Pieter C. A. Bruijnincx and Robertus J. M. Klein Gebbink of the University of Utrecht established (Chem. Eur. J. 2013, 19, 15012) a robust one-pot protocol for epoxidation, epoxide hydrolysis and periodate cleavage, for the net oxidative cleav­age of the alkene 11 to the aldehydes 12 and 13. Tomoki Ogoshi of Kanazawa University observed (Org. Lett. 2013, 15, 3742) that permanganate with a phase transfer catalyst could selectively oxidize the linear alkene 14 to 15 in the presence of branched alkenes. Davood Azarifar of Bu-Ali Sina University devised (Synlett 2013, 24, 1377) the reagent 17 as a useful alternative to ozone, as illustrated by the oxidation of 16 to 18. Ning Jiao of Peking University effected (J. Am. Chem. Soc. 2013, 135, 11692) the unsymmetrical cleavage of the alkene 19 to the nitrile aldehyde 20. Tiow-Gan Ong of the Academia Sinica added (Org. Lett. 2013, 15, 5358) 22 to the alkene 21 to give the linear product 23. This could be hydrolyzed to the acid, or reduced and hydrolyzed to the aldehyde. Joost N. H. Reek of the University of Amsterdam isomerized (ACS Catal. 2013, 3, 2939) the terminal alkene of 24 to the internal alkene, then hydroformylated that directly to give the α-methyl branched alde­hyde 25.
Alkylated Stereogenic Centers: The Jia Synthesis of (−)-Goniomitine
Authors: Taber Douglass F.
Published: November 2020

John W. Wong of Pfizer and Kurt Faber of the University of Graz used (Adv. Synth. Catal. 2014, 356, 1878) a wild-type enzyme to reduce the nitrile 1 to 2 in high ee. Takafumi Yamagami of Mitsubishi Tanabe Pharma described (Org. Process Res. Dev. 2014, 18, 437) the practical diastereoselective coupling of the racemic acid 3 with the inexpensive pantolactone 4 to give, via the ketene, the ester 5 in high de. Takeshi Ohkuma of Hokkaido University devised (Org. Lett. 2014, 16, 808) a Ru/Li catalyst for the enantioselective addition of in situ generated HCN to an N-acyl pyrrole 6 to give 7 in high ee. Yujiro Hayashi of Tohoku University found (Chem. Lett. 2014, 43, 556) that an aldehyde 8 could be condensed with formalin, leading in high ee to the masked aldehyde 9. Stephen P. Fletcher of the University of Oxford prepared (Org. Lett. 2014, 16, 3288) the lactone 12 in high ee by adding an alkyl zirconocene, prepared from the alkene 11, to the unsaturated lactone 10. In a remarkable display of catalyst control, Masakatsu Shibasaki of the Institute of Microbial Chemistry and Shigeki Matsunaga of the University of Tokyo opened (J. Am. Chem. Soc. 2014, 136, 9190) the racemic aziridine 13 with malonate 14 using a bimetallic catalyst. One enantiomer of the aziridine was converted specifically to the branched product 15 in high ee. The other enantiomer of the aziridine was converted to the regioisomeric opening product. Kimberly S. Peterson of the University of North Carolina at Greensboro used (J. Org. Chem. 2014, 79, 2303) an enantiomerically-pure organophosphate to selec­tively deprotect the bis ester 16, leading to 17. Chunling Fu of Zhejiang University and Shengming Ma of the Shanghai Institute of Organic Chemistry showed (Chem. Commun. 2014, 50, 4445) that an organocatalyst could mediate the brominative oxi­dation of 18 to 19. The ee of the product was easily improved via selective crystalliza­tion of the derived dinitrophenylhydrazone. James P. Morken of Boston College developed (Org. Lett. 2014, 16, 2096) condi­tions for the allylation of an allylic acetate such as 20 with 21, to deliver the coupled product 22 with high maintenance of ee.
C–O Ring Construction: The Smith Synthesis of (+)-18-epi-Latrunculol A
Authors: Taber Douglass F.
Published: November 2020

James A. Bull of Imperial College London showed (Angew. Chem. Int. Ed. 2014, 53, 14230) that the malonate 1 could readily be cyclized to the oxetane 2. Davide Ravelli of the University of Pavia functionalized (Adv. Synth. Catal. 2014, 356, 2781) the α position of the oxetane 3 with 4, leading to 5. Frank Glorius of the Westfälische Wilhelms-Universität Münster hydrogenated (Angew. Chem. Int. Ed. 2014, 53, 8751) the furan 6 to give 7 in high ee. Jia-Rong Chen and Wen-Jing Xiao of Central China Normal University converted (Eur. J. Org. Chem. 2014, 4714) the initial Henry adduct from 8 into the cyclic ether 9. Anil K. Saikia of the Indian Institute of Technology, Guwahati cyclized (J. Org. Chem. 2014, 79, 8592) the ene–yne 10 to the ketone 11. Richard C. D. Brown of the University of Southampton developed (Org. Lett. 2014, 16, 5104) a chiral auxiliary that effectively directed the oxidative cyclization of the diene 12 to 13. The chiral auxiliary could be recovered and reused. K. A. Woerpel of New York University showed (Org. Lett. 2014, 16, 3684) that, depending on the solvent, 15 could be added to 14 to give either 16 or 17. Samuel J. Danishefsky of Columbia University and the Memorial Sloan-Kettering Cancer Center also observed (Chem. Eur. J. 2014, 20, 8731) a marked solvent effect on the diastereoselectivity of the reduction of 18 to 19. Xiaoming Feng of Sichuan University added (Chem. Eur. J. 2014, 20, 14493) the ketone 20 to Danishefsky’s diene 21 to give 22 in high ee. Jhillu Singh Yadav of the Indian Institute of Chemical Technology effected (Tetrahedron Lett. 2014, 55, 3996) intramolecular opening of the oxetane of 23 to give, with clean inversion, the cyclic ether 24. Chun-Yu Ho of the South University of Science and Technology, taking advan­tage (J. Org. Chem. 2014, 79, 11873) of the superior chelating ability of the allyl ether, selectively cyclized 25 to 26. Xuegong She of Lanzhou University used (Angew. Chem. Int. Ed. 2014, 53, 10789) a gold catalyst to convert 27 into the eight-membered ring ether 28.
C–O Ring Construction: The Oger/Lee/Galano Synthesis of 7(RS)-ST-Δ8-11-dihomo-Isofuran
Authors: Taber Douglass F.
Published: November 2020

Shaorong Yang and Huanfeng Jiang of the South China University of Technology assembled (Angew. Chem. Int. Ed. 2014, 53, 7219) the β-lactone 3 by the Pd-catalyzed addition of 2 to the alkyne 1. Jack R. Norton of Columbia University observed (J. Am. Chem. Soc. 2015, 137, 1036) that the vanadium-mediated reduc­tive cyclization of 4 proceeded by a free radical mechanism, leading to the cis 3,4-disubstituted tetrahydrofuran 5. The cyclization of 6 to 7 developed (J. Org. Chem. 2015, 80, 965) by Glenn M. Sammis of the University of British Columbia also involved H atom transfer. Amy R. Howell of the University of Connecticut devised (J. Org. Chem. 2015, 80, 5196) the ring expansion of the β-lactone 8 to the tet­rahydrofuran 9. Dmitri V. Filippov and Jeroen D. C. Codée of Leiden University showed (J. Org. Chem. 2015, 80, 4553) that the net reductive alkylation of the lac­tone 10 led to 11 with high diastereocontrol. A. Stephen K. Hashmi of the Ruprecht-Karls-Universität Heidelberg optimized (Chem. Eur. J. 2015, 21, 427) the gold-mediated rearrangement of the ester 12 to the lactone 13. This reaction apparently proceeded by the coupling of the metalated lac­tone with a propargylic carbocationic species. Benjamin List of the Max-Planck-Institut für Kohlenforschung developed (Angew. Chem. Int. Ed. 2015, 54, 7703) an organocatalyst that mediated the addition of 15 to 14, leading to 16 in high ee. Scott E. Denmark of the University of Illinois published (Nature Chem. 2015, 6, 1056) a detailed study of the enantioselective cyclization of 17 to 18. Shunichi Hashimoto of Hokkaido University established (Tetrahedron Lett. 2015, 56, 1397) that his catalyst was effective for the cycli­zation of 19 to 20. Debendra K. Mohapatra of the Indian Institute of Chemical Technology showed (J. Org. Chem. 2015, 80, 1365) that allyl trimethylsilane could trap the intermediate from the cyclization of 21, leading to 22 with high diastereocontrol. Young-Ger Suh of Seoul National University used (Chem. Commun. 2015, 51, 9026) a Pd catalyst to cyclize 23 to (−)-deguelin 24. John Montgomery of the University of Michigan showed (Org. Lett. 2015, 17, 1493) that the Ni-catalyzed reduc­tive cyclization of 25 to 26 proceeded with high diastereoselectivity.
Substituted Benzenes: The Garg Synthesis of Tubingensin A
Authors: Taber Douglass F.
Published: November 2020

John F. Hartwig of the University of California, Berkeley devised (Science 2014, 343, 853) conditions for the regioselective silylation of an arene 1 to give 2. The silyl group can directly be converted, inter alia, to halo, amino, alkyl, or hydroxyl. Jin-Quan Yu of Scripps La Jolla effected (Angew. Chem. Int. Ed. 2014, 53, 2683) regioselective alkenylation of the arene 3 with 4 to give 5. Wei-Liang Duan of the Shanghai Institute of Organic Chemistry described (Org. Lett. 2014, 16, 500) a related alkenyl­ation protocol. Deping Wang of Henyang Normal University developed (Eur. J. Org. Chem. 2014, 315) inexpensive conditions for the conversion of an aryl bromide 6 to the corre­sponding phenol 7. Mamoru Tobisu and Naoto Chatani of Osaka University used (J. Am. Chem. Soc. 2014, 136, 5587) a Ni catalyst to convert the lactam 8 to the aryl boro­nate 9. Patrick J. Walsh of the University of Pennsylvania found (Adv. Synth. Catal. 2014, 356, 165) conditions for the clean monoarylation of the amide 11 with 10 to give 12. In an application of the Catellani approach, Zhi- Yuan Chen of Jiangxi Normal University coupled (Chem. Eur. J. 2014, 20, 4237) the aryl iodide 13 with 14 to give the amino ester 15. Frederic Fabis of the Université de Caen-Basse-Normandie used (Chem. Eur. J. 2014, 20, 7507) Pd to catalyze the ortho halogenation (and alkoxylation) of the N-sulfonylamide 16 to give 17. Wen Wan of Shanghai University and Jian Hao of Shanghai University and the Shanghai Institute of Organic Chemistry effected (Chem. Commun. 2014, 50, 5733) ortho azidination of the aniline 18 with 19, leading to 20. Jianbo Wang of Peking University found (Angew. Chem. Int. Ed. 2014, 53, 1364) that the N-aryloxy amide 21 could be combined with the α-diazo ester 22 to give the ortho-alkenyl phenol 23. Silas P. Cook of Indiana University uncovered (Org. Lett. 2014, 16, 2026) remarkably simple conditions for the enantiospecific cyclization of 24 (65% ee) to 25 (63% ee). The development of arynes as reactive intermediates continues unabated. Xiaoming Zeng of Xi’an Jiaotong University developed (Org. Lett. 2014, 16, 314) the reagent 27 for the bis-functionalization of the aryne derived from 26.
Metal-Mediated C–C Ring Construction: The Sun/Lin Synthesis of Huperzine A
Authors: Taber Douglass F.
Published: November 2020

Zachary T. Ball of Rice University found (Chem. Sci. 2014, 5, 1401) that the on-bead performance of a designed Rh- peptide complex was markedly superior to the corre­sponding solution catalysis for the addition of 2 to 1 to give 3. Jin-Quan Yu of Scripps/La Jolla achieved (J. Am. Chem. Soc. 2014, 136, 8138) remarkable ee in the conversion of 4 to 5. Adriaan J. Minnaard of the University of Groningen developed (Adv. Synth. Catal. 2014, 356, 2061) practical conditions for enantioselective conjugate addi­tion– enolate trapping, converting 6 to 8. Alexandre Alexakis of the University of Geneva had reported (Org. Lett. 2014, 16, 118) related results. Jérôme Waser of the Ecole Polytechnique Fédérale de Lausanne assembled (J. Am. Chem. Soc. 2014, 136, 6239) the amino cyclopentane 11 by adding 9 to 10. Jean-Luc Vasse of the Université de Reims used (Org. Lett. 2014, 16, 1506) the Schwartz reagent to cyclize 12 to 13. Eric V. Johnston and Armando Córdova of the University of Stockholm combined (Angew. Chem. Int. Ed. 2014, 53, 3447) Pd and organocatalysis in a cascade of first oxi­dation of 14, then conjugate addition by 15, then cyclization to 16. Professor Alexakis found (Org. Lett. 2014, 16, 2006) that the enolate from con­jugate addition to 17 could be trapped with a nitroalkene 18 to give, after in situ Nef reaction, the 1,4-diketone 19. Fangzhi Peng and Zhihui Shao of Yunnan University added (Chem. Eur. J. 2014, 20, 6112) malonate to the nitro alkene 20 to give an inter­mediate that could be carried to the cyclohexanone 21. Masahisa Nakada of Waseda University devised (Tetrahedron Lett. 2014, 55, 1100) a cascade conjugate reduc­tion—intramolecular conjugate addition to cyclize 22 to 23. Hye-Young Jang of Ajou University dimerized (Synthesis 2014, 46, 1329) cinnamaldehyde 24 with nitrometh­ane to give the fully-substituted cyclohexanol 25. In a remarkable cascade transformation, Joëlle Prunet of the University of Glasgow used (Org. Lett. 2014, 16, 3300) the Zhang Ru catalyst to cyclize 26 to the taxol skeleton 27. In an even more remarkable transformation, Professor Nakada showed (Tetrahedron Lett. 2014, 55, 1597) that cascade conjugate addition– conjugate addition converted 28 to 29, having the rare chair- boat- chair skeleton of the biologically potent fusidic acid and brasilicardin A.
The Li Synthesis of Daphenylline
Authors: Taber Douglass F.
Published: November 2020

The genus Daphniphyllum consists of 25–30 species of evergreen trees and shrubs of south Asia. The leaves and roots are widely used in Chinese herbal medicine. About 250 alkaloids, many with complex polycyclic structures, have been isolated from these species. Of these, daphenylline 3 is unique in incorporating a benzene ring. Ang Li of the Shanghai Institute of Organic Chemistry envisioned (Nature Chem. 2013, 5, 679) a route to 3 based on the diastereoselective intramolecular Michael cyclization of 1 to 2. Following the work of Piers (J. Org. Chem. 1996, 61, 8439), the preparation of 1 began with the Birch reduction of 4, followed by hydrolysis. Epoxidation followed by elimination and acetylation led to the racemic acetate 5. Hydrolysis with pig liver esterase left one enantiomer of the acetate, that was transesterified with methoxide to give 6 in high ee. Mitsunobu coupling of 6 with the o-nitrobenzenesulfonamide 7 gave 8. After some experimentation, selective α¢-silylation was effected with TBDPSOTf, setting the stage for gold-catalyzed Conia cyclization to 9. Deprotection of the amine fol­lowed by acylation with 10 gave 1, that cyclized smoothly to 2 as a 10:1 ratio of diastereomers. The arene of 3 was constructed by converting 2 into the corresponding vinyl tri­flate. Pd-mediated coupling with 11 gave 12. Under irradiation with strict exclusion of oxygen, 12 cyclized to the dihydro aromatic, that on warming with DBU in the pres­ence of air was oxidized to 13. To close the last ring of 3, the ketone 13 was further oxidized to the enone 14. Desilylation of 14 followed by exposure to Ph3P/I2 gave the iodide 15, that was cyclized under reductive free radical conditions to 16. The hydrogenation of 16 under Pd catalysis delivered the incorrect diastereomer, perhaps because migration to the endocyclic alkene preceded reduction. This problem was solved by using the Crabtree Ir catalyst. Modified Krapcho decarbomethoxylation then gave 17, that was reduced to daphenylline 3.
A Child’s Grief
Authors: Rosenstein Donald L. , Yopp Justin M.
Published: November 2020

Several months after Catie died, Steve asked his sister-in-law to watch his daughters for a few hours so he could spend time with his six-year-old son. David seemed to be doing well but Steve sensed he needed a little one-on-one time with his Dad. They spent the morning together cooking breakfast, playing outside, and building Legos at the kitchen table. David loved having his father’s undivided attention. After they had been playing for a few minutes, Steve asked him how much he thought about his mother. I still feel bad about what I did—about how I made Mommy die.” “Wait, what?” “Because of when I hurt Mommy. Remember? That day she came home from the hospital and I hurt her real bad.” “That day” had occurred nearly two years earlier. Excited to finally have his mother back home, David jumped into her arms and gave her a big hug. Catie winced and immediately grabbed her right shoulder, which was still tender from surgery and radiation. David immediately let go and backed away. His mother, now grimacing, tried to take deep breaths to ease the pain. After a few minutes, she told him that she was okay but that he needed to be gentler with her. Steve had not thought about the incident since the day it happened. Considering all he and his family had been through, it had barely registered in his memory. Sitting at the kitchen table, he asked his son what he remembered. David talked about how he made his mother sick by hugging her too hard. Since he had made her sick, he was the reason she died. “Buddy, no. No, no, no. That’s not it at all.” Realizing that his son had been thinking this way for almost two years made Steve nauseous. He placed his hands on David’s shoulders and looked him in the eyes, making sure he had his full attention. He explained that the hug had absolutely nothing to do with his mother dying. “You and your sisters were the reasons that Mommy lived as long as she did.
The Ring Thing
Authors: Rosenstein Donald L. , Yopp Justin M.
Published: November 2020

The ancient Egyptians were the first to use a wedding ring as a symbol of love and fidelity. Bands were usually made from grass or hemp and worn on the fourth finger of the left hand, which was believed to include the vein that led directly to the heart. The circular shape of the ring—with no beginning and no end—represented eternal love. Over the centuries, societies throughout the world adapted the tradition to fit their own cultures. It was once customary in the United States for only the bride to wear a ring, but this changed during and after the marriage boom that followed World War II. The number of men wearing wedding bands more than quadrupled, and today, double-ring marriage ceremonies are the norm. None of the men in the group had anticipated that “until death do you part” would occur so early in his marriage. After their wives died, what their wedding rings symbolized, and what should be done with them, was far from clear. One evening as the group settled in, Joe reached toward the center of the table to pick out his sub and bag of chips when one of us (Don) noticed something different about his left hand. “Joe, you took off your ring.” All eyes turned to Joe’s left hand. A strip of pale white skin that had been shielded from the sun for nearly twenty years circled the base of his fourth finger. Before that moment, the men had never discussed the subject of wedding rings. The prospect of dating again had compelled Joe to make the change. “It’s not that I’m interested in anyone in particular. In fact, even thinking about going out with someone right now is kind of overwhelming. But, damn, I don’t want to be lonely for the rest of my life. I hope that someday I’ll feel for someone else the way I felt for Joy.” Joe took off his ring because he wanted to believe that one day that time would come.
Posttraumatic Growth
Authors: Rosenstein Donald L. , Yopp Justin M.
Published: November 2020

An old clinical pearl passed down by mental health professionals holds that patients can be the “last to know” that they are getting better. Clinicians often notice improvements in mood, energy, and outlook before the patient appreciates these changes. We saw a variation of this phenomenon in the fathers. The men frequently pointed out to one another areas of progress and moments of growth even when they were unable to see similar changes in themselves. In the months following Deanna’s death, Neill struggled to hold on to a career in the private healthcare industry that he had spent years building. Traveling several nights a week for work had been manageable when Deanna was alive. However, as the sole parent of four children, Neill knew he wouldn’t be able to maintain this schedule. Neill met with his supervisors and asked if he could reduce the number of days he had to be on the road. Unfortunately, the job required a minimum amount of travel that was simply too much for him to manage and he reluctantly resigned. Neill couldn’t bring himself to conduct an extensive job search in the rapidly changing healthcare field. Instead, he reached out to a friend who needed help managing local apartment complexes. The job wasn’t glamorous and paid less than what Neill had been earning but it offered flexible hours, required no travel, and gave him the time he needed to care for his children. Even as Neill began his new job, his focus remained on his family. When either of his younger children was too sick to go to school, he remained at home for the day. If he stayed up late helping his older children complete a science project or term paper, he went to work the next morning more exhausted than usual. Despite feeling physically and emotionally drained, Neill discovered something unexpected: He was growing closer to his children. He and his teenage son, Jack, were communicating better than ever. Their long and difficult conversation about the circumstances leading up to Deanna’s death had been a turning point in their relationship.
Hard-Earned Wisdom
Authors: Rosenstein Donald L. , Yopp Justin M.
Published: November 2020

In 1994, Kenneth Schwartz, a forty-year-old healthcare attorney from Boston, was diagnosed with advanced lung cancer. At different times during his progressive illness, he was deeply moved by aspects of his care that were less strictly medical or technical: a calming visit from a nurse prior to surgery; a personal connection with an anesthesiology resident from his neighborhood; and, toward the end of his life, the kindness and perspective provided by his oncologist. Shortly before his death, Mr. Schwartz founded a non-profit organization to promote the kind of compassionate care that had meant so much to him. Two decades later, the Schwartz Center for Compassionate Healthcare reaches millions of patients and hundreds of thousands of caregivers to realize its founder’s vision of more humane care for the seriously ill. A cornerstone of the Center’s work is the Schwartz Rounds program, which brings healthcare providers from multiple disciplines together for frank discussions about the emotional and psychosocial challenges of caring for patients. More than five hundred healthcare organizations around the world host these ongoing, non-traditional conferences. A few years ago, the organizer of Schwartz Rounds at UNC invited us to lead an upcoming conference. She was aware of our work with the single fathers support group and wanted us to address the challenges that spouses face when caring for a partner with a terminal illness. At the next group meeting, we mentioned this request to the men and asked them for their advice. Each father had been an eyewitness to the end of his wife’s life and knew well how that heartbreaking time had impacted his entire family. Not surprisingly, they had a lot to say about end-of-life care and how it could be improved. Karl was particularly passionate. “I’ve actually thought about this a lot since Susan died. Obviously, the patient is the focus, but I think it’s also important for doctors to appreciate what the family goes through—especially when there are kids at home and the spouse is a co-parent. That dynamic alone influences so many things.”