Department of Process & Analytical Chemistry, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
Org Lett. 2016 Jul 1;18(13):3218-21. doi: 10.1021/acs.orglett.6b01456. Epub 2016 Jun 23.
3-(Hetero)arylindazoles are important motifs in several biologically active compounds. Mild and flexible palladium-mediated Negishi reaction conditions are reported for the introduction of (hetero)aryl moieties at the 3-position of N(2)-SEM-protected indazoles in high yields. The requisite Zn-species are readily obtained via regioselective deprotonation and subsequent transmetalation. The methodology tolerates a variety of functional groups on both coupling partners and has been extended to bis-haloarene and heteroarene coupling partners where the most reactive halogen reacts first, leaving the second halogen for subsequent functionalization.
3-(杂)芳基吲唑是许多具有生物活性的化合物中的重要结构单元。本文报道了温和、灵活的钯介导的 Negishi 反应条件，可在 N(2)-SEM 保护的吲唑的 3-位高收率地引入(杂)芳基。所需的 Zn 物种可通过区域选择性去质子化和随后的转金属化来轻易获得。该方法对偶联物上的各种官能团具有良好的耐受性，并已扩展到双卤代芳烃和杂芳烃偶联物中，其中最活泼的卤素首先反应，留下第二个卤素用于后续官能化。
