Directed <i>ortho</i>-Lithiation: Observation of an Unexpected 1‑Lithio to 3‑Lithio Conversion of 1‑Lithio-naphthyllithium Compounds with an <i>ortho</i>-Directing 2‑(Dimethylamino)methyl Group

Regioselectivity is an important aspect in the design of organic protocols involving Directed <i>ortho</i>-Lithiation (DoL) of arenes, in particular with those arenes containing heteroatom substituents as directing groups. The DoL of 2-[(dimethylamino)­methyl]­naphthalene (dman) that proceeds with low regioselectivity was revisited by varying both the nature of the lithiating reagent (either <i>n</i>-BuLi or <i>t</i>-BuLi) and/or the solvent (pentane or diethyl ether); the 3-deuterated substrate, 3-Ddman, was also investigated as a substrate to compare to that of dman. The 3-lithio regioisomer exists as tetranuclear [2-(Me₂NCH₂)­C₁₀H₆Li-3]₄, <b>1</b>, both in the solid state (X-ray) and in solution (NMR). The 1-lithio regioisomer, <b>2a</b>, is insoluble; in the presence of additional coordinating solvents (Et₂O) or ligands (dman), it exists as dinuclear [2-(Me₂NCH₂)­C₁₀H₆Li-1]₂·L (coordinated L = Et₂O: <b>2b</b>, dman: <b>2c</b>) in apolar solvents. Heating solutions of <b>2c</b> in toluene-<i>d</i>₈ (to 90 °C) induced a surprisingly clean and quantitative 1-lithio to 3-lithio conversion of the 1-lithio-naphthalene isomer. This type of reaction is rare in organolithium chemistry and has obvious significant implications for the design of regioselective DoL protocols; this thus represents the synthetically useful protocol for the DoL of dman in a one-pot/two-step process in toluene solution. The results of the use of 3-Ddman in these reactions gives strong credence to a mechanism involving formation of the heteroleptic species [(2-(Me₂NCH₂)­C₁₀H₆-1)­(2-(Me₂NCH₂)­C₁₀H₆-3)­Li₂]·[dman], <b>A</b>, as the key intermediate. Intramolecular <i>trans</i>-lithiation takes place with <b>A</b>; dman becomes selectively lithiated at its 3-position, while the formerly 1-lithio-naphthalene fragment, acting as a highly unusual <i>ortho</i>-lithiating reagent, is converted into the N-coordinated amine, dman. In this intramolecular DoL process, free dman can be considered to act as a <i>catalyst