Giovanni Maestri

Expeditious synthesis of phenanthridines from benzylamines via dual palladium catalysis.

A method for the synthesis of phenanthridines from benzylamines and aryl iodides which uses a dual palladium-catalyzed process is developed. The domino sequence ends via an intramolecular amination and an oxidative dehydrogenation. No protecting group or prefunctionalization of the amine is required, and the process uses dioxygen as the terminal oxidant.

A catalytic synthesis of selectively substituted biaryls through sequential intermolecular coupling involving arene and ketone C–H bond functionalization

Selectively substituted biaryls containing a ketone unit are obtained under mild conditions in satisfactory yields by a simple reaction of ortho-substituted aryl iodides and ketones in the presence of palladium and norbornene as catalysts.

Palladium/Norbornene Catalytic System: Chelation as a Tool To Control Regioselectivity of Pd(IV) Reductive Elimination

Palladium/norbornene joint catalysis gives rise to a unique system in which the three most common formal oxidation states of the metal are at work in the same cycle (0, II, and IV). This paper summarizes a selection of synthetic applications and the feasibility of Pd(IV) formation by oxidative addition of aryl halides. On this intermediate, the presence of a suitable chelating group could trigger unexpected aryl-norbornyl coupling, further broadening the scope of readily available polycyclic frameworks.

Synthesis of marmycin A and investigation into its cellular activity

Anthracyclines such as doxorubicin are used extensively in the treatment of cancers. Anthraquinone-related angucyclines also exhibit antiproliferative properties and have been proposed to operate via similar mechanisms, including direct genome targeting. Here, we report the chemical synthesis of marmycin A and the study of its cellular activity. The aromatic core was constructed by means of a one-pot multistep reaction comprising a regioselective Diels-Alder cycloaddition, and the complex sugar backbone was introduced through a copper-catalysed Ullmann cross-coupling, followed by a challenging Friedel-Crafts cyclization. Remarkably, fluorescence microscopy revealed that marmycin A does not target the nucleus but instead accumulates in lysosomes, thereby promoting cell death independently of genome targeting. Furthermore, a synthetic dimer of marmycin A and the lysosome-targeting agent artesunate exhibited a synergistic activity against the invasive MDA-MB-231 cancer cell line. These findings shed light on the elusive pathways through which anthraquinone derivatives act in cells, pointing towards unanticipated biological and therapeutic applications.

Formal base-free homolytic aromatic substitutions via photoredox catalysis

We developed a simple and convenient method to assemble biaryls exploiting a photoredox catalyst and visible light. Diazonium salts generate aryl radicals that could then add on unactivated (hetero)arenes and the sequence eventually delivers products via formal homolytic aromatic substitutions. The direct C–H arylation of these usually unreactive substrates is achieved at room temperature using low catalyst loadings and shows broad functional group tolerance.

Boosting catalyst activity in cis-selective semi-reduction of internal alkynes by tailoring the assembly of all-metal aromatic tri-palladium complexes

Highly symmetric [Pd3]+ clusters that present delocalized metal-metal bonds can catalyse the selective semi-reduction of internal alkynes to cis-alkenes. Studies on factors governing the formation of all-metal aromatics enabled the design of an optimised catalytic system that delivers cis-alkenes with almost complete selectivity on a gram scale with very low catalyst loadings (0.03 mol%).

Silica-supported sulfonic acids as recyclable catalyst for esterification of levulinic acid with stoichiometric amounts of alcohols

Summary Converting biomass into value-added chemicals holds the key to sustainable long-term carbon resource management. In this context, levulinic acid, which is easily obtained from cellulose, is valuable since it can be transformed into a variety of industrially relevant fine chemicals. Here we present a simple protocol for the selective esterification of levulinic acid using solid acid catalysts. Silica supported sulfonic acid catalysts operate under mild conditions and give good conversion and selectivity with stoichiometric amounts of alcohols. The sulfonic acid groups are tethered to the support using organic tethers. These tethers may help in preventing the deactivation of the active sites in the presence of water.

Pd-Catalyzed/Iodide-Promoted α-Arylation of Ketones for the Regioselective Synthesis of Isocoumarins

A variety of isocoumarins have been synthesized directly from 2-halobenzoates and ketones through a palladium-catalyzed α-arylation step followed by an intramolecular cyclization process. The addition of iodide anions to the reaction mixture increased yields and selectivities especially when 2-bromobenzoates were employed. This phosphine-free one-pot synthesis features a high functional group tolerance and gives access to richly decorated isocoumarins. This general methodology was successful in the total synthesis of Xyridin A, an important natural product with antibacterial and antifungal activity.

Batch versus Flow Acetalization of Benzaldehyde with HKUST‐1: Diffusion Pathways and Performance Comparison

Understanding the poisoning and deactivation pathways of metal–organic frameworks (MOFs) is an essential goal to boost their application as robust and efficient catalysts in chemical transformations relevant to industrial processes. Herein, the acetalization reaction of benzaldehyde with methanol was investigated by using [Cu3(BTC)2] (BTC=1,3,5‐benzenetricarboxylate) as a catalyst. The reaction was performed under batch and continuous flow conditions, and the conversion of benzaldehyde into 1,1‐dimethoxytoluene proceeded efficiently in the presence of a modest amount of water. Nevertheless, a drastic reduction in the catalytic activity was observed after recycling the MOF for repetitive batch experiments and after prolonged continuous flow tests. Pore clogging of the MOF and partial crystal‐structure modifications, gathered from XRD and pore analyses, suggested grinding the catalyst prior to application; the ground catalyst showed a considerable enhancement in catalytic performance.

Selective monomethyl esterification of linear dicarboxylic acids with bifunctional alumina catalysts

An environmentally friendly protocol for the selective protection of dicarboxylic acids is reported using methanol as a cheap esterifying agent and alumina as a heterogeneous catalyst; the selectivity of the process has been ascribed to a balanced acidity/basicity of the bifunctional alumina catalyst.