New In Situ Trapping Metalations of Functionalized Arenes and Heteroarenes with TMPLi in the Presence of ZnCl₂ and Other Metal Salts

Abstract

The addition of TMPLi to a mixture of an aromatic or heteroaromatic substrate with a metal salt such as MgCl2, ZnCl2, or CuCN at -78 °C first leads to lithiation of the arene followed by transmetalation with the metal salt to afford functionalized organometallic compounds of Mg, Zn, or Cu. This in situ trapping method allows an expedited metalation (-78 °C, 5 min) of a range of sensitive pyridines (bearing a nitro, ester, or cyano group) and allows the preparation of kinetic regioisomers of functionalized aromatic compounds or heterocycles not otherwise available by standard metalating agents, such as TMPMgCl⋅LiCl or TMPZnCl⋅LiCl.

Adding a Structural Context to the Deprotometalation and Trans‐Metal Trapping Chemistry of Phenyl‐Substituted Benzotriazole

“…With only modest success in trying to fill the structuralg aps in knowledge between reactants and iodinated productsi nt he mixed lithium-zinc base system (see below), we turnedt oarelated lithium-aluminium system that has previously provided valuablei nsights into related deprotometalation of anisole [8] and N,N-dimethylphenylethylamine (DMPEA). [9] An added incentive for including aluminium is the paucityo fc rystallographically characteriseda luminium benzotriazoles with ar are exception being as eries of phenoxybenzotriazole derivatives studied for their photoluminescent properties.…”

“…[10] In the lithium-aluminiums ystem in question, LiTMP (TMP = 2,2,6,6-tetramethylpiperidide) performst he metalation of the CÀHs ubstrate, whereas the dialkylaluminium amide iBu 2 Al(TMP) performs the trans-metal trapping of the developing C À carbanion. As was explained elsewhere, [8] we do not use the more commont erm transmetalation as it usually signifies the exchange of metals in separate compounds, whereas herein, the aluminium compound inserts into the CÀLi bond to trap and simultaneously stabiliset he carbanion within the one mixed lithium-aluminiumc ompound, hence,t rans-metal trapping seems more appropriate. We first tested the lithiation of 1 with LiTMP on its own.…”

“…, [8] so LiTMP is free to deprotonate the triazole (note that TMP aluminates have been found to be weak bases compared to lithium bases, generally incapable of deprotonating CÀHb onds). The reaction was carried out in two different stoichiometries with one or two molar equivalents of the base mixture to one equivalent of the triazole (Scheme 3).…”

“…To quantify the process, as eries of temperature-dependent 2D [ ,v alues that are consistent with conformational rearrangementd ynamics rather than bond breaking and making. To explore more closely the conformations and to firmly establish the nature of the solution-phase speciesrepresenting 4,wemadestrides towards assigning the data to allow key through-space information,a cquired by 2D [ 8 ]toluene cooled to 213 Ka tw hich temperature the exchange process wass ufficiently arrested to ensure that the NOESYd ata were dominated by genuine NOEs, exchange cross-peaks being suppressed below the level of detection. With the assignment of the aromatic-proton resonances confirmed at this temperature, we used these and the representative crystal structure of 4 to determine the most likely NOE cross-peak assignments.…”

Functionalization of Quinoxalines by Using TMP Bases: Preparation of Tetracyclic Heterocycles with High Photoluminescene Quantum Yields

“…[17] The zincated intermediate could be subjected to bromination, as well as copper-mediateda llylation with 3-bromo-2-methylpropenef urnishing compounds 8a and 8b.A lternatively,d ifunctionalized quinoxaline 7d was magnesiated by using TMPMgCl·LiCl (3,1 .5 equiv,0 8C, 1.5 h). The magnesiated speciesw as quenched with halides affording compounds 8c and 8d in 72-73 %y ield.…”