Using the Vapourtec E-Series flow chemistry system researchers from the Ludwig-Maximilians-Universitat Munchen have shown a procedure for functionalizing a range of heterocycles and various sensitive acrylates using the strong, non-nucleotide Knochel-Hauser base TMPMgCl.LiCl and the subsequent quenching with various electrophiles. The ability of the advanced Vapourtec V-3 pump to continuously process reagents of this type allows for the multi-gram scale-up of these reactions previously limited to small scale.
Continuous flow conditions with high rates of heat transfer and faster mixing give rise to more convenient, non-cryogenic conditions and improved selectivity’s compared to the equivalent batch reaction. The magnesiation of pyridines, pyrimidines, thiophenes, thiazoles and functionalized acrylates are described in excellent yields.
The magnesiation and quenching with neat DMF of 3-bromo-pyridine to give the formylated pyridine gave an excellent yield of 84%. The Vapourtec V-3 pump allowed the group to scale this reaction from 1.7 mmol to 45 mmol requiring no further optimisation. This was far superior to the batch conditions that was limited to 10 mmol due to the complication of competing oligomerization reaction occurring.Find out more Published papers
Read this paper on the Angewandte Chemie International Edition website.