PhotoPhos · Photoinduced Decarboxylative Phosphorylations
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-09-01 → 2023-08-31
- EU contribution
- €224,934
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Photoinduced Decarboxylative Phosphorylations
Periodic Reporting for period 1: Reporting period: 2021-09-01 to 2023-08-31 Summary of the context and overall objectives of the project: Alkyl phosphonates play a ubiquitous role across diverse domains such as pharmaceuticals, agrochemicals, and materials science. Streamlining their synthesis could be significantly enhanced by harnessing readily available C(sp3) alkyl radicals—a versatile class of synthetic intermediates derived from carboxylic acid precursors under photocatalytic conditions. Presently, challenges persist in effecting alkyl radical addition to phosphite reagents due to their inherent low reactivity with phosphites and reversible addition through a-scission. This work proposes the introduction of a novel phosphite reagent termed 'BecaP,' characterized by a radical-stabilizing catechol group and an efficient leaving moiety, specifically designed for trapping alkyl radicals. Utilizing visible light as a sustainable energy source, this reagent facilitates the synthesis of alkyl phosphonates in an irreversible manner. Leveraging recent advancements in decarboxylative borylation pathways, this initiative aims to significantly broaden photochemical methodologies, pioneering novel techniques for synthesizing organophosphorus compounds. The envisioned project, situated at the University of Bristol, represents a pioneering endeavor seeking to expand the frontiers of synthetic chemistry. Its success hinges upon the generation, transfer, and dissemination of knowledge, fostering an environment conducive to innovation. Moreover, this endeavor aligns with a comprehensive training plan, fostering professional development while contributing to the advancement of synthetic methodologies in this domain. • What is the problem/issue being addressed? This project aims to address two key questions: 1. Development of novel visible-light-mediated photocatalytic decarboxylative phosphonylation methods for the broad range of C(sp 3 ) alkyl radicals, which was unprecedented by visible light photocatalysis before. 2. Applications of the developed method in the late-stage phosphonylations of drugs and synthesis of biologically active molecules e.g. Phaclofen • Why is it important for society? Organic chemistry is integral to the well-being of our society. It is through inventing and developing new reactions that we can identify the next generation of drugs, agrochemicals, and pharmaceuticals. From this perspective, the use of visible light to promote phosphonylation reactions might offer great opportunities in terms of sustainability. • What are the overall objectives? 1 To develop novel approaches for the preparation of alkyl phosphonates. 2 To develop a robust phosphite reagent for less reactive alkyl radicals. 3 To apply the developed method in drug synthesis and late-stage drug modifications.
Data: CORDIS, © European Union
Project objective
This proposed Fellowship brings together an Experienced Researcher from India (Ph.D. in Germany and Postdoc in Japan with an excellent academic and research background), with expertise in photocatalysis, methodology, and total synthesis, with an internationally recognized Host Laboratory in the UK under the expert supervision of Prof. Varinder K. Aggarwal FRS. His research interests focus on total synthesis, asymmetric synthesis, photoredox-driven processes, and the development of new reactivity in organic chemistry, in particular, boron chemistry.The successful realization of this highly interdisciplinary project will:➢Enhance European excellence in organic synthesis and catalysis, which are fundamentally important branches of chemistry.➢Enable the ER to acquire new skills in the field of organophosphorus chemistry, EDA complexes, metal-free reactions, and to develop new drug candidates in collaboration with a partner pharmaceutical company, which will expand his scientific knowledge and network.This proposed phosphorylation project is based on a new synthetic method recently developed in the host laboratory for photoinduced C-B bond formation under photocatalyst- and metal-free conditions. The proposed methodology will access highly valuable α-aminophosphonic acids from feedstock α-amino carboxylic acids, through a decarboxylative phosphorylation process driven by visible light. α-Aminophosphonic acids are used as antibiotics, herbicides, antitumor agents, and enzyme inhibitors, with broad applications in many areas of agriculture and medicine. To maximize the impact and application of the proposed decarboxylative phosphorylation in organic synthesis, enantioselective variants will also be developed to provide highly valuable enantioenriched α-aminophosphonic acids. Initially, an auxiliary approach with a chiral phosphorylating reagent will be used, before the extension to an enantioselective catalytic process using a chiral Brønsted acid catalyst.
Original text from CORDIS.
Participants
- UNIVERSITY OF BRISTOL · BRISTOLCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union