New in situ trapping metalations of functionalized arenes and heteroarenes with TMPLi in the presence of ZnCl2 and other metal salts.

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.

Preparation of stereodefined secondary alkyllithium compounds.

We have developed a practical stereoretentive iodine/lithium-exchange process that allows the stereodefined preparation of cis- and trans-cycloalkyllithium compounds from their corresponding stereodefined iodides. Quenching with electrophiles offers stereospecific access to both cis- (up to 96% cis) and trans-cycloalkyl derivatives (up to 99% trans). A detailed study of the thermodynamic stabilities, stereochemical behavior, and reactivities of axially and equatorially substituted cyclohexyllithium reagents is reported. Ab initio calculations demonstrate that the formation of oligomeric cyclohexyllithium structures is pivotal for explaining the observed stereochemical preference.

Preparation of functionalized indoles and azaindoles by the intramolecular copper-mediated carbomagnesiation of ynamides.

Variations on a theme: A mild and general intramolecular copper-mediated carbomagnesiation procedure for the synthesis of functionalized indoles as well as 4-, 5-, 6-, and 7-azaindoles starts from readily available ynamides. Subsequent reactions with various electrophiles provides polyfunctional N-heterocycles in good yields.