Synthesis of 3-aryl-2-phosphinoimidazo[1,2-a]pyridine ligands for use in palladium-catalyzed cross-coupling reactions

Abstract

3-Aryl-2-phosphoimidazo[1,2-a]pyridine ligands were prepared via two complimentary synthetic routes and were evaluated in the Suzuki–Miyaura and Buchwald–Hartwig amination cross-coupling reactions.

Synthesis of 3-aryl-1-phosphinoimidazo[1,5-a]pyridine ligands for use in Suzuki–Miyaura cross-coupling reactions

“…2 ). 46 In this current work, we have developed synthetic protocols to access 3-aryl-1-phosphinoimidazo[1,5- a ]pyridine ligands 4 from 2-aminomethylpyridine (3) as our starting material.…”

“…As from our previous investigations, we successfully synthesized our phosphorus ligands via the palladium-catalyzed cross-coupling phosphination reaction using the iodo precursors with DIPPF ligand in the presence of Cs 2 CO 3 as the base in 1,4-dioxane under reflux. 46 Iodo substrates 10a–j were successfully phosphinated at the C-1 position via the palladium-catalyzed reaction with diphenylphosphine and dicyclohexylphosphine to give new ligands 4a–s in low to moderate yields. 49 Many attempts to attach a di- tert -butylphosphine group to the iodo intermediates met with complete failure.…”

“…Our success in achieving excellent selectivity with our 2,3-diiodoimidazo[1,2- a ]pyridine in our previous work did not translate well to this system. 46 No selectivity was observed when attempting to phosphinate or to couple an aryl ring onto the 1,3-diiodoimidazo[1,5- a ]pyridine system, usually yielding a rough 1 : 1 ratio of inseparable regioisomers.…”

Suzuki‐Miyaura and Buchwald‐Hartwig Cross‐Coupling Reactions Utilizing a Set of Complementary Imidazopyridine Monophosphine Ligands

“…To the best of our knowledge, no one has investigated the catalytic activity of cross‐coupling reactions based on imidazopyridines as heterocyclic ligand types. Recently, our group disclosed the preparation of monophosphine ligands such as 3‐aryl‐2‐phosphinoimidazo[1,2‐ a ]pyridine 1 [32] and 3‐aryl‐1‐phosphinoimidazo[1,5‐ a ]pyridine 2 [33] and showcased them in selected brief cross‐coupling reactions (Figure 2). These two ligands possess hemilable N ‐chelating group providing weak coordinating property, offering potential for dynamic interaction for catalyst longevity, has high potential of ligand tunability with steric and electronic properties by the incorporation of different aryl rings, and finally has tunable P‐donor group providing electron richness.…”