Direct ortho-Cupration: A New Route to Regioselectively Functionalized Aromatics

When talking about directed ortho-metallation (DoM), most people think about organolithium bases, but the use of Lipshutz-type amidocuprates can change that.

Directed ortho-metallation (DoM) is a widely spread method for the functionalization of aromatic compounds, working on many different substrates including heterocyclic ones. However, most applications of DoM involve the use of an organolithium base at low temperature, experimental conditions that make difficult the scale-up of these reactions. A combined study by groups in Japan and United Kingdom offers now a new experimental protocol based in the use of Lipshutz-type amidocuprates. These amidocuprates are still prepared at low temperature from the usual starting materials (LiTMP, nBuLi and MeLi) but they offer higher regioselectivity than organolithium bases and fewer side reactions. The arylcopper intermediates can be successfully used for trapping with several electrophiles.

J. Am. Chem. Soc., 2007, 129 (49), pp. 15102–15103. See: 10.1021/ja074669i