Studying competitive lithiations at alpha-, ortho-, and benzylic positions in various N-protected aniline derivatives

The directing effects of the t-BuOCONH– (NHBoc) and the t-BuCONH– (NH–pivaloyl) groups have been investigated on a series of differently substituted anilines. Depending on the nature of the directing group and the substrate, lithiation either occurred in the ortho-, benzylic-, or alpha-position. In general, it was observed that ortho-lithiation is the least facile process and alpha-lithiation slightly favored compared to lithiation in the benzylic position. However, it was found that minor changes in the starting materials led to different regioselectivity in the metalation process. For example, changing substituents from methyl to ethyl can result in completely different regioselectivity. As final conclusion, a graphical guideline for lithiation experiments is presented.