Making War and Building Peace examines how well United Nations peacekeeping missions work after civil war. Statistically analyzing all civil wars since 1945, the book compares peace processes that ...had UN involvement to those that didn't. Michael Doyle and Nicholas Sambanis argue that each mission must be designed to fit the conflict, with the right authority and adequate resources. UN missions can be effective by supporting new actors committed to the peace, building governing institutions, and monitoring and policing implementation of peace settlements.
The combination of two or more unsaturated structural units to form cyclic organic compounds is commonly referred to as cycloaddition, and the combination of two unsaturated structural units that ...forms a six-membered ring is formally either a 5 + 1-, 4 + 2-, 2 + 2 + 2-, or 3 + 3-cycloaddition. Occurring as concerted or stepwise processes, cycloaddition reactions are among the most useful synthetic constructions in organic chemistry. Of these transformations, the concerted 4 + 2-cycloaddition, the Diels–Alder reaction, is by far the best known and most widely applied. However, although symmetry disallowed as a concerted process and lacking certifiable examples until recently, stepwise 3 + 3-cycloadditions offer advantages for the synthesis of a substantial variety of heterocyclic compounds, and they are receiving considerable attention. In this Account, we present the development of stepwise 3 + 3-cycloaddition reactions from virtual invisibility in the 1990s to a rapidly growing synthetic methodology today, involving organocatalysis or transition metal catalysis. With origins in organometallic or vinyliminium ion chemistry, this area has blossomed into a viable synthetic transformation for the construction of six-membered heterocyclic compounds containing one or more heteroatoms. The development of 3 + 3-cycloaddition transformations has been achieved through identification of suitable and compatible reactive dipolar adducts and stable dipoles. The reactive dipolar species is an energetic dipolar intermediate that is optimally formed catalytically in the reaction. The stepwise process occurs with the reactive dipolar adduct reacting as an electrophile or as a nucleophile to form the first covalent bond, and this association provides entropic assistance for the construction of the second covalent bond and the overall formal 3 + 3-cycloaddition. Organocatalysis is well developed for both inter- and intramolecular synthetic transformations, but the potential of transition metal catalysis for 3 + 3-cycloaddition has only recently emerged. The key to the rapid development of the transition metal-based methodology has been recognition that certain catalytically generated vinylcarbenes are effective dipolar adducts for reactions with stable dipolar compounds, including aryl and vinyl ylides. In particular, metallo-enolcarbenes that are generated catalytically from conveniently prepared stable enoldiazoacetates or from donor–acceptor cyclopropenes are highly effective dipolar adducts for 3 + 3-cycloaddition. The electron-donating oxygen of the silyl ether enhances electrophilic ring closure to the metal-bound carbon of the initial adduct from vinylogous addition, and this enhancement inhibits the alternative 3 + 2-cycloaddition across the carbon–carbon double bond of the vinylcarbene. Catalytically generated metallo-enolcarbenes react under mild conditions with a broad spectrum of compatible stable dipoles, including nitrones, azomethine imines, ylides, and certain covalent precursors of stable dipoles, to form 3 + 3-cycloaddition products having the β-ketoester functionality (in dihydrooxazines, tetrahydropyridazines, pyrazolidinone and pyraxole derivatives, dihydroquinolines, and quinolizidines, for example) in high yield. Two ways to access these metallo-enolcarbenes, either by dinitrogen extrusion from enoldiazoacetate esters or by rearrangement of donor–acceptor cyclopropenes, enhance the versatility of the process. The 3 + 3-cycloaddition methodology is a complementary strategy to 4 + 2-cycloaddition for the synthesis of heterocyclic compounds having six-membered rings. High levels of enantioselectivity are obtained with the use of chiral ligands on transition metal catalysts that include those on dirhodium(II) and silver(I).
Toss the olefin into the porphyrin: The development of chiral cobalt(II)–porphyrin catalysts by straightforward coupling processes has made possible the additions of diazocarbonyl compounds to a ...broad spectrum of olefins to access functionalized cylopropanes. The cyclopropanation reactions demonstrate high product yields, exceptional diastereoselectivity, and excellent enantiocontrol.
Catalytic Carbene Insertion into C−H Bonds Doyle, Michael P; Duffy, Richard; Ratnikov, Maxim ...
Chemical reviews,
2010-Feb-10, Letnik:
110, Številka:
2
Journal Article
Recenzirano
The catalytic insertion of carbene into carbon-hydrogen bonds is examined. Although few of these reactions have produced the desired result, the potential for forming carbon-carbon bonds keeps ...researchers interested.
A highly enantioselective preparation of substituted pyrrolidines and 1,2-oxazinanes has been achieved via stereoretentive 3 + 2/3 + 3-cycloaddition of nonracemic donor–acceptor cyclopropanes with ...imines, triazines, and nitrones in good to high yields with broad scope under mild reaction conditions. In comparison with the well-documented approach to donor–acceptor cyclopropane reactions using racemic cyclopropane reactants and a catalyst with chiral ligands, this report features applications of enantioenriched donor–acceptor cyclopropanes as cycloadduct reactants with achiral catalysts.
The isotopic labelling of small molecules is integral to drug development and for understanding biochemical processes. The preparation of carbon-labelled α-amino acids remains difficult and time ...consuming, with established methods involving label incorporation at an early stage of synthesis. This explains the high cost and scarcity of C-labelled products and presents a major challenge in 11C applications (11C t1/2 = 20 min). Here we report that aldehydes catalyse the isotopic carboxylate exchange of native α-amino acids with *CO2 (* = 14, 13, 11). Proteinogenic α-amino acids and many non-natural variants containing diverse functional groups undergo labelling. The reaction probably proceeds via the trapping of *CO2 by imine-carboxylate intermediates to generate iminomalonates that are prone to monodecarboxylation. Tempering catalyst electrophilicity was key to preventing irreversible aldehyde consumption. The pre-generation of the imine carboxylate intermediate allows for the rapid and late-stage 11C-radiolabelling of α-amino acids in the presence of 11CCO2.Carbon-labelled α-amino acids are valuable compounds in drug development and nuclear medicine, but are difficult and time consuming to prepare. Now, an aldehyde-catalysed method has been developed for the direct C1-labelling of α-amino acids using *CO2 (* = 14, 13, 11), providing access to many proteinogenic and non-natural labelled α-amino acids.
The localization of RNAs critically contributes to many important cellular processes in an organism, such as the establishment of polarity, asymmetric division and migration during development. ...Moreover, in the central nervous system, the local translation of mRNAs is thought to induce plastic changes that occur at synapses triggered by learning and memory. Here, we will critically review the physiological functions of well‐established dendritically localized mRNAs and their associated factors, which together form ribonucleoprotein particles (RNPs). Second, we will discuss the life of a localized transcript from transcription in the nucleus to translation at the synapse and introduce the concept of the ‘RNA signature’ that is characteristic for each transcript. Finally, we present the ‘sushi belt model’ of how localized RNAs within neuronal RNPs may dynamically patrol multiple synapses rather than being anchored at a single synapse. This new model integrates our current understanding of synaptic function ranging from synaptic tagging and capture to functional and structural reorganization of the synapse upon learning and memory.
In this review, our understanding of the mechanisms and regulation of dendritic mRNA localization is synthesized into a ‘sushi belt’ model of mRNA transport and translational control in neurons.
A chiral copper(I) complex catalyzes reactions of symmetric diaziridines with enol diazo compounds, which react through N−N bond ring opening in a formal 3+3 cycloaddition to form four chiral centers ...with high stereocontrol. A broad spectrum of bridged dinitrogen heterocycles were obtained in high yields and excellent diastereo‐ and enantioselectivities from γ‐substituted enol diazoacetates, while their geometrical isomers gave different enantioselectivities. Donor–acceptor cyclopropenes formed from the geometrical isomers of the γ‐substituted enol diazoacetates underwent catalytic ring opening to give only the Z isomer of the metalloenolcarbene intermediate, provided excellent yields and selectivities for the 1,5‐diazabicyclon.3.1non‐2‐ene derivatives.
Symmetric diaziridines underwent N−N bond ring opening in a formal 3+3 desymmetrization cycloaddition with enol diazo compounds. A chiral copper(I) complex catalyzes the enantioselective variant of this process. The use of donor–acceptor‐substituted cyclopropenes as the metalloenolcarbene precursors in the presence of the same chiral CuI/bisoxazoline complex delivered various chiral 1,5‐diazabicyclon.3.1non‐2‐enes with better enantioselectivity.
![The [3 + 3]-Cycloaddition A...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0001-4842/small "The [3 + 3]-Cycloaddition Alternative for Heterocycle Syntheses: Catalytically Generated Metalloenolcarbenes as Dipolar Adducts")
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