Construction of Quaternary Stereocenters by Palladium‐Catalyzed Carbopalladation‐Initiated Cascade Reactions

The enantioselective synthesis of molecules containing quaternary stereocenters is a field of intense research interest and development. Among the known organic transformations, carbopalladation‐initiated domino transformations constitutes a general method for the construction of compounds containing cyclic or spiro quaternary stereocenters. In this Minireview, recent achievements in palladium‐catalyzed domino Heck/C?H functionalizations and developments in enantioselective carbopalladation‐initiated domino processes are summarized.     

Copper‐Catalyzed Enantioselective Construction of Tertiary Propargylic Sulfones

Tertiary propargylic sulfones are of significant importance in organic synthesis and medicinal chemistry, but to date no general asymmetric synthesis approach has been developed. We disclose a versatile copper‐catalyzed sulfonylation of propargylic cyclic carbonates using sodium sulfinates that allows the construction of propargylic sulfones featuring elusive quaternary stereocenters. This method provides the first successful example of such an enantioselective propargylic sulfonylation, features high asymmetric induction, wide functional group tolerance, and scalability, and enables attractive product diversification.     

Palladium‐Catalyzed Construction of Quaternary Stereocenters by Enantioselective Arylation of γ‐Lactams with Aryl Chlorides and Bromides

Herein, we report the first Pd‐catalyzed enantioselective arylation of α‐substituted γ‐lactams. Two sets of conditions were developed for this transformation, allowing for the use of either aryl chlorides or bromides as electrophiles. Utilizing a highly electron‐rich dialkylphosphine ligand we have been able to construct α‐quaternary centers in good yields (up to 91 % yield) and high enantioselectivities (up to 97 % ee).     

Nonlinear Optical Switching in Regioregular Porphyrin Covalent Organic Frameworks

Covalent organic frameworks (COFs) have garnered immense scientific interest among porous materials because of their structural tunability and diverse properties. However, the response of such materials toward laser‐induced nonlinear optical (NLO) applications is hardly understood and demands prompt attention. Three novel regioregular porphyrin (Por)‐based porous COFs—Por‐COF‐HH and its dual metalated congeners Por‐COF‐ZnCu and Por‐COF‐ZnNi—have been prepared and present excellent NLO properties. Notably, intensity‐dependent NLO switching behavior was observed for these Por‐COFs, which is highly desirable for optical switching and optical limiting devices. Moreover, the efficient π‐conjugation and charge‐transfer transition in ZnCu‐Por‐COF enabled a high nonlinear absorption coefficient (β=4470 cm/GW) and figure of merit (FOM=σ₁/σ_o, 3565) value compared to other state‐of‐the‐art materials, including molecular porphyrins (β≈100–400 cm/GW), metal–organic frameworks (MOFs; β≈0.3–0.5 cm/GW), and graphene (β=900 cm/GW).     

Disulfide‐Unit Conjugation Enables Ultrafast Cytosolic Internalization of Antisense DNA and siRNA

Development of intracellular delivery methods for antisense DNA and siRNA is important. Previously reported methods using liposomes or receptor‐ligands take several hours or more to deliver oligonucleotides to the cytoplasm due to their retention in endosomes. Oligonucleotides modified with low molecular weight disulfide units at a terminus reach the cytoplasm 10 minutes after administration to cultured cells. This rapid cytoplasmic internalization of disulfide‐modified oligonucleotides suggests the existence of an uptake pathway other than endocytosis. Mechanistic analysis revealed that the modified oligonucleotides are efficiently internalized into the cytoplasm through disulfide exchange reactions with the thiol groups on the cellular surface. This approach solves several critical problems with the currently available methods for enhancing cellular uptake of oligonucleotides and may be an effective approach in the medicinal application of antisense DNA and siRNA.     

Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal PtII Metallacycle

Metal‐driven self‐assembly afforded a multitude of fascinating supramolecular coordination complexes (SCCs) with applications as catalysts, host–guest, and stimuli‐responsive systems. However, the interest in the biological applications of SCCs is only starting to emerge and thorough characterization of their behavior in biological milieus is still lacking. Herein, we report on the synthesis and detailed in‐cell tracking of a Pt₂L₂ metallacycle. We show that our hexagonal supramolecule accumulates in cancer cell nuclei, exerting a distinctive blue fluorescence staining of chromatin resistant to UV photobleaching selectively in nucleolar G4‐rich regions. SCC co‐localizes with epitopes of the quadruplex‐specific antibody BG4 and replaces other well‐known G4 stabilizers. Moreover, the photophysical changes accompanying the metallacycle binding to G4s in solution (fluorescence quenching, absorption enhancement) also take place intracellularly, allowing its subcellular interaction tracking.     

Chemical Bonding in Polarised Push–Pull Ethylenes

1,1‐Diamino‐2,2‐bis(triflyl)ethylenes with both twisted and planar structures around the partial “C=C” bond were synthesised. Bonding properties in these compounds were analysed by an experimental approach using high‐resolution X‐ray diffraction data treated with X‐ray wavefunction refinement (XWR). In the twisted compound, a dominant contribution of the charge‐separated resonance structure was revealed. On the contrary, the nearly planar compound still showed π‐bonding character, however, with a considerable contribution of the charge‐separated resonance structure.     

Lewis Base/Brønsted Acid Co‐catalyzed Enantioselective Sulfenylation/Semipinacol Rearrangement of Di‐ and Trisubstituted Allylic Alcohols

An enantioselective sulfenylation/semipinacol rearrangement of 1,1‐disubstituted and trisubstituted allylic alcohols was accomplished with a chiral Lewis base and a chiral Brønsted acid as cocatalysts, generating various β‐arylthio ketones bearing an all‐carbon quaternary center in moderate to excellent yields and excellent enantioselectivities. These chiral arylthio ketone products are common intermediates with many applications, for example, in the design of new chiral catalysts/ligands and the total synthesis of natural products. Computational studies (DFT calculations) were carried out to explain the enantioselectivity and the role of the chiral Brønsted acid. Additionally, the synthetic utility of this method was exemplified by an enantioselective total synthesis of (?)‐herbertene and a one‐pot synthesis of a chiral sulfoxide and sulfone.     

Secondary-Ion Mass Spectrometry Images Cardiolipins and Phosphatidylethanolamines at the Subcellular Level

Millions of diverse molecules constituting the lipidome act as important signals within cells. Of these, cardiolipin (CL) and phosphatidylethanolamine (PE) participate in apoptosis and ferroptosis, respectively. Their subcellular distribution is largely unknown. Imaging mass spectrometry is capable of deciphering the spatial distribution of multiple lipids at subcellular levels. Here we report the development of a unique 70 keV gas-cluster ion beam that consists of (CO₂)_n⁺(n>10 000) projectiles. Coupled with direct current beam buncher-time-of-flight secondary-ion mass spectrometry, it is optimized for sensitivity towards high-mass species (up to m/z 3000) at high spatial resolution (1 μm). In combination with immunohistochemistry, phospholipids, including PE and CL, have been assessed in subcellular compartments of mouse hippocampal neuronal cells and rat brain tissue.