Iodination-Group-Transfer Reactions to Generate Trisubstituted Iodoalkenes with Regio- and Stereochemical Control

The regio- and stereodefined synthesis of trisubstituted alkenes remains a significant synthetic challenge. Herein, a method is developed for producing regio- and stereodefined trisubstituted iodoalkenes by diverting intermediates from an iodination-electrophilic-cyclization mechanism. Specifically, cyclized sulfonium ion-pair intermediates are diverted to alkenes by ring-opening with nucleophilic iodide. Alternatively, scavenging of the iodide by AgOTf prevents ring-opening, enabling isolation of the sulfonium ion-pair intermediate. Isolation of the ion pair enables access to complementary reactivity, including ring-opening by alternative nucleophiles (i.e., amines), yielding trisubstituted acyclic alkenes and an example acyclic tetrasubstituted alkene. X-ray crystallographic determination of reaction intermediates and products confirms that the initial electrophilic-cyclization step sets the stereo- and regiochemistry of the product. The products serve as synthetic building blocks by readily participating in downstream functionalization reactions, including oxidation, palladium-catalyzed cross-coupling, and nucleophilic displacement.

Automated summary

A method is developed for producing regio- and stereodefined trisubstituted iodoalkenes by diverting intermediates from an iodination-electrophilic-cyclization mechanism. The method involves the ring-opening of cyclized sulfonium ion-pair intermediates with nucleophilic iodide to form alkenes. The isolation of the sulfonium ion-pair intermediate allows access to complementary reactivity and the products serve as synthetic building blocks.