Taming Fluorophenyl Organometallic Reagents

20 December 2004

The well-known instability of ortho-fluoroaryl Grignard reagents confronted process chemists at Merck (UK) when they wanted to prepare tertiary alcohols such as (3) in multi-kilogram quantities.

They have developed high-yielding and practical procedures for the preparation of 2,5-difluorophenyl Grignard (1) and the corresponding organolithium (2). Thermochemical investigations showed that the Grignard reagent (1) is stable for up to 4 hours below —10oC, whereas the organolithium (2) degrades at temperatures above —45oC (with or without TMEDA).

* J.P.Scott et al., SYNLETT, 2004, (9), 1646-1648.