Volume 62, Issue 21 e202217723
Research Article

Mechanochemical Approach for Air-Tolerant and Extremely Fast Lithium-Based Birch Reductions in Minutes

Dr. Yunpeng Gao

Dr. Yunpeng Gao

Division of Applied Chemistry, Graduate School of Engineering, Hokkaido University, 060-8628 Sapporo, Hokkaido, Japan

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Prof. Dr. Koji Kubota

Corresponding Author

Prof. Dr. Koji Kubota

Division of Applied Chemistry, Graduate School of Engineering, Hokkaido University, 060-8628 Sapporo, Hokkaido, Japan

Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, 060-0021 Sapporo, Hokkaido, Japan

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Prof. Dr. Hajime Ito

Corresponding Author

Prof. Dr. Hajime Ito

Division of Applied Chemistry, Graduate School of Engineering, Hokkaido University, 060-8628 Sapporo, Hokkaido, Japan

Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, 060-0021 Sapporo, Hokkaido, Japan

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First published: 21 March 2023
Citations: 25

Graphical Abstract

A mechanochemical Birch reduction is reported for the first time. The newly developed ball-milling method does not require an inert atmosphere or other special precautions. Notably, the reaction reached completion within one minute for most of the investigated substrates. The present study thus provides a novel, operationally simple, rapid, and scalable alternative to conventional solution-based Birch reduction.

Abstract

Birch reduction has been widely used in organic synthesis for over half a century as a powerful method to dearomatize arenes into 1,4-cyclohexadiene derivatives. However, the conventional Birch reduction reaction using liquid ammonia requires laborious procedures to ensure inert conditions and low temperatures. Although several ammonia-free modifications have been reported, the development of an operationally simple, efficient, and scalable protocol remains a challenge. Herein, we report an ammonia-free lithium-based Birch reduction in air without special operating conditions using a ball-milling technique. This method is characterized by its operational simplicity and an extremely short reaction time (within 1 min), probably owing to the in situ mechanical activation of lithium metal, broad substrate scope, and no requirement for dry bulk solvents. The potential of our flash Birch reaction is also demonstrated by the efficient reduction of bioactive target molecules and gram-scale synthesis.

Conflict of interest

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.

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