In conclusion, we have developed SPAAC with secondary interactions including aminal-imine and boronic acid ester formations. The reaction rate-acceleration of SPAAC by boronic acid ester was much more effective, and SPAAC proceeded regioselectively. Therefore, the secondary interaction is a promising strategy for promoting and regioselective SPAAC. It was expected that the presence of a hydroxy group on cyclooctynes would contribute to the improvement of their lipophilicity. We are now developing alkyne 4a-and azide 5counterparts that could bind various molecules such as biomolecules and fluorescent molecules.