Science of Synthesis

Crockett, M. P.; Aguirre, L. S.; Chen, S.-K.; Sk, M. R.; Thomas, A. A., Science of Synthesis Knowledge Updates, (2025) 1, 55.

General Introduction

The impact of lithium on society cannot be overstated. Lithium has changed our world in momentous ways, from serving as a key component in our mobile phone batteries, allowing us to stay connected with people anywhere around the world, to providing us with the means to access numerous pharmaceuticals, improving our everyday lives.[‌1‌,‌2‌] In its elemental form, lithium metal is the most powerful reductant among the alkaline earth metals and, as such, has been harnessed in many chemical pursuits. A particularly outstanding example of the success of lithium metal was the development of reductive metalation reactions for the preparation of organolithium reagents, which have provided, and still offer, solutions to many synthetic challenges.[‌3‌] This is exemplified by the lack of success in the recent pursuit of less-pyrophoric processes to bypass the routine employment of lithium metal, especially at early stages of starting-material synthesis.[‌4‌] Perhaps, the success of lithium metal over the decades lies in its practicality, scalability, reproducibility, and standardized experimental setup.[‌5‌] In this regard, this chapter is an update on the most significant advances in the use of lithium metal in synthesis from 2013 to the first half of 2023. For the sake of clarity, the focus of this chapter is centered on highlighting the employment of lithium metal for the reduction of organic substrates, with a special emphasis on advances in experimental technique and substrate scope (‌Scheme 1‌). The chapter is organized into three main sections to emphasize the advances in the design of lithium metal sources (Section ‌8.1.1.4.1‌), strategies in experimental design and setup (Section ‌8.1.1.4.2‌), and synthetic approaches to access organic compounds (Section ‌8.1.1.4.3‌).

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References