American Chemical Society
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Direct ortho Cupration:  A New Route to Regioselectively Functionalized Aromatics

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posted on 2007-12-12, 00:00 authored by Shinya Usui, Yuichi Hashimoto, James V. Morey, Andrew E. H. Wheatley, Masanobu Uchiyama
We have developed a direct regio- and chemoselective method for generating functionalized aromatic cuprate compounds through deprotonative directed ortho cupration using TMP(tetramethylpiperidino)-cuprates (R(TMP)Cu(CN)Li2; R = alkyl, phenyl, or TMP) that are prepared by mixing of CuCN, RLi, and lithium tetramethylpiperidide (LTMP) in THF. Deprotonative cupration of various functionalized benzenes with TMP-cuprate proved effective for the direct generation of o-functionalized copper aromatic and heteroaromatic derivatives, particularly those with electrophilic functional groups, such as cyano, amide, and halogens. Direct cupration, followed by electrophilic trapping, provided a convenient preparative method for 1,2- or 1,2,3-multisubstituted aromatic compounds. The functionalized aromatic cuprate intermediates were also found to undergo oxidation reactions very efficiently and with high regio- and chemoselectivity to afford functionalized phenol, ligand(hetero)-coupling, or homocoupling products by appropriately changing the oxidants and cuprates.