Investigation of Straightforward, Photoinduced Alkylations of Electron‐Rich Heterocompounds with Electron‐Deficient Alkyl Bromides in the Sole Presence of 2,6‐Lutidine

Fuks, Elina; Huber, Laura; Schinkel, Thea; Trapp, Oliver

doi:10.1002/ejoc.202001003

Cited by 13 publications

(10 citation statements)

References 61 publications

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“…During the mechanistic investigation of a light-induced α-alkylation according to MacMillan, it was observed that although the photosensitizer could be omitted, the base 2,6-lutidine is indispensable for a successful reaction. ,, …”

Section: Mechanistic Considerationsmentioning

confidence: 99%

(Photoredox) Organocatalysis in the Emergence of Life: Discovery, Applications, and Molecular Evolution

Bechtel,

Ebeling,

Huber

et al. 2023

Acc. Chem. Res.

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Conspectus Life as we know it is built on complex and perfectly interlocking processes that have evolved over millions of years through evolutionary optimization processes. The emergence of life from nonliving matter and the evolution of such highly efficient systems therefore constitute an enormous synthetic and systems chemistry challenge. Advances in supramolecular and systems chemistry are opening new perspectives that provide insights into living and self-sustaining reaction networks as precursors for life. However, the ab initio synthesis of such a system requires the possibility of autonomous optimization of catalytic properties and, consequently, of an evolutionary system at the molecular level. In this Account, we present our discovery of the formation of substituted imidazolidine-4-thiones (photoredox) organocatalysts from simple prebiotic building blocks such as aldehydes and ketones under Strecker reaction conditions with ammonia and cyanides in the presence of hydrogen sulfide. The necessary aldehydes are formed from CO2 and hydrogen under prebiotically plausible meteoritic or volcanic iron-particle catalysis in the atmosphere of the early Earth. Remarkably, the investigated imidazolidine-4-thiones undergo spontaneous resolution by conglomerate crystallization, opening a pathway for symmetry breaking, chiral amplification, and enantioselective organocatalysis. These imidazolidine-4-thiones enable α-alkylations of aldehydes and ketones by photoredox organocatalysis. Therefore, these photoredox organocatalysts are able to modify their aldehyde building blocks, which leads in an evolutionary process to mutated second-generation and third-generation catalysts. In our experimental studies, we found that this mutation can occur not only by new formation of the imidazolidine core structure of the catalyst from modified aldehyde building blocks or by continuous supply from a pool of available building blocks but also by a dynamic exchange of the carbonyl moiety in ring position 2 of the imidazolidine moiety. Remarkably, it can be shown that by incorporating aldehyde building blocks from their environment, the imidazolidine-4-thiones are able to change and adapt to altering environmental conditions without undergoing the entire formation process. The selection of the mutated catalysts is then based on the different catalytic activities in the modification of the aldehyde building blocks and on the catalysis of subsequent processes that can lead to the formation of molecular reaction networks as progenitors for cellular processes. We were able to show that these imidazolidine-4-thiones not only enable α-alkylations but also facilitate other important transformations, such as the selective phosphorylation of nucleosides to nucleotides as a key step leading to the oligomerization to RNA and DNA. It can therefore be expected that evolutionary processes have already taken place on a small molecular level and have thus developed chemical tools that change over time, representing a hidden layer on the path to enzyma...

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Section: Mechanistic Considerationsmentioning

confidence: 99%

(Photoredox) Organocatalysis in the Emergence of Life: Discovery, Applications, and Molecular Evolution

Bechtel,

Ebeling,

Huber

et al. 2023

Acc. Chem. Res.

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“…[73] In 2020, Trapp and co-workers explored a straightforward and photoinduced alkylation of heterocompounds with alkyl bromides under light irradiation (Scheme 17). [76] Some substituted furan, thiophene, pyrrole and indole derivatives were obtained through this photocatalyzed approach. The formation of colored EDA complex 92 from colorless 2,6-lutidine and colorless electron-deficient alkyl bromide was confirmed by UV/Vis spectra.…”

Section: Alkylation Of Aromatic Compoundsmentioning

confidence: 99%

Progress in Photoinduced Radical Reactions using Electron Donor‐Acceptor Complexes

et al. 2021

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Photocatalyzed organic synthesis transformation is a remarkable green synthetic strategy because of the advantages of operational simplicity, high chemoselectivities, cheap, and environmental benignancy, along with the extensive applications in the fields of organic, pharmaceutical and functional material chemistry. Generally, photoredox catalysts or photosensitizers are necessary for the generation of their excited states to perform the successive oxidative or reductive reactions through the single electron transfer (SET) or energy transfer (ET) process. Furthermore, the exploration of a colored electron donor-acceptor (EDA) complex or a charge transfer (CT) complex between an electron-rich and an electron-poor substrate provides the chance to deliver the excited intermediate under the irradiation of light, resulting in the formation of radical activate species through a single electron transfer to induce successive various radical reactions. These reactions were performed without the need of any external photocatalysts under mild reaction conditions. Herein, this review focuses on the recent progress on photoinduced radical addition reactions, radical borylations, reductive reactions, radical-radical cross-coupling reactions, degradation reactions and radical cascade cyclization via EDA complexes. We highlight these novel green synthetic methodologies and applications, as well as the mechanisms. This review will help to provide references for organic and medicinal chemists who are charmed by these green organic photochemical transformations based on EDA complexes.

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“…Following the reaction progress by 1 H NMR shows the formation of intermediate I2 (Figure SI3), which upon the addition of water converts to a corresponding carboxylic acid 5 or into product 4 upon addition of 2,6-lutidine as the base. On the basis of these experiments and related literature precedents, − a possible reaction mechanism is shown in Scheme c. The pyrazolo[1,2- a ]pyrazole 1 was first excited with visible light to form the excited 1* , which underwent single electron transfer (SET) with diethyl bromomalonate to generate the corresponding radical cation of 1 .…”

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confidence: 93%

“…When the N -methylpyrrole substituted bicycle 1 was reacted under standard conditions, the corresponding N -acryloyl substituted pyrazole 4o was isolated in a 15% yield, together with the C5′ malonyl substituted derivative 4o′ in a 50% yield. The coupling of this electron-deficient malonate radical at the C2 position with electron-rich arenes, such as pyrroles, thiophenes, and furans under visible light-mediated conditions was documented by Stephenson, Trapp, Noël, and Wu . To demonstrate the scalability of the method, a gram-scale experiment was performed to give 4a with a comparable 80% product yield…”

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confidence: 99%

Visible-Light Driven Selective C–N Bond Scission in anti-Bimane-Like Derivatives

et al. 2021

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In the present study, we report the photochemical transformation of pyrazolo[1,2-a]pyrazolone substrates that reach an excited state upon irradiation with visible light to initiate the homolytic C–N bond cleavage process that yields the corresponding N1-substituted pyrazoles. Moreover, chemoselective heterolytic C–N bond cleavage is possible in the pyrazolo[1,2-a]pyrazole core in the presence of bromomalonate.

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Investigation of Straightforward, Photoinduced Alkylations of Electron‐Rich Heterocompounds with Electron‐Deficient Alkyl Bromides in the Sole Presence of 2,6‐Lutidine

Cited by 13 publications

References 61 publications

(Photoredox) Organocatalysis in the Emergence of Life: Discovery, Applications, and Molecular Evolution

(Photoredox) Organocatalysis in the Emergence of Life: Discovery, Applications, and Molecular Evolution

Progress in Photoinduced Radical Reactions using Electron Donor‐Acceptor Complexes

Visible-Light Driven Selective C–N Bond Scission in anti-Bimane-Like Derivatives

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