Organic comprehensive experimental design of the tunable regioselective 7-endo or 6-exo iodocyclization of olefins

Currently, the design of organic chemistry comprehensive experiments in our university is mainly based on the continuous synthesis experiment of the target compound, to consolidate the theoretical knowledge, proficient operation, and testing of the problem. However, in these experiments, students often focus on specific operations and lack thinking about the influence of different experimental operations and reaction conditions on reaction selectivity and experimental results, which is not conducive to discovering new problems and phenomena in experiments. Organic synthesis methodology is one of the main research directions of organic chemistry, focusing on the study of organic chemical reactions and mechanisms. Through reasonable synthesis methods and reaction condition design, more complex and functional organic molecules can be synthesized. The main strategy is to change one reaction condition while keeping others unchanged to find out the optimal conditions for the reaction based on multiple experiments. Given the lack of experimental content, including organic synthesis methodology strategies in the current undergraduate organic chemistry laboratory teaching at our university, the tunable regioselective 7-endo or 6-exo iodine cyclization reaction of olefins was developed as an organic chemistry comprehensive teaching experiment.

In this experiment, O-homoallyl benzimidate was used as the template substrate and N-iodosuccinimide (NIS) was used as the iodination reagent, and the effects on the selectivity and experimental results of the intramolecular electrophilic iodine cyclization reaction were investigated by changing the solvent, temperature, base, and gas atmosphere. The specific teaching practice process is as follows: First, the teacher shared experimental documents with students to familiarize them with experimental content and design questions (such as reaction conditions that affect the experimental results and the separation, purification, and identification methods of the products) and guides the students to preview the experimental content and improve their subjective initiative. Second, the teacher combined the standard reaction conditions of the 7-endo or 6-exo iodine cyclization reaction and conducted experimental design according to different solvents, temperatures, bases, and gas atmospheres, and students conducted the experiment in groups. In each group, two to three students conducted experiments with standard and variable conditions of the two iodine cyclizations in parallel. Finally, students in each group summarized and shared their experimental phenomena, records, and results. Then, they analyzed and discussed the overall data to understand the influence of different experimental variables on the reaction selectivity and results.

Through the investigation of different experimental conditions such as solvent, temperature, base, and gas atmosphere, the comprehensive experiment introduced the exploration strategy of organic synthesis methodology into the teaching experiment, prompted students to think about the impact of the change of reaction conditions on the reaction selectivity and experimental results, deepened their understanding of the reaction mechanism, and stimulated students' interest in learning and scientific research. The experiment includes preparation of substrates and optimization of reaction conditions, which allows students to practice the basic process of organic synthesis methodology research and realizes the purpose of combining teaching experiments and scientific research experiments. The experiment has the characteristics of cheap and easy-to-find reagents, simple and efficient substrate preparation, mild and controllable reaction conditions, and appropriate reaction time, so it is very suitable for comprehensive experimental teaching for undergraduates.

This comparative research approach to organic synthesis methodology not only allows students to practice fundamental scientific research processes in organic synthesis experiments but also effectively stimulates their enthusiasm while cultivating their abilities in scientific research innovation and comprehensive practical skills, thereby achieving the integration of teaching experiments with scientific research experiments.