Scalable Palladium-Catalyzed C(sp3)–H Carbonylation of Alkylamines in Batch and Continuous Flow,Organic Process Research & Development

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Scalable Palladium-Catalyzed C(sp3)–H Carbonylation of Alkylamines in Batch and Continuous Flow
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2023-03-15 , DOI: 10.1021/acs.oprd.2c00378
Jacek Zakrzewski ₁ , Polina Yaseneva ₂ , Connor J. Taylor _{3,

4} , Matthew J. Gaunt _{1,

4,

5} , Alexei A. Lapkin _{1,

4}

Affiliation

Development of scalable processes for C(sp3)–H oxidative carbonylation of alkylamines is reported to provide convenient access to the β-lactam scaffol d. A study of the kinetics of the process revealed that the reaction is CO-limited even at elevated pressures and that there is an optimal CO concentration for the most effective outcome─this understanding led to an increase in the turnover number from 7 to 420 in the optimized process. Two scalable processes were then developed: a batch process, characterized by a very low catalyst loading, and a continuous process for an oxidative C–H carbonylation reaction that uses a copper-tube-flow reactor as a heterogeneous source of Cu²⁺ oxidant. The continuous process was tested on oxidative carbonylation of several alkylamines, yielding very good results with virtually no optimization required. This study thereby builds upon the utility of flow chemistry applications to oxidative carbonylations and scalable metal-catalyzed processes more generally.

中文翻译：

可扩展的钯催化 C(sp3)–H 烷基胺在分批和连续流中的羰基化反应

据报道，开发用于烷基胺的 C(sp3)-H 氧化羰基化的可扩展工艺可以方便地获得 β-内酰胺支架 d。对该过程的动力学研究表明，即使在高压下，该反应也是 CO 限制的，并且存在最佳 CO 浓度以获得最有效的结果——这种理解导致营业额从 7 增加到 420优化过程。然后开发了两个可扩展的工艺：一个以非常低的催化剂负载为特征的间歇工艺，以及一个使用铜管流式反应器作为 Cu 2+ 的非均相来源的氧化 C-H 羰基化反应的连续^工艺氧化剂。连续过程在几种烷基胺的氧化羰基化反应中进行了测试，产生了非常好的结果，几乎不需要优化。因此，这项研究建立在流动化学应用到氧化羰基化和更普遍的可扩展金属催化过程的效用之上。

更新日期：2023-03-15

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