康 · 学术 | Reaction of the Day No. 1158

DalPhos Nickel-Catalyzed C2?H Arylation of 1,3-Azoles Using a Dual-Base SystemNicholas E. Bodé and Mark Stradiotto*Department of Chemistry, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada—Org. Lett. 2023, 25 (49), 8809-8813.Recommended by Shi Li_ MOCABSTRACT: Mark Stradiotto etal report a versatile method for C2 functionalization of (benz)oxazoles and (benzo)thiazoles employing a tert-butylimino-tri(pyrrolidino)phosphorane/sodium trifluoroacetate (BTPP/NaTFA) “dualbase” system in combination with an air-stable Ni(II) precatalyst containing either CyPAd-DalPhos or PhPAd-DalPhos. These catalyst systems enable access to a reaction scope that encompasses a range of challenging oxidative addition partners, including (hetero)aryl chlorides as well as pivalates, tosylates, and other related phenol derivatives. The utility of this method is demonstrated through the derivatization of an active pharmaceutical ingredient and 5 mmol synthesis of a thiazole derivative.Background and This WorkCatalyst OptimizationSelected Substrate ScopeNi-catalyzed C2?H Arylation of (benzo)thiazolesSummary and CommentsProf. Mark Stradiotto’s group reported  a broadly useful Ni-catalyzed protocol for the C2?H arylation of 1,3-azoles with diverse and pharmaceutically relevant (hetero)aryl chlorides and phenol derived electrophiles. This protocol makes use of a BTPP/NaTFA dual-base system in combination with air-stable Ni(II) precatalysts (5 or 10 mol %) featuring CyPAd-DalPhos or PhPAd-DalPhos for transformations of (benz)oxazoles and (benzo)thiazoles, respectively, thus circumventing the use of more expensive phosphazene base (P2-Et) and air-sensitive Ni(COD)2 (≥10 mol %). These results probe the mechanisms of such C?C cross-couplings, particularly in comparison to related C?N and C?O bond-forming reactions.Mark Stradioto教授小组报道了一种镍催化的1,3-唑类衍生物C2?H键与各种药物相关的（杂）芳基氯化物或酚类衍生物等亲电试剂的碳氢键芳基化反应。该反应使用BTPP/NaTFA双碱体系和含有CyPAd-DalPhos或PhPAd-DalPhos空气稳定的Ni（II）预催化剂（5或10mol%）组合，分别实现了（苯并）噁唑和（苯并）噻唑的转化，避免使用更昂贵的磷腈碱（P2-Et）和空气敏感的Ni(COD)2（≥10mol%)。特别是与相关的C?N和C?O键形成反应相比, 该小组发现了C?C键交叉偶联的不同反应机制。