A Comprehensive History of Arynes in Natural Product Total Synthesis

A comprehensive historical review of arynes in natural product total synthesis is presented. Researchers accomplished the task of generating total syntheses, which utilized arynes in ways that built complexity or introduced motifs essential to the completion of their targets. The methods by which the researchers accomplished this task reflected the versatility of arynes as reactive intermediates for synthesis. The first instance in which arynes were applied to the total synthesis of natural products was reported by Kametani and coworkers at Tohoku University in 1967. Kametani's synthesis of cryptaustoline and cryptowoline marked the beginning of a long-term research program to utilize aryne intermediates in alkaloid synthesis that would continue for a period of more than 10 years.