Selective functionalization of pyridines and diazines via nucleophilic addition to heterocyclic phosphonium salts

2018 Fall.Includes bibliographical references.Nitrogen heterocycles, specifically pyridines and pyrimidines, are common motifs found in pharmaceuticals, agrochemicals and materials. Site-selective functionalization of these azines are highly sought after for medicinal chemistry purposes. It has previously been found in our lab that heterocyclic phosphonium salts can potentially serve as a useful functional handle to selectively functionalize these valuable scaffolds. This work describes the utility of heterocyclic phosphonium salts as electrophiles to selectively form C-O, C-S, C-N and C-Se bonds in a diverse range of pyridines and diazines. First, the addition of thiolate nucleophiles to heterocyclic phosphonium salts to selectively form heteroaryl thioethers is described. This coupling reaction proceeds through deprotonation of the alkyl thiol followed by addition of the heterocyclic phosphonium salt under mild conditions. The reaction scope was tested for a variety of alkyl thiol nucleophiles as well as different pyridine phosphonium salts. The extent of the method's utility was demonstrated through late-stage functionalization of some complex pharmaceuticals. Additionally, initial results on the reactivity of sulfinate nucleophiles with heterocyclic phosphonium salts is communicated. Second, aromatic heteronucleophiles were explored for reactivity with heterocyclic phosphonium salts. Aromatic heteronucleophiles can be classified as either exocyclic or endocyclic. Exocyclic aromatic heteronucleophiles, such as phenols, thiophenols and anilines, were able to be selectively coupled to azines and pharmaceuticals. Endocyclic aromatic heteronucleophiles, such as pyrroles, pyrazoles and imidazoles, also proved to be compatible. All these nucleophiles were able to be coupled to complex drug-like fragments as well as other bioactive molecules via the phosphonium ion. The method also enabled a convergent coupling reaction between two elaborate coupling partners to form a novel tyrosine kinase inhibitor that would be difficult to access using conventional methods

Radical-Mediated Anti-Markovnikov Hydrophosphonation of Olefins

The radical-mediated addition of triphenylphosphonium tetrafluoroborate to olefins (hydrophosphonation) is reported. Both standard radical initiators and photochemical conditions are effective, up to the gram scale. The phosphonium salts are shown to serve as Z-selective Wittig olefination reagents, even without purification

Towards Putting the ‘P’ in Perovskite: Exploring the Reactivity of Phosphonium Salts with Group 14 Halides

Inorganic/organic hybrid perovskites have emerged as synthetic materials that exhibit light-harvesting properties. Although perovskites with alkylammonium cations have been previously reported, a perovskite family with phosphonium cations has not been investigated. Firstly, a library of phosphonium salts was made with the intention of further reaction with the group 14 halides towards creating a perovskite crystal. The composition of these salts were elucidated via NMR spectroscopy, and the crystal structures of three of the phosphonium salts were determined. The phosphonium iodide salts were then reacted with the lead, tin, and germanium iodides and bromides to discover if variant perovskitic structures are obtained. The reaction of lead(II) iodide with various phosphonium salts produced a charge-balanced network of PbI3- fragments connecting in a face-sharing octahedral motif. These phosphonium-templated iodoplumbates were found to possess semi-conducting properties, as suggested by the results of UV-Vis and their high thermal stability was confirmed by TGA experiments. Three novel crystal structures were isolated from reaction of phosphonium salts with tin(II) and tin(IV) iodide, each of them producing an iodostannate anion with a unique geometry. In a reaction with SnI4 an unpredictable oxidation of starting material produced a potentially Lewis acidic tin(IV) cation. Finally, the reaction of phosphonium salts with germanium(II) halides produced charge-balanced compounds with an ABX3 general formula that did not crystallize in a perovskitic manner. Germanium(IV) iodide formed a series of co-crystals when reacted with the phosphonium iodide salts. These species were found to form Ge-I‧‧‧‧I halogen-bonding interactions

Organic phosphonium salts

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Amide Synthesis through the In Situ Generation of Chloro- and Imido-Phosphonium Salts

We describe a methodology for the amidation of carboxylic acids by generating phosphonium salts in situ from N-chlorophthalimide and triphenylphosphine. Aliphatic, benzylic, and aromatic carboxylic acids can be transformed into their amide counter parts using primary and secondary amines. This functional group interconversion is achieved at room temperature in good to excellent yields. Mechanistic work shows the in situ formation of chloro- and imido-phosphonium salts that react as activating agents for carboxylic acids and generate an acyloxy-phosphonium species

INVESTIGATION INTO THE ADDITION OF BENZOIC ACID AND STYRENE OXIDE & EFFECT OF PHOSPHONIUM SALTS FOR FLAME RETARDANCY IN POLYURETHANE FILMS

INVESTIGATION INTO THE ADDITION OF BENZOIC ACID AND STYRENE OXIDE & EFFECT OF PHOSPHONIUM SALTS FOR FLAME RETARDANCY IN POLYURETHANE FILMS An Abstract of the Thesis by Salehin Mahbub The thesis will be divided into two sections. First, the synthesis of a 1,2-hydroxy ester was performed using styrene oxide and benzoic acid using several different catalysts and solvents. This project was chosen because there is a limited number of studies in literature and they did not report a systematic study. Various catalysts will be used in this study such as tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium fluoride, tetrabutylammonium iodide to determine the effects of the halide on the reaction. The solvents chosen for this research were toluene, isopropanol, butanol and THF to determine solvents effects. Samples were analyzed by Fourier-transform infrared (FT-IR) spectroscopy and Nuclear magnetic resonance (NMR) spectroscopy. FTIR was used to determine reaction completion and NMR was used to determine the ratio of the regioisomers. The second part of the research is the study of the effects of novel phosphonium salts on flame retardancy. New flame resistant materials are required industrially to replace halogenated flame retardants since these compounds have a negative environmental impact. In this study, phosphonium salts and triphenyl phosphate were incorporated into polyurethane films. FT-IR was used to characterize the polymer. Polyurethane films containing phosphonium salts and triphenyl phosphate were characterized by a burn test and thermogravimetric analysis (TGA) to determine their effect on flame retardancy and thermal stability

Synthesis of stereodefined 1-aryl(heteroaryl) substituted 1,2-bis(2-bromopyridin-3-yl)ethenes by selective tandem Suzuki-Miyaura Cross-coupling reactions

In this communication we show the preparation of stereodefined trisubstituted alkenes 2 can be achieved by sequential selective Suzuki-Miyaura reactions of 2-bromo-3-(2,2-dibromovinyl)pyridines. The potentiality of this strategy to obtain 5-aryl-1,10-phenanthrolines is also demonstrated

Effects of α,β-unsaturated sulphones and phosphonium salts on ecto-ATPase activity and contractile responses mediated via P2x-purinoceptors

1. 1. In the guinea-pig urinary bladder and vas deferens, several α,β-unsaturated sulphones and phosphonium salts that were tested inhibited ecto-ATPase activity. The sulphones were more active in the bladder but the phosphonium salts were more effective in the vas deferens. 2. 2. These compounds either potentiated or inhibited purinergic contractile responses in the guinea-pig urinary bladder and vas deferens. 3. 3. α,β-Unsaturated sulphones and phosphonium salts represent a new promising class of compounds, capable of modulating purinergic neurotransmission. © 1995