Microtubing‐Reactor‐Assisted Aliphatic C−H Functionalization with HCl as a Hydrogen‐Atom‐Transfer Catalyst Precursor in Conjunction with an Organic Photoredox Catalyst

• Published in: Angewandte Chemie International Edition Vol. 57; no. 39; pp. 12661 - 12665
• Main Authors: Deng, Hong‐Ping, Zhou, Quan, Wu, Jie
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 24.09.2018; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Aliphatic compounds; Alkanes; Alkylation; Allyl compounds; Catalysis; Catalysts; Chemical reactions; Chemistry; Chemistry, Multidisciplinary; Chlorine; C−H functionalization; Ethane; Hydrogen; Hydrogen bonds; hydrogen chloride; hydrogen-atom transfer; Irradiation; Light irradiation; photocatalysis; Physical Sciences; Precursors; Reactors; Science & Technology; stop-flow microtubing reactors; Ultraviolet radiation; MILD; ACTIVATION; OXYGENATION; hydrogen-atom transfer; hydrogen chloride; stop-flow microtubing reactors; BONDS; 9-MESITYL-10-METHYLACRIDINIUM; GAS; C-H functionalization; photocatalysis; ALKANES; C−H functionalization
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201804844

Chlorine radical, which is classically generated by the homolysis of Cl2 under UV irradiation, can a hydrogen atom from an unactivated C(sp3)−H bond. We herein demonstrate the use of HCl as an effective hydrogen‐atom‐transfer catalyst precursor activated by an organic acridinium photoredox catalyst under visible‐light irradiation for C−H alkylation and allylation. The key to success relied on the utilization of microtubing reactors to maintain the volatile HCl catalyst. This photomediated chlorine‐based C−H activation protocol is effective for a variety of unactivated C(sp3)−H bond patterns, even with primary C(sp3)−H bonds, as in ethane. The merit of this strategy is illustrated by rapid access to several pharmaceutical drugs from abundant unfunctionalized alkane feedstocks. Cl‐ever cats: HCl was used as a hydrogen‐atom‐transfer catalyst precursor and activated to give chlorine radicals by an acridinium photoredox catalyst under visible‐light irradiation in a microtubing reactor, which was effective in retaining the volatile HCl catalyst. This photomediated C−H activation strategy enabled the efficient alkylation and allylation of a variety of unactivated, even primary, C(sp3)−H bonds (see scheme).