Effect of Different Dialkylamino Groups on the Regioselectivity of Lithiation of O-Protected 3-(Dialkylamino)phenols

Article abstract of DOI:10.1021/jo00215a020

The lithiation of 3-(dialkylamino)phenols (dialkylamino = 1-pyrrolidynyl, 1-piperidinyl, 4-morpholinyl, and dimethylamino) O-protected by a methyl, a methoxymethyl, or a carbamoyl group (X) has been studied.The results demonstrate that the site of lithiation depends on the relative ortho-directing capacities of both the dominant OX and the dialkylamino groups.With the moderate ortho-directing methoxy group the lithiation occurs exclusively (1b and 1c) or predominantly (1a) ortho to both substituents.The site of lithiation of the N,N-dialkyl-3-(methoxymethoxy)anilines 4a-c depends on the solvent used and on the type of dialkylamino group.With a strong ortho-directing group such as carbamoyloxy (9a,b,d) the lithiation takes place at the least hindered ortho position.In the absence of an electrophile the lithiated carbamates 9a,d and 10a,d rearrange stereospecifically to the corresponding benzamides 13a,d and 14a,d, respectively.