Harnessing [1,4], [1,5], and [1,6] Anionic Fries‐type Rearrangements by Reaction‐Time Control in Flow

• Published in: Angewandte Chemie International Edition Vol. 56; no. 27; pp. 7863 - 7866
• Main Authors: Kim, Heejin, Inoue, Keita, Yoshida, Jun‐ichi
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 26.06.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: aryllithium intermediates; Chemistry; Chemistry, Multidisciplinary; flow chemistry; Fries rearrangement; Intermediates; Lithium; microreactors; Migration; Physical Sciences; reactive intermediates; Science & Technology; Temperature effects; OXIDATION; REACTORS; FLASH CHEMISTRY; aryllithium intermediates; reactive intermediates; MICROREACTOR SYSTEM; microreactors; ALKOXYCARBONYL GROUPS; CHEMICAL-SYNTHESIS; GENERATION; Fries rearrangement; LITHIATION; TECHNOLOGY; flow chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201704006

A series of anionic Fries‐type rearrangements of carbamoyl‐substituted aryllithium intermediates were controlled by using flow microreactor systems. For the [1,4] and [1,5] rearrangements, the aryllithium intermediate formed before carbamoyl migration and the lithium alkoxide formed after carbamoyl migration can be selectively subjected to subsequent reactions with electrophiles by precisely controlling the residence time and temperature (−25 to −50 °C). In contrast, the [1,6] rearrangement is rather slow even at −25 °C. The absence of crossover products indicates the intramolecular nature of the carbamoyl group migration. Under control: A series of anionic Fries‐type rearrangements of carbamoyl‐substituted aryllithium species were controlled by using flow microreactor systems. For the [1,4] and [1,5] rearrangements, the aryllithium and lithium alkoxide intermediates formed before or after carbamoyl migration can be selectively subjected to subsequent reactions with electrophiles by precisely controlling the residence time and temperature.