Tetrafluoropyridazíne: a scaffold for the synthesis of highly functionalised heterocycles

There is a great desire for the synthesis of new heteroaromatic compounds, which have a range of applications from pharmaceuticals to materials. These industries require large numbers of heterocyclic derivatives for their screening programmes, however many common routes for the synthesis of aromatic heterocycles do not allow for the flexible introduction of a diverse range of substituents. Our approach involves the use of tetrafluoropyridazine as a scaffold for the synthesis of a diverse range of heteroaromatic systems. Perfluorinated heteroaromatic compounds, such as tetrafluoropyridazíne, are highly reactive towards displacements by nucleophilic species. Sequential nucleophilic aromatic substitution reactions of 4,5,6- trifluoropyridazin-3(2H) one have been studied and a range of polysubstituted systems synthesised. Similarly, reactions of tetrafluoropyridazine with dinucleophiles have been utilised to yield ring-fijsed products, many of which are rare heterocyclic substructures. This approach has allowed the synthesis of a small library of compounds based on the pyridazine ring system with moderate skeletal and substituent diversity. The synthesis of some non-halogenated products by displacement of all ring fluorine atoms has also been reported

Fluorination of organoboron compounds

Methods for the fluorination of organoboron compounds are described. This review will cover the fluorination of aromatic and aliphatic systems using both electrophilic and nucleophilc sources of fluorine. Emerging methods for radiofluorination using 18F for the synthesis of PET-imaging agents are also described

Rh-catalyzed arylation of fluorinated ketones with arylboronic acids

The Rh-catalyzed arylation of fluorinated ketones with boronic acids is reported. This efficient process allows access to fluorinated alcohols in high yields under mild conditions. Competition experiments suggest that difluoromethyl ketones are more reactive than trifluoromethyl ketones in this process, despite their decreased electronic activation, an effect we postulate to be steric in origin

Effects of Replacing Oxygenated Functionality with Fluorine on Lipophilicity

The replacement of oxygenated functionality (hydroxy and alkoxy) with a fluorine atom is a commonly used bioisosteric replacement in medicinal chemistry. In this paper, we use molecular matched-pair analysis to better understand the effects of this replacement on lipophilicity. It seems that the reduced log P of the oxygenated compound is normally dominant in determining the size of this difference. We observe that the presence of additional electron-donating groups on an aromatic ring generally increases the difference in lipophilicity between an oxygenated compound and its fluorinated analogue, while electron-withdrawing groups lead to smaller differences. Ortho-substituted compounds generally display a reduced difference in log P compared to para- and meta-substituted compounds, particularly if an ortho-substituent can form an intramolecular hydrogen bond. Hydrogen-bond acceptors remote to an aromatic ring containing fluorine/oxygen can also reduce the difference in log P between oxygen- and fluorine-substituted compounds

Transition-metal-free homologative cross-coupling of aldehydes and ketones with geminal bis(boron) compounds

We report a transition-metal-free coupling of aldehydes and ketones with geminal bis(boron) building blocks which provides the coupled, homologated carbonyl compound upon oxidation. This reaction not only extends an alkyl chain containing a carbonyl group, it also simultaneously introduces a new carbonyl substituent. We demonstrate that enantiopure aldehydes with an enolizable stereogenic center undergo this reaction with complete retention of stereochemistry

One-pot synthesis of difluoromethyl ketones by a difluorination/fragmentation process

Difluoromethyl ketones are an under-studied class of ketones which have great potential as useful building blocks for materials and drug design. Here we report a simple and convenient synthesis of this class of compounds via a one-pot difluorination/fragmentation of 1-trifluoromethyl-1,3-diketones which should now allow the chemistry of difluoromethyl ketones to be fully developed

Quantifying the heterogeneity of soil compaction, physical soil properties and soil moisture across multiple spatial scales [Abstract]

Quantifying the heterogeneity of soil compaction, physical soil properties and soil moisture across multiple spatial scales [Abstract

The role of perceived threat in Australians’ endorsement of asylum-seeker policies

Australia’s treatment of asylum seekers continues to polarise public debate. The present study sought to investigate the factors that may influence an individual’s endorsement of deterrence-based government policies. Using the integrated threat theory of prejudice, the present study examined the role of perceived threat in shaping Australian voters’ political attitudes toward asylum seekers. A total of 255 Australian citizens completed an online questionnaire that assessed their support for aspects of government policy and their perceptions of asylum seekers as a threat. Hierarchical multiple regression analyses were used to examine the combined and unique influences of perceived threat and sociodemographic factors on overall and individual government policy endorsement. Results indicated that various types of threat (realistic, symbolic, and negative stereotypes) were significant predictors of policy support. Practical implications regarding the development of anti-discriminatory strategies and directions for future research are discussed

Formation of Boron Enolates by Nucleophilic Substitution

Enolates have proven to be one of the key building blocks available to the synthetic chemist. Here we summarize a novel strategy for their preparation, involving the addition of α-borylated nucleophiles to esters to yield boron enolates. The enolates prepared by the addition of lithiated geminal bis(boron) compounds to esters can be trapped with two equivalents of halogen and alkyl electrophiles to yield α,α-difunctionalized compounds

Fluorination as a route towards unlocking the hydrogen bond donor ability of phenolic compounds in self-assembled monolayers

We report on the comparative performance of a simple diphenol and its fluorinated analogue as hydrogen-bond-donating building blocks for the formation of multicomponent self-assembled monolayers. The fluorinated molecule is found to be a significantly more effective building block than its unfluorinated counterpart