Stereospecific syn-dichlorination of allylic amines enabled by identification of a superior stereo-directing group

• Published in: Communications chemistry Vol. 7; no. 1; pp. 277 - 7
• Main Authors: Im, Jeong Kyun, Choi, Jun-Ho, Chung, Won-jin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/403/935; 639/638/549/972; 639/638/77/889; Alkenes; Amines; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Chlorine; Molecular structure; Organic chemistry; Reaction mechanisms; Reagents
• ISSN: 2399-3669; 2399-3669
• DOI: 10.1038/s42004-024-01365-2

Alteration of a well-established reaction mechanism for access to different molecular structures is an inherently intriguing research subject. In that context, syn -stereospecific alkene dihalogenation draws attention as a long-standing problem in synthetic organic chemistry. The simplest approach would be the incorporation of an additional stereo-inverting step within the traditional anti -dihalogenation process. Surprisingly, this seemingly trivial idea turned out challenging, and no suitable stereo-directing group was known before our work. Herein, we describe a highly efficient syn -dichlorination of N -protected allylic amines through the anchimeric assistant phenomenon that has been inapplicable to alkene dihalogenation. Upon rational identification of a superior stereo-director, 1,8-naphthalimide, our practical reaction conditions with mild and convenient dichlorinating reagents can accommodate the formerly unemployable aryl alkenes in excellent yields (>95%) and stereospecificity (>50:1). DFT calculation suggests a concerted internal trapping mechanism without a discrete carbocationic species, which accounts for the conservation of the stereochemical integrity. Vicinal dihalogenation of alkenes is anti -stereospecific under conventional reaction conditions, however, syn -stereospecific alkene dihalogenation remains less explored. Here, the authors identify 1,8-naphthalimide as a superior stereo-director to achieve efficient syn -dichlorination of N -protected allylic amines with excellent yields and stereospecificity.