Chloral Hydrate as a Water Carrier for the Efficient Deprotection of Acetals,Dithioacetals, and Tetrahydropyranyl Ethers in Organic Solvents

The efficient deprotection of several acetals, dithioacetals, and tetrahydropyranyl (THP) ethers under ambient conditions, using chloral hydrate in hexane, is described. Excellent yields were realized for a wide range of both aliphatic and aromatic substrates. The method is characterized by mild conditions (room temperatures or below), simple workup, and the ready availability of chloral hydrate. High chemoselectivity was also observed in the deprotection, acetonides, esters, and amides being unaffected under the reaction conditions. Products were generally purified chromatographically and identified spectrally. These results constitute a novel addition to current methodology involving a widely employed deprotection tactic in organic synthesis. It seems likely that the mechanism of the reaction involves adsorption of the substrate on the surface of the sparingly soluble chloral hydrate.     

Selective Aldehyde Reduction in Ketoaldehydes with NaBH4-Na2CO3-H2O at Room Temperatures

A variety of aliphatic and aromatic ketoaldehydes were reduced to the corresponding ketoalcohols with a mixture of sodium borohydride (1.2 equivalents) and sodium carbonate (sixfold molar excess) in water. Reactions were performed at room temperatures over (typically) 2 h, and yields of isolated products generally ranged from 70% to 85%. A bis-carbonate-borane complex, [(BH₃)₂CO₂]^2? 2Na⁺, possibly formed from the reagent mixture, is likely the active reductant. The moderated reactivity of this acylborane species would explain the chemoselectivity observed in the reactions. The readily available reagents and the mild aqueous conditions make for ease of operation and environmental compatibility, and make a useful addition to available methodology.     

Useful Extensions of the Henry Reaction: Expeditious Routes to Nitroalkanes and Nitroalkenes in Aqueous Media

The products of the Henry nitroaldol reaction from nitromethane and several aldehydes were reduced to the corresponding nitroalkanes with (n-Bu)₃SnH in water under microwave irradiation (80 °C/10 min), or dehydrated to the corresponding nitroalkenes with K₂CO₃ in water (generally 0–5 °C/20 min). Both “one-pot” reactions occur in excellent yields across a range of aliphatic and aromatic (including heteroaromatic) substrates. It seems likely that the deoxygenation of the nitroaldols occurs via coordination of an oxygen atom of the nitro group with a tin atom, which facilitates hydride delivery in the transition state. The elimination of water from the nitroaldols in mild base is likely driven by the stability of the conjugated nitroalkene products. The elimination required workup with 2 N HCl, which likely displaces a nitroalkane-nitroalkene equilibrium towards the latter. These extensions of the Henry reaction lead to products not easily obtained otherwise.     

Gd‐TEMDO: Design,Synthesis, and MRI Application

A simple Ugi tetrazole multicomponent reaction allows the synthesis of a novel macrocyclic cyclen derivative with four appendant tetrazole arms in just two steps in excellent yields. This ligand, called TEMDO, turns out to have a high complexation affinity with lanthanoid metals. Here we describe the design, synthesis, solid‐state structure, binding constant, and some MRI applications of the Gd‐TEMDO complex as the first example of a congeneric family of oligo‐amino tetrazoles.     

Autophagy Caught in the Act: A Supramolecular FRET Pair Based on an Ultrastable Synthetic Host–Guest Complex Visualizes Autophagosome–Lysosome Fusion

A supramolecular FRET pair based on the ultrahigh binding affinity between cyanine 3 conjugated cucurbit[7]uril (CB[7]‐Cy3) and cyanine 5 conjugated adamantylamine (AdA‐Cy5) was exploited as a new synthetic tool for imaging cellular processes in live cells. Confocal laser scanning microscopy revealed that CB[7]‐Cy3 and AdA‐Cy5 were intracellularly translocated and accumulated in lysosomes and mitochondria, respectively. CB[7]‐Cy3 and AdA‐Cy5 then formed a host–guest complex, reported by a FRET signal, as a result of the fusion of lysosomes and mitochondria. This observation not only indicated that CB[7] forms a stable complex with AdA in a live cell, but also suggested that this FRET pair can visualize dynamic organelle fusion processes, such as those involved in the degradation of mitochondria through autophagy (mitophagy), by virtue of its small size, chemical stability, and ease of use.     

Enthalpic and entropic contributions to the basicity of cycloalkylamines

Large-ring cycloalkylamines are slightly less basic than other cycloalkylamines such as cyclohexylamine, even though all have tetrahedral carbons and are strain-free. To understand why, enthalpy and entropy for protonation of a series of cycloalkylamines were accurately determined by isothermal titration calorimetry in 3 : 1 methanol–water. The study required resolving a discrepancy between these measurements and those in pure water. The data show that the lower basicity of large-ring cycloalkylamines is not due to enthalpy but to a more negative entropy of protonation. Computations show that this can be attributed in part to an entropy of conformational mixing, but the dominant contribution is steric hindrance to solvation, also corroborated by computation.

Large-ring cycloalkylamines are slightly less basic than other cycloalkylamines such as cyclohexylamine, even though all have tetrahedral carbons and are strain-free.     

Mono‐allyloxylated Cucurbit[7]uril Acts as an Unconventional Amphiphile To Form Light‐Responsive Vesicles

Serendipitously, mono‐allyloxylated cucurbit[7]uril (AO₁CB[7]) was discovered to act as an unconventional amphiphile which self‐assembles into light‐responsive vesicles (AO₁CB[7]VC) in water. Although the mono‐allyloxy group, directly tethered on the periphery of CB[7], is much shorter (C4) than the hydrophobic tails of conventional amphiphiles, it played an important role in vesicle formation. Light‐activated transformation of the allyloxy group by conjugation with glutathione was exploited as a remote tool to disrupt the vesicle. The vesicle showed on‐demand release of cargo upon irradiation by a laser, after they were internalized into cancer cells. This result demonstrated the potential of AO₁CB[7]VC as a new type of light‐responsive intracellular delivery vehicle for the release of therapeutic cargo, within cells, on demand.