Stereo-controlling Strategies for Underdeveloped Organic Dihalogenations

Won-jin Chung

Department of Chemistry, Gwangju Institute of Science and Technology

E-mail: wjchung@gist.ac.kr

Conventional electrophilic dihalogenation of alkenes generally proceeds via an anti-addition pathway through the intermediacy of a cationic three-membered cyclic halonium species.¹ This well-established transformation is one of the most widely utilized organic reactions because of its highly predictable stereospecificity.² However, it is extremely challenging to alter the diastereochemical course, and consequently, the complementary syn-dihalogenation process has been considerably under-developed,³ requiring new mechanistic approaches. Only recently, a few notable achievements were made by inverting one of the stereocenters after anti-addition using a carefully designed reagent system.⁴ Our group investigated report a conceptually distinctive strategy for the simultaneous double electrophilic activation of the two alkene carbons from the same side. Then, the resulting vicinal leaving groups can be displaced iteratively by nucleophilic halides to complete the syn-dihalogenation. For this purpose, thianthrenium dication was employed,⁵ and all possible combinations of chlorine and bromine were added onto internal alkenes successfully with excellent syn-stereospecificity.⁶ Of particular note is the regiodivergent syn-bromochlorination, in which both constitutional isomers can be accessed simply by reversing the addition sequence. Furthermore, the unprecedented syn-dibromination is also noteworthy.

References

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3. (a) Cresswell, A. J.; Eey, S. T.-C.; Denmark, S. E. Angew. Chem. Int. Ed.2015, 54, 15642. (b) Yoshimitsu, T.; Fukumoto, N.; Tanaka, T. J. Org. Chem.2009, 74, 696. (c) Denton, R. M.; Tang, X.; Przeslak, A. Org. Lett.2010, 12, 4678. (d) Yoshimitsu, T.; Fukumoto, N.; Nakatani, R.; Kojima, N.; Tanaka, T. J. Org. Chem.2010, 75, 5425. (e) Yoshimitsu, T.; Nakatani, R.; Kobayashi, A.; Tanaka, T. Org. Lett.2011, 13, 908.

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5. (a) Chen, J.; Li, J.; Plutschack, M. B.; Berger, F.; Ritter, T. Angew. Chem. Int. Ed.2020, 59, 5616. (b) Juliá, F.; Yan, J.; Paulus, F.; Ritter, T. J. Am. Chem. Soc.2021, 143, 12992.

6. Moon, H.; Jung, J.; Choi, J.-H.; Chung, W.-j. Nat. Commun.2024, 15, 3710.

* 졸업논문 교과목 수강자 세미나 필수 참석 안내
석사, 석박통합, 박사과정이 수강하는 <졸업논문연구학점 1~6>수강자는 학과에서 개최하는 목요일 정규세미나에 반드시 참석해야함.

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