Scalable Synthesis of Strained Cyclooctyne Derivatives

Modifications to the Popik synthesis of aza-dibenzocyclooctyne (DIBAC) derivatives are described, which avoids tedious purifications and dramatically improves the yield. A new and analogous route to biarylazacyclooctynone (BARAC) through an amide disconnection was also attempted. The BARAC derivatives prepared were found to be unstable under the conditions employed, undergoing a known rearrangement. Finally, the synthesis of a difluoro-DIBAC …