Demkiw Krystyna M, Remmerswaal Wouter A, Sheikh Asma, Sheikh Ibrahim N, Witt Collin H, Codée Jeroen D C, Woerpel K A
Department of Chemistry, New York University, 100 Washington Square East, New York, New York 10003, United States.
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2300 RA, The Netherlands.
J Org Chem. 2025 Jul 18;90(28):9673-9687. doi: 10.1021/acs.joc.4c03128. Epub 2025 Jul 3.
Tetrahydropyran acetals bearing a fluorine atom adjacent to the acetal carbon atom can undergo highly stereoselective substitution reactions with nucleophilic alkenes to give the 1,2- products. By contrast, the chlorine- and bromine-substituted acetals give the 1,2- products. These results can be understood by considering oxocarbenium ion intermediates and their conformational preferences, which are dictated by hyperconjugative effects from axial substituents, with F ≪ H < Cl < Br. Reactions of the corresponding five-membered-ring acetals are also 1,2- selective in the case of fluorine and 1,2- selective with chlorine- and bromine-substituted acetals, but selectivities showed different trends of reactivity vs selectivity. The reactions with the five-membered-ring acetal were interpreted as requiring anomeric halides as reactive intermediates because of the conditions required to obtain substitution products.
在缩醛碳原子相邻位置带有氟原子的四氢吡喃缩醛，可与亲核烯烃发生高度立体选择性的取代反应，生成1,2 - 产物。相比之下，氯代和溴代缩醛也生成1,2 - 产物。通过考虑氧鎓离子中间体及其构象偏好可以理解这些结果，其由轴向取代基的超共轭效应决定，顺序为F ≪ H < Cl < Br。相应的五元环缩醛的反应在氟的情况下也是1,2 - 选择性的，而氯代和溴代缩醛则是1,2 - 选择性的，但选择性显示出不同的反应性与选择性趋势。由于获得取代产物所需的条件，与五元环缩醛的反应被解释为需要异头卤化物作为反应中间体。
