Development of Scalable Routes to 1-Bicyclo[1.1.1]pentylpyrazoles

The application of bicyclo[1.1.1]pentanes (BCPs) as phenyl bioisosteres has garnered significant attention, as these structural motifs can improve the physiochemical profiles of drug candidates. Despite the potential of using 1-bicyclo[1.1.1]pentylpyrazoles (BCPPs) as 1-phenylpyrazole bioisosteres, this area remains underexplored because of the relative lack of reliable synthetic methods for the preparation of BCPPs. Herein we address this synthetic gap and report the development of novel and scalable routes to generate a host of BCPPs.