Zhang Xin, Ren Jingyun, Tan Siu Min, Tan Davin, Lee Richmond, Tan Choon-Hong
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371 Singapore.
Science and Mathematics Cluster, Singapore University of Technology and Design, 8 Somapah Road, 487372 Singapore.
Science. 2019 Jan 25;363(6425):400-404. doi: 10.1126/science.aau7797.
Bimolecular nucleophilic substitution (S2) plays a central role in organic chemistry. In the conventionally accepted mechanism, the nucleophile displaces a carbon-bound leaving group X, often a halogen, by attacking the carbon face opposite the C-X bond. A less common variant, the halogenophilic S2X reaction, involves initial nucleophilic attack of the X group from the front and as such is less sensitive to backside steric hindrance. Herein, we report an enantioconvergent substitution reaction of activated tertiary bromides by thiocarboxylates or azides that, on the basis of experimental and computational mechanistic studies, appears to proceed via the unusual S2X pathway. The proposed electrophilic intermediates, benzoylsulfenyl bromide and bromine azide, were independently synthesized and shown to be effective.
双分子亲核取代反应（S2）在有机化学中起着核心作用。在传统公认的机理中，亲核试剂通过进攻与碳相连的离去基团X（通常是卤素）的C-X键对面的碳面，来取代该离去基团。一种不太常见的变体，即亲卤S2X反应，涉及X基团从正面进行初始亲核进攻，因此对背面位阻不太敏感。在此，我们报道了一种由硫代羧酸盐或叠氮化物引发的活化叔溴化物的对映收敛取代反应，基于实验和计算机理研究，该反应似乎通过不寻常的S2X途径进行。所提出的亲电中间体，苯甲酰基亚磺酰溴和溴化叠氮，已被独立合成并证明是有效的。
