An alternative synthesis of cycloalkyl-substituted CPA catalysts and application in asymmetric protonation reactions

Abstract

An alternative synthesis of cycloalkyl-substituted CPA catalysts is reported. A Negishi coupling offers improved yields and purity of the necessary 1,3,5-tri(cycloalkyl)benzenes. Limitations in the use of commercial organozinc reagents have been identified and a robust procedure for the preparation of these reagents is detailed. Similarly, a robust procedure for the key Kumada coupling is also provided. The route is demonstrated by preparation of three different tri(cycloalkyl)aryl-substituted CPAs and the utility of these catalysts in asymmetric protonation reactions is shown.