Cross-Coupling of Secondary Alkyltrifluoroborates with Aryl Chlorides

secondary alkyltrifluoroborates - cross-coupling - aryl chlorides - parallel microscale experimentation

Significance

This valuable synthetic method demonstrates the usefulness of the parallel microscale experimentation approach in the development of new methodology in synthetic chemistry. Conditions for a smooth Pd-catalyzed cross-coupling between secondary alkyltrifluoroborates and aryl or heteroaryl chlorides have been found after the screening of a number of phosphine ligands. The parallel microscale experimentation is proved to be a very promising method of investigation in synthetic chemistry that will find more and more applications not only in industry, but also in the academic research.

Comment

The experimentation was performed in 10 mmol scale in a 96-plate reactor, and 12 ligands were screened for each substrate, so that the optimization required much less time compared to standard optimization technique. The cross-coupling of isopropyl organometallics is often complicated by the formation of a linear product. As it is shown by the given experimental data, this side reaction takes place to a various extent with different substrate-catalyst pairs and the results are often difficult to predict. That makes a fast screening procedure for cross-coupling reactions quite desirable.