Introduction 2643 2. Nucleophilic Addition of Organometallic Reagents to N-Acyl Pyridinium Salts 2644 2.1. Regioselective Additions to N-Acyl Pyridinium Species and Their Derivatives 2644 2.1.1. Influence of Pyridine Ring Substituents on Regioselectivity of Addition 2646 2.1.2. Control of Regio-and Diastereoselectivity by the Introduction of Removable Blocking Groups 2648 2.2. Synthesis of 4-Pyridones: 1,2-Addition to 4-Methoxypyridines 2649 2.2.1. Diastereoselective Addition to 3-Trialkylsilyl-4-methoxypyridines 2651 2.2.2. Application in the Synthesis of Natural Products Containing Chiral Piperidine Units 2652 2.3. Diastereoselective 1,2-Addition to N-Imidoyl Pyridinium Salts 2652 2.4. Enantioselective 1,2-Addition Controlled by a Chiral Catalyst 2657 2.5. Diastereoselective 1,4-Addition Controlled by Pyridine 3-Substituents 2657 3. Nucleophilic Addition to N-Alkyl Pyridinium Salts and Their Derivatives 2659 3.1. Regioselective Additions to N-Alkyl Pyridinium SaltsNature of the Nucleophile 2659 3.1.1. Organometallic Reagents as Nucleophiles 2659 3.1.2. Cyanide as Nucleophile 2663 3.2. Diastereoselective Additions of Organometallic Reagents to N-Alkyl Pyridinium Salts 2663 3.3. Regioselective Additions of Enolates to N-Alkyl Pyridinium Salts 2666 3.3.1. Wenkert Procedure: Seminal Work 2667 3.3.2. Wenkert Procedure: Addition of Nucleophiles Positioned at the Nitrogen of Indole Derivatives 2670 3.3.3. Wenkert Procedure: Addition of Enolates Located at the C-2/C-3 Position of Indoles 2671 3.3.4. Addition of Miscellaneous Nucleophiles to N-Alkyl Pyridinium Species 2674 4. Nucleophilic Additions to N-Heteroatom Pyridinium Species 2676 4.1. Nucleophilic Additions to Pyridine N-Oxides and N−O Salts 4.1.1. Properties, Synthesis, and Deprotection of Pyridine N-Oxides 4.1.2. Addition of Grignard Reagents to Pyridine N-Oxides 4.1.3. Addition of Cyanide Nucleophiles via Reissert-Type Reactions 4.1.4. Addition of Hetero Nucleophiles to Pyridine N-Oxides and N−O Salts 4.

The four-membered oxetane ring has been increasingly exploited for its contrasting behaviors: its influence on physicochemical properties as a stable motif in medicinal chemistry and its propensity to undergo ring-opening reactions as a synthetic intermediate. These applications have driven numerous studies into the synthesis of new oxetane derivatives. This review takes an overview of the literature for the synthesis of oxetane derivatives, concentrating on advances in the last five years up to the end of 2015. These methods are clustered by strategies for preparation of the ring and further derivatization of preformed oxetane-containing building blocks. Examples of the use of oxetanes in medicinal chemistry are reported, including a collation of oxetane derivatives appearing in recent patents for medicinal chemistry applications. Finally, examples of oxetane derivatives in ring-opening and ring-expansion reactions are described.

Molecular rotors have emerged as versatile probes for microscopic viscosity in live cells, however, the exclusive localisation of rotors in the plasma membrane has remained elusive. We report the synthesis, spectroscopic characterisation and live cell imaging of a new BODIPY-based molecular rotor suitable for mapping viscosity in the cell plasma membrane.

Despite their wide use in academia as metal-carbene precursors, diazo compounds are often avoided in industry owing to concerns over their instability, exothermic decomposition, and potential explosive behavior. The stability of sulfonyl azides and other diazo transfer reagents is relatively well understood, but there is little reliable data available for diazo compounds. This work first collates available sensitivity and thermal analysis data for diazo transfer reagents and diazo compounds to act as an accessible reference resource. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and accelerating rate calorimetry (ARC) data for the model donor/acceptor diazo compound ethyl (phenyl)diazoacetate are presented. We also present a rigorous DSC dataset with 43 other diazo compounds, enabling direct comparison to other energetic materials to provide a clear reference work to the academic and industrial chemistry communities. Interestingly, there is a wide range of onset temperatures (T onset ) for this series of compounds, which varied between 75 and 160 °C. The thermal stability variation depends on the electronic effect of substituents and the amount of charge delocalization. A statistical model is demonstrated to predict the thermal stability of differently substituted phenyl diazoacetates. A maximum recommended process temperature (T D24 ) to avoid decomposition is estimated for selected diazo compounds. The average enthalpy of decomposition (ΔH D ) for diazo compounds without other energetic functional groups is −102 kJ mol −1 . Several diazo transfer reagents are analyzed using the same DSC protocol and found to have higher thermal stability, which is in general agreement with the reported values. For sulfonyl azide reagents, an average ΔH D of −201 kJ mol −1 is observed. High-quality thermal data from ARC experiments shows the initiation of decomposition for ethyl (phenyl)diazoacetate to be 60 °C, compared to that of 100 °C for the common diazo transfer reagent p-acetamidobenzenesulfonyl azide (p-ABSA). The Yoshida correlation is applied to DSC data for each diazo compound to provide an indication of both their impact sensitivity (IS) and explosivity. As a neat substance, none of the diazo compounds tested are predicted to be explosive, but many (particularly donor/acceptor diazo compounds) are predicted to be impact-sensitive. It is therefore recommended that manipulation, agitation, and other processing of neat diazo compounds are conducted with due care to avoid impacts, particularly in large quantities. The full dataset is presented to inform chemists of the nature and magnitude of hazards when using diazo compounds and diazo transfer reagents. Given the demonstrated potential for rapid heat generation and gas evolution, adequate temperature control and cautious addition of reagents that begin a reaction are strongly recommended when conducting reactions with diazo compounds.