The lithiation of 2,4-lutidine (1) with non-nucleophilic bases, such as lithium diisopropylamide (LDA) and lithium diethylamide (LDEA) affords different regioisomers under similar reaction conditions. The mechanism of these reactions and the factors determining selectivity have not been well understood.

The present endeavor explores experimental and quantum chemical approaches to investigate factors that determine regioselectivity of the reaction. It has been found that transition states of LDA/LDEA determine regioselectivity and the presence of acatalyst (LiCl) plays a vital role. The LDA mediated lithiation of 1 proceeds through a disolvated open dimer of LDA, leading to a 2-methyl lithiated product. LDEA mediated lithiation is dominated by a route involving interception of 1 with a trisolvated monomer-based transition state of LDEA resulting in a 4-methyl lithiated product. The mechanism is supported by LiCl catalyzed reactions. LiCl has also been found to effect a change in selectivity of the lithiation of BF₃-complexed 2,4-lutidine.

2，4-二甲基吡啶（1）与非亲核碱，例如二异丙基氨基化锂（LDA）和二乙基氨基化锂（LDEA）的锂化在相似的反应条件下提供了不同的区域异构体。这些反应的机理和决定选择性的因素还没有被很好地理解。

目前的努力探索了实验和量子化学方法，以研究决定反应区域选择性的因素。已经发现LDA / LDEA的过渡态决定区域选择性，并且催化剂（LiCl）的存在起着至关重要的作用。LDA介导的1的锂化过程通过LDA的脱溶剂的开放二聚体进行，从而产生2-甲基锂化的产物。LDEA介导的锂化作用主要由以下途径决定：LDEA的三溶剂化基于单体的过渡态会截获1，从而产生4-甲基锂化产物。该机理由LiCl催化的反应支持。还发现LiCl影响BF ₃锂化的选择性-复合的2,4-二甲基吡啶。