Visible Light Activation of Boronic Esters Enables Efficient Photoredox C(sp2)-C(sp3) Cross-Couplings in Flow

• Published in: Angewandte Chemie (International ed.) Vol. 55; no. 45; pp. 14085 - 14089
• Main Authors: Lima, Fabio, Kabeshov, Mikhail A., Tran, Duc N., Battilocchio, Claudio, Sedelmeier, Joerg, Sedelmeier, Gottfried, Schenkel, Berthold, Ley, Steven V.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 02.11.2016; Wiley; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: boronic esters; Chemistry; Chemistry, Multidisciplinary; Communication; Communications; cross-coupling; flow chemistry; photoredox catalysis; Physical Sciences; Science & Technology; synthetic methods; ORGANIC-SYNTHESIS; DIRECT ARYLATION; ALKYL; NICKEL CATALYSIS; DIAZO-COMPOUNDS; SINGLE-ELECTRON TRANSMETALATION; C-H BONDS; BENZYLIC ETHERS; cross-coupling; photoredox catalysis; ARYL; DUAL CATALYSIS; boronic esters; synthetic methods; flow chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201605548

We report herein a new method for the photoredox activation of boronic esters. Using these reagents, an efficient and high‐throughput continuous flow process was developed to perform a dual iridium‐ and nickel‐catalyzed C(sp2)–C(sp3) coupling by circumventing solubility issues associated with potassium trifluoroborate salts. Formation of an adduct with a pyridine‐derived Lewis base was found to be essential for the photoredox activation of the boronic esters. Based on these results we were able to develop a further simplified visible light mediated C(sp2)–C(sp3) coupling method using boronic esters and cyano heteroarenes under flow conditions. Solubility rules! A high‐throughput flow process was developed to perform a dual Ir/Ni‐catalyzed photoredox C(sp2)–C(sp3) coupling of boronic esters by circumventing solubility issues associated with potassium trifluoroborate salts. Formation of a Lewis acid–base adduct with a pyridine‐derived Lewis base was found to be essential for the photoredox activation of the boronic esters (see scheme).