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 crosscoupling 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

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... 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. R 3 R 1 R 2 BF 3 K + Hal (1.1-1.3 equiv) R 1 , R 2 = Me, c-Pent, Cy Pd(OAc) 2 (2-5 mol%), n-BuPAd 2 (3-7.5 mol%) Cs 2 CO 3 (3 equiv), PhMe-H 2 O (10:1) R 3 R 2 R 1 R 3 = 2-MeO, 4-Ac, 3,5-diMeO, 4-CF 3 , etc. Hal = Cl, Br, I OMe OMe Me Me O Me Me Me MeO N N Me N F N X = Cl, 87% yield X = Cl, 78% yield X = Cl, 51% yield X = Br, 77% yield X = Cl, 87% yield X = Cl, 88% yield X = Cl, 77% yield X = Br, 87% yield S e l e c t e d e x a m p l e s : SYNFACTS Contributors: