Periodic Reporting for period 1 - PhotoCuRiOT (Visible Light-Mediated Copper Photoredox-Catalyzed Ring-Opening Transformations of Activated Small Ring Aza-Heterocycles and Carbacycles)
Okres sprawozdawczy: 2018-04-01 do 2020-03-31
The ever-growing social interest in environmental protection and minimization of energy consumption have instigated the synthetic chemists to look for alternatively activate small organic molecules. Visible-light-mediated photoredox catalysis has been enjoying a renaissance lately. The process harnesses the sustainable solar energy and thus instigate chemical reactions through single-electron transfer or energy transfer events under mild and environmentally benign conditions. Due to their unique and multifarious reactivity profile, visible-light photocatalysts enable challenging yet rewarding bond constructions that are impossible under standard approaches, thereby paving the way towards achieving hitherto inconceivable chemical transformations and broadly impacting the field of organic synthesis, materials science and pharmaceutical chemistry.
The primary objectives of PhotoCuRiOT were the demonstration of the concept of visible-light-induced homolysis (VLIH) unambiguously and the development of novel synthetic tactics by photooxidation of small molecules to generate open-shell intermediates that can be productively harnessed for the synthesis of a range of high-value functional motifs. Considering the earth abundance, low cost, and low toxicity, Cu(I/II)-based complexes, especially copper(I/II) phenanthroline derivatives, have been planned to use as efficient photocatalysts instead of commonly-used Ru or Ir-based complexes. The initial plan involved the employment of small ring aza-heterocycles and aminocarbacyles which would supposedly get photooxidized by an in situ generated Cu(II) photocatalyst via VLIH, to generate reactive amino radical cationic intermediates that could undergo successive ring-opening and annulation with suitably functionalized nucleophiles to produce biologically significant cyclic and acyclic nitrogenous organic compounds. PhotoCuRiOT has also aimed to bridge the gap between the fields of medicine and energy by enabling facile and highly selective synthesis of a wide array of high-value organic compounds by utilizing first-row transition metal (e.g. Cu) complexes as environmentally benign photoredox catalysts and visible-light as a sustainable source of energy.
The project has achieved most of its objectives and milestones in terms of technical aspects and developments, discovered new directions in earth-abundant metal-complex-based visible-light photocatalysis, and it has fully achieved its parallel objectives regarding the researcher’s training, transfer of knowledge, and fostering his development towards an independent researcher.
The primary objectives of PhotoCuRiOT were the demonstration of the concept of visible-light-induced homolysis (VLIH) unambiguously and the development of novel synthetic tactics by photooxidation of small molecules to generate open-shell intermediates that can be productively harnessed for the synthesis of a range of high-value functional motifs. Considering the earth abundance, low cost, and low toxicity, Cu(I/II)-based complexes, especially copper(I/II) phenanthroline derivatives, have been planned to use as efficient photocatalysts instead of commonly-used Ru or Ir-based complexes. The initial plan involved the employment of small ring aza-heterocycles and aminocarbacyles which would supposedly get photooxidized by an in situ generated Cu(II) photocatalyst via VLIH, to generate reactive amino radical cationic intermediates that could undergo successive ring-opening and annulation with suitably functionalized nucleophiles to produce biologically significant cyclic and acyclic nitrogenous organic compounds. PhotoCuRiOT has also aimed to bridge the gap between the fields of medicine and energy by enabling facile and highly selective synthesis of a wide array of high-value organic compounds by utilizing first-row transition metal (e.g. Cu) complexes as environmentally benign photoredox catalysts and visible-light as a sustainable source of energy.
The project has achieved most of its objectives and milestones in terms of technical aspects and developments, discovered new directions in earth-abundant metal-complex-based visible-light photocatalysis, and it has fully achieved its parallel objectives regarding the researcher’s training, transfer of knowledge, and fostering his development towards an independent researcher.
Early attempts to oxidize N-activated and donor-acceptor aziridines with Cu(I/II)-photocatalysts and subsequent reaction with various nucleophiles met with little success. Moreover, similar work on photocatalytic ring-opening reactions of aziridines with nucleophiles as originally proposed in the project was published concurrently. Therefore, the subsequent focus of the project objectives was directed towards developing novel photooxidative transformations of other small organic molecules by employing various first-row transition metal-based photocatalysts. In this vein, the use of Cu in visible-light photoredox catalysis and its recent upsurge have been chronicled and highlighted in a top tier journal (Science 2019, 364, eaav9713) where it was shown that Cu(I) and Cu(II) complexes can act as standalone photocatalysts, in situ generated Cu(I)-substrate complexes can be photoexcited, Cu can be used in cooperative photoredox-Cu dual catalysis, and other miscellaneous ways.
Fluorinated and trifluoromethylated organic compounds are of great importance in medicinal chemistry as they productively enhance the pharmacological and physicochemical properties of the molecules. Cognizant of these facts, diverse functionalization of organic chemical feedstocks such as olefins was next undertaken to directly access new chemical spaces which would otherwise be difficult to access. An extensively long screening study with different photocatalysts including Cu(I/II)-based phenanthroline derivative complexes, commonly employed Ir(III)- and Ru(II)-based photocatalysts, Fukuzumi’s catalyst, and first-row transition metal-based [Fe(III), Co(II), Ni(II), Cu(II), and Zn(II)] tetraphenylporphyrin complexes was carried out for efficient oxotrifluoromethylation of vinyl arenes without any significant success. Then, the researcher explored the possibility of a newer class of Fe(II)-based photocatalysts and synthesized a range of photoactive Fe(II)-complexes. Subsequently, a novel process for visible-light-induced Fe(III)-catalyzed photooxidative bifunctionalization of olefins has been developed. The method provides easy access to a wide range of α-trifluoromethylated ketones, ketoazides, and oxoarylsulfonylated derivatives from vinyl arenes in good yields. The developed process can be exploited in the late-stage functionalization of biologically important molecules. The results of the studies are being prepared in a manuscript and will be communicated in the form of a journal article in due course. During the duration of the project, the researcher was also involved in an ongoing work dealing with unusual cycloaddition of amine substituent-containing polycyclic compounds. The results are also in the process of being communicated in a top tier journal for publication.
Fluorinated and trifluoromethylated organic compounds are of great importance in medicinal chemistry as they productively enhance the pharmacological and physicochemical properties of the molecules. Cognizant of these facts, diverse functionalization of organic chemical feedstocks such as olefins was next undertaken to directly access new chemical spaces which would otherwise be difficult to access. An extensively long screening study with different photocatalysts including Cu(I/II)-based phenanthroline derivative complexes, commonly employed Ir(III)- and Ru(II)-based photocatalysts, Fukuzumi’s catalyst, and first-row transition metal-based [Fe(III), Co(II), Ni(II), Cu(II), and Zn(II)] tetraphenylporphyrin complexes was carried out for efficient oxotrifluoromethylation of vinyl arenes without any significant success. Then, the researcher explored the possibility of a newer class of Fe(II)-based photocatalysts and synthesized a range of photoactive Fe(II)-complexes. Subsequently, a novel process for visible-light-induced Fe(III)-catalyzed photooxidative bifunctionalization of olefins has been developed. The method provides easy access to a wide range of α-trifluoromethylated ketones, ketoazides, and oxoarylsulfonylated derivatives from vinyl arenes in good yields. The developed process can be exploited in the late-stage functionalization of biologically important molecules. The results of the studies are being prepared in a manuscript and will be communicated in the form of a journal article in due course. During the duration of the project, the researcher was also involved in an ongoing work dealing with unusual cycloaddition of amine substituent-containing polycyclic compounds. The results are also in the process of being communicated in a top tier journal for publication.
This MSCA has expanded the boundaries of visible-light-induced photocatalysis in contemporary synthetic organic chemistry in many ways. Photoredox catalysis has been enjoying a renewed interest from the community of synthetic organic chemists as it provides easy access to alternate reactivities of myriad organic molecules, thereby paving the way to developing novel transformations. Recognizing its efficiency and significance in synthetic methodology, pharmaceutical and chemical industries are also adopting and accommodating this new mode of activation by photoredox catalysis and are continuously contributing towards building newer large-scale photoreactor set-ups. They are moving to the flow technology to merge photocatalysis and flow reaction techniques to synthesize value-added products in a short time. However, to make the process profitable, ideal flow technology should include the use of inexpensive photocatalysts with broad reactivity profiles. PhotoCuRiOT has successfully made a significant contribution to this end by (1) highlighting and popularizing various use of copper in photocatalysis in a high-impact journal and thereby welcoming the community of synthetic chemists to explore and expand the Cu-photochemistry, and (2) synthesizing inexpensive Fe(II)-complexes which could induce a range of photooxidative processes such as oxotrifluoromethylation, oxoazidation, and oxoarylsulfonylation of vinyl arenes under air. The high solubility of the Fe(II)-complexes with appropriate counteranions makes these suitable for their use in flow reaction set-ups. Moreover, the developed synthetic transformations successfully achieve efficient installation of trifluoromethyl groups from inexpensive source to common chemical feedstocks (olefins) that would help chemists for late-stage functionalization of natural products and drug candidates to enhance their pharmacological properties – a useful synthetic method even relevant at this pandemic time when there is a desperate need of new antibiotics and antiviral drugs in the society.