Aryl and heteroaryl rings are omnipresent in small molecule drugs, and examples bearing multiple substitutions at benzylic positions are ubiquitous across a range of pharmaceutical families. The comparative acidity of α-aryl protons makes organolithium mediated deprotonation-substitution protocols an attractive strategy for effecting substitutions at benzylic positions. In this review, we survey recent advances in benzylic lithiation chemistry, including 1) lithiations facilitated by heteroatom-appended directing groups, 2) lateral lithiations enabled by directing groups attached in the aryl ortho-position, as well as 3) examples remote from any Lewis basic group. Recent 4) heterobenzylic and 5) stereoselective benzylic lithiations are also summarized.

小分子药物中普遍存在芳基和杂芳基环，在苄基位置带有多个取代基的例子在一系列药物家族中无处不在。α-芳基质子的比较酸度使得有机锂介导的去质子化-取代规程成为影响苄基位置上的取代的有吸引力的策略。在这篇综述中，我们调查了苄基锂化化学的最新进展，包括1）通过杂原子附加的导向基团促进的锂化，2）通过在芳基邻位连接的导向基团实现的侧向锂化，以及3）远离任何位置的例子刘易斯基本组。还总结了最近的4）杂苄基和5）立体选择性苄基锂化。