DIRECTED METALATION OF AROMATIC ALDIMINES WITH LITHIUM 2,2,6,6-TETRAMETHYLPIPERIDIDE

N-Cyclohexyl aromatic aldimines are ortho-lithiated or o-methyl-lithiated with 2 equiv of lithium 2,2,6,6-tetramethylpiperidide (LTMP) in THF solution it -15-degrees-C. The lithiated intermediates generally reacted with alkyl halides or CO2 to provide ortho- functionalized aldimine products which could be readily converted to the corresponding aldehydes by hydrolysis with aqueous 4 M HCI. Aromatic aldimines derived from (+/-)-trans-2-methylcyclohexylamine or 3-amino-2,4-dimethylpentane are resistant toward C=N addition with 1 equiv of n-BuLi at 0-degrees-C in THF solution; however, they are also surprisingly resistant toward directed metalation reactions with either LTMP or n-BuLi. Exceptions to the ortho-directing and o-methyl-directing effects of the aldimine group were observed in a reaction of 3-methylthiophene-2-carboxaldehyde cyclohexylimine (7) with LTMP, followed by CH3I, which gave a 9:1 mixture of 3,5-dimethylthiophene-2-carboxaldehyde cyclohexylimine (22) and 5-ethyl-3-methylthiophene-2-carboxaldehyde cyclohexylimine (23), and a reaction of p-tolualdehyde 2,4-dimethylpent-3-ylimine (11) with either n-BuLi or LTMP, followed by CH3I, which gave p-ethylbenzaldehyde 2,4-dimethylpent-3-ylimine (25).