Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran

2021/11/04 by James Burrows, Shogo Kamo, Kazunori Koide · 3 citations
Chemistry · #Asymmetric Hydrogenation and Catalysis #Asymmetric Synthesis and Catalysis #Advanced Synthetic Organic Chemistry

paper · doi:10.1126/science.abk3099

openalex publication_date 2021/11/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

The Birch reduction dearomatizes arenes into 1,4-cyclohexadienes. Despite substantial efforts devoted to avoiding ammonia and cryogenic conditions, the traditional, cumbersome, and dangerous procedure remains the standard. The Benkeser reduction with lithium in ethylenediamine converts arenes to a mixture of cyclohexenes and cyclohexanes; this is operationally easier than the Birch reduction but does not afford 1,4-cyclohexadienes. Here, we report a Birch reduction promoted by lithium and ethylenediamine (or analogs) in tetrahydrofuran at ambient temperature. Our method is easy to set up, inexpensive, scalable, rapid, accessible to any chemical laboratory, and capable of reducing both electron-rich and electron-deficient substrates. Our protocol is also compatible with organocuprate chemistry for further functionalization.

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