An Alternative Synthesis of Cycloalkyl-Substituted CPA Catalysts and Application in Asymmetric Protonation Reactions**

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.

Automated summary

An alternative synthesis of cycloalkyl-substituted CPA catalysts using Negishi coupling and Kumada coupling has been reported for improved yields and purity. The limitations of commercial organozinc reagents were identified and a robust procedure for their preparation was detailed. The route was demonstrated by preparing three different tri(cycloalkyl)aryl-substituted CPAs and their utility in asymmetric protonation reactions was shown.