Science of Synthesis

Sanz, R.; Suárez-Pantiga, S., Science of Synthesis Knowledge Updates, (2025) 1, 99.

General Introduction

This is an update to the Science of Synthesis contribution on aryl- and hetaryllithium compounds (Section 8.1.14),[‌1‌] with a particular focus on the latter. Lithiated hetarenes are highly versatile reagents that facilitate the functionalization of these heterocycles as well as the assembly of molecules that incorporate these valuable heteroaromatic rings. Since ca. 2004, many studies describing the synthesis and reactivity of hetaryllithium compounds have been reported in the literature. Various reviews have summarized these advances.[‌2‌–‌8‌] In addition, lithium bases have been extensively reviewed.[‌9‌,‌10‌] Additionally, the continuous development of novel directed ortho metalation or directed remote metalation reactions has expanded the scope of accessible hetaryllithium compounds.[‌11‌–‌13‌] Similarly, in recent years, the combination of organolithium reagents with halogen-dance reactions[‌14‌–‌16‌] or flow chemistry[‌17‌–‌23‌] has significantly changed the availability and applicability of transient organolithium (hetaryllithium) species in synthesis. Due to the vast nature of this topic, this chapter mainly focuses on selected recent advances achieved in this field since ca. 2004. However, previous key contributions are also mentioned to provide a broader vision in this research area. Beyond this chapter are reactions involving cooperative metalation with bimetallic main group bases of lithium and another element[‌24‌–‌27‌] that have a diverse and vast range of applications in synthesis such as, for example, the Knochel–Hauser bases, and that typically proceed through metalation pathways different from lithiation.[‌28‌] In general terms, this current update follows the structure of the previous chapter, although a few additional sections have been included. In each section, the synthesis of the hetaryllithium as well as selected reactivity and further applications are summarized.

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References