Efficient Cross-Coupling of Secondary Alkyltrifluoroborates with Aryl Chlorides-Reaction Discovery Using Parallel Microscale Experimentation

摘要

Cross-coupling reactions and, in particular, the Suzuki-Miyaura reaction are among the most important reactions in modern organic synthesis. Although there are many effective protocols for the cross-coupling of secondary alkyl halides with aryl-metallics, the complementary cross-coupling of secondary (and potentially enantiomerically enriched) organometallics with aryl halides is a notable and significant unsolved problem. There have been at least two isolated examples of secondary boronic acids being cross-coupled. In the earliest example, cyclopen-tylboronic acid was cross-coupled in good yield with an aryl chloride (eq l). The second partners .seobutylboronic acid with an aryl bromide generating a mixture of the desired sec-butylarene along with the undesired isomerized n-butylated derivative (eq 2). However, in neither study was there development toward identifying a general solution to the challenge of cross-coupling secondary organometallics.