Publications

Visible-Light Paternò-Büchi Dearomatisation Process Towards the Construction of Oxeto-Indolinic Polycycles

Javier Mateos, Alberto Vega-Peñaloza, Pietro Franceschi, Francesco Rigodanza, Xavier Companyó,* Philip Andreetta, Giorgio Pelosi, Marcella Bonchio, and Luca Dell’Amico *

Abstract

A variety of highly functionalised N-containing polycycles (35 examples) are synthetised from simple indoles and aromatic ketones through a mild visible-light Paternò-Büchi process. Tetrahydrooxeto[2,3-b]indole scaffolds, with up to three contiguous all-substituted stereocenters, are generated in high yield (up to >98%) and excellent site- regio- and diastereocontrol (>20:1). The use of visible light (405 or 465 nm) ensures enhanced performances by switching off undesired photodimerisation side reactions. The reaction can be easely implemented under a microfluidic photoreactor with improved productivity (up to up to 0.176 mmol·h-1) and generality. Mechanistic investigations revealed that two alternative reaction mechanisms can account for the excellent regio- and diasterecontrol observed.

Chem. Sci.,  2020, DOI: 10.1039/D0SC01569E

h

Naphthochromenones: Organic Bimodal Photocatalysts Engaging in Both Oxidative and Reductive Quenching Processes

Javier Mateos, Francesco Rigodanza, Alberto Vega, Andrea Sartorel, Mirco Natali, Tommaso Bortolato, Giorgio Pelosi, Xavier Companyó, Marcella Bonchio, Luca Dell’Amico*

Abstract

12 different naphthochromenone photocatalysts (PCs) have been synthesized at gram–scale, combining absorption features across the UV–Vis spectrum, up to 440 nm with an extremely wide redox window (up to 3.22 eV) that is accessible using simple visible light irradiation sources (CFL or LED). Their excited state redox potentials, PC*/PC ●– = up to 1.65 V and PC ●+ /PC* up to –1.77 V vs SCE, are such that these novel PCs can engage in both oxidative and reductive quenching mechanisms with strong thermodynamic requirements . Converging absorption/emission spectroscopy and cyclic voltammetry we delineate robust structure–properties relationships, that are further supported by time–dependent density functional theory (TD–DFT) calculations. The potential of these bimodal PCs has been benchmarked in thermodynamically challenging photocatalytic processes, were strong oxidative (> 1.46 V) and strong reductive power (< –1.96 V) is required. Further advantages are given by their simple recovery and reuse – up to four times, without any significant loss in their photocatalytic performances. The ability of efficiently catalysing mechanistically opposite oxidative/reductive photoreactions is a unique feature for organic photocatalysts. This new class of molecules represents a decisive advancement towards generality, sustainability and cost efficiency in photoredox catalysis.

Angew. Chem. Int. Ed. 2020, 59, 1302-1312. DOI: 10.1002/anie.201912455

Profiling the Privileges of Pyrrolidine-Based Catalysts in Asymmetric Synthesis: From Polar to Light-Driven Radical Chemistry

Alberto Vega-Peñaloza, Suva Paria, Marcella Bonchio, Luca Dell’Amico*, Xavier Companyó*

Abstract

Asymmetric catalysis is a rapidly evolving field in synthetic chemistry. This is due to the growing needs of stereoselective synthetic routes to access enantiopure natural products and bioactive molecules. An efficient approach involves the use of readily available and robust catalysts, while ensuring high yields and stereocontrol. In this scenario, the pyrrolidine-based catalyst has played a dominant role over the past decades. Interestingly, simple scaffold modifications result in dramatic physicochemical and reactivity changes. These features have facilitated the generation of different catalyst variants for the development of highly diversified asymmetric transformations. In this Perspective, we analyze the structural evolution of the pyrrolidine-based catalyst, moving from polar to light-induced radical processes. We discuss the concepts underpinning the most relevant scaffold modifications while defining structure–reactivity relationships. The present work will encourage a rational scaffold design toward unprecedented reactivity pathways and improved catalytic performances.

ACS Catal. 2019, 9, 6058-6072. DOI:  10.1021/acscatal.9b01556

Acetaldehyde Silyl Enol Ethers in Enantioselective Mukaiyama Aldol Reactions: Enzyme-Like Organocatalysis in Action

Luca Dell’Amico*, Franca Zanardi*

Abstract

Touched for the very first time! It is herein highlighted how acetaldehyde silyl enol ethers undergo enantioselective Mukaiyama aldol reaction with aliphatic and aromatic aldehydes. The chemistry relies on the use of the highly efficient and substrate‐selective imidodiphosphorimidate catalyst, which displays some of the features of enzymatic catalysis.

Angew. Chem. Int. Ed. 2019, 58, 3264-3266. DOI:  10.1002/anie.201812964

Microfluidic light-driven synthesis of tetracyclic molecular architectures

Javier Mateos, Nicholas Meneghini, Marcella Bonchio, Nadia Marino, Tommaso Carofiglio, Xavier Companyó* and Luca Dell’Amico*

Abstract

Herein we report an effective synthetic method for the direct assembly of highly functionalized tetracyclic pharmacophoric cores. Coumarins and chromones undergo diastereoselective [4 + 2] cycloaddition reactions with light-generated photoenol intermediates. The reactions occur by aid of a microfluidic photoreactor (MFP) in high yield (up to >98%) and virtually complete diastereocontrol (>20:1 dr). The method is easily scaled-up to a parallel setup, furnishing 948 mg of product over a 14 h reaction time. Finally, a series of manipulations of the tetracyclic scaffold obtained gave access to valuable precursors of biologically active molecules.

Beilstein J. Org. Chem. 2018,14, 2418–2424. DOI :10.3762/bjoc.14.219 

Transition Metal‐Free CO2 Fixation into New Carbon–Carbon Bonds

Alessio Cherubini‐Celli, Javier Mateos, Marcella Bonchio*, Luca Dell’Amico*, Xavier Companyó*

Abstract

CO2 is the ultimate renewable carbon source on Earth and the essential C1 building block for carbohydrate biosynthesis in photosynthetic organisms. Modern synthetic chemistry is facing the key challenge of developing fundamental transformations, such as C−C bond formation, in a sustainable and efficient manner from renewable sources. In this Minireview, the most significant methods recently reported for CO2 fixation under transition metal‐free conditions are summarized, organized into three different chapters according to the nature of the chemical transformation that forges the new C−C bond. The focus is on the mechanistic aspects of the different CO2 activation modes, with specific attention to those systems that operate under catalytic conditions.

ChemSusChem 2018,11, 3056–3070. DOI : 10.1002/cssc.201801063

A microfluidic photoreactor enables 2-methylbenzophenone light-driven reactions with superior performance

Javier Mateos, Alessio Cherubini-Celli, Tommaso Carofiglio, Marcella Bonchio, Nadia Marino, Xavier Companyó* and Luca Dell’Amico*

Abstract

Light-driven reactions of 2-methylbenzophenones (2-MBPs) occur with improved yields (up to >98%) and reaction rates (up to 0.240 mmol h−1) by using a tailored microfluidic photoreactor (MFP). For the first time, coumarins were converted into 4-benzylated chromanones in high yields (50–93%) and diastereoselectivity (up to >20 : 1 dr), thus by-passing their photo-dimerisation end-reaction

Chem. Commun., 2018, 54, 6820-6823 . DOI: 10.1039/C8CC01373J