From Cycloalkanols to Heterocycles via Nitrogen Insertion.

A variety of cyclic alcohols are found to undergo nitrogen insertion by subjection to O-mesitylsulfonylhydroxylamine. Critical to a successful process is the use of fluorinated alcoholic solvents, which ensures sufficient substrate activation to allow engagement with the ambiphilic aminating agent. This transition-metal-free nitrogen insertion provides access to a variety of medicinally relevant heterocycles such as pyrrolidenes, quinolines, and benzazepines (24 examples). Furthermore, combination with a photochemical Norrish-Yang-type cyclization allows an unprecedented access to indoles from ortho-substituted acetophenones.

Wacker Oxidation of Methylenecyclobutanes: Scope and Selectivity in an Unusual Setting.

Methylenecyclobutanes are found to undergo Wacker oxidation via a semi-pinacol-type rearrangement. Key to a successful process is the use of tert-butyl nitrite as oxidant, which not only enables efficient catalyst turn-over but also ensures high Markovnikov-selectivity under mild conditions. Thus, cyclopentanones (26 examples) can be accessed in an overall good yield and excellent selectivity (up to 97 % yield, generally >99 : 1 ketone:aldehyde ratio). Stereochemical analysis of the reaction sequence reveals migration aptitudes in line with related 1,2-shifts. By introducing a pyox ligand to palladium, prochiral methylenecyclobutanes can be desymmetrized, thus realizing the first enantioselective Wacker oxidation.

Stereospecific Nitrogen Insertion Using Amino Diphenylphosphinates: An Aza-Baeyer-Villiger Rearrangement.

Amino diphenylphosphinates, which are commercially available or easily prepared from hydroxylamine, undergo ring expansion of cyclobutanones toward γ-lactams under mild conditions. A reaction pathway profoundly different from the common Beckmann reaction is achieved through the ambivalent character of the aminating agent. Thus, rearrangement occurs from a Criegee-like intermediate prior to the formation of the oxime species, which is corroborated by mechanistic experiments. Based on this observation, the migrating aptitude of the adjacent groups is analyzed and found to be in line with the parent Baeyer-Villiger reaction rendering a regioselective (up to >99:1 rr), stereospecific (>99% enantiospecificity), and chemoselective (>99%) insertion process possible. The method thus qualifies for late-stage skeletal editing as showcased by the synthesis of Rolipram and its N-alkylated analogs.

Dynamic kinetic resolution of transient hemiketals: a strategy for the desymmetrisation of prochiral oxetanols.

Identification of an electron poor trifluoroacetophenone allows the formation of uniquely stable hemiketals from prochiral oxetanols. When exposed to a cobalt(ii) catalyst, efficient ring-opening to densely functionalized dioxolanes is observed. Mechanistic studies suggest an unprecedented redox process between the cobalt(ii) catalyst and the hemiketal that initiates the oxetane-opening. Based on this observation, a dynamic kinetic resolution of the transient hemiketals is explored that uses a Katsuki-type ligand for stereoinduction (up to 99 : 1 dr and 96 : 4 er) and allows a variety of 1,3-dioxolanes to be accessed (20 examples up to 98% yield).

Identifying climate refugia for high-elevation Alpine birds under current climate warming predictions.

Identifying climate refugia is key to effective biodiversity conservation under a changing climate, especially for mountain-specialist species adapted to cold conditions and highly threatened by climate warming. We combined species distribution models (SDMs) with climate forecasts to identify climate refugia for high-elevation bird species (Lagopus muta, Anthus spinoletta, Prunella collaris, Montifringilla nivalis) in the European Alps, where the ecological effects of climate changes are particularly evident and predicted to intensify. We considered future (2041-2070) conditions (SSP585 scenario, four climate models) and identified three types of refugia: (1) in-situ refugia potentially suitable under both current and future climate conditions, ex-situ refugia suitable (2) only in the future according to all future conditions, or (3) under at least three out of four future conditions. SDMs were based on a very large, high-resolution occurrence dataset (2901-12,601 independent records for each species) collected by citizen scientists. SDMs were fitted using different algorithms, balancing statistical accuracy, ecological realism and predictive/extrapolation ability. We selected the most reliable ones based on consistency between training and testing data and extrapolation over distant areas. Future predictions revealed that all species (with the partial exception of A. spinoletta) will undergo a range contraction towards higher elevations, losing 17%-59% of their current range (larger losses in L. muta). We identified ~15,000 km2 of the Alpine region as in-situ refugia for at least three species, of which 44% are currently designated as protected areas (PAs; 18%-66% among countries). Our findings highlight the usefulness of spatially accurate data collected by citizen scientists, and the importance of model testing by extrapolating over independent areas. Climate refugia, which are only partly included within the current PAs system, should be priority sites for the conservation of Alpine high-elevation species and habitats, where habitat degradation/alteration by human activities should be prevented to ensure future suitability for alpine species.

Protected area characteristics that help waterbirds respond to climate warming.

Protected area networks help species respond to climate warming. However, the contribution of a site's environmental and conservation-relevant characteristics to these responses is not well understood. We investigated how composition of nonbreeding waterbird communities (97 species) in the European Union Natura 2000 (N2K) network (3018 sites) changed in response to increases in temperature over 25 years in 26 European countries. We measured community reshuffling based on abundance time series collected under the International Waterbird Census relative to N2K sites' conservation targets, funding, designation period, and management plan status. Waterbird community composition in sites explicitly designated to protect them and with management plans changed more quickly in response to climate warming than in other N2K sites. Temporal community changes were not affected by the designation period despite greater exposure to temperature increase inside late-designated N2K sites. Sites funded under the LIFE program had lower climate-driven community changes than sites that did not received LIFE funding. Our findings imply that efficient conservation policy that helps waterbird communities respond to climate warming is associated with sites specifically managed for waterbirds.

Las redes de áreas protegidas ayudan a las especies a responder al calentamiento climático. Sin embargo, se sabe muy poco sobre la contribución de las características ambientales y relevantes para la conservación de un sitio a estas respuestas. Investigamos cómo la composición de las comunidades no reproductivas de aves acuáticas (97 especies) en la red (3,018 sitios) Natura 2000 de la Unión Europea (N2K) cambió en respuesta a los incrementos de la temperatura durante más de 25 años en 26 países europeos. Medimos la reorganización comunitaria con base en series temporales de abundancia recolectadas durante el Censo Internacional de Aves Acuáticas en relación con los objetivos de conservación de los sitios N2K, el periodo de asignación de fondos y el estado del plan de manejo. La composición comunitaria de las aves acuáticas en los sitios con planes de manejo y designados explícitamente para su protección cambió más rápidamente en respuesta al calentamiento climático que en otros sitios N2K. Los cambios comunitarios temporales no se vieron afectados por el periodo de asignación a pesar de una mayor exposición al incremento de la temperatura dentro de los sitios N2K de asignación tardía. Los sitios financiados por el programa LIFE tuvieron menos cambios comunitarios causados por el clima que los sitios que no recibieron este financiamiento. Nuestros hallazgos sugieren que la política de conservación eficiente que ayuda a las comunidades de aves acuáticas a responder al calentamiento climático está asociada con sitios específicamente gestionados para las aves acuáticas.

Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ-Lactams.

Asymmetric access to γ-lactams is achieved via a cyclobutanone ring expansion using widely available (1S,2R)-1-amino-2-indanol for chiral induction. Mechanistic analysis of the key N,O-ketal rearrangement reveals a Curtin-Hammett scenario, which enables a downstream stereoinduction (up to 88:12 dr) and is corroborated by spectroscopic, crystallographic, and computational studies. In combination with an easy deprotection protocol, this operationally simple sequence allows the synthesis of a range of optically pure γ-lactams, including those bearing all-carbon quaternary stereocenters. In addition, the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin further demonstrates the synthetic utility and highlights the general applicability of the presented method.

Benefits of protected areas for nonbreeding waterbirds adjusting their distributions under climate warming.

Climate warming is driving changes in species distributions and community composition. Many species have a so-called climatic debt, that is, shifts in range lag behind shifts in temperature isoclines. Inside protected areas (PAs), community changes in response to climate warming can be facilitated by greater colonization rates by warm-dwelling species, but also mitigated by lowering extirpation rates of cold-dwelling species. An evaluation of the relative importance of colonization-extirpation processes is important to inform conservation strategies that aim for both climate debt reduction and species conservation. We assessed the colonization-extirpation dynamics involved in community changes in response to climate inside and outside PAs. To do so, we used 25 years of occurrence data of nonbreeding waterbirds in the western Palearctic (97 species, 7071 sites, 39 countries, 1993-2017). We used a community temperature index (CTI) framework based on species thermal affinities to investigate species turnover induced by temperature increase. We determined whether thermal community adjustment was associated with colonization by warm-dwelling species or extirpation of cold-dwelling species by modeling change in standard deviation of the CTI (CTISD ). Using linear mixed-effects models, we investigated whether communities in PAs had lower climatic debt and different patterns of community change than communities outside PAs. For CTI and CTISD combined, communities inside PAs had more species, higher colonization, lower extirpation, and lower climatic debt (16%) than communities outside PAs. Thus, our results suggest that PAs facilitate 2 independent processes that shape community dynamics and maintain biodiversity. The community adjustment was, however, not sufficiently fast to keep pace with the large temperature increases in the central and northeastern western Palearctic. Our results underline the potential of combining CTI and CTISD metrics to improve understanding of the colonization-extirpation patterns driven by climate warming.

Beneficios de las Áreas Protegidas para las Aves Acuáticas No Reproductoras que Están Ajustando su Distribución Debido al Calentamiento Climático Resumen El calentamiento climático está generando cambios en la distribución y en la composición comunitaria de las especies. Muchas de ellas tienen una deuda climática, es decir, los cambios en la distribución se atrasan con respecto a los cambios en las isoclinas térmicas. Dentro de las áreas protegidas (APs), los cambios comunitarios como respuesta al calentamiento climático pueden facilitarse mediante tasas mayores de colonización por especies de climas cálidos, pero también pueden mitigarse al reducir las tasas de extirpación de las especies de climas fríos. Se requiere una evaluación de la importancia relativa de los procesos de colonización-extirpación para orientar las estrategias de conservación que buscan la reducción de la deuda climática y la conservación de las especies. Analizamos las dinámicas de colonización-extirpación que participan en los cambios comunitarios como respuesta al clima dentro y fuera de las APs. Para realizar lo anterior, usamos datos tomados durante 25 años de la presencia de aves acuáticas no reproductoras en el Paleártico occidental (97 especies, 7,071 sitios, 39 países, 1993-2017). Usamos un marco de trabajo del índice de temperatura comunitaria (ITC) basado en las afinidades térmicas de las especies para así investigar la rotación de especies inducida por el incremento en la temperatura. Determinamos si el ajuste térmico en la comunidad estuvo asociado con la colonización por especies de climas cálidos o con la extirpación de especies de climas fríos al modelar el cambio mediante una desviación estándar del ITC (ITCDS ). Con los modelos lineales de efectos mixtos investigamos si las comunidades dentro de las APs tenían una deuda climática más baja y patrones diferentes de cambio comunitario que las comunidades localizadas fuera de las APs. Con la combinación del ITC y deL ITCDS , las comunidades dentro de las APs tuvieron más especies, una mayor colonización, una menor extirpación y una deuda climática más baja (16%) que las comunidades fuera de las APs. Por lo tanto, nuestros resultados sugieren que las APs facilitan dos procesos independientes que moldean las dinámicas comunitarias y mantienen la biodiversidad. Sin embargo, el ajuste comunitario no fue lo suficientemente rápido para mantener el paso de los grandes incrementos en la temperatura de las regiones central y noreste del Paleártico occidental. Nuestros resultados resaltan el potencial que tiene la combinación de las medidas del ITC y del ICTDS para mejorar el entendimiento de los patrones de colonización-extirpación causados por el calentamiento climático.

Effectiveness of the European Natura 2000 network to sustain a specialist wintering waterbird population in the face of climate change.

Analysis of coordinated Greater Scaup (Aythya marila) count data from the last 30 years showed a 38.1% decrease in wintering numbers in North-West Europe, from 309,000 during 1988-1991 to c.192,300 individuals during 2015-2018. Annual trends in wintering numbers differed throughout the range. Numbers decreased in the UK, Ireland, and in the Netherlands, while numbers were stable in Denmark. Germany, Poland, Sweden, and Estonia showed increasing numbers, suggesting a shift in the distribution of the species within its wintering grounds towards the east and north. Higher temperatures in northern and eastern areas were correlated with the range shift of the wintering distribution. Deaths from bycatch drowning of Scaup in fishing gear have significantly decreased in recent decades in the Netherlands, where currently the greatest threat is considered the deterioration of food resources. The increasing concentration of wintering Scaup in coastal Poland and Germany (where lack of effective implementation of conservation measures fail to protect the species from the impacts of bycatch and declining food quality) pose major threats to the entire population.

Enantioselective Desymmetrization of Cyclobutanones: A Speedway to Molecular Complexity.

Cyclobutanones hold a privileged role in enantioselective desymmetrization because their inherent ring strain allows for a variety of unusual reactions to occur. Current strategies include α-functionalization, rearrangement, and C-C bond activation to directly convert cyclobutanones into a wide range of enantiomerically enriched compounds, including many biologically significant scaffolds. This Minireview provides an overview of state-of-the-art methods that generate complexity from prochiral cyclobutanones in a single operation.

Recent advances in the synthesis of gem-dimethylcyclobutane natural products.

Covering: January 2000 to July 2018 gem-Dimethylcyclobutanes are a common motif found in a multitude of natural products, and thus these structures have captivated synthetic chemists for years. However, until the turn of the century, most synthetic efforts relied upon the use of widely available terpenes, such as pinene or caryophyllene, that already contain the gem-dimethylcyclobutane motif. This approach limits the scope of molecules that can be accessed readily. This review highlights recent syntheses in which the gem-dimethylcyclobutane is assembled via de novo approaches. An outlook on the future of this research area is also provided.

Allenoates in Enantioselective [2+2] Cycloadditions: From a Mechanistic Curiosity to a Stereospecific Transformation.

Identification of a novel catalyst-allenoate pair allows enantioselective [2+2] cycloaddition of α-methylstyrene. To understand the origin of selectivity, a detailed mechanistic investigation was conducted. Herein, two competing reaction pathways are proposed, which operate simultaneously and funnel the alkenes to the same axially chiral cyclobutanes. In agreement with the Woodward-Hoffmann rules, this mechanistic curiosity can be rationalized through a unique symmetry operation that was elucidated by deuteration experiments. In the case of 1,1-diarylalkenes, distal communication between the catalyst and alkene is achieved through subtle alteration of electronic properties and conformation. In this context, a Hammett study lends further credibility to a concerted mechanism. Thus, extended scope exploration, including ß-substitution on the alkene to generate two adjacent stereocenters within the cyclobutane ring, is achieved in a highly stereospecific and enantioselective fashion (33 examples, up to >99:1 er).

A Route to 2-Substituted 3-Cyanopyrroles: Synthesis of Danaidal and Suffrutine A.

The title compounds were prepared in a two-step sequence from 4,4-dimethoxybutyronitrile and the respective esters by Claisen condensation and subsequent Paal-Knorr pyrrole synthesis. The sequence could be performed as a one-pot procedure delivering the pyrroles in yields of 47-72% over two steps (13 examples). Intramolecular variants of the method were applied to the total synthesis of danaidal and suffrutine A from the respective trityl-protected ω-amino alkanoates.

Pyrrole as a Directing Group: Regioselective Pd(II)-Catalyzed Alkylation and Benzylation at the Benzene Core of 2-Phenylpyrroles.

Pyrrole has been employed for the first time as a directing group in the Pd(II)-catalyzed ortho-functionalization of C(sp(2))-H bonds. A variety of substituted 2-phenylpyrroles were successfully methylated, alkylated, or benzylated in the ortho-position of the benzene ring, yielding the respective 2-substituted pyrrol-2-yl benzenes (36 examples, 51-93% yield). Neither additives nor additional ligands were required to perform the reaction, which was routinely conducted with PdBr2 as the catalyst and Li2CO3 as the base. Mechanistically, there is evidence that precoordination of palladium to the pyrrole enables the regioselective ortho-attack.

Rapid climate driven shifts in wintering distributions of three common waterbird species.

Climate change is predicted to cause changes in species distributions and several studies report margin range shifts in some species. However, the reported changes rarely concern a species' entire distribution and are not always linked to climate change. Here, we demonstrate strong north-eastwards shifts in the centres of gravity of the entire wintering range of three common waterbird species along the North-West Europe flyway during the past three decades. These shifts correlate with an increase of 3.8 °C in early winter temperature in the north-eastern part of the wintering areas, where bird abundance increased exponentially, corresponding with decreases in abundance at the south-western margin of the wintering ranges. This confirms the need to re-evaluate conservation site safeguard networks and associated biodiversity monitoring along the flyway, as new important wintering areas are established further north and east, and highlights the general urgency of conservation planning in a changing world. Range shifts in wintering waterbirds may also affect hunting pressure, which may alter bag sizes and lead to population-level consequences.