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

Abstract

The merger of manganese-catalyzed C–H functionalization with electrosynthesis enabled C(sp3)–H azidation devoid of chemical oxidants or photochemical irradiation. Detailed mechanistic studies are supportive of a manganese(iii/iv) electrocatalysis.

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

“…Recently, the Ackermann group disclosed a convenient manganese-catalyzed late-stage C–H azidation of bioactive molecules bearing unactivated C sp3 –H bonds facilitated by electricity ( Scheme 5 ) [ 43 ]. Several pharmaceutically active molecules were committed to the external oxidant-free reaction conditions and were shown to undergo chemoselective azidation.…”

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…The azide group is another powerful organic function present for example in zidovudine, a worldwide known anti-HIV drug, but also in its derivatives (61 and 62) (Scheme 22A), which can present 10-times higher activities against HIV replication [143]. In 2020 the same group reported the use of a manganese catalyst in the azidation of inert C(sp 3 )-H bonds using organic electrosynthesis in a straightforward procedure, enabling the azidation of a series of primary, secondary and tertiary alkyl moieties (Scheme 22B and C) [144]. In general, the new methodology proved to be resource-economic and straightforward, operating under mild conditions without the need of directing groups, using traceless electrons as sole redox reagents, presenting high scope and chemoselectivity.…”

“…However, some of them were obtained as an ortho/meta mixture, with higher selectivity towards the ortho-isomers (Scheme 43B). Using the same method, the authors also described the success-ful synthesis of flurbiprofen (144), a potent anti-inflammatory drug [211], that was obtained in a four-step procedure, starting from the commercially available 3-iodofluorobenzene (Scheme 43C).…”

Evolution of Earth‐Abundant 3 d‐Metallaelectro‐Catalyzed C−H Activation: From Chelation‐Assistance to C−H Functionalization without Directing Groups

“…Thus, C(sp 3 )−H azidations were realized using a readily available manganese(III) complex 58 and NaN 3 as the azide source (Scheme 20). [52] This concept does neither require a redox mediator, nor a directing group for step‐and atom‐economical syntheses. Non‐activated C(sp 3 )−H bonds were likewise converted to the corresponding azidation products 57 in good to excellent yields.…”

“…The corresponding manganese(III) azide 60 and manganese(IV) diazide 61 complexes were independently synthesized and the reaction mechanism was investigated by means of cyclic voltammetry, UV‐vis absorption studies and control experiments [52] . Cyclic voltammogram of the isolated diazido manganese(IV) complex 61 and the manganese(III)chloro complex 58 in the presence of tetrabutylammonium azide revealed identical redox events, being suggestive of the intermediacy of a manganese(IV) species in this manganaelectro‐catalyzed C−H azidation reaction (Scheme 21).…”