Selective C(sp³)−H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in Flow

Abstract

A mild and selective C(sp3)−H aerobic oxidation enabled by decatungstate photocatalysis has been developed. The reaction can be significantly improved in a microflow reactor enabling the safe use of oxygen and enhanced irradiation of the reaction mixture. Our method allows for the oxidation of both activated and unactivated C−H bonds (30 examples). The ability to selectively oxidize natural scaffolds, such as (−)‐ambroxide, pregnenolone acetate, (+)‐sclareolide, and artemisinin, exemplifies the utility of this new method.

Catalytic Aerobic Oxidation of C(sp3)−H Bonds

“…[135] Thespecies generating the radical can alter the possible products formed as exemplified for sclareolide with organocatalysis (C2:C3) (Scheme 19) versus photoredox (C2:C1) (Scheme 25). [135] Thespecies generating the radical can alter the possible products formed as exemplified for sclareolide with organocatalysis (C2:C3) (Scheme 19) versus photoredox (C2:C1) (Scheme 25).…”

Pushing the boundaries of C–H bond functionalization chemistry using flow technology

“…The reaction was carried out in a 5 ml PFA capillary reactor at atmospheric pressure in 45 min residence time under 365 nm LED irradiation. The methodology was applied to the oxidation of terpenoid natural products, including the gram scale oxidation (1.5 h residence time, 10 ml reactor volume) of the sesquiterpene antimalarial, artemisinin [239]. Due to the electrophilic nature of the Scheme 73 Air oxidation of ethylbenzene to acetophenone or benzoic acid in flow catalyst, both methods allow the site-selective oxidation of a methylene group to a ketone [240,241].…”

Japan Prize: A. Yoshino / Merck–Banyu Lectureship: N. Kumagai / DECHEMA Prize: T. Noël

“…Noël and his group are interested in the development of new catalytic strategies and technologies for chemical synthesis, and he was honored for his work on continuous photochemical conversion in microfluidic systems. He has reported in Angewandte Chemie on the visible‐light‐mediated arylation of cysteine in batch and flow, and on selective C(sp 3 )−H aerobic oxidation enabled by photocatalysis in flow …”