Scope and Limitations of Lithium-Ethylenediamine-THF-Mediated Cleavage at the α-Position of Aromatics: Deprotection of Aryl Methyl Ethers and Benzyl Ethers under Mild Conditions

The scope and limitation of lithium-ethylenediamine-THF-mediated reductive bond cleavage at the α-position of aromatics were examined. Very mild conditions such as lithium metal (5 equiv) and ethylenediamine (7 equiv) in oxygen-free THF were quite effective for the demethylation of aromatic ethers even at as low as -10 °C. Allyl benzyl ethers were also deprotected under these conditions with very little change of the allylic alcohol moiety. Through this study, 2,6-dimethylbenzyl (m-xylylmethyl, MXM) group was developed as an alternative of benzyl group, which is readily cleavable under the above mentioned reductive conditions.