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Herein, a scalable and practical process to prepare trans-4-fluorocyclohexylamine hydrochloride (1a) is described. By exploitation of the embedded gem-difluoride motif in the commercially available...

In this paper, we study the backward problem for the stochastic parabolic heat equation driven by a Wiener process. We show that the problem is ill-posed by violating the continuous dependence on the input data. In order to restore stability, we apply a filter regularization method which is completely new in the stochastic setting. Convergence rates are established under different a priori assumptions on the sought solution.

Nitriles are found in many bioactive compounds, and are among the most versatile functional groups in organic chemistry. Despite many notable recent advances, however, there are no approaches that may be used for preparation of di- or trisubstituted alkenyl nitriles. Related approaches which are broad in scope and can deliver the desired products in high stereoisomeric purity are especially scarce. Here, we describe the development of several efficient catalytic cross-metathesis strategies, which provide direct access to a considerable range of Z- or E-disubstituted cyano-substituted alkenes or their corresponding trisubstituted variants. Depending on the reaction type, a molybdenum-based monoaryloxide pyrrolide (MAP) or chloride (MAC) complex may be the optimal choice. The utility of the approach, enhanced by an easy-to-apply protocol for utilization of substrates bearing an alcohol or a carboxylic acid moiety, is highlighted in the context of applications to synthesis of biologically active compounds., Graphical Abstract

An operationally simple in situ protection/deprotection strategy that significantly expands the scope of kinetically controlled catalytic Z- and E-selective olefin metathesis is introduced. We demonstrate that, prior to the addition of a sensitive Mo- or Ru-based complex, treatment of a hydroxy- or a carboxylic acid-containing olefin with commercially available HB(pin) or readily accessible HB(trip)(2) (pin = pinacolato, trip = 2,4,6-tri(iso-propyl)phenyl) for 15 minutes is sufficient for efficient generation of a desired product. Routine workup leads to quantitative deprotection. A range of stereochemically defined Z- or E-alkenyl chlorides, bromides, fluorides, and boronates or Z-trifluoromethyl-substituted alkenes with a hydroxy- or a carboxylic acid group were thus prepared in 51–97% yield and 93% to >98% stereoselectivity. The substrates, HB(pin), and cross-partners were used as received. We also show that, regardless of whether a polar functional unit is present or not, a small amount of HB(pin) (e.g., 10 mol %) may be used to remove residual water, significantly enhancing efficiency (i.e., lower catalyst loading).

The development of catalyst-controlled stereoselective olefin metathesis processes has been a pivotal recent advance in chemistry. The incorporation of appropriate ligands within complexes based on molybdenum, tungsten and ruthenium has led to reactivity and selectivity levels that were previously inaccessible. Here we show that molybdenum monoaryloxide chloride complexes furnish higher-energy (Z) isomers of trifluoromethyl-substituted alkenes through cross-metathesis reactions with the commercially available, inexpensive and typically inert Z-1,1,1,4,4,4-hexafluoro-2-butene. Furthermore, otherwise inefficient and non-stereoselective transformations with Z-1,2-dichloroethene and 1,2-dibromoethene can be effected with substantially improved efficiency and Z selectivity. The use of such molybdenum monoaryloxide chloride complexes enables the synthesis of representative biologically active molecules and trifluoromethyl analogues of medicinally relevant compounds. The origins of the activity and selectivity levels observed, which contradict previously proposed principles, are elucidated with the aid of density functional theory calculations.

Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: the potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation). Kinetically controlled Z-selective RCM reactions have been reported, but the only available metathesis approach for accessing macrocyclic E-olefins entails selective removal of the Z-component of a stereoisomeric mixture by ethenolysis, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization-a particularly serious problem when the E-alkene is energetically less favoured. Here, we show that dienes containing an E-alkenyl-B(pinacolato) group, widely used in catalytic cross-coupling, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E-macrocyclic alkenes. The reaction is promoted by a molybdenum monoaryloxide pyrrolide complex and affords products at a yield of up to 73 per cent and an E/Z ratio greater than 98/2. We highlight the utility of the approach by preparing recifeiolide (a 12-membered-ring antibiotic) and pacritinib (an 18-membered-ring enzyme inhibitor), the Z-isomer of which is less potent than the E-isomer. Notably, the 18-membered-ring moiety of pacritinib-a potent anti-cancer agent that is in advanced clinical trials for treating lymphoma and myelofibrosis-was prepared by RCM carried out at a substrate concentration 20 times greater than when a ruthenium carbene was used.

A major shortcoming in olefin metathesis, a chemical process that is central to research in several branches of chemistry, is the lack of efficient methods that kinetically favor E isomers in the product distribution. Here we show that kinetically E-selective cross-metathesis reactions may be designed to generate thermodynamically disfavored alkenyl chlorides and fluorides in high yield and with exceptional stereoselectivity. With 1.0 to 5.0 mole % of a molybdenum-based catalyst, which may be delivered in the form of air- and moisture-stable paraffin pellets, reactions typically proceed to completion within 4 hours at ambient temperature. Many isomerically pure E-alkenyl chlorides, applicable to catalytic cross-coupling transformations and found in biologically active entities, thus become easily and directly accessible. Similarly, E-alkenyl fluorides can be synthesized from simpler compounds or more complex molecules.

This report presents a brief literature review of childhood poverty in Vietnam, reviews national policies affecting childhood poverty, identifies key audiences for the Young Lives study, describes research results and draws provisional conclusions from the first round of data collection from Young Lives in Vietnam. Vietnam is one of the few countries to have seen a significant drop in poverty over the past decade. According to the World Bank, the total poverty rate fell from 57 per cent in 1992-93 to 37 per cent in 1997-98. Despite this achievement, there is growing concern about inequality and the vulnerability of poor children. There are no official data on the numbers of children working, but various NGO reports have shown that many work in very hazardous and difficult conditions. Laws to protect children and prevent exploitation of their labour are poorly enforced. Vietnam has high rates of school enrolment, but disparities exist for children in poorer, rural regions. Other problems include low completion rates, low quality of teaching, and fewer years of schooling compared with regional competitors. While 95 per cent of children have been immunised, fewer children in poorer quintiles have been fully immunised. Infant mortality rates are improving, but the gap between poor and non-poor households has widened and is more severe in poorer provinces. Malnutrition has declined considerably, but is still very prevalent, with rates varying from 28 per cent in relatively prosperous south-eastern Vietnam to 58 per cent in the central highlands. Over the past two decades policymakers in Vietnam have focused on economic growth, poverty reduction, and industrialisation. Social sector reforms have been undertaken, and programmes such as the Hunger Eradication and Poverty Reduction Programme have targeted the most disadvantaged groups. Young Lives data contributes to the formulation of policy and programmes that are more favourable to poor children in Vietnam. From the preliminary findings detailed in this report, the authors make a number of provisional conclusions and outline their implications for policy relating to questions of rural poverty, health, child nutrition, gender inequality, education, income diversification, and access to basic services.

This report presents a brief literature review of childhood poverty in Vietnam, reviews national policies affecting childhood poverty, identifies key audiences for the Young Lives study, describes research results and draws provisional conclusions from the first round of data collection from Young Lives in Vietnam. Vietnam is one of the few countries to have seen a significant drop in poverty over the past decade. According to the World Bank, the total poverty rate fell from 57 per cent in 1992-93 to 37 per cent in 1997-98. Despite this achievement, there is growing concern about inequality and the vulnerability of poor children. There are no official data on the numbers of children working, but various NGO reports have shown that many work in very hazardous and difficult conditions. Laws to protect children and prevent exploitation of their labour are poorly enforced. Vietnam has high rates of school enrolment, but disparities exist for children in poorer, rural regions. Other problems include low completion rates, low quality of teaching, and fewer years of schooling compared with regional competitors. While 95 per cent of children have been immunised, fewer children in poorer quintiles have been fully immunised. Infant mortality rates are improving, but the gap between poor and non-poor households has widened and is more severe in poorer provinces. Malnutrition has declined considerably, but is still very prevalent, with rates varying from 28 per cent in relatively prosperous south-eastern Vietnam to 58 per cent in the central highlands. Over the past two decades policymakers in Vietnam have focused on economic growth, poverty reduction, and industrialisation. Social sector reforms have been undertaken, and programmes such as the Hunger Eradication and Poverty Reduction Programme have targeted the most disadvantaged groups. Young Lives data contributes to the formulation of policy and programmes that are more favourable to poor children in Vietnam. From the preliminary findings detailed in this report, the authors make a number of provisional conclusions and outline their implications for policy relating to questions of rural poverty, health, child nutrition, gender inequality, education, income diversification, and access to basic services.

In Vietnam there is growing concern about the potential social impact of rapid economic changes. The extent and type of social connectedness within communities, or social capital, may be changing. Studies from other developing countries have demonstrated that social capital is often independently associated with various indicators of well-being, including such aspects of human capital as health and education. Social capital can be thought of as the ‘value’ of social relationships, reflecting the quality and quantity of relationships in a given population, most commonly those within a community. Most research acknowledges that high levels of social capital can be associated with exclusion of outsiders, restrictions on individual freedoms and reinforcement of harmful norms. This paper offers the first quantitative examination of maternal social capital and its effects upon child health in Vietnam. It shows that high levels of maternal social capital may positively affect child health by enabling mothers to access more services and more assets, such as jobs, money, and goods. It may also improve maternal physical and/or mental health. While previous research in developed and developing countries has demonstrated positive associations between adult social capital and adult indicators of well-being, the association between maternal social capital and child health has not been previously examined.

A major shortcoming in olefin metathesis, a chemical process that is central to research in several branches of chemistry, is the lack of efficient methods that kinetically favor E isomers in the product distribution. Here we show that kinetically E-selective cross-metathesis reactions may be designed to generate thermodynamically disfavored alkenyl chlorides and fluorides in high yield and with exceptional stereoselectivity. With 1.0 to 5.0 mole % of a molybdenum-based catalyst, which may be delivered in the form of air- and moisture-stable paraffin pellets, reactions typically proceed to completion within 4 hours at ambient temperature. Many isomerically pure E-alkenyl chlorides, applicable to catalytic cross-coupling transformations and found in biologically active entities, thus become easily and directly accessible. Similarly, E-alkenyl fluorides can be synthesized from simpler compounds or more complex molecules., National Institutes of Health (U.S.) (grant GM-59426)

Olefin metathesis has had a large impact on modern organic chemistry, but important shortcomings remain: for example, the lack of efficient processes that can be used to generate acyclic alkenyl halides. Halo-substituted ruthenium carbene complexes decompose rapidly or deliver low activity and/or minimal stereoselectivity, and our understanding of the corresponding high-oxidation-state systems is limited. Here we show that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides. Transformations are promoted by small amounts of a catalyst that is generated in situ and used with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents, and proceed to high conversion at ambient temperature within four hours. We obtain many alkenyl chlorides, bromides and fluorides in up to 91 per cent yield and complete Z selectivity. This method can be used to synthesize biologically active compounds readily and to perform site- and stereoselective fluorination of complex organic molecules.

This article 'The effect of plant nutrition on water balance components and crop growth in rainfed lowland rice.' appeared in the International Rice Research Notes series, created by the International Rice Research Institute (IRRI) to expedite communication among scientists concerned with the development of improved technology for rice and rice-based systems. The series is a mechanism to help scientists keep each other informed of current rice research findings. The concise scientific notes are meant to encourage rice scientists to communicate with one another to obtain details on the research reported.

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Background A limited number of studies on long-term effects of particulate matter with aerodynamic diameter < 2.5 μm (PM2.5) on health suggest it can be an important cause of morbidity and mortality. In Asia where air quality is poor and deteriorating, local data on long-term effects of PM2.5 to support policy on air quality management are scarce. Objectives We assessed long-term effects of PM2.5 on the mortality in a single Asian city. Methods For 10–13 years, we followed up a cohort of 66,820 participants ≥ 65 years of age who were enrolled and interviewed in all 18 Elderly Health Centres of the Department of Health, Hong Kong, in 1998–2001. Their residential addresses were geocoded into x- and y-coordinates, and their proxy exposures to PM2.5 at their addresses in 1 × 1 km grids were estimated from the U.S. National Aeronautics and Space Administration (NASA) satellite data. We used Cox regression models to calculate hazard ratios (HRs) of mortality associated with PM2.5. Results Mortality HRs per 10-μg/m3 increase in PM2.5 were 1.14 (95% CI: 1.07, 1.22) for all natural causes, 1.22 (95% CI: 1.08, 1.39) for cardiovascular causes, 1.42 (95% CI: 1.16, 1.73) for ischemic heart disease, 1.24 (95% CI: 1.00, 1.53) for cerebrovascular disease, and 1.05 (95% CI: 0.90, 1.22) for respiratory causes. Conclusions Our methods in using NASA satellite data provide a readily accessible and affordable approach to estimation of a sufficient range of individual PM2.5 exposures in a single city. This approach can expand the capacity to conduct environmental accountability studies in areas with few measurements of fine particles. Citation Wong CM, Lai HK, Tsang H, Thach TQ, Thomas GN, Lam KB, Chan KP, Yang L, Lau AK, Ayres JG, Lee SY, Chan WM, Hedley AJ, Lam TH. 2015. Satellite-based estimates of long-term exposure to fine particles and association with mortality in elderly Hong Kong residents. Environ Health Perspect 123:1167–1172; http://dx.doi.org/10.1289/ehp.1408264