SO1: Develop electricity-triggered enantioselective organocatalytic cascade processes to rapidly synthesise chiral lactones, piperidines, and tetralins with high enantiopurity. The cascades will capitalise upon the electro-reactivity of chiral iminium ions to generate molecular complexity from simple substrates
Two novel methods for constructing enantioenriched heterocyclic products have been partially developed. These methods employ chiral amine and chiral aluminum metal complexes as catalysts under electricity and photoelectrochemical conditions, respectively (see Section 1.2 for details). The scientific objective SO1 has been met with these new approaches, although further optimization is needed. Currently, the methods achieve 65% yield and 11% enantiomeric excess (ee). Future success in optimizing these methods is anticipated to meet the milestones (M1.1–2) for synthesizing 15 examples of compound 6 and 10 examples of compound 8 with high enantiopurity.
Additionally, during the project period, a new organocatalytic Birch reduction method utilizing photochemistry was discovered. The manuscript detailing this innovative work is nearing submission to a high-impact scientific journal (M4.1).
SO2: Functionalize and modify the compounds obtained using the above methodologies to access previously elusive natural-like scaffolds, followed by demonstration of the applicability of the methodology to industrial R&D through biological screening and scale-up of the electrochemical protocol.
The method is still undergoing optimization, which has delayed the synthesis of target compounds for functionalization. Consequently, we were unable to advance to industrial R&D applications, including biological screening and scale-up of the electrochemical protocol. Further work is required to achieve the desired yields and enantiopurity before these applications can be explored.
TO-1: To expand my knowledge of cascade reactions and asymmetric organocatalysis
Significant knowledge has been acquired in the areas of electrochemistry, asymmetric organocatalysis, and photoredox catalysis through rigorous scientific experimentation, training, and discussions with colleagues both within the institution and at conferences.
TO-2: To improve technical knowledge
Extensive technical knowledge has been gained in using electricity and light to drive chemical reactions. The fellow has received comprehensive training in operating and modulating electrochemical equipment and various LED systems, including high-power blue, green, purple, and UV light sources. They have also gained expertise in using irradiation reactors equipped with cooling systems to maintain optimal reaction conditions.
The fellow has developed skills in photophysical studies to gain a deeper understanding of photochemical processes at the molecular level. This includes techniques such as emission quenching, transient absorption spectroscopy, quantum yield measurement, and UV-Vis absorption spectroscopy.
In addition, the fellow has conducted extensive organic synthesis throughout the project. Through hands-on experimentation and problem-solving, they have significantly advanced their skills in organic synthesis, broadening their practical knowledge and technical capabilities.
TO-3: To gain expertise in drug discovery
Expertise in drug discovery was a key objective of the project. However, progress in this area was limited due to the challenges faced in achieving successful outcomes with the developed technology. The inability of the technology to produce viable drug candidates impacted the advancement of this objective.
Despite these challenges, connections with industry partners provided valuable insights and contributed to a broader understanding of the drug discovery process. Collaborations and discussions with the company helped in gaining a better grasp of the practical applications and requirements in the field, although they did not fully compensate for the project's limitations in delivering drug candidates. This experience underscored the importance of integrating both scientific and industrial perspectives in advancing drug discovery efforts.
TO-4: To improve my writing and communication skills
Significant progress was made in enhancing scientific writing and communication skills throughout the project. The fellow actively engaged in drafting scientific literature, contributing to the preparation of manuscripts for publication. This hands-on experience with writing and revising scientific documents provided valuable practice in articulating complex ideas clearly and effectively.
Additionally, the fellow improved their oral communication skills through regular presentations in group meetings, where they discussed research progress and findings with colleagues. Participation in international conferences, such as the 4th International Conference on Hydrogen Atom Transfer (iCHAT 2024) held in Rome, Italy, in June 2024, further bolstered these skills. Presenting research to a broader audience at such conferences not only enhanced the fellow's ability to convey scientific concepts but also provided opportunities for networking and receiving constructive feedback from experts in the field.
TO-5: To develop mentoring and supervising skills
During the project, the fellow developed strong mentoring and supervising skills by guiding laboratory members and directly supervising one PhD student. This involved providing practical and scientific support, ensuring alignment with project goals, and fostering the student’s research development.
TO-6: To improve my management and leadership skills
During the project, Prof. Melchiorre provided guidance on planning and coordinating research, delivering results, managing financial resources, and handling administrative tasks. Additionally, ICIQ (the original host institution) offered the “Leadership in Action for Postdocs” course (BIST-Vitae), which equipped me with tools for managing a research team, as well as skills in financial and time management.
TO-7: To improve my awareness of the importance of sustainability
The fellow enhanced their understanding of sustainable chemistry with guidance from Prof. Melchiorre and through participation in seminars and training activities organized by ICIQ, the original host institution. This knowledge was further expanded during the transition to the University of Bologna, where continued emphasis was placed on reducing the environmental impact of research practices.
