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.

Repurposing π Electrophilic Cyclization/Dealkylation for Group Transfer.

A metal-free regio- and stereocontrolled group-transfer route toward the synthesis of trisubstituted alkenes is described. In this route, an electrophilic heterocyclization is followed by ring-opening group transfer. Specifically, a thioboration reaction transforms readily available alkynyl sulfide precursors into alkenyl boronates and alkenyl sulfides with defined regio- and stereochemistry in one synthetic step using commercially available B-chlorocatecholborane (ClBcat). Mechanistic studies identified the likely pathway as proceeding through zwitterionic rather than haloborated intermediates. The regio- and stereochemistry set in the initial cyclization step is preserved in the final acyclic alkene product, producing alkenes with up to four modifiable substituents with predictable regio- and stereochemistry. Downstream functionalization reactions showcase the versatility of the substitutions of the resulting alkenes. The mechanistic concept maps onto future reaction designs, given the abundance of known electrophiles and nucleophiles for electrophilic heterocyclization/dealkylation sequences.