PHOTOCAMSYN · Photocatalytic Reductive Coupling of Imines: A New Platform for Chiral Amine Synthesis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-06-21 → 2020-06-20
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Photocatalytic Reductive Coupling of Imines: A New Platform for Chiral Amine Synthesis
1.1 Objectives Scientific training objectives: - Photochemical reactions and photoredox catalysis: Dr Shiomi has started a wide range investigation on a new type of photoredox catalysis. Although reverse polarity reductive functionalization of secondary amides via a dual iridium catalyzed hydrosiliration and SET strategy had been studied, the new catalytic system has not been reached as a scientific satisfied stage. - New asymmetric reaction optimization: Dr Shiomi carried out the research and optimization of a new organocatalized intramolecular ’-disubstituted nitroalkene-tethered cyclohexanone desymmetrisation which got access to bicyclic compounds in excellent yield (95%) and superb enantioselectivity (99.2%). - Novel synthetic strategies development: Dr Shiomi has carried out an intensive program towards the discovery of new reactions with important applications in the synthesis of complex molecules, involves oxidative lactamization reaction of aminodiol derivatives which allow access to a highly complex tricyclic skeleton (Madangamine core). Furthermore, biologically active marine alkaloid, Madangamine E, was synthesized by newly developed synthetic pathway. Although this natural product target is different from the initial proposal, madangamines are highly important and challenging synthetic target in terms of the biological activity (anti-cancer) and requisition of high-level synthetic organic chemistry. - Structure determination by X-ray diffraction, spectroscopy, etc: Dr Shiomi has carried out an intensive hands-on training on X-ray diffraction and has been responsible (together with a DPhil student from the group) of running all X-ray diffraction studies of the researchers in Dixon group). - Computational caluculations: Dr Shiomi has carried out computational DFT calculations on newly developed asymmetric catalysis with Mr. Yamazaki (D.Phil student in Dixon group) and Dr. Hamlin (Vrije Universiteit Amsterdam, Amsterdam, Netherlands).
Data: CORDIS, © European Union
Project objective
Chiral α-branched amines and their derivatives are commonplace in pharmaceuticals, agrochemicals and biologically relevant natural products. Accordingly, the development of new synthetically powerful methods for their synthesis, and/or further functionalisation, through new carbon-carbon bond forming processes is both important and timely from academic and industrial perspectives. Such chiral α-branched amine motifs can be accessed from electrophilic imine substrates, through direct addition of carbon-centered nucleophiles such as organometallic reagents and electron rich π-nucleophiles. This traditional approach takes advantage of the easy formation of imines and their natural polarity and has led to numerous developments over the years. Whilst nucleophilic addition reactions dominate the chemistry of imines, polarity reversal is possible but requires the careful design of imine precursors able to stabilise anionic intermediates following deprotonation. Free radical chemistry offers the possibility to reverse the polarity of imine derivatives; the formal addition of a hydrogen atom to the C=N π-bond can generate a nucleophilic α-amino radical able to react with alkenes and alkynes. However, to date these approaches have been limited by the way the radical is generated. Here we propose a new and broadly applicable ‘umpolung’ approach to access chiral α-branched amine motifs directly from imine substrates. Our plan is to design and develop a new reductive photochemical system that will allow the direct generation of ‘free’ nucleophilic α-amino radical species capable of undergoing a broad range of synthetically useful carbon-carbon bond forming processes. This non-classical umpolung strategy has a wealth of untapped synthetic potential and will allow the development of new modes of reactivity each in turn rendering new suites of synthetic methodologies including catalytic asymmetric versions.
Original text from CORDIS.
Participants
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union