bluuebunny/crossref_metadata_2025 huggingface dataset:
The Koshi’s Revenge
Authors: Colopy Cheryl
Published: November 2020

The Koshi spoke during the monsoon of 2008. She opened a new path, just as Dinesh Mishra predicted. The river breached an apparently ill-constructed and certainly ill-maintained embankment. A photo taken as the flood began shows the ridge of sand dissolving as water poured through a widening gap in the embankment and flowed southeast. In both Nepal and Bihar, villages and farms that had not seen a flood for the past half century were devastated. The embankments on the Koshi had already breached seven times at various spots downriver. This time the entire river below the Siwalik range in Nepal, where the land flattens, had essentially jumped out of its straitjacket and returned to one of its old channels—one it had flowed down two centuries ago. In Nepal the Koshi River is known as the Saptakoshi, or “seven Koshis,” because seven Himalayan rivers merge to create it. The Tamur flows down from Kanchenjunga in eastern Nepal near its border with Bhutan and India; the Arun comes down from Tibet. Out of the Khumbu comes the Dudh Koshi, the milky blue river that entranced me on the way up to Gokyo. The Dudh Koshi joins the Sun Koshi, which is also fed by the Tama Koshi, which in turn receives water from the Rolwaling Khola and Tsho Rolpa, the threatening glacial lake I visited during the monsoon of 2006. From farther west, toward Kathmandu, come the Likhu and the Indrawati. The latter receives the as yet undiverted waters of the Melamchi Khola. These seven tributaries of the Saptakoshi drain more than a third of the Nepal Himalaya, the wettest and highest of the great range, which includes the Khumbu and Ngozumpa glaciers. The Koshi drains almost thirty thousand square miles. It is Nepal’s largest river and one of the largest tributaries of the Ganga. Less than ten miles above the plains, three of these great rivers come together in a final merging: the Sun Koshi from the west, the Arun from the north, the Tamur from the east.
Susu
Authors: Colopy Cheryl
Published: November 2020

“You’ll never get a dolphin with a digital camera,” Sushant Dey said, as we floated with the current on the Ganga. “They’re only on the surface for a second. By the time the shutter clicks, it’s already gone.” Early one morning in April 2007 I walked down to the bottom of a wide concrete stairway just outside Bhagalpur in the Indian state of Bihar to board an old fishing boat. Where the stairs met the river, the prow of the twenty-foot-long boat rested on the riverbank. A narrow plank, its ends positioned on the bank and the edge of the prow, allowed me to board. Sushant Dey and his brother Subhasis were taking me out to look for dolphins before the heat built up, when the dolphins might still be looking for food. Dolphins jump out of the water when they’re hunting, which they typically do early in the morning and again in the evening. The boatman tried repeatedly to start the wooden boat’s old diesel engine. Finally it coughed and caught; we chugged upriver a short way. He turned off the engine and we floated. After a few minutes, I heard a swish of water. A slick muscular body slipped back into the river before I could get a good look. A few minutes passed: another swish. I was looking in the wrong place and missed him. In spite of Sushant’s warning that my effort would be in vain, I tried again and again to catch a dolphin, pointing my camera to a likely spot on the opaque graygreen water where the animal might surface after I had missed a breach. Then I missed again. The Ganga flowed smoothly. It was about a half mile wide now, in the dry season. In the monsoon it grows to three miles wide and can be twenty-five feet higher in some places. The boatman took us to places where the dolphins were known to rest in the deep waters. I got half a dozen good glimpses as a dolphin surfaced briefly to breathe: an arc of dark gray, a shiny comma.
Where the Rivers End
Authors: Colopy Cheryl
Published: November 2020

It’s not yet dawn. The Bon Bibi is anchored. Some members of the crew have risen and one has brought hot water to the dining room. I have some tea to warm me as I lean on the deck rail, looking out over the silent river this December morning. Our guide and my fellow travelers are still asleep below in cozy bunks draped with mosquito nets. Looking to the nearby shore where we walked yesterday, I see the forest guards’ cottages, crumpled by cyclone Sidr’s winds and water. All is quiet. And the fishing skiff that anchored near us yesterday evening is silent too. Perhaps the men fished all night and are still sleeping in the morning chill. I walk around to the other side of the deck. Just a few yards away there’s a log floating down the gentle current toward the Bay of Bengal. Or wait. Maybe, it’s a crocodile heading obliquely across the wide mouth of the river? No, it must be just a clump of vegetation moving in the slight swells of water. Then the clump sinks slightly at both ends. I feel a surge of excitement. The shape is closer to me than any of the crocodiles the boat captain tried to approach as they sunned themselves on the shore upriver yesterday. They always slithered back down the sand and into the water before we could get a good look. There’s little light now, and still unsure, not trusting my aging eyes, I peer intently at the dark hump. It seems to sink imperceptibly again, until finally it slips under the water altogether. The shape moved as quietly and slowly as leaves floating on the surface of the water might, but clumps of vegetation don’t usually vanish underwater quite like that. Fifteen minutes later our young, long-haired Bangladeshi guide asks me, smiling slyly, if I had my glasses on when I made this sighting. When I insist I did, he’s convinced this is a good sign. Apparently this is the first sighting of a crocodile near the Bay since cyclone Sidr the previous month.
Wind Power in Canada
Authors: Valentine Scott
Published: November 2020

In August 2007, the ice sheets choking off Canada’s Northwest Passage receded, permitting passage without the aid of an icebreaker for the first time in Canada’s 150-year history. Although this development presents economic opportunities, it also exposes enormous ecological threats that, 50 years ago, former Prime Minister Pierre Trudeau professed Canada should strive to avoid. Lamentably, Canada has played a role in this environmentally invidious development due to the greenhouse gas (GHG) emissions it has produced in prolific quantities over the course of its comparatively short history. This chapter highlights the barriers to developing a cohesive national energy strategy in a federal system where the states—or in Canada’s case, the provinces—enjoy constitutional sovereignty over electricity generation. More than any other case study covered in this book, this study on Canada demonstrates how political institutions can produce conditions that make it difficult to fully exploit wind power potential, despite public support for such an outcome. As of the end of 2012, Canada boasts the ninth highest amount of installed wind power capacity in the world. Based on this statistic alone, it is tempting to conclude that Canada’s wind power development policies merit recognition for being comparatively successful. However, in order to equitably assess performance in stimulating wind power development, one must also take into consideration the contextual factors which influence wind power development potential. When one does so, it becomes apparent that when it comes to wind power, Canada is a Ferrari in a world dominated by Fords. Three factors, in particular, bestow Canada with an astonishing high degree of realizable wind power potential. First, although geographically Canada is the world’s second-largest nation, it enjoys one of the lowest population density ratios in the world demand. The strategic benefit of Canada’s sheer size is that wind farms could be geographically dispersed to significantly attenuate the threats posed by wind intermittency. Wind conditions are impacted by disparate atmospheric conditions as one traverses the nearly 6,000 km from Canada’s east coast to west coast.
Feasible Worlds
Authors: Steinberg Paul F.
Published: November 2020

What would the world be like if high-speed trains arrived every ten minutes to whisk you away to the city of your choice? It would be a lot like Japan. What if our computers and coffee makers were not dumped in toxic landfills at the end of their lifecycle, but were instead reused as raw materials for new consumer products? Just ask Western Europeans. What if instead of crafting environmental rules in secret, governments were required to share all of the information shaping their decisions with any citizen who demanded it? The answer can be found in the United States. The differences among the “worlds” experienced by citizens of Japan, Europe, and the United States stem in large part from variation in the rules underpinning them. In Japan, a national system of bullet trains (shinkansen) came about not because of an inevitable march of technological progress. It was the result of national and local rules that transformed a disjointed collection of railways into an integrated national system—a system that has not had a single fatal accident since its inauguration in 1964. In Europe, new rules make corporations responsible for collecting and recycling the electronic goods they sell to consumers. Because they must safely dispose of any toxic substances in their products, these companies have a strong incentive to remove heavy metals and other poisons from the manufacturing process. In the United States, the Freedom of Information Act empowers citizens to demand that government agencies send them all pertinent documents describing the rationale behind their decisions—a degree of transparency that is unheard of in Japan or Europe. Of course, these states of the world did not always exist. They were brought into being through deliberate acts of social change in which old rules were tossed and new ones put in place. Yet many people find the thought of social change too daunting. It seems unrealistic, out of reach. Compared to the dizzying pace of change in technology and popular culture, it appears that progress on big social problems like poverty alleviation, human rights, and environmental sustainability moves at glacial speed.
Justice: The Meramec River at Times Beach and Mohandas Gandhi
Authors: Lane Belden C.
Published: November 2020

The spring-fed Meramec River wanders for 218 miles through six Missouri counties before it flows into the Mississippi eighteen miles south of St. Louis. It cuts across the northeastern corner of the Ozark Plateau, carving out bluffs of white dolomite limestone along its way. The stream passes by Onondaga Cave, Meramec State Park, and Meramec Caverns, becoming a lazy river fed by smaller tributaries and floated by weekend adventurers. Overhanging sycamores and cottonwoods crowd its banks. Springs and caves invite floaters to tie up their canoes and explore. Mussel beds are plentiful, as are crappie, rainbow trout, and channel cat. The name “Meramec,” in fact, comes from an Algonquin word meaning “ugly fish” or “catfish.” I’ve put the kayak into the water at the river’s Allenton access south of I-44 near Eureka, Missouri. Paddling eight miles downstream, I’ve stopped for the night just past the old Route 66 bridge near Times Beach. Today Times Beach is a ghost town, but it’s still remembered as the site of the worst environmental disaster in Missouri history. In the early 1970s, the country’s largest civilian exposure to dioxin (TCDD) occurred here along the banks of the Meramec. Waste oil containing the toxic chemical used in making Agent Orange was spread on the town streets in order to keep down the dust. The Environmental Protection Agency ended up buying out the entire town and incinerating everything. All that’s left of Times Beach today is what locals refer to as the “town mound,” a long raised embankment of incinerated dirt covered with grass. Since 1999, the site has been turned into Route 66 State Park, commemorating the Mother Road of public highways, begun in 1926. Historic Route 66 was the first of America’s cross-country highways, extending from Chicago to Los Angeles. It crossed the Meramec River at this point. Known as “The Main Street of America,” the road symbolized the nation’s fascination with the automobile and the movement west. “Get your kicks on Route Sixty- Six” crooned Nat King Cole in his R & B classic of the 1940s. Today the old concrete bridge over the river goes nowhere.
The Forgotten Standards Movement: The Coleman Report, the Defense Department, and a Nascent Push for Educational Accountability
Authors: Mehta Jal
Published: November 2020

The late 1960s and early 1970s are remembered for many things, but educational accountability is not foremost among them. A time when the nation was ripped asunder by fights over Vietnam, when women burned bras, and when African Americans took to the streets seemed hardly a propitious moment for an educational movement emphasizing technocratic rationality to come to the forefront. Yet although overshadowed in the educational arena by conflicts over desegregation, community control, free schools, and open classrooms, a relatively quiet movement led primarily by state bureaucrats did in fact initiate the beginnings of an educational accountability movement. Between 1963 and 1974, no fewer than 73 laws were passed seeking to create standards or utilize a variety of scientific management techniques to improve schooling. These efforts at rationalization in some ways followed the same trajectory as the efficiency reforms five decades earlier and the standards movement to follow two decades later. First came the invocation of a crisis, this time born of rising demands for greater equity and increasing dissatisfaction with the quality of the schools. Second, into this void stepped the new logic of rationalizing reform, this time drawn from a set of techniques pioneered by the Rand Corporation and popularized by the Department of Defense, which promised a new approach to defining objectives, measuring goals, and aligning available resources. And third, humanists and educators were once again the primary opponents of the reform, objecting to the quantification of schooling and the limited view of educational improvement that underlay the rationalizing reform. In all of these respects, the now almost forgotten accountability efforts of the 1960s and 1970s resembled the other two accountability movements of the 20th century. However, the other two movements mobilized a broad range of elites behind their reforms, whereas in this case real political support remained thin. The narrow base of support kept the programs from spreading or being implemented more widely; this effort never gained the kind of power or traction that the earlier and later ones did.
The Professor: 1937– 1939
Authors: Lorbiecki Marybeth
Published: November 2020

The windswept wastelands of the Dust Bowl made it clear to many Americans how fragile the human place in nature is. Suddenly, schools across the country wanted to teach conservation, erosion prevention, and wildlife management. Letters piled up on Leopold’s desk, asking his advice. Leopold replied with a list of resources, but his overriding message was that nature was the best teacher. At fifty-one, Leopold had seven graduate students and a full flock of undergraduates. With a blend of affection and awe, they called him “the Professor.” Marie McCabe, the wife of graduate student Robert McCabe, was quite surprised when she first met the Professor. “I had expected him to be a combination of Abe Lincoln and Thomas Jefferson. Here he was, extremely gracious, but of ordinary size and appearance, not at all handsome … showing no sign of being an author and absolute authority on everything.” Game Management 118 had become a campus favorite. Robert S. Ellarson, a Leopold wildlifer, recalled his first meeting: “The class had assembled before the Professor arrived. Soon the clicking of steel-cleated heels signalled his approach. When he arrived and stood before the class, I was impressed by the bold, virile, almost macho appearance of the man. And I was absolutely enthralled by the lecture that followed.” On Saturdays, the class traveled to the arboretum (which was slowly growing toward a natural state) or to various research plots. In the field, Leopold pointed out such elements as animal tracks and rubbings, scat, browsed plants, nests and burrows, gullies and runoff tracks, ground cover and foliage, and rock formations. Then he asked questions, pushing the students to put together the signs they had seen, to draw for themselves a recent and not-so-recent history of the plot of land: . . . Look at the trees in the yard and the soil in the field and tell us whether the original settler carved his farm out of prairie or woods. Did he eat prairie chicken or wild turkey for his Thanksgiving? What plants grew here originally which do not grow here now? Why did they disappear? What did the prairie plants have to do with creating the corn-yielding capacity of this soil? Why does this soil erode now but not then?. . .
The Endangered Species and Youth: Keeping All the Cogs and Wheels
Authors: Lorbiecki Marybeth
Published: November 2020

I have something to show you. I just got it by overnight delivery.” My student’s face was a blaze of eagerness. From his backpack, he pulled out a small box. Seconds later, magically cupped in his hands was a tiny, neon lime green frog with black eyes. This was hardly the fare for a usual student–teacher appointment. But Blake Klocke is no ordinary university student, though he appears so—the same blue jeans and backpack uniform, laptop at the ready. The difference is not his red hair and freckles, but his amphibian excitement. On his laptop, he displayed for me dozens of frog-related book-marked websites, which he explained aglow with enthusiasm. He had been raising frogs since he was nine, being part of a rescue train across the world of hobbyists who have been keeping the genetic strains of frogs alive in their homes as they are being extinguished in the wilds. Zoos don’t have the space or the avid visiting publics to care about these small, diverse members of the living community, so without the care of personal frog lovers like Blake in raising captive-bred endangered amphibians, our world would have lost these strands of life’s web. The black-eyed tree frog is a critically endangered Central American species that is decreasing so rapidly that scientists predict it will be reduced by 80% in the wild in ten years by the life-sucking, zombie-like Chytrid fungus that is wiping out full populations. “Once my frogs have young, I can get you some so you can raise your own,” Blake offered, ready to convert me to the simple joys of amphibian care. Blake has experienced this excitement from his youth on, and his outdoors adventures have created a love in him that will carry him far— far beyond the lakes and wetlands near Eagan, Minnesota, where he first started catching tadpoles. This finding the “drama in the bush” is just what Leopold had been advocating in his classes, radio talks to young farmers, and writings about the sport of amateur naturalist studies.
Organic Functional Group Transformation
Authors: Taber Douglass F.
Published: November 2020

Susumu Saito of Nagoya University developed (Angew. Chem. Int. Ed. 2011, 50, 3006) Fe-catalyzed conditions, compatible with alkenes, for converting an alcohol 1 to the amine 2. Corey R. J. Stephenson of Boston University took advantage (Nature Chem. 2011, 3, 140) of photoredox catalysis to convert an alcohol 3 to the iodide 4. Jing-Mei Huang of the South China University of Technology condensed (J. Org. Chem. 2011, 76, 3511) the halide 5 with benzaldehyde and aqueous ammonia to give the imine 6. Young Hoon Jung of Sungkyunkwan University used (Tetrahedron Lett. 2011, 52, 1901) chlorosulfonyl isocyanate to convert a benzylic (or allylic) ether 7 into the urethane 8. David Crich of Centre de Recherche de Gif coupled (Org. Lett. 2011, 13, 2256) the isocyanate 9 with the acid 10 to give the amide 11. Tobias Ritter of Harvard University effected (J. Am. Chem. Soc. 2011, 133, 1760) α-hydroxylation of the acidic ketone 12 by exposure to O2 in the presence of a Pd catalyst. Gowravaram Sabitha of the Indian Institute of Chemical Technology, Hyderabad, activated (Org. Lett. 2011, 13, 382) Pd(OH)2 by exposure to H2 , then used the activated catalyst to isomerize the allylic alcohol 14 to the aldehyde 15 . Richard C. Hartley of the University of Glasgow combined (Tetrahedron Lett. 2011, 52, 3020) commercial Nysted reagent and Cp2 TiCl2 to methyl-enate the ester 16. The enol ether 17 is a versatile intermediate, giving, inter alia, the methyl ketone by hydrolysis, or the α-hydroxy ketone on exposure to peracid. The activation of alkynes continues to be an area of vigorous investigation. Lukas Hintermann of the Technische Universitä t München devised (J. Am. Chem. Soc. 2011, 133, 8138) a Ru catalyst for the hydration of 18 to the aldehyde 19. Issa Yavari of Tarbiat Modares University effected (Tetrahedron Lett. 2011, 52, 668) oxidation of 20 to the N-sulfonyl amidine 22. Craig A. Merlic of UCLA coupled (Org. Lett. 2011, 13, 2778) 24 with the vinyl boronate derived from 23 to give the silyl enol ether 25. Li-Biao Han of AIST Tsukuba prepared (Chem. Commun. 2011, 47, 2333) 28 by adding 27 to 26.
Best Synthetic Methods: Oxidation and Reduction
Authors: Taber Douglass F.
Published: November 2020

Johannes G. de Vries of DSM Pharmaceuticals prepared (Chem. Commun. 2009, 3747) Fe nanoparticles that selectively mediated the hydrogenation of Z alkenes and not trisubstituted alkenes. This should allow the conversion of 1 to 2. In the course of a synthesis (Tetrahedron Lett. 2009, 50, 4368) of centrolobine, Teck-Peng Loh of Nanyang Technological University employed an elegant protocol for the reduction of the secondary bromide 3. István Markó of the Université catholique de Louvain observed (Tetrahedron 2009, 65, 10930) that toluates such as 5 can be reduced smoothly with SmI2 to the corresponding C-H. Dan Yang of the University of Hong Kong devised (Organic Lett. 2009, 11, 3302) a triethylsilane-based procedure for the reductive amination of aldehydes and ketones such as 7. Jon A. Tunge of the University of Kansas developed (J. Am. Chem. Soc. 2009, 131, 16626) a complementary protocol for the conversion of an aldehyde or ketone to the protected amine 12. Mark T. Hamann of the University of Mississippi established (Tetrahedron Lett. 2009, 50, 3901) that a nitroaromatic 13 could be reduced in the presence of an acid chloride 14 to deliver the amide 15 directly. Matthias Beller of the Universität Rostock (Angew. Chem. Int. Ed. 2009, 48, 9507) and Hideo Nagashima of Kyushu University (Angew. Chem. Int. Ed. 2009, 48, 9511; J. Am. Chem. Soc. 2009, 131, 15032) reported parallel investigations of the silane-based reduction of an amide 16 to the amine 17. Xue-Long Hou of the Shanghai Institute of Organic Chemistry demonstrated (Tetrahedron Lett. 2009, 50, 5578) that a terminal alkyne 18 could be oxidized to the α-acetoxy ketone 19. Philippe Renaud of the Universität Bern and Armido Studer of West fälische-Wilhelms-Universität established (Angew. Chem. Int. Ed. 2009, 48, 6037) that both zinc enolates and silyl enol ethers could combine with chlorocatechol borane followed by TEMPO to give the α-oxygenated ketone. Stephen P. Marsden of the University of Leeds devised (Tetrahedron Lett. 2009, 50, 6106) a protocol for oxidizing a primary amine 18 to the benzoxazole 24, which has the oxidation state of the carboxylic acid.
Enantioselective Preparation of Alcohols and Amines
Authors: Taber Douglass F.
Published: November 2020

Renat Kadyrov of Evonik Degussa and Magnus Rueping of RWTH Aachen developed (Angew. Chem. Int. Ed. 2009, 49, 7556) an effective catalyst for the enantioselective hydrogenation of an α-hydroxy ketone 1 to the 1,2-diol 2 . Yong-Gui Zhou of the Dalian Institute of Chemical Physics showed (J. Org. Chem. 2009, 74, 5633) that a sultam such as 3 could be reduced with high ee to the sulfonamide 4. They also used this same approach to prepare both α-aryl and α,α-diaryl amines. David W. C. MacMillan of Princeton University described (Angew. Chem. Int. Ed. 2009, 49, 5121) the optimized enantioselective α-chlorination of an aldehyde 5 and the direct processing of the product to the epoxide 6. Erick M. Carreira of ETH Zürich reported (Synlett 2009, 2076) an alternative route to high ee epoxides by decarbonylation of an epoxy aldehyde 7. James P. Morken of Boston College established (J. Am. Chem. Soc. 2009, 131, 13210) a procedure for the enantioselective bis borylation of a terminal alkene 9, leading after oxidation to the 1,2-diol 10. Ben L. Feringa of the University of Groningen took advantage (J. Am. Chem. Soc. 2009, 131, 9473) of their alternative Wacker conditions to convert a primary allylic carbonate 11 to the protected β-amino aldehyde 12. Chao-Shan Da of Lanzhou University devised (Organic Lett. 2009, 11, 5578) additives that allow the direct enantioselective addition of a Grignard reagent 14 to an aldehyde. The enantioselective addition of substituted ketenes to aldehydes has long been established. Yun-Ming Lin of the University of Toledo developed (Synlett 2009, 1675) a catalyst system for the enantioselective addition of ketene 17 itself. An alkenyl silane 19 can readily be prepared from the corresponding terminal alkene (J. Org. Chem. 2010, 75, 1701). Koichi Mikami of the Tokyo Institute of Technology showed (J. Am. Chem. Soc. 2009, 131, 13922) that such alkenyl silanes add to ethyl glyoxylate 20 with high ee. Amir H. Hoveyda of Boston College devised (J. Am. Chem. Soc. 2009, 131, 18234) a procedure for the enantioselective conversion of a terminal alkyne 22 to the 1,2-bis boryl alkane, which he took on directly to the coupled product 24.
Enantioselective Construction of Alkylated Centers: The Maier Synthesis of Platencin
Authors: Taber Douglass F.
Published: November 2020

Jaesook Yun of Sungkyunkwan University devised (J. Org. Chem. 2009, 74, 4232) a method, based on conjugate addition to a cyano alkyne, for the preparation of nitriles such as 1 with high geometric control. Enantioselective conjugate reduction then delivered the doubly arylated stereogenic center of 2 in high ee. Pher G. Andersson of Uppsala University described (J. Am. Chem. Soc. 2009, 131, 8855) a similar approach to diarylated ternary stereogenic centers. Motomu Kanai and Masakatsu Shibasaki of the University of Tokyo developed (J. Am. Chem. Soc. 2009, 131, 3858) a complementary approach to dialkylated stereogenic centers based on enantioselective conjugate cyanation of α-methylene N-acylpyrroles such as 3. Cathleen M. Crudden of Queen’s University established (J. Am. Chem. Soc. 2009, 131, 5024) that a benzylic organoborane, prepared by enantioselective hydroboration of styrene, coupled with an aryl iodide such as 6 in good yield and with > 90% retention of ee. Kwunmin Chen of National Taiwan Normal University devised ( Adv. Synth. Cat. 2009, 351, 1273) an organocatalyst for the enantioselective Michael addition of an α,α,-dialkyl aldehyde such as 9 to a nitroalkene. Wenhu Duan of the East China University of Science and Technology and Wei Wang of the University of New Mexico together developed (Organic Lett. 2009, 11, 2864) an organocatalyst for the enantioselective addition of nitromethane 12 to an unsaturated ketone such as 11. Xiaodong Shi of West Virginia University found (Angew. Chem. Int. Ed. 2009, 48, 1279) that commercial diphenyl prolinol effectively promoted enantioselective conjugate addition of 15 to 14. Enantioselective methods for the construction of alkylated quaternary centers have also been put forward. Kin-ichi Tadano of Keio University devised (Tetrahedron Lett. 2009, 50, 1139) a glucose-derived chiral auxiliary that effectively directed the absolute sense of the alkylation of 17. Li Deng of Brandeis University reported (Tetrahedron 2009, 65, 3139) further details of his elegant Cinchona -mediated conjugate addition of 19 to 20. Francesca Marini of the Università degli Studi di Perugia extended (Adv. Synth. Cat. 2009, 351, 103) this approach to selenones, effecting, over two steps, enantioselective vinylation.
Enantioselective Construction of Alkylated Stereogenic Centers
Authors: Taber Douglass F.
Published: November 2020

Xiang-Ping Hu and Zhuo Zheng of the Dalian Institute of Chemical Physics developed (Organic Lett. 2009, 11, 3226; J. Org. Chem. 2009, 74, 9191) a family of Rh catalysts for the enantioselective hydrogenation of allylic phosphonates such as 1. Hon Wai Lam of the University of Edinburgh established (J. Am. Chem. Soc. 2009, 131, 10386) that an alkenyl heterocycle 3 could be reduced with high ee. The product 4 could be hydrolyzed to the carboxylic acid. Ken Tanaka of the Tokyo University of Agriculture and Technology showed (J. Am. Chem. Soc. 2009, 131, 12552) that an isopropenyl amide 6 could be hydroacylated with high ee. Gregory C. Fu of MIT observed (J. Am. Chem. Soc. 2009, 131, 14231) that nitromethane 9 could be added to the allenyl amide 8 to give 10, the product of γ-bond formation. Robert K. Boeckman Jr. of the University of Rochester devised (Organic Lett. 2009, 11, 4544) what appears to be a general protocol for the construction of alkylated ternary and quaternary centers: enantioselective hydroxymethylation of an aldehyde 11. In another approach to the construction of alkylated quaternary centers, Varinder K. Aggarwal of the University of Bristol demonstrated (Angew. Chem. Int. Ed. 2009, 48, 6289) that an enantiomerically enriched trifluoroborate salt 14 could be added to an aromatic aldehyde 15 with retention of absolute configuration. The salt 14 was prepared from the corresponding high ee secondary benzyl alcohol. Weinreb amides are versatile precursors to a variety of functional groups. Stephen G. Davies of the University of Oxford devised (Organic Lett. 2009, 11, 3254) a chiral Weinreb amide equivalent 17 that could be alkylated with high de. The minor diastereomer from the alkylation was readily separable by silica gel chromatography. Keiji Maruoka of Kyoto University established (Angew. Chem. Int. Ed. 2009, 48, 5014) that a chiral phase transfer catalyst was effective for the enantioselective alkylation of the alkynyl ester 19. Emmanuel Riguet of the Université de Reims Champagne-Ardenne developed (Tetrahedron Lett. 2009, 50, 4283) an improved catalyst for the enantioselective addition of malonate 22 to cyclohexenone 21.
Stereocontrolled Construction of C-O Rings: The Seeberger/Hilvert Synthesis of KDN
Authors: Taber Douglass F.
Published: November 2020

Simple thought it appears, there has not been a good protocol for opening an epoxide 1 with a stabilized enolate. Ferdinando Pizzo of the Università di Perugia developed (Tetrahedron Lett. 2010, 51, 1566) a solution to this problem. Masahiro Terada of Tohoku University found (Angew. Chem. Int. Ed. 2010, 49, 1858) that under organocatalysis, the prochiral 4 condensed with aromatic aldehydes with high relative and absolute stereocontrol. Jon T. Njardarson, now at the University of Arizona, showed (Angew. Chem. Int. Ed. 2010, 49, 1648) that the geometry of the epoxide 7 dictated the relative configuration of the product dihydrofuran 8. John P. Wolfe of the University of Michigan devised (Organic Lett. 2010, 12, 1268) conditions for the diastereocontrolled cyclization of 9 to 10. Robert Britton of Simon Fraser University observed (Organic Lett. 2010, 12, 1716) that the microwave-induced closure of 12 proceeded with clean inversion. Christian B. W. Stark of the Universität Leipzig established ( Angew. Chem. Int. Ed. 2010, 49, 1587) that the Ru-mediated oxidative cyclization of 14 to 15 was also highly diastereocontrolled. Two all-trans diastereomers could emerge from the cascade aldol condensation of 16 with an aldehyde. Takashi Yamazaki of the Tokyo University of Agriculture and Technology devised (Organic Lett. 2010, 12, 268) conditions for the selective preparation of either diastereomer. Xuegong She of Lanzhou University uncovered (J. Am. Chem. Soc. 2010, 132, 1788) conditions for the Pt-mediated cyclization of the simple substrate 18 to the tetrahydropyran 19. Michael J. Zacuto of Merck Process established (Organic Lett. 2010, 12, 684) the Ru-catalyzed cyclization of 20 to 21. When an OH was not available, NH insertion was also efficient. Fabien Gagosz of the Ecole Polytechnique Palaiseau devised (J. Am. Chem. Soc. 2010, 132, 3543) the mechanistically distinct Au-mediated cyclization of 22 to 23. Glenn C. Micalizio of Scripps/Florida used (J. Am. Chem. Soc. 2010, 132, 7602) the protocol he had developed to couple 24 and 25 to give a intermediate trisubstituted alkene. Oxidative cleavage of the alkene delivered the ketone, which under acidic conditions cyclized to the spiroketal 26.
Organocatalyzed C-C Ring Construction: The Thomson Synthesis of Streptorubin B
Authors: Taber Douglass F.
Published: November 2020

Jinxing Ye of the East China University of Science and Technology used (Tetrahedron Lett. 2011, 52, 2715) the Hayashi catalyst to direct the addition of 2 to 1, to give the cyclopropane 3. Jia-Rong Chen and Wen-Jing Xiao of Central China Normal University employed (J. Org. Chem. 2011, 76, 281) a urea catalyst for the addition of 5 to 4. Yasumasa Hamada of Chiba University devised (Tetrahedron Lett. 2011, 52, 987) a different urea catalyst for the addition of 7 to 8, to control both the absolute and relative configuration of 9. Jiyong Hong of Duke University showed (Tetrahedron Lett. 2011, 52, 2468) that the imidazolium-mediated cyclization of 10 proceeded with high diastereoselectivity to give 11. Yixin Lu of the National University of Singapore optimized (J. Am. Chem. Soc. 2011, 133, 1726) a dipeptide-derived phosphine to catalyze the addition of 12 to 13. Karl A. Scheidt of Northwestern University combined (Angew. Chem. Int. Ed. 2011, 50, 1678) a triazolium catalyst with super-stoichiometric Ti(O- i Pr)4 to effect the addition of 15 to 4, to give 16. En route to malyngamide C, Xiao-Ping Cao of Lanzhou University condensed (J. Org. Chem. 2011, 76, 3946) the prochiral commercial monoketal 17 with nitrosobenzene, using proline as a catalyst, to prepare 18. Hong Wang of Miami University showed (Angew. Chem. Int. Ed. 2011, 50, 3484) that a lanthanide-complexed α-amino amide was effective for catalyzing the addition of the prochiral 19 to 4, to give 20. Alexandre Alexakis of the Université de Genève and John C. Stephens of the National University of Ireland, Maynooth, established (Angew. Chem. Int. Ed. 2011, 50, 5095) that the Hayashi catalyst was effective for mediating the addition of 22 to 21, to give the diene 23. Ying-Chun Chen of Sichuan University and Karl Anker Jørgensen of Aarhus University used (J. Am. Chem. Soc. 2011, 133, 5053) the same catalyst for the addition of 24 to 25. The Hayashi catalyst appeared again in the report (Chem. Comm. 2011, 47, 3828) by Magnus Reuping of RWTH Aachen University of the addition of 27 to 28.
The Nakada Synthesis of (-)-FR182877
Authors: Taber Douglass F.
Published: November 2020

The Streptomyces metabolite (-)-FR182877 3 binds to and stabilizes microtubules, showing the same potency of anticancer activity as Taxol (paclitaxel). Masahisa Nakada of Waseda University assembled (Angew. Chem. Int. Ed. 2009, 48, 2580) the hexacyclic ring system of 3 by the tandem intramolecular Diels-Alder–intramolecular hetero Diels-Alder cyclization of 1, generating seven new stereogenic centers in a single step. The construction of the pentaene substrate 1 started with the known aldehyde 4, prepared by homologation of commercial ethyl 3-methyl-4-oxocrotonate. Addition of the propionyl oxazolidine anion 5 proceeded with high diastereocontrol, to give 6. The acyl oxazolidinone was not an efficient acylating agent, so it was converted to the Weinreb amide. Protection and deprotection then delivered the allylic acetate 7. The key step in the pentaene assembly was the carefully optimized Negishi-Wipf methylation of 8, followed by Pd-mediated coupling of the alkenyl organometallic so generated with the allylic acetate, to give 9. Condensation of the derived keto phosphonate 11 with the known aldehyde 12 then delivered the enone 13. The Nakada group has worked extensively on the intramolecular Diels-Alder reaction of substrates such as 1. They have shown that protected anti diols such as 1 cyclize with substantial diastereocontrol and in the desired sense. In contrast, cyclizations of protected syn diols proceed with poor diastereocontrol. The enone 13 was therefore reduced to the anti diol and protected, leading to 14 . Oxidation of 14 at room temperature led to a complex mixture, but slow oxidation at elevated temperature delivered 2 . Although the yield of 2 was not much better than if the reactions were carried out sequentially, first the intramolecular Diels-Alder cyclization, then the intramolecular hetero Diels-Alder cyclization, with the cascade protocol pure 2 was more readily separated from the reaction matrix. With 2 in hand, there was still the challenge of assembling the seven-membered ring. Cyclization was effected with an intramolecular Heck protocol. The two diastereomers of the allylic alcohol 15 cyclized with comparable efficiency. Ir-catalyzed alkene migration then converted the allylic alcohols to a mixture of ketones, which was equilibrated to give the more stable diasteromer.
The Nicolaou Synthesis of (+)-Hirsutellone B
Authors: Taber Douglass F.
Published: November 2020

(+)-Hirsutellone B 3, isolated from the insect pathogenic fungus Hirsutella nivea BCC 2594, shows good activity (MIC = 0.78 μg/mL) against Mycobacterium tuberculosis. Approaching the synthesis of 3, K. C. Nicolaou of Scripps/La Jolla envisioned and reduced to practice (Angew. Chem. Int. Ed. 2009, 49, 6870) a spectacular tandem intramolecular epoxide opening: internal Diels-Alder cyclization (1 2) that established all three of the carbocyclic rings of 3 with the proper relative and absolute configuration. The construction of 1 began with commercial ( R) -(+)-citronellal 4. Wittig homologation established the ( Z )-iodide 5. Selective ozonolysis followed by condensation with the phosphorane 7 set the stage for Jørgensen-Córdova (Tetrahedron Lett. 2006, 47, 99) epoxidation with H2O2 and a catalytic amount of the Hayashi catalyst 9. Condensation of 10 with the phosphorane 11 followed by Cu-catalyzed coupling of 12 with the organostannane 13 completed the assembly of 1. This approach underscores the strategic advantages of the Jørgensen-Córdova epoxidation over the Sharpless protocol. It is not necessary to reduce the aldehyde to the allyic alcohol, then reoxidize. Furthermore, the Jørgensen-Córdova epoxidation, using catalytic 9, is operationally easier than the Sharpless procedure, which often uses stoichiometric amounts of tartrate ester. The cyclization of 1 proceeded by way of 13, with the newly formed stereogenic center having the diene equatorial on the cyclohexane. Endo cycloaddition catalyzed by the Lewis acid in the solution then gave 2. The facility with which the cyclization of 13 set both the substituents and the stereogenic centers of 2 raises the possibility that the biosynthesis might also follow such an internal [4 + 2] cycloaddition. To complete the synthesis of 3, it was necessary to construct the strained paracyclophane. The authors took advantage of the facile cyclization of the thiolate liberated from 18, then installed the ring-contracted alkene with a Ramburg-Bäcklund rearrangement of 19. They completed the synthesis of (+)-hirsutellone B 3 by exposing the ketone 21 to NH3 in CH3OH/H2O.
The Garg Synthesis of (±)-Aspidophylline A
Authors: Taber Douglass F.
Published: November 2020

The pentacyclic Apocynaceae alkaloid aspidophylline A 3 reverses drug resistance in resistant KB cells. In developing a strategy for the assembly of 3, Neil K. Garg of UCLA envisioned (J. Am. Chem. Soc. 2011, 133, 8877) the intramolecular Pd-catalyzed cyclization of 1 to 2. The starting material for the cyclohexenone derivative 1 was the known tricyclic anhydride 7. This was readily available in gram quantities by oxidation of the commercial pyridone 4. The double decarboxylation to 8 was delicate but could be effected by iterative small-batch microwave heating. Protection of 8 followed by fragmentation and alkylation than delivered 1. The intramolecular Heck cyclization of 1 indeed proceeded smoothly, giving the bicyclic diene 2. Deprotection of the ketone revealed a doubly activated enone, which could be selectively reduced under modifi ed dissolving metal conditions to give the keto ester 12. Alkylation of the lithium enolate with allyl iodide then gave 13, predominantly as the diastereomer illustrated. Reduction followed by selective Johnson-Lemieux oxidative cleavage of the terminal alkene then completed the construction of the diol 14. The vision for the final assembly of the alkaloid was to effect interrupted Fischer indolization of an alkylated cyclohexanone such as 15. To this end, several bicyclic ketones were explored, but none was successful. Finally, attention was turned to the more rigid tricyclic lactone 15. Happily, exposure of 15 to phenylhydrazine in the presence of trifluoroacetic acid led to an intermediate that was not isolated, but directly combined with methanolic K2CO3 to open the lactone, allowing closure of the tetrahydrofuran ring, to give 16. Simple arene sulfonamides can be advantageous in synthesis, as they do not appear as rotameric mixtures in NMR, and are often crystalline. Nevertheless, they have not commonly been used because of the perceived difficulty of deprotection. Sonication of 16 with Mg powder in methanol containing solid NH4Cl led to smooth desulfonylation. Formylation then completed the synthesis of aspidophylline A 3.
Parkinsonism Treatment for Those Already on Medications
Authors: Ahlskog J. Eric
Published: November 2020

The previous chapter provided instructions for starting and adjusting carbidopa/levodopa, but specifically pertained to those individuals on no other drugs for parkinsonism or those on only a low carbidopa/levodopa dosage. In this chapter, we focus on people who are taking other drugs for parkinsonism either with or without carbidopa/levodopa. As mentioned earlier, people with DLB or PDD are prone to hallucinations and delusions, which can be exacerbated by drugs for parkinsonism. Carbidopa/levodopa is the least likely to worsen or provoke these problems; however, this is true only if it is used alone (i.e., without other parkinsonism drugs). Carbidopa/levodopa is also the most efficacious drug for parkinsonism. Thus it is reasonable to take the approach that carbidopa/levodopa should be the sole treatment for parkinsonism in DLB or PDD. Whereas using carbidopa/levodopa by itself is often tolerated, adding it to other parkinsonian medications may provoke problems, especially hallucinations or delusions. Hence, before starting carbidopa/levodopa, it is wise to scrutinize the medication list and eliminate other parkinsonism drugs, one by one. There are two general rules of thumb regarding these medications: 1 It is not necessary to change drugs if things are going well and are expected to continue. 2 Change only one medication at a time (but if there are severe drug side effects, the physician may take more aggressive action). Some drugs are worse offenders than others and will be prioritized with that in mind. Note that a variety of schemes may be employed to taper off a drug. The drug-elimination schedules provided below are somewhat arbitrary and other similar schedules may work as well. The most important factor is the total time to reduce the dosage down to zero. The longer a person has been on a medication and the higher the dosage, the more prolonged the taper. The clinician needs to work closely with the patient as this is being done. Parkinsonism may transiently worsen when these drugs are eliminated; however, this typically can subsequently be reversed with carbidopa/levodopa adjustments.
Permeability Estimation
Authors: Doveton John H.
Published: November 2020

Because it is a measure of flow, permeability is a vector quantity, as contrasted with conventional petrophysical log data, which are responses to static properties of the rock. In the absence of a direct measurement of permeability, predictions must be inferred from the rock framework characteristics that control the ability of fluids to move through the rock. In this chapter, we consider methods that predict absolute permeability, that is, permeability with respect to a single fluid. This is the most widely used meaning of the term and would be immediately applicable to aquifers. In engineering applications to reservoirs, a relative permeability is assigned to each fluid phase, so that relative fluid rates and volumes can be characterized explicitly. Although the fundamental physics of permeability in tubes has been understood for many years, reliable estimations are difficult to make in all but the simplest rock types. As we shall see, one approach attempts to adapt modifications to a tube model to accommodate the complexity of pore-system geometry. This model-driven methodology tends to be favored by engineers and contrasts with a data-driven geological approach that applies empirical relationships from core data from mercury porosimetry measurements. The most fundamental property used to predict permeability is that of pore volume. Both porosity and permeability are routine measurements from core analysis. If a useable relationship can be developed to predict permeability from porosity, then predictions of permeability can be made in wells that were logged with conventional measurements but not cored. The simplest quantitative methods used to predict permeability from logs have been keyed to empirical equations of the type: . . . log k = P +Q.Φ or log k = P +Q.log Φ. . . where P and Q are constants determined from core measurements and applied to log measurements of porosity (Φ) to generate predictions of permeability (k). These equations are the basis for statistical predictions of permeability in regression analysis, where porosity is the independent variable and logarithmically scaled permeability is the dependent variable. The fitted function minimizes the sum of the squared deviations of the permeability about the trend line.