Controlling the Assembly of Cellulose-Based Oligosaccharides through Sequence Modifications.

Peptides and nucleic acids with programmable sequences are widely explored for the production of tunable, self-assembling functional materials. Herein we demonstrate that the primary sequence of oligosaccharides can be designed to access materials with tunable shapes and properties. Synthetic cellulose-based oligomers were assembled into 2D or 3D rod-like crystallites. Sequence modifications within the oligosaccharide core influenced the molecular packing and led to the formation of square-like assemblies based on the rare cellulose IVII allomorph. In contrast, modifications at the termini generated elongated aggregates with tunable surfaces, resulting in self-healing supramolecular hydrogels.

Bottom-Up Approach to Understand Chirality Transfer across Scales in Cellulose Assemblies.

Cellulose is a polysaccharide that displays chirality across different scales, from the molecular to the supramolecular level. This feature has been exploited to generate chiral materials. To date, the mechanism of chirality transfer from the molecular level to higher-order assemblies has remained elusive, partially due to the heterogeneity of cellulose samples obtained via top-down approaches. Here, we present a bottom-up approach that uses well-defined cellulose oligomers as tools to understand the transfer of chirality from the single oligomer to supramolecular assemblies beyond the single cellulose crystal. Synthetic cellulose oligomers with defined sequences self-assembled into thin micrometer-sized platelets with controllable thicknesses. These platelets further assembled into bundles displaying intrinsic chiral features, directly correlated to the monosaccharide chirality. Altering the stereochemistry of the oligomer termini impacted the chirality of the self-assembled bundles and thus allowed for the manipulation of the cellulose assemblies at the molecular level. The molecular description of cellulose assemblies and their chirality will improve our ability to control and tune cellulose materials. The bottom-up approach could be expanded to other polysaccharides whose supramolecular chirality is less understood.

Manganese(I)-Catalyzed H-P Bond Activation via Metal-Ligand Cooperation.

Here we report that chiral Mn(I) complexes are capable of H-P bond activation. This activation mode enables a general method for the hydrophosphination of internal and terminal α,ß-unsaturated nitriles. Metal-ligand cooperation, a strategy previously not considered for catalytic H-P bond activation, is at the base of the mechanistic action of the Mn(I)-based catalyst. Our computational studies support a stepwise mechanism for the hydrophosphination and provide insight into the origin of the enantioselectivity.

The Role of Early-Career Chemists in European Policy-Making.

Global societal challenges emphasize the importance of collaboration between scientists and policy-makers, while the participation of a diverse group of professionals, including early-career scientists, is critical towards a sustainable future. The European Young Chemists' Network (EYCN) has been actively working with the European Chemical Society (EuChemS) to create a platform for early-career chemists in policy advice. This article comments on the possible roles of scientists in policy-making and provides an overview of relevant initiatives and platforms at the European level that could facilitate involvement. Opportunities for participation in policy advice from the perspective of early-career chemists are discussed and examples of impact are provided, hoping to stimulate further discussions and engagement in policy-making.

Diastereoselective Double C-H Functionalization of Chiral Ferrocenes with Heteroaromatics.

Diastereoselective double C-H heteroarylation of chiral ferrocenes provides valuable compounds with multiple functionalities using mild reaction conditions and simple reagents. Pd-Complexes with chiral mono-protected amino acids afforded corresponding heteroarylated ferrocenyl amines in good yields and high diastereomeric purities. In this way, a variety of indole, thiophene, pyrrole, or furan substituents were introduced to the ferrocene moiety. Furthermore, a range of relevant functional groups, for example ketone, ester, chloro, nitro, or silyl, are tolerated by this method. An alternative combination of amino acid and ferrocenyl amine configurations was leveraged to provide the complementary diastereomeric products. The products of C-H heteroarylation can be transformed into corresponding phosphines. Absolute configurations of CH-activation products were confirmed by the combination of X-ray crystallographic analysis and CD spectroscopy. 19 F NMR kinetic study and DFT calculations provided insights into the reaction mechanism and reasons governing stereoinduction.

Hybrid Peptide-Thiourea Catalyst for Asymmetric Michael Additions of Aldehydes to Heterocyclic Nitroalkenes.

Bifunctional organocatalysis combining covalent and noncovalent activation is presented. The hybrid peptide-thiourea catalyst features a N-terminal proline moiety for aldehyde activation and a thiourea unit for electrophile activation. This catalyst effectively promotes asymmetric Michael additions of aldehydes to challenging but biologically relevant heterocycle-containing nitroalkenes. The catalyst can be used under solvent-free conditions. Spectroscopic and density functional theory studies elucidate the catalyst structure and mode of action.

Progress and challenges in the synthesis of sequence controlled polysaccharides.

The sequence, length and substitution of a polysaccharide influence its physical and biological properties. Thus, sequence controlled polysaccharides are important targets to establish structure-properties correlations. Polymerization techniques and enzymatic methods have been optimized to obtain samples with well-defined substitution patterns and narrow molecular weight distribution. Chemical synthesis has granted access to polysaccharides with full control over the length. Here, we review the progress towards the synthesis of well-defined polysaccharides. For each class of polysaccharides, we discuss the available synthetic approaches and their current limitations.

Asymmetric copper-catalyzed conjugate additions of organometallic reagents in the syntheses of natural compounds and pharmaceuticals.

Access to enantiopure complex molecular structures is crucial for the development of new drugs as well as agents used in crop-protection. In this regard, numerous asymmetric methods have been established. Copper-catalyzed 1,4-additions of organometallic reagents are robust C-C bond formation strategies applicable in a wide range of circumstances. This review analyses the syntheses of natural products and pharmaceutical agents, which rely on the application of asymmetric Cu-catalyzed conjugate additions of various organometallic reagents. A wide range of available organometallics, e.g. dialkylzinc, trialkylaluminum, Grignard, and organozirconium, can now be used in conjugate additions to address various synthetic challenges present in targeted natural compounds. Furthermore, efficient catalysts allow high levels of stereofidelity over a diverse array of starting Michael acceptors.

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure.

Chiral derivatives of γ-aminobutyric acid are widely used as medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er.

Trapping of chiral enolates generated by Lewis acid promoted conjugate addition of Grignard reagents to unreactive Michael acceptors by various electrophiles.

Here we show trapping of chiral enolates with carbenium ions, Michael acceptors, and bromine. Silyl ketene aminals, disilyl acetals, and aza-enolates were obtained via Lewis acid mediated enantioselective conjugate addition of Grignard reagents to unsaturated amides, carboxylic acids and alkenyl heterocycles.