Synergistic catalysis: Michael addition of acyl-pyridines

A new diastereo- and enantioselective strategy for the functionalization of 2-acetyl-pyridine with α,β-unsaturated aldehydes has been investigated through synergistic catalysis. In particular, the aim of the work was to use cinnamaldehydes bearing different substituents on the phenyl group and to study its effect on the yield, conversion and stereoselectivity of the reaction. The reaction mechanism involves combined iminium ion and transition metal catalysis in a synergistic fashion and proceeds with two consecutives Michael additions, followed by final intramolecular aldol condensation to yield the formation of three new stereogenic carbons, with high to excellent stereoselectivities. The structures of the molecules obtained were fully characterized by NMR spectroscopy. After having assigned the relative configuration by NOE-NMR and 2D-COSY experiments, conformational analysis was performed by DFT calculations to find the most stable molecular conformations. The absolute configuration of each diastereoisomer was then eventually assigned by quantum mechanical simulations of the Electronic and Vibrational Circular Dichroism spectra

Exploring new aspects of radical molecular machinery: studies and perspectives in the field of paramagnetic architectures.

The challenge of achieving molecular devices able to reproduce the impressive features of biological nano-machines has been attracting the interest of many scientists during the last decades. At present, several examples of artificial molecular machines based on mechanically interlocked molecules (MIMs) have been reported, which are able to perform a wide set of highly complex motions. On the other hand, the increasing complexity of molecular machines designed by scientists requires also new analytical approaches capable to characterize the nanoscale processes affecting these kind of systems. To this aim, the covalent incorporation of stable paramagnetic moieties inside the structure of artificial MIMs enables to use Electronic Paramagnetic Resonance spectroscopy (EPR) for monitoring the dynamics of the target structures. In this scenario, this research focused on the design, synthesis and EPR study of novel supramolecular architectures containing persistent nitroxide groups and employable in the field of radical molecular machines. The Chapter 3 of this manuscript describes the design, synthesis and EPR reduction kinetic studies of two novel crown-ether macrocycles containing a persistent nitroxide group into their structure. In Chapter 4 the use of 2-phenyl-2-cyanopropanoic acid as single fuel for promoting the full back and forth cycle of motions of an acid-base switchable nitroxide-labelled rotaxane was investigated. In the investigation reported in Chapter 5, EPR studies combined with GC-MS analysis were performed for monitoring the aerobic catalytic cycle of oxidation of 4-methoxy benzyl alcohol in the presence of a nitroxide-based macrocycle and cerium ammonium nitrate as co-catalyst. Chapter 6 describes the synthesis of a novel synthetic crown-ether macrocycle containing a stable nitroxide moiety into the structure and the EPR investigation of its complexation properties toward organic and inorganic guests

Synergistic catalysis: Highly enantioselective acetyl aza-arene addition to enals

A novel catalytic enantioselective methodology based on synergistic catalysis for the synthesis of chiral 2‐acyl pyridines and pyrazines is reported. The strategy involves the metal–Lewis acid activation of acetyl aza‐arenes and the secondary‐amine activation of enals. The proposed mechanism is supported by DFT calculations

Rotaxane-catalyzed aerobic oxidation of primary alcohols

Nitroxide radicals are widely utilized as catalysts for the oxidation of primary alcohols. Here, the aerobic catalytic oxidation cycle of nitroxide radicals has been implemented within a mechanically interlocked rotaxane architecture consisting of a paramagnetic crown ether, which is confined by a molecular axle containing a dialkylammonium station and a 1,2,3-triazole unit. The rotaxane is engineered to exploit the oxidation of a primary alcohol: the primary catalyst is the wheel, a nitroxide radical capable of altering its oxidation state during the catalytic cycle, while the co-oxidant is the Cerium(IV)/O2 couple. The synthesis of the proposed rotaxane, along with its characterization using EPR, HRMS, voltammetry and NMR data, is reported in the paper. The aerobic catalytic oxidation cycle was further investigated using EPR,NMR and GC-MS analyses. This study can aid in the design of autonomously driven molecular machines that exploit the aerobic catalytic oxidation of nitroxide radicals