Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light.

Rajdip Chowdhury,My Linh Tong,Xiang Yin,Stefanie V Kohlhepp,Zhunzhun Yu,Abraham Mendoza

doi:10.1021/jacs.0c09678

Rajdip Chowdhury, My Linh Tong + Show 4 more

Open Access

https://doi.org/10.1021/jacs.0c09678

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Abstract

Photoexcited dihydronicotinamides like NADH and analogues have been found to generate alkyl radicals upon reductive decarboxylation of redox-active esters without auxiliary photocatalysts. This principle allowed aliphatic photocoupling between redox-active carboxylate derivatives and electron-poor olefins, displaying surprising water and air-tolerance and unusually high coupling rates in dilute conditions. The orthogonality of the reaction in the presence of other carboxylic acids and its utility in the functionalization of DNA is presented, notably using visible light in combination with NADH, the ubiquitous reductant of life.

Highlights

Visible light is a prime stimulus to control the conformation of chemical bonds,[1] or their cleavage.1a,2 The phototriggered formation of chemical bonds can enable frontier research in medicine and biology,[3] but their development is still a challenge in comparison to thermal click reactions[4] due to the slower rate and the need for UV-light and/or photocatalysts.[5]
Photo-cross-linking methods still rely on unstable precursors like azirines or cyclopropanones.5a,6 On the other hand, recent C−C coupling reactions using photobiocatalytic systems have shown great promise but these are still limited to activated substrates with auxiliary photosensitizers and electron donors.[7]
The reaction of the NADH model BNAH (5) with the redox-active ester 2a and the acrylate acceptor 3a was studied under blue light illumination (λ = 450 nm) without photocatalysts or additives (Scheme 2).8f−l To our delight, the desired decarboxylative coupling product 4a was obtained in high yield using DMSO as solvent

Summary

■ INTRODUCTION

Visible light is a prime stimulus to control the conformation of chemical bonds,[1] or their cleavage.1a,2 The phototriggered formation of chemical bonds can enable frontier research in medicine and biology,[3] but their development is still a challenge in comparison to thermal click reactions[4] due to the slower rate and the need for UV-light and/or photocatalysts.[5]. The redox potential of NADH and its analogs (Eox{5} = 0.57 V vs Ag/Ag+) is insufficient to activate redox-active esters (Ered{2} ∼ − 1.1 ± 0.1 V vs Ag/Ag+).[13] These dihydronicotinamides are potent single-electron reductants in the excited state (Eox*{5} = −2.60 V vs Ag/Ag+),[14,15] but their short lifetimes in solution (τ{5*} ∼ 0.7 ns)[16] have limited their application as autonomous photoreductants.[14,17,18] At the onset of our work, these reagents required additional (photo)catalysts8f−l,18,19 or enzymes[20] under rigorously anhydrous and degassed conditions to drive reductive couplings.

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES

Employing Photoredox Catalysis for DNA-Encoded Chemistry