Lithium Diisopropylamide-Mediated Ortholithiations: Lithium Chloride Catalysis

Abstract

Ortholithiations of a range of arenes mediated by lithium diisopropylamide (LDA) in THF at -78 °C reveal substantial accelerations by as little as 0.5 mol % LiCl (relative to LDA). Substrate dependencies suggest a specific range of reactivity within which the LiCl catalysis is optimal. Standard protocols using unpurified commercial samples of n-butyllithium to prepare LDA or commercially available LDA show marked batch-dependent rates--up to 100-fold--that could prove significant to the unwary practitioner. Other lithium salts elicit more modest accelerations. The mechanism is not discussed.

Gespaltene Persönlichkeit von Lithiumchlorid: Salzeffekte in metallorganischen Synthesen

“…[3] [7] die viele Arene und Heterocyclen, welche gegenüber konventionellen Reagentien normalerweise inert sind, effizient magnesiieren. Turbo-Magnesiierungsreagentien tolerieren funktionelle Gruppen wie Ester-, Keton-und Nitrilgruppen besser als konventionelle Organolithiumreagentien, sind aber gegenüber empfindlicheren Gruppen unverträglich (Aldehyd-, Nitrogruppen).…”

TMP-cadmiate: A Base for Efficient and Chemoselective Deprotonative Metallation Reactions of Aromatic Compounds

“…Under the same reaction conditions, the iodide 1b was isolated in 9% yield using the former, and did not form using the latter (entries 2 and 3). A possible effect of lithium chloride [23] or TMEDA [24] on the course of the reaction was discarded.…”

LiTMP Trans‐Metal‐Trapping of Fluorinated Aromatic Molecules: A Comparative Study of Aluminum and Gallium Carbanion Traps

“…Collum and co-workers demonstrated arate enhancement on lithiating various fluorinated aromatics using lithium diisopropylamide in THF at À78 8 8Cbya dding catalytic quantities of LiCl. [8] Knochel and co-workers disclosed that specific aryllithium species can be selectively trapped from amixture of isomers by transmetalation with asubstoichiometric quantity of dichlorozirconocene. [9] Here we approach these challenging metalations through trans-metal-trapping (TMT), where two non-interacting organometallic reagents work in tandem (Scheme 1).…”

“…Thesolution stability of gallated fluoroarene 6 was probed by monitoring its 1 HNMR spectra in C 6 D 6 over time against 8 ]THF shows little sign of decomposition, even after 6days,signifying that donor solvents enhance the stability of these systems,a nd evidence points to SSIP constitutions of these gallated structures.Arelated factor regarding the stability enhancement of the gallium complexes is the greater fluorophilicity of aluminum. Thus formation of Al À Fb onds is promoted, hastening decomposition.…”