Stroup Bryan W, Szklennik Paul V, Forster Cornelia J, Serrano-Wu Michael H
Global Discovery Chemistry, Novartis Institutes for BioMedical Research Inc, Cambridge, MA 02139, USA.
Org Lett. 2007 May 10;9(10):2039-42. doi: 10.1021/ol070695+. Epub 2007 Apr 21.
The chemoselective functionalization of 5-bromo-2-chloro-3-fluoropyridine (1c) is described. Catalytic amination conditions (Pd2dba3, Xantphos, base) afford exclusively the bromide substitution product (2) for both secondary amines and primary anilines. A reversal in chemoselectivity is observed under neat conditions in the absence of palladium catalysis, with substitution at the 2-chloro position preferred to generate 3. Last, selective substitution of the 3-fluoro group is achieved under SNAr conditions to afford the dihalo adduct (4).
描述了5-溴-2-氯-3-氟吡啶（1c）的化学选择性官能团化反应。催化胺化条件（Pd2dba3、Xantphos、碱）对于仲胺和伯苯胺均专一性地得到溴取代产物（2）。在无钯催化的纯态条件下观察到化学选择性发生反转，优先在2-氯位置发生取代生成3。最后，在亲核芳香取代（SNAr）条件下实现了3-氟基团的选择性取代，得到二卤加合物（4）。
