Enantioselective halogenative semi-pinacol rearrangement: a stereodivergent reaction on a racemic mixture

An efficient, quantitative deracemization strategy for optically inactive allylic cycloalkanols has been achieved using the biphasic halogenative semi-pinacol reaction protocol. The resultant β-halo spiroketones, containing three contiguous stereogenic centers, were easily recovered with high diastereomeric and enantiomeric purities following conventional silica gel chromatography. The optically active products could be further manipulated chemically, affording synthetically interesting scaffolds with complete preservation of stereoisomeric integrity

A Strategy to Synthesize Molecular Knots and Links Using the Hydrophobic Effect

Conventional approaches to the synthesis of molecular knots and links mostly rely on metal templation. We present here an alternative strategy that uses the hydrophobic effect to drive the formation of complex interlocked structures in water. We designed an aqueous dynamic combinatorial system that can generate knots and links. In this system, the self-assembly of a topologically complex macrocycle is thermodynamically favored only if an optimum packing of all its components minimizes the hydrophobic surface area in contact with water. Therefore, the size, geometry, and rigidity of the initial building blocks can be exploited to control the formation of a specific topology. We illustrate the validity of this concept with the syntheses of a Hopf link, a Solomon link, and a trefoil knot. This latter molecule, whose self-assembly is templated by halides, binds iodide with high affinity in water. Overall, this work brings a fresh perspective on the synthesis of topologically complex molecules: Solvophobic effects can be intentionally harnessed to direct the efficient and selective self-assembly of knots and links

Synchronized On/Off Switching of Four Binding Sites for Water in a Molecular Solomon Link

A molecular Solomon link adopts different conformations in acetonitrile (1) and in water (2). Contrary to expectations, the main driving force of the transformation is not the change in medium polarity, but the cooperative binding of about four molecules of water, forming a tiny droplet in the central cavity of 2. Mechanistic studies reveal that the four binding sites can simultaneously switch between an inactive state (unable to bind water) and an active state (able to bind water) during the transformation. Spatial and temporal coordination of switching events is commonly observed in biological systems but has been rarely achieved in artificial systems. Here, the concerted activation of the four switchable sites is controlled by the topology of the whole molecule

Enantioselective Halogenative Semi-Pinacol Rearrangement: Extension of Substrate Scope and Mechanistic Investigations

The present Full Paper article discloses a survey of our recent results obtained in the context of the enantioselective halogenation-initiated semi-pinacol rearrangement. Commencing with the fluorination/semi-pinacol reaction first and moving to the heavier halogens (bromine and iodine) second, the scope and limitations of the halogenative phase-transfer methodology will be discussed and compared. An extension of the fluorination/semi-pinacol reaction to the ring-expansion of five-membered allylic cyclopentanols will be also described, as well as some preliminary results on substrates prone to desymmetrization will be given. Finally, the present manuscript will culminate with a detailed mechanistic investigation of the canonical fluorination/semi-pinacol reaction. Our mechanistic discussion will be based on in situ reaction progress monitoring, complemented with substituent effect, kinetic isotopic effect and non-linear behaviour studies

Enantioselective Catalytic Fluorinative Aza-semipinacol Rearrangement

An efficient and highly stereoselective fluorinative aza-semipinacol rearrangement is described. The catalytic reaction requires use of Selectfluor in combination with the chiral, enantiopure phosphate anion derived from acid L3. Under optimized conditions, cyclopropylamines A were transformed into β-fluoro cyclobutylimines B in good yields and high levels of diastereo- and enantiocontrol. Furthermore, the optically active cyclobutylimines were reduced diastereoselectively with L-Selectride in the corresponding fluorinated amines C, compounds of significant interest in the pharmacological industry

Imine-based [2]catenanes in water

We report the efficient condensation of imine-based macrocycles from dialdehyde A and aliphatic diamines Bn in pure water. Within the libraries, we identified a family of homologous amphiphilic [2]catenanes, whose self-assembly is primarily driven by the hydrophobic effect. The length and odd-even character of the diamine alkyl linker dictate both the yield and the conformation of the [2]catenanes, whose particular thermodynamic stability further shifts the overall equilibrium in favour of imine condensation. These findings highlight the role played by solvophobic effects in the self-assembly of complex architectures

Intracluster ligand rearrangement: an NMR-based thermodynamic study

Ligand and metal exchange reactions are powerful methods to tailor the properties of atomically precise metal nanoclusters. Hence, a deep understanding of the mechanisms behind the dynamics that rule the ligand monolayer is crucial for its specific functionalization. Combining variable-temperature NMR experiments and dynamic-NMR simulations, we extract the thermodynamic activation parameters of a new exchange reaction: the intracluster ligand rearrangement between the two symmetry-unique positions in [Ag25(DMBT)18]− and [Ag24Au(DMBT)18]− clusters. We report for the first time that this peculiar intracluster modification does not seem to proceed via metal–sulphur bond breaking and follows a first-order rate law, being therefore a process independent from the well-described collisional ligand exchange.</p

Role of Intercluster and Interligand Dynamics of [Ag₂₅(DMBT)₁₈]⁻ Nanoclusters by Multinuclear Magnetic Resonance Spectroscopy

Even though gold and silver belong to the same group of the periodic table, they provide significantly different nanocluster (NC) structures in terms of both nuclearities and ligand coordination motifs. Until today, only one isostructural gold analogue has been found for silver nanoclusters, [Ag25(DMBT)18]−, and it is only obtained by using 2,4-dimethylbenzenethiol (DMBT) as the ligand. Our study of the dynamics of DMBT ligands in metal NCs using multinuclear magnetic resonance spectroscopy demonstrates that DMBT favors the formation of two types of interligand interactions, i.e., H−π and π–π. These interactions stabilize the entire nanocluster, yet we observe that thermal and chemical stimuli have the capability to weaken the [Ag25(DMBT)18]− structure triggering irreversible decomposition. Moreover, employing 2D-NMR spectroscopy we demonstrate the intercluster exchange of DMBT ligands and their temperature dependence