Part I: Stereospecific syn-dihalogenations and regiodivergent syn-bromochlorination of alkenes via vicinal double activation strategy Part II: Catalytic, stereodivergent, diastereospecific dichlorination and site-selective syn-interhalogenation of alkenes via traceless stereo- modulation

Abstract

Part I. Whereas the conventional anti-dihalogenation of alkenes is a valuable synthetic tool with highly predictable stereospecificity, accessing the complementary syn-dihalogenation pathway remains challenging because of the restricted reaction mechanisms. To address the issue, a conceptually distinctive strategy is reported for the simultaneous vicinal double electrophilic activation of an alkene from the same side using a thianthrenium dication, followed by iterative displacement with nucleophilic halides. This method successfully enables the syn-dihalogenation of internal alkenes with all possible chlorine and bromine combinations, particularly achieving regiodivergent syn-bromochlorination. Notably, this protocol resolves critical limitations in the field by demonstrating the first highly stereoselective syn-dibromination of notoriously difficult aryl alkenes. Furthermore, the use of two different halogens results in unusual site-selectivity inaccessible via traditional methods, while the complementary behavior of geometrical isomers allows for rare stereoconvergent dibromination from E/Z mixtures. Collectively, this work provides a robust solution for syn-dihalogenation of both alkyl and aryl alkenes.

Part II. Direct access to syn-dihalogenation of alkenes requires an innovative alteration of the welldefined conventional mechanism and thus is considered an intriguing challenge in the field of organohalogen synthesis. Despite the remarkable recent achievements, including our own, there is still room for improvement in terms of the substrate scope, operational convenience, and mechanistic diversity. Here, by inverting the typical electronic properties of the electrophilic alkene activator and the halogen nucleophiles, a simple catalytic system was devised that operates via a reversed alkene addition sequence. After the initial formation of the chloriranium intermediate, the triflate anion serves as a traceless stereo-director that temporarily participates, alters the stereochemistry, and readily disappears. This mechanism is deceptively straightforward, but such a dual characteristic modulator must have delicately balanced nucleophilicity and leaving group ability at the same time. Upon realization of these conflicting criteria, the substrate scope of syn-dichlorination has been substantially generalized to include both E/Z-alkenes as well as more challenging cycloalkenes. Also, the unique halogen-first mechanism exhibited an unusual facial selectivity with respect to the pre-existing stereocenter. Furthermore, expanding the halogen scope to Br and I enabled site-selective syn-interhalogenation. In addition, the presence or absence of a stereo-modulator enabled stereodivergent dichlorination. Therefore, through our work, the syndihalogenation chemistry has been greatly diversified.