Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles,Chemical Science

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Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles
Chemical Science ( IF 7.6 ) Pub Date : 2021-09-15 , DOI: 10.1039/d1sc04176b
Jeff Y F Wong ₁ , Christopher G Thomson ₁ , Filipe Vilela _{1,

2} , Graeme Barker _{1,

2}

Affiliation

Tetrazoles play a prominent role in medicinal chemistry due to their role as carboxylate bioisosteres but have largely been overlooked as C–H functionalisation substrates. We herein report the development of a high-yielding and general procedure for the heterobenzylic C–H functionalisation of 5-alkyltetrazoles in up to 97% yield under batch conditions using a metalation/electrophilic trapping strategy. Through the use of thermal imaging to identify potentially unsafe exotherms, a continuous flow procedure using a flash chemistry strategy has also been developed, allowing products to be accessed in up to 95% yield. This enabled an extremely high productivity rate of 141 g h⁻¹ to be achieved on an entry-level flow system.

中文翻译：

快速化学可实现 5-烷基四唑的高生产率金属化取代

四唑由于其作为羧酸生物等排体的作用而在药物化学中发挥着重要作用，但作为 C-H 功能化底物在很大程度上被忽视了。我们在此报告了使用金属化/亲电捕获策略在批量条件下对 5-烷基四唑进行杂苄基 C-H 官能化的高产率和通用程序的开发，产率高达 97%。通过使用热成像来识别潜在不安全的放热，还开发了使用快速化学策略的连续流动程序，使产品的产率高达 95%。这使得在入门级流系统上实现了 141 gh ^-1的极高生产率。

更新日期：2021-09-22

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