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. 2020 Dec 28;12(8):2890-2897.
doi: 10.1039/d0sc05924b.

Mangana(iii/iv)electro-catalyzed C(sp3)-H azidation

Tjark H Meyer  1   2 , Ramesh C Samanta  1   2 , Antonio Del Vecchio  1 , Lutz Ackermann  1   2
Affiliations

Mangana(iii/iv)electro-catalyzed C(sp3)-H azidation

Tjark H Meyer et al. Chem Sci. .

Abstract

Manganaelectro-catalyzed azidation of otherwise inert C(sp3)-H bonds was accomplished using most user-friendly sodium azide as the nitrogen-source. The operationally simple, resource-economic C-H azidation strategy was characterized by mild reaction conditions, no directing group, traceless electrons as the sole redox-reagent, Earth-abundant manganese as the catalyst, high functional-group compatibility and high chemoselectivity, setting the stage for late-stage azidation of bioactive compounds. Detailed mechanistic studies by experiment, spectrophotometry and cyclic voltammetry provided strong support for metal-catalyzed aliphatic radical formation, along with subsequent azidyl radical transfer within a manganese(iii/iv) manifold.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Manganaelectro-catalyzed azidation.
Scheme 2
Scheme 2. Proof of concept electro C(sp3)–H azidation.
Scheme 3
Scheme 3. Reaction scope of manganaelectro-catalyzed C(sp3)–H azidation. [a] Standard conditions: substrate (0.5 mmol), NaN3 (4.0 mmol), [Mn2] (2.5 or 5.0 mol%), LiClO4 (0.5 mmol), MeCN/AcOH (5 mL, 1 : 1), a nitrogen atmosphere, 10 h, 25 °C, and constant current electrolysis at 8.0 mA in an undivided cell. All yields are isolated products; ratios for site-selectivity are determined by 1H-NMR of the crude mixture. [b] At 50 °C. [c] 3,4-Dihydronaphthalen-1(2H)-one 3 was detected in 10% from crude 1H-NMR with 1,3,5-trimethoxy benzene as the internal standard. [d] Standard conditions for 20 h.
Scheme 4
Scheme 4. Gram-scale manganaelectro-catalyzed C–H azidation (4.30 F).
Scheme 5
Scheme 5. Mechanistic investigation of manganaelectro-catalyzed azidation of unactivated C(sp3)–H bonds. (a) Radical trap experiments. (b) Competition experiment. (c) Kinetic experiments. (d) Chronoamperometric studies at 0.8 V vs. Ag/Ag+. (e) Stoichiometric synthesis of well-defined manganese(iii) azide and manganese(iv) diazide complexes. (f) UV-vis spectroscopic studies: (i) MeCN (0.04 mM) was used as the solvent at 25 °C. (ii) MeCN/AcOH (1 : 1, 0.05 mM) was used as the solvent at 25 °C.
Scheme 6
Scheme 6. Cyclic voltammetry: MeCN (0.3 mm) and LiClO4 (0.1 m) was used as the electrolyte and Ag/AgCl (3 M) as the reference electrode, at 25 °C and a scanning rate of 100 mV s−1.
Fig. 1
Fig. 1. Proposed mechanism for manganaelectro-catalyzed C(sp3)–H azidation.
See this image and copyright information in PMC

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